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A number sign (#) is used with this entry because of evidence that acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate (ARLIAK) is caused by homozygous or compound heterozygous mutation in the SLC13A3 gene (606411) on chromosome 20q13. Description Acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate (ARLIAK) is an autosomal recessive disorder characterized by acute reversible neurologic deterioration in the context of a febrile illness. The disorder is associated with transient leukoencephalopathy on brain imaging concurrent with the acute episode, as well as persistently increased excretion of dicarboxylic acids, particularly alpha-ketoglutarate (summary by Dewulf et al., 2019). Clinical Features Dewulf et al. (2019) reported 2 unrelated patients with a similar acute febrile-induced neurologic disorder associated with reversible leukoencephalopathy and increased urinary excretion of alpha-ketoglutarate. The first patient presented at age 15 years with acute neurologic deterioration, drowsiness, dysarthria, and ataxia 2 days after a febrile illness. Brain imaging showed white matter abnormalities in the periventricular regions and corpus callosum, as well as in other regions. Laboratory studies showed increased urinary excretion of alpha-ketoglutarate, succinate, fumarate, and N-acetylaspartate (NAA). These organic acids were also increased in the cerebrospinal fluid (CSF). The patient had complete resolution of all neurologic symptoms and almost complete resolution of white matter abnormalities after recovering from the acute illness. He had no recurrent episodes during a 10-year follow-up. The second patient presented with a similar phenotype during a febrile illness at age 5 years. She had hypotonia, abnormal movements, and dysarthria associated with white matter abnormalities and increased urinary alpha-ketoglutarate and NAA. CSF analysis showed increased lactate, but studies of other organic acids were not performed. She had a rapid improvement with persistent mild ataxia, but had a similar episode 6 years later. One year later, brain imaging showed some residual mild white matter abnormalities and cerebellar atrophy. Both patients had persistent urinary excretion of dicarboxylic acids, mainly alpha-ketoglutarate. Inheritance The transmission pattern of ARLIAK in the families reported by Dewulf et al. (2019) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 unrelated patients with ARLIAK, Dewulf et al. (2019) identified homozygous or compound heterozygous mutations in the SLC13A3 gene (606411.0001-606411.0003). There were 2 missense mutations and 1 splice site mutation. Transfection of the 2 missense mutations into HEK293 cells showed that both caused a significant reduction in transport of alpha-ketoglutarate, succinate, and NAA compared to wildtype. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. INHERITANCE \- Autosomal recessive MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Encephalopathy, acute \- Neurologic decompensation, acute \- Drowsiness \- Ataxia \- Dysarthria \- Abnormal movements \- Leukoencephalopathy, reversible, transient \- Mild white matter abnormalities may persist LABORATORY ABNORMALITIES \- Increased urinary dicarboxylic acids \- Increased urinary alpha-ketoglutarate \- Increased urinary fumarate \- Increased urinary succinate \- Increased urinary NAA \- Increased CSF alpha-ketoglutarate \- Increased CSF NAA \- Increased CSF lactate MISCELLANEOUS \- Episodes are triggered by febrile illness \- Symptoms during the acute illness mostly resolve \- Variable severity and persistence of abnormal neurologic symptoms \- Two unrelated patients have been reported (last curated April 2019) MOLECULAR BASIS \- Caused by mutation in the solute carrier family 13 (sodium-dependent dicarboxylate transporter), member 3 gene (SLC13A3, 606411.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LEUKOENCEPHALOPATHY, ACUTE REVERSIBLE, WITH INCREASED URINARY ALPHA-KETOGLUTARATE	None	26,700	omim	https://www.omim.org/entry/618384	2019-09-22T15:42:12	{"omim": ["618384"]}
Darier disease is a skin condition characterized by wart-like blemishes on the body. The blemishes are usually yellowish in color, hard to the touch, mildly greasy, and can emit a strong odor. The most common sites for blemishes are the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear. The mucous membranes can also be affected, with blemishes on the roof of the mouth (palate), tongue, inside of the cheek, gums, and throat. Other features of Darier disease include nail abnormalities, such as red and white streaks in the nails with an irregular texture, and small pits in the palms of the hands and soles of the feet. The wart-like blemishes characteristic of Darier disease usually appear in late childhood to early adulthood. The severity of the disease varies over time; affected people experience flare-ups alternating with periods when they have fewer blemishes. The appearance of the blemishes is influenced by environmental factors. Most people with Darier disease will develop more blemishes during the summertime when they are exposed to heat and humidity. UV light; minor injury or friction, such as rubbing or scratching; and ingestion of certain medications can also cause an increase in blemishes. On occasion, people with Darier disease may have neurological disorders such as mild intellectual disability, epilepsy, and depression. Learning and behavior difficulties have also been reported in people with Darier disease. Researchers do not know if these conditions, which are common in the general population, are associated with the genetic changes that cause Darier disease, or if they are coincidental. Some researchers believe that behavioral problems might be linked to the social stigma experienced by people with numerous skin blemishes. A form of Darier disease known as the linear or segmental form is characterized by blemishes on localized areas of the skin. The blemishes are not as widespread as they are in typical Darier disease. Some people with the linear form of this condition have the nail abnormalities that are seen in people with classic Darier disease, but these abnormalities occur only on one side of the body. ## Frequency The worldwide prevalence of Darier disease is unknown. The prevalence of Darier disease is estimated to be 1 in 30,000 people in Scotland, 1 in 36,000 people in northern England, and 1 in 100,000 people in Denmark. ## Causes Mutations in the ATP2A2 gene cause Darier disease. The ATP2A2 gene provides instructions for producing an enzyme abbreviated as SERCA2. This enzyme acts as a pump that helps control the level of positively charged calcium atoms (calcium ions) inside cells, particularly in the endoplasmic reticulum and the sarcoplasmic reticulum. The endoplasmic reticulum is a structure inside the cell that is involved in protein processing and transport. The sarcoplasmic reticulum is a structure in muscle cells that assists with muscle contraction and relaxation by releasing and storing calcium ions. Calcium ions act as signals for a large number of activities that are important for the normal development and function of cells. SERCA2 allows calcium ions to pass into and out of the cell in response to cell signals. Mutations in the ATP2A2 gene result in insufficient amounts of functional SERCA2 enzyme. A lack of SERCA2 enzyme reduces calcium levels in the endoplasmic reticulum, causing it to become dysfunctional. SERCA2 is expressed throughout the body; it is not clear why changes in this enzyme affect only the skin. Some researchers note that skin cells are the only cell types expressing SERCA2 that do not have a "back-up" enzyme for calcium transport. This dependence on the SERCA2 enzyme may make skin cells particularly vulnerable to changes in this enzyme. The linear form of Darier disease is caused by ATP2A2 gene mutations that are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. There have been no known cases of people with the linear form of Darier disease passing it on to their children. ### Learn more about the gene associated with Darier disease * ATP2A2 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. The linear form of Darier disease is generally not inherited but arises from mutations in the body's cells that occur after conception. These alterations are called somatic mutations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Darier disease	c1852296	26,701	medlineplus	https://medlineplus.gov/genetics/condition/darier-disease/	2021-01-27T08:25:39	{"gard": ["6243"], "mesh": ["C565125"], "omim": ["124200"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that orofaciodigital syndrome XIV (OFD14) is caused by homozygous or compound heterozygous mutation in the C2CD3 gene (615944) on chromosome 11q13. Clinical Features Thauvin-Robinet et al. (2014) reported a 4-year-old boy, born of consanguineous parents, with a severe form of orofaciodigital syndrome. Facial features included microcephaly (-5 SD) with trigonocephaly, telecanthus, upslanting palpebral fissures, microretrognathia, cleft palate, cleft and lobulated tongue, buccal frenula, lingual hamartoma, absent epiglottis, and supernumerary teeth. He had broad and duplicated halluces, postaxial polydactyly of the hands, and micropenis. Neurologic features included retinopathy and severe intellectual disability with no speech. Brain imaging showed vermian hypoplasia with the molar tooth sign, hypoplasia of the corpus callosum, subarachnoid cysts in the posterior fossa, and incomplete myelination of the white matter. A similarly affected sib, who also had cardiac manifestations, died in the neonatal period. In an unrelated family, a 22-week-old fetus was found to have postaxial polydactyly of the hands and broad, duplicated halluces similar to the first patient. Dysmorphic facial features, microcephaly, and micropenis were also reported in the fetus. Cortes et al. (2016) described 2 fetuses from a Lebanese-Palestinian family with a 'skeletal ciliopathy.' In the first fetus (G2P1), prenatal ultrasound showed Dandy-Walker malformation, short tubular bones, polydactyly, and renal cysts. Autopsy revealed a female fetus with facial dysmorphism including microphthalmia, hypertelorism, flat and broad nasal bridge, dysplastic and posteriorly rotated ears, micrognathia, and high-arched palate, as well as preaxial polydactyly of the feet presenting as a duplicated and bent hallux, brachydactyly, short ribs, short bent tubular bones, trident acetabula, and a number of ductal kidney cysts. The anus was anteriorly located, and atypical lung lobation, symmetrical liver, and mobile cecum were observed. The brain was not examined, in accordance with parental wishes. The second fetus (G3P1) was male and exhibited similar features, including preaxial polydactyly of the hands and feet that presented as duplication of the thumb and triplication of the hallux, and postaxial polydactyly of the hands. In addition, atrial septal defect, ambiguous genitalia with micropenis, and mobile cecum were observed. Brain autopsy showed holoprosencephaly, Dandy-Walker malformation with a dilated cisterna magna and vermis aplasia, cerebellar hypoplasia, polymicrogyria, and hydrocephalus. The authors noted clinical overlap between various forms of orofaciodigital syndrome (OFDS) and short-rib thoracic dysplasia syndromes (see 208500). Boczek et al. (2018) studied 5 patients from 3 families with 'ciliopathy pedigrees' and mutations in the C2CD3 gene (see MOLECULAR GENETICS). In family 1, the proband had microcephaly, orofacial clefting, natal tooth on mandibular alveolus, lingual masses, microretrognathia, bilateral retinal colobomas, postaxial polydactyly of the feet and left hand, bilateral cryptorchidism, and hypotonia. MRI showed a Dandy-Walker malformation, molar tooth sign (MTS), bilateral symmetric hyposulcation of the brain with rudimentary/absent sylvian fissures, insula, and operculum, subependymal gray matter heterotopia, and rudimentary-appearing hippocampal formations. Renal ultrasound showed bilateral pelviectasis, and echocardiogram revealed a small patent ductus arteriosus (PDA). At 23 months of age, the patient was tracheostomy- and gastrostomy-dependent, and had global developmental delays and sleep-disordered breathing. His older sister, who had a clinical diagnosis of OFD, exhibited similar congenital anomalies, including microcephaly, ankyloglossia, bifid tongue, tongue hamartomas, incomplete cleft of the upper lip, polydactyly of all 4 extremities, and bilateral optic nerve colobomas. She also had global developmental delay, and MRI showed a simplified gyral pattern, limbic system hypoplasia, mild cerebellar hypoplasia, and gray matter heterotopia. In the second family, 2 pregnancies were terminated due to occipital encephalocele on prenatal ultrasound at 13 to 14 weeks. Other abnormalities included sloping forehead, bifid tongue, microretrognathia, ventricular septal defect, and short webbed neck. In family 3, the male proband exhibited significant micrognathia, malformed nodular tongue with absence of the anterior third of the tongue, tight frenulum, bilaterally low-set posteriorly rotated ears, bulbous nose with long vertical crease, and very mild epispadias. Brain MRI showed MTS, dilation of third and fourth ventricles, midline cerebellar cleft, and thinning of the corpus callosum with atrophy of the posterior aspect of the body and absence of the splenium, features which the authors noted were consistent with a diagnosis of Joubert syndrome. Skeletal survey and renal ultrasound were normal. At last follow-up, the patient was being fed via gastrostomy to prevent aspiration, and had bilateral retina colobomas, global hypotonia with stiff upper extremities, and developmental delays. Inheritance The transmission pattern of OFD14 in the family reported by Thauvin-Robinet et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In a 4-year-old boy with orofaciodigital syndrome, Thauvin-Robinet et al. (2014) identified a homozygous truncating mutation in the C2CD3 gene (R62X; 615944.0001). The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Sequencing the coding exons of the C2CD3 gene in 34 patients with OFD identified 1 fetus who was compound heterozygous for 2 mutations in the C2CD3 gene (615944.0002 and 615944.0003). Functional studies of the 3 variants were not performed, but Thauvin-Robinet et al. (2014) demonstrated that C2CD3 is required for cilium assembly and function, consistent with OFD being a ciliopathy. Moreover, hypomorphic or null mutations in this gene in mice cause a phenotype consistent with a ciliopathy. From a cohort of 43 French Canadian patients from 35 families diagnosed with Joubert syndrome (see 213300), Srour et al. (2015) identified 2 sibs (family 472) who were compound heterozygous for a missense (G1743C) and a nonsense (R1977X) mutation in the C2CD3 gene. The patients exhibited MTS and severe global developmental delay with hypotonia and ataxia, but information regarding oral, facial, and digital features was not reported. In 2 fetuses with a 'skeletal ciliopathy' from a Lebanese-Palestinian family, Cortes et al. (2016) identified compound heterozygosity for a missense (W65C) and a nonsense (I477X) mutation in the C2CD3 gene. In 5 children from 3 unrelated 'ciliopathy pedigrees,' Boczek et al. (2018) performed whole-exome sequencing and identified compound heterozygous mutations in the C2CD3 gene in all (see, e.g., 615944.0004 and 615944.0005). The unaffected parents were each heterozygous for 1 of the mutations, which were either not present or present at extremely low frequency (less than 0.001%) in the gnomAD database. Noting the phenotypic diversity exhibited by their patients, the authors concluded that biallelic variants in C2CD3 can cause a spectrum of ciliopathy disorders. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (-5 SD) \- Trigonocephaly Face \- Facial dysmorphism \- Micrognathia \- Microretrognathia Ears \- Dysplastic ears \- Low-set ears \- Posteriorly rotated ears Eyes \- Telecanthus \- Upslanting palpebral fissures \- Retinitis \- Retinal coloboma \- Optic nerve coloboma Mouth \- Cleft lip \- Maxillary alveolar clefting \- Mandibular alveolar clefting \- Cleft palate \- Cleft tongue \- Lobulated tongue \- Lingual hamartoma \- Lingual lipoma \- Lingual fibroma \- Buccal frenula Teeth \- Supernumerary teeth \- Natal teeth CARDIOVASCULAR Heart \- Cardiac malformation \- Ventricular septal defect \- Atrial septal defect Vascular \- Patent ductus arteriosus RESPIRATORY Larynx \- Absent epiglottis: Lung \- Atypical or absent lung lobation CHEST Ribs Sternum Clavicles & Scapulae \- Short ribs ABDOMEN Liver \- Symmetrical liver Gastrointestinal \- Anteriorly placed anus \- Mobile cecum \- Feeding by gastrostomy tube GENITOURINARY External Genitalia (Male) \- Micropenis \- Epispadias Internal Genitalia (Male) \- Cryptorchidism Kidneys \- Bilateral pelviectasis \- Ductal cysts SKELETAL Skull \- Microcephaly Pelvis \- Trident acetabulum Limbs \- Short bent tubular bones Hands \- Postaxial polydactyly \- Preaxial polydactyly Feet \- Postaxial polydactyly \- Broad, duplicated halluces or triplicated halluces NEUROLOGIC Central Nervous System \- Intellectual disability, severe \- Global developmental delay \- Hypotonia \- Lack of speech \- Corpus callosum hypoplasia \- Vermian hypoplasia \- Vermian aplasia \- Midline cerebellar cleft \- Cerebellar hypoplasia \- Hippocampal hypoplasia \- Limbic system hypoplasia \- Holoprosencephaly \- Molar tooth sign \- Dandy-Walker malformation \- Hyposulcation of brain \- Simplified gyral pattern \- Polymicrogyria \- Subependymal gray matter heterotopia \- Dilation of ventricles \- Dilation of cisternal magna \- Subarachnoid cysts \- Incomplete myelination \- Occipital encephalocele MISCELLANEOUS \- Onset in utero MOLECULAR BASIS \- Caused by mutation in the C2 calcium-dependent domain-containing protein 3 gene (C2CD3, 615944.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	OROFACIODIGITAL SYNDROME XIV	c4014780	26,702	omim	https://www.omim.org/entry/615948	2019-09-22T15:50:30	{"omim": ["615948"], "orphanet": ["434179"], "synonyms": ["Microcephaly-cerebral malformation-orofaciodigital syndrome", "OFD14", "Oral-facial-digital syndrome type 14"]}
Camera et al. (1993) described a girl with semilobar holoprosencephaly, confirmed by computer tomography, and primary craniosynostosis involving the coronal and lambdoid sutures. No abnormalities of visceral organs were reported. At the age of 3 years, she demonstrated small vertebral bodies, coxa valga, and hypoplastic terminal phalanges of fingers. Ultrasonographic examination of the fetus during a second pregnancy of the couple showed an association of semilobar holoprosencephaly and craniosynostosis. The face was nondiagnostic of holoprosencephaly in both sibs. Camera et al. (1993) named this possibly autosomal recessive complex of primary craniosynostosis and holoprosencephaly the Genoa syndrome. Skel \- Small vertebral bodies \- Coxa valga Head \- Primary coronal and lambdoid craniosynostosis Neuro \- Semilobar holoprosencephaly Limbs \- Hypoplastic terminal phalanges of fingers Inheritance \- ? Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HOLOPROSENCEPHALY, SEMILOBAR, WITH CRANIOSYNOSTOSIS	c1832424	26,703	omim	https://www.omim.org/entry/601370	2019-09-22T16:14:55	{"mesh": ["C537684"], "omim": ["601370"], "orphanet": ["2163"], "synonyms": ["Alternative titles", "GENOA SYNDROME"]}
## Summary ### Clinical characteristics. Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital profound bilateral sensorineural hearing loss and long QTc, usually >500 msec. Prolongation of the QTc interval is associated with tachyarrhythmias, including ventricular tachycardia, episodes of torsade de pointes ventricular tachycardia, and ventricular fibrillation, which may culminate in syncope or sudden death. Iron-deficient anemia and elevated levels of gastrin are also frequent features of JLNS. The classic presentation of JLNS is a deaf child who experiences syncopal episodes during periods of stress, exercise, or fright. Fifty percent of individuals with JLNS had cardiac events before age three years. More than half of untreated children with JLNS die before age 15 years. ### Diagnosis/testing. The diagnosis of JLNS is established in a child with congenital sensorineural deafness, long QT interval, and presence of biallelic pathogenic variants in either KCNQ1 or KCNE1. ### Management. Treatment of manifestations: Cochlear implantation to treat hearing loss; beta-adrenergic blockers for long QT interval (Note: Beta-blocker treatment is only partially effective.); implantable cardioverter defibrillators (ICDs) for those with a history of cardiac arrest and/or failure to respond to other treatments; ensure availability of automated external defibrillators where appropriate; standard treatment for those with iron-deficiency anemia. Prevention of secondary complications: Special precautions during anesthesia are necessary because of the increased risk for cardiac arrhythmia. Surveillance: Beta-blocker dose should be regularly assessed for efficacy and adverse effects, with evaluation every three to six months during rapid growth phases; periodic evaluations of ICDs for inappropriate shocks and pocket or lead complications. Agents/circumstances to avoid: Drugs that cause further prolongation of the QT interval; activities known to precipitate syncopal events in persons with long QT syndrome. Evaluation of relatives at risk: Hearing evaluation by standard newborn hearing screening programs and electrocardiograms for at-risk sibs; molecular genetic testing to confirm the diagnosis if the pathogenic variants in an affected family member are known. Pregnancy management: Consideration should be given as to whether a mother who has a fetus affected with JLNS herself has long QT syndrome. Other: Training for family members in cardiopulmonary resuscitation; use of an ID bracelet explaining the diagnosis; notifying local emergency medical services of high-risk persons with JLNS. ### Genetic counseling. JLNS is inherited in an autosomal recessive manner. Parents of a child with JLNS are usually heterozygotes; rarely, only one parent is heterozygous (i.e., the proband has one inherited and one de novo pathogenic variant). Parents may or may not have the long QT syndrome (LQTS) phenotype. At conception, each sib of an affected individual usually has a 25% chance of being affected with JLNS, a 50% chance of being a carrier of a JLNS-causing pathogenic variant and potentially at risk for LQTS, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family are known. ## Diagnosis ### Suggestive Findings Jervell and Lange-Nielsen syndrome (JLNS) should be suspected in a proband with the following features: * Profound congenital sensorineural deafness * Long QTc interval (>500 msec), often manifest as syncope, most often elicited by emotion or exercise. Note: Normal QTc interval in males is <440 msec and in post-pubertal females is <460 msec. ### Establishing the Diagnosis The diagnosis of JLNS is established in a proband with the above suggestive findings. Identification of biallelic pathogenic variants in either KCNQ1 or KCNE1 confirms the diagnosis, particularly if clinical features are inconclusive. Note: (1) It is not currently known how many children with molecularly confirmed JLNS have a borderline QTc interval (440-500 msec) or a normal QTc interval. (2) Hearing loss commonly occurs in individuals with long QT syndrome (LQTS). The hearing loss may be entirely unrelated to the etiology of the LQTS, particularly if the hearing loss is moderate. Molecular genetic testing approaches can include serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Serial single-gene testing. Sequence analysis of KCNQ1 is performed first and followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. If only one or no KCNQ1 pathogenic variant is identified, sequence analysis of KCNE1 should be performed next. In countries with KCNQ1 founder variants (e.g., Norway) KCNQ1 sequencing should be carried out with knowledge of these variants to ensure they will be detected (see Molecular Genetics) [Tranebjærg et al 1999, Tranebjærg 2004, Berge et al 2008, Siem et al 2008]. * A multigene panel that includes KCNE1, KCNQ1 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing, mitochondrial sequencing, and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Jervell and Lange-Nielsen Syndrome View in own window Gene 1, 2Proportion of JLNS Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 KCNE1<10% 6~100% 7See footnote 8 KCNQ1~90% 6>95%1 family 9, 10 1\. Genes are listed alphabetically. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. In a study of ten families, nine had pathogenic variants in KCNQ1 [Tyson et al 2000]. Of 63 families, six (9.5%) had pathogenic variants in KCNE1 [Schwartz et al 2006]. None of the individuals of Norwegian ancestry with JLNS have been shown to have KCNE1 pathogenic variants [Tranebjærg et al 1999, Berge et al 2008, Siem et al 2008]. Pathogenic variants have been found in either KCNQ1 or KCNE1 in 94% of individuals with clinical JLNS undergoing molecular testing [Schwartz et al 2006]. 7\. Three variants in KCNE1, all detectable by Sanger sequencing, have been associated with JLNS [Schulze-Bahr et al 1997, Tyson et al 1997]. 8\. No deletions or duplications of KCNE1 have been reported to cause JLNS. 9\. Sung et al [2014] 10\. Both deletion and duplication of one or more exons of KCNQ1 are known to cause long QT syndrome [Zehelein et al 2006, Eddy et al 2008, Sung et al 2014]; their frequency is unknown. ## Clinical Characteristics ### Clinical Description The classic presentation of JLNS is a deaf child who experiences syncopal episodes during periods of stress, exercise, or fright. Hearing loss. All individuals with molecularly confirmed JLNS have profound bilateral congenital sensorineural deafness (see Deafness and Hereditary Hearing Loss Overview). Long QTc. Individuals with JLNS have a QTc interval greater than 500 msec (average 550 msec), indicating increased time for ventricular depolarization and repolarization [Winbo et al 2012, Winbo et al 2014]. Abnormal cardiac depolarization and repolarization may result in tachyarrhythmias (including ventricular tachycardia, episodes of torsade de pointes ventricular tachycardia, and ventricular fibrillation), which may culminate in syncope or sudden death. QTc prolongation in JLNS, particularly when severe, appears to be associated with increased risk for death in infancy (SIDS). In the Schwartz et al [2006] study of 135 families with JLNS, the QTc was markedly prolonged (557±65 msec); 50% of individuals had cardiac events before age three years, with emotion and exercise being the primary triggers. Although more than half of untreated children with JLNS die before age 15 years, some individuals are reported to have survived several syncopal episodes during adulthood. Note, however, that selection bias for severely affected individuals cannot be excluded: individuals with putative JLNS but no clinical manifestations other than deafness until adulthood (and to age 50 years in one individual) have been described. Anemia. Individuals with KCNQ1-related JLNS have an increased incidence of iron deficiency anemia and hypergastrinemia [Winbo et al 2013]. This may be due to loss of the KCNQ1 potassium channels and reduced gastric acid secretion. Other. The sex ratio among individuals with JLNS is even, but females are at lower risk for cardiac arrest/sudden death [Schwartz et al 2006]. Vestibular dysfunction was found in 14/14 deaf individuals with JLNS, irrespective of previous cochlear implantation. The proposed mechanism was disruption of the endolymph homeostasis [Winbo & Rydberg 2015] Physical examination is unremarkable except for deafness. Heterozygotes. Individuals who are heterozygous for pathogenic variants associated with JLNS usually have normal hearing. In some heterozygotes, QTc prolongation, fainting, and sudden death never occur. In contrast, some individuals heterozygous for pathogenic variants associated with JLNS may have QTc prolongation associated with fainting and death heritable in an autosomal dominant manner. This form of LQTS is called Romano-Ward syndrome (RWS). Histopathology of temporal bone. Histologic examination of a few temporal bones was performed prior to the availability of molecular genetic testing, but not since. In one Norwegian individual with JLNS resulting from homozygosity for the c.572_576del pathogenic variant in KCNQ1, histopathologic examination of the temporal bones showed severe atrophy of the stria vascularis and the organ of Corti with absence of cochlear nerve fibers [Tranebjærg L & Merchant SM, unpublished data (2012)]. ### Phenotype Correlations by Gene Among six asymptomatic individuals reported by Schwartz et al [2006], two had biallelic KCNQ1 pathogenic variants and four had biallelic KCNE1 pathogenic variants, further confirming the milder presentation of JLNS associated with KCNE1 pathogenic variants compared to JLNS associated with KCNQ1 pathogenic variants. KCNQ1. Individuals with KCNQ1-related JLNS have an increased incidence of iron deficiency anemia and hypergastrinemia [Winbo et al 2013]. ### Genotype-Phenotype Correlations Among 63 individuals who were genotyped, 33% were compound heterozygotes [Schwartz et al 2006]. No clinical difference was evident between persons with at least one inactivating variant (e.g., insertion/deletion, splice variant, truncation) and those with missense variants. ### Nomenclature Lange-Nielsen syndrome has also been called cardioauditory syndrome of Jervell and Lange-Nielsen and surdo-cardiac syndrome. JLNS is now appreciated to be a true syndrome, in which the cardiac and cochlear pathologies are attributable to a common molecular etiology. Although there are several case reports in the older literature of individuals with long QT syndrome and non-profound hearing loss, in many of these reports it is likely that the hearing loss and prolonged QT interval have different etiologies (see Differential Diagnosis). ### Prevalence Prevalence varies depending on the population studied: * Norway has an unusually high prevalence of at least one in 200,000 [Tranebjærg et al 1999]. This prevalence stems from four Norwegian founder variants [Berge et al 2008, Siem et al 2008, Winbo et al 2012]. * Sweden also has a prevalence of one in 200,000 based on a study of preadolescent children, identifying 19 affected individuals from 13 families. Eight KCNQ1 pathogenic variants were identified, of which p.Arg518Ter constituted 12/24 alleles [Winbo et al 2012]. Founder variants accounted for 83% of pathogenic variants [Winbo et al 2014]. * In a study of 350 children with congenital deafness in Turkey, one in 175 had JLNS [Ocal et al 1997]. * A particular missense KCNQ1 variant has been identified in the heterozygous state in autosomal dominant LQTS and in the homozygous state in JLNS in a few individuals from Finland; however, prevalence of JLNS was not increased in Finland [Piippo et al 2001]. * An overview of worldwide occurrence was published by Tranebjærg [2004] These data are the best available; however, diagnostic criteria using a QTc >440 msec in children are likely to include some false positives, perhaps as many as 15%-20% [Allan et al 2001]. The design of the review by Schwartz et al [2006] did not allow refinement of prevalence estimates. ## Differential Diagnosis Deafness and prolonged QTc with or without long QT syndrome (LQTS) both have multiple etiologies, including genetic and environmental causes. In many individuals with both deafness and prolonged QTc (or LQTS), the deafness and prolonged QTc (or LQTS) have separate etiologies. All of these possibilities must be considered in each affected individual, particularly in the absence of parental consanguinity or an affected sib. The following considerations are relevant in an individual who has both deafness and prolonged QTc: * Prior to the availability of molecular genetic testing, the diagnosis of Jervell and Lange-Nielsen syndrome (JLNS) was based on clinical criteria alone. (Romano-Ward syndrome was commonly diagnosed in persons with LQTS and normal hearing.) * Some children with JLNS may be misdiagnosed with epilepsy and incorrectly treated with antiepileptic drugs before the correct diagnosis of JLNS is established [Tranebjærg et al 1999]. Long QT syndrome. Long QT multigene panels may include testing for a number of the genes related to disorders discussed in this section. Note: The genes involved and methods used vary by laboratory. Romano-Ward syndrome. The term "Romano-Ward syndrome" (RWS) refers to forms of long QT syndrome with a purely cardiac electrophysiologic disorder, inherited in an autosomal dominant manner (LQTS types 1-3, type 5, type 6, and types 9-15). RWS is characterized by QT prolongation and T-wave abnormalities on ECG and the ventricular tachycardia torsade de pointes (TdP). The diagnosis of RWS is made on the basis of a prolonged QT interval on ECG, clinical presentation, and family history; or identification of a pathogenic variant in one or more of the 15 genes known to be associated with LQTS (of which KCNQ1, KCNH2, and SCN5A are the most common) in the absence of profound congenital sensorineural deafness (the presence of which is highly suggestive of Jervell and Lange-Nielsen syndrome). Individuals with pathogenic variants in KCNE1 may also have atrial fibrillation [Olesen et al 2012]. Diagnostic criteria have been established for the resting ECG QTc value in the absence of specific conditions known to lengthen the QTc interval. For a summary of the genes known to be associated with RWS, see Long QT Syndrome. Only KCNQ1 and KCNE1 have been implicated in both RWS and JLNS. Timothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. Typical cardiac findings include a rate-corrected QT interval >480 msec, functional 2:1 AV block with bradycardia, tachyarrhythmias, and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). Andersen-Tawil syndrome is characterized by a triad of episodic flaccid muscle weakness (i.e., periodic paralysis), ventricular arrhythmias and prolonged QT interval, and anomalies including low-set ears, widely spaced eyes, small mandible, fifth-digit clinodactyly, syndactyly, short stature, and scoliosis. Acquired causes of QTc interval prolongation include the following: * Electrolyte abnormalities: hypokalemia, hypomagnesemia, hypocalcemia * Malnutrition or liquid protein diet * Drugs: vasodilators, tricyclic antidepressants, organophosphates, antihistamines, phenothiazines, procainamide, disopyramide, quinidine, and many others. For a complete, updated list see www.crediblemeds.org (registration required). * Primary myocardial problems: cardiomyopathy, myocarditis, ischemia * Central nervous or autonomic system injury; subarachnoid hemorrhage; stellate ganglion blockade Hearing loss. The differential diagnosis for hearing loss includes consideration of other forms of syndromic and nonsyndromic disorders, as well as acquired disorders. For more information on hereditary hearing loss, see Deafness and Hereditary Hearing Loss Overview. One disorder that should be noted specifically is DFNB1, the most common autosomal recessive form of nonsyndromic hearing loss. DFNB1 is characterized by congenital, non-progressive, mild-to-profound sensorineural hearing impairment. No other associated medical findings are present. Diagnosis of DFNB1 depends on molecular genetic testing to identify biallelic pathogenic variants in GJB2 (sequence variants as well as variants in upstream cis-regulatory elements [GJB6 deletions] that alter expression of the gap junction beta-2 protein [connexin 26]). JLNS should be suspected in any infant who has profound bilateral sensorineural hearing loss, no identifiable GJB2 pathogenic variants, and a normal physical examination. Brugada syndrome is characterized by cardiac conduction abnormalities (ST-segment abnormalities in leads V1-V3 on ECG and a high risk for ventricular arrhythmias) that can result in sudden death. Sudden infant death syndrome (SIDS) (OMIM 272120). Data from multicenter studies indicate that 9.5% of infants with SIDS may be heterozygous for functionally significant variants in one of the known LQTS-related genes. Sudden arrhythmic death may thus be an important contributor to SIDS; it is unknown what proportion of infants with SIDS have or would develop profound hearing impairment. Implementation of universal neonatal hearing screening, supplemented with early electrocardiography, may have the potential to identify high-risk children. However, a recent large population study did not find a higher incidence of JLNS in newborns identified with hearing loss by universal screening [Chang et al 2014]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Jervell and Lange-Nielsen syndrome (JLNS), the following evaluations are recommended if they have not already been completed: * Formal audiology evaluation for extent of hearing loss * Cardiac examination including calculation of QTc * A three-generation family history that focuses on cardiac disease, syncope, and hearing ability * Complete blood count to screen for anemia. If anemia is present, screening for iron deficiency is recommended. * Consultation with a clinical geneticist ### Treatment of Manifestations Hearing loss in JLNS may be treated successfully with cochlear implantation, an intervention that does not interfere with bipolar pacemakers [Green et al 2000, Chorbachi et al 2002] (see Deafness and Hereditary Hearing Loss Overview). To date, the cumulative published experience includes approximately 20 individuals with JLNS who have received cochlear implantation. Of note, the diagnosis of JLNS was only verified with molecular genetic testing in four Norwegian individuals, all of whom had pathogenic variants in KCNQ1. An increase in sound-related syncopal episodes was noted after cochlear implantation in one child [Al-Aama et al 2015]. Note: Although cochlear implantation appears to be safe, special precautions are necessary during anesthesia because of the increased risk for cardiac arrhythmia [Daneshi et al 2008, Siem et al 2008, Yanmei et al 2008]. One affected individual died during a perioperative cardiac arrest [Broomfield et al 2010]. Cardiac issues. The main goal in management of JLNS is prevention of syncope, cardiac arrest, and sudden death. Note that efficacy of beta-blocker treatment is only partial: 51% of treated individuals had cardiac events and 27% had cardiac arrest or sudden death. Even with additional therapies (e.g., pacemaker, implantable cardioverter/defibrillator, left sympathetic denervation), 18 (56%) of 32 individuals experienced additional symptoms, including sudden death in seven [Schwartz et al 2006]. * Administration of beta-adrenergic blockers has been the traditional first-line medical therapy for cardiac events, but more aggressive, immediate treatment may be appropriate. Cardiac events in JLNS frequently occur despite beta blockade [Schwartz et al 2006]. Goldenberg et al [2006] demonstrated markedly increased mortality in individuals with JLNS treated exclusively with beta blockers in comparison to individuals with Romano-Ward syndrome. A mortality rate of 35% over five years was observed for individuals receiving beta blockers exclusively; 86% of individuals treated exclusively with beta blockers experienced a cardiac event. The interactions of beta blockers with other medical conditions (e.g., asthma, diabetes mellitus, depression) should also be considered. Propranolol and nadolol have been shown to be more effective than metoprolol in suppressing cardiac events [Chockalingam et al 2012, Winbo et al 2014]. A recent consensus statement advocates use of nadolol as the preferred beta blocker for drug therapy of individuals with long QT syndrome [Ackerman et al 2017]. * Implantable cardioverter defibrillators (ICDs) should be considered in individuals with a history of cardiac arrest or failure to respond to other treatments [Goel et al 2004]. More recent recommendations have strongly urged ICD placement for high-risk individuals, defined by the following criteria [Schwartz et al 2006]: * QTc interval >550 msec * Syncope before age five years * Male gender, age >20 years with KCNQ1 pathogenic variant * The risk for sudden cardiac death appears to be low in individuals younger than age five years, but medical therapy should be administered early in these high-risk individuals and ICD placement considered after age five years [Richter & Brugada 2006]. * In certain cases, the availability of automated external defibrillators in the home, workplace, or school may be applicable, as is appropriate CPR training of family members and those who have regular contact with individuals with JLNS. * Left cardiac sympathetic denervation has been effective for some individuals. Iron deficiency anemia. The treatment of iron deficiency anemia should follow standard guidelines. ### Prevention of Primary Manifestations See Treatment of Manifestations regarding prevention of syncope, cardiac arrest, and sudden death. ### Prevention of Secondary Complications Special precautions during anesthesia are necessary because of the increased risk for cardiac arrhythmia [Daneshi et al 2008, Siem et al 2008, Yanmei et al 2008]. ### Surveillance Beta-blocker dose should be regularly assessed for efficacy and adverse effects, and doses altered as needed. Because dose adjustment is especially important in growing children, evaluation is appropriate every three to six months during rapid growth phases. Regular, periodic evaluation of implantable cardioverter defibrillators (ICDs) for inappropriate shocks and pocket or lead complications is indicated. ### Agents/Circumstances to Avoid The following should be avoided: * Drugs that cause further prolongation of the QT interval or provoke torsade de pointes; see www.crediblemeds.org for a complete and updated list (registration required). * Triggers for intense or sudden emotion; activities that are known to precipitate syncopal events in individuals with long QT syndrome, including: * Competitive sports * Amusement park rides * Frightening movies * Jumping into cold water A cardiologist should make recommendations for activity restrictions based on the effectiveness of medical intervention. ### Evaluation of Relatives at Risk It is appropriate to evaluate sibs and parents of a proband in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures. * If the pathogenic variants in the family are known, molecular genetic testing can be used to clarify the genetic status of at-risk family members. * If the pathogenic variants in the family are not known, ECG testing should be undertaken to evaluate for QT prolongation. * Standard newborn screening programs are sufficient to identify hearing loss in children with JLNS. Because of the relationship between JLNS and long QT syndrome, ECG should be considered for relatives at risk for JLNS even if they have normal hearing. If the JLNS-causing pathogenic variants in an affected family member are known, molecular genetic testing of a relative with congenital profound sensorineural hearing loss is recommended to confirm the diagnosis of JLNS. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Consideration should be given as to whether a mother who has a fetus affected with JLNS herself has long QT syndrome [Seth et al 2007]. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. ### Other Family members of individuals with JLNS should be trained in cardiopulmonary resuscitation (CPR) as up to 95% of individuals with JLNS have a cardiac event before adulthood [Schwartz et al 2006]. Affected individuals should wear an ID bracelet explaining their diagnosis. It is appropriate to notify local emergency medical services (EMS) of high-risk persons, including those with JLNS [Hazinski et al 2004]. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Jervell and Lange-Nielsen Syndrome	c0022387	26,704	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1405/	2021-01-18T21:16:59	{"mesh": ["D029593"], "synonyms": ["JLNS"]}
A number sign (#) is used with this entry because episodic encephalopathy due to thiamine pyrophosphokinase deficiency, also known as thiamine metabolism dysfunction syndrome-5 (THMD5), is caused by homozygous or compound heterozygous mutation in the TPK1 gene (606370) on chromosome 7q35. Description Episodic encephalopathy due to thiamine pyrophosphokinase deficiency is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits (summary by Mayr et al., 2011). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270). Clinical Features Mayr et al. (2011) reported 5 individuals from 3 unrelated families with variable manifestations of thiamine pyrophosphokinase deficiency. Two sisters had the most severe phenotype compared to the other patients. The older sister showed developmental delay from the first year of life, and lost the ability to walk after an infection-induced encephalopathic episode at age 15 months. During this episode, she had increased serum and CSF lactate. She started to walk again at 3 years of age, but continued to show muscular hypotonia and delayed psychomotor development. She had 2 further crises with encephalopathy and lactic acidosis triggered by viral infections, and died during the last crisis at the age of 8.5 years. Her sister had normal development until 18 months when she developed recurrent encephalopathic episodes associated with mildly increased CSF lactate and resulting in gait and truncal ataxia, dystonia, and eventual loss of ability to walk. She died at the age of 3.5 years during a viral infection. Both girls showed episodic increased urinary alpha-ketoglutaric acid. The second family included a brother and sister born of consanguineous Iraqi parents. Both showed normal development during the first 3 years of life, but developed progressive spasticity, dystonia, and eventual loss of gait starting at age 4. The girl lost the ability to speak, developed seizures, and was wheelchair-bound at age 11 years; however, cognition was intact. Brain MRI showed global brain atrophy and increased signal intensities in the globus pallidus, and MR spectroscopy showed a lactate peak in the basal ganglia. Urinary organic acids showed elevated alpha-ketoglutaric acid and 3-hydroxyisovaleric acid. She also had mild left ventricular hypertrophy. Her younger brother had progressive dystonia, walking difficulties, and mild microcephaly, but he had adequate cognitive development at age 7 years, and brain MRI was normal. The index patient from the third family had the mildest phenotype. Beginning at age 2 years, he had several episodes of dizziness and vertigo, as well as intermittent gait ataxia, but all episodes showed spontaneous remission. At age 10.5 years, he had a severe and prolonged episode of encephalopathy with loss of speech, headache, seizures, and extensor plantar responses, progressing to dysarthria, intention tremor, confusion, episodic ataxia, and nystagmus, and resulting in coma. Serum and CSF lactate were increased, and MRI showed changes in the white matter of the cerebellum, increased signal intensities in the corticospinal tract at the medulla oblongata, and slightly increased intensities in the dorsal pons. This episode was followed by slow regression of clinical signs in the following months. At age 17 years, he had normal mental development and attended high school; the only residual signs were dysphonia and mild paresis of the soft palate. Biochemical Features Muscle biopsy samples from 3 of the patients reported by Mayr et al. (2011) showed normal or only mildly affected activities for all respiratory chain complexes and the pyruvate dehydrogenase complex. However, mitochondrial oxidation rates of pyruvate-containing substrates were significantly reduced and demonstrated to be due to a deficiency of thiamine cofactor. Serum thiamine pyrophosphate was decreased, even though all 3 patients were under oral thiamine supplementation. Clinical Management Mayr et al. (2011) found that 2 of 3 patients with THMD5 treated with oral thiamine supplementation stabilized and even improved to some extent after therapy. However, the third patient showed no clear improvement after 2 years of treatment with thiamine. Inheritance The transmission pattern of THMD5 in the families reported by Mayr et al. (2011) was consistent with autosomal recessive inheritance. Molecular Genetics In 5 patients from 3 unrelated families with THMD5, Mayr et al. (2011) identified homozygous or compound heterozygous mutations in the TPK1 gene (606370.0001-606370.0005). INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Left ventricular hypertrophy (1 patient) MUSCLE, SOFT TISSUES \- Hypotonia \- Pyruvate oxidation defect \- Decreased thiamine pyrophosphate NEUROLOGIC Central Nervous System \- Encephalopathic episodes, often associated with infection \- Dizziness, episodic \- Normal cognition \- Delayed psychomotor development (1 patient) \- Hypotonia \- Spasticity \- Dystonia \- Ataxia \- Disturbed gait \- Loss of gait (in some) \- Loss of speech (1 patient) \- Seizures (1 patient) \- Abnormal white matter signals, in the basal ganglia or cerebellum seen on brain MRI METABOLIC FEATURES \- Lactic acidosis, episodic \- Metabolic crises LABORATORY ABNORMALITIES \- Increased urinary alpha-ketoglutaric acid, intermittent \- Decreased serum thiamine pyrophosphate MISCELLANEOUS \- Highly variable phenotype \- Onset in early childhood \- Some features may be progressive \- Encephalopathic episodes associated with increased serum and CSF lactate \- Thiamine supplementation may be beneficial MOLECULAR BASIS \- Caused by mutation in the thiamine pyrophosphokinase gene (TPK1, 606370.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	THIAMINE METABOLISM DYSFUNCTION SYNDROME 5 (EPISODIC ENCEPHALOPATHY TYPE)	c3280866	26,705	omim	https://www.omim.org/entry/614458	2019-09-22T15:55:10	{"omim": ["614458"], "orphanet": ["293955"], "synonyms": ["Alternative titles", "ENCEPHALOPATHY, EPISODIC, DUE TO THIAMINE PYROPHOSPHOKINASE DEFICIENCY"]}
16q24.3 microdeletion syndrome is a recently described syndrome associated with variable developmental delay, facial dysmorphism, seizures and autistic spectrum disorder. ## Epidemiology It has been clinically and molecularly characterized in 4 patients. ## Clinical description Facial dysmorphism includes high forehead, large ears, smooth philtrum, pointed chin and wide mouth. Anomalies of the brain and neonatal thrombocytopenia can be observed. ## Etiology This syndrome is caused by an interstitial deletion encompassing 16q24.3. These de novo deletions were characterized by comparative genomic hybridization (CGH) microarray and fluorescence in situ hybridization (FISH). They vary in size, the common region of overlap is only 90 kb and comprises two candidates genes, ANKRD11 (Ankyrin Repeat Domain 11) and ZNF778 (Zinc Finger 778). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	16q24.3 microdeletion syndrome	c4304594	26,706	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261250	2021-01-23T19:10:16	{"gard": ["10935"], "icd-10": ["Q93.5"], "synonyms": ["Del(16)(q24.3)", "Monosomy 16q24.3"]}
Viral disease spread by a type of mouse Lassa fever Other namesLassa hemorrhagic fever Community education material for Lassa fever SpecialtyInfectious disease SymptomsFever, headaches, bleeding[1] ComplicationsDeafness[1] Usual onset1–3 weeks following exposure[1] CausesLassa virus[1] Risk factorsExposure to rodents in West Africa[1] Diagnostic methodLaboratory testing[1] Differential diagnosisEbola, malaria, typhoid fever[1] TreatmentSupportive[1] Prognosis1% risk of death[1] Frequency400,000 cases per year[2] Deaths5,000 deaths per year[2] Lassa fever, also known as Lassa hemorrhagic fever (LHF), is a type of viral hemorrhagic fever caused by the Lassa virus.[1] Many of those infected by the virus do not develop symptoms.[1] When symptoms occur they typically include fever, weakness, headaches, vomiting, and muscle pains.[1] Less commonly there may be bleeding from the mouth or gastrointestinal tract.[1] The risk of death once infected is about one percent and frequently occurs within two weeks of the onset of symptoms.[1] Of those who survive, about a quarter have hearing loss, which improves within three months in about half of these cases.[1] The disease is usually initially spread to people via contact with the urine or feces of an infected multimammate mouse.[1] Spread can then occur via direct contact between people.[1] Diagnosis based on symptoms is difficult.[1] Confirmation is by laboratory testing to detect the virus's RNA, antibodies for the virus, or the virus itself in cell culture.[1] Other conditions that may present similarly include Ebola, malaria, typhoid fever, and yellow fever.[1] The Lassa virus is a member of the Arenaviridae family of viruses.[1] There is no vaccine.[3] Prevention requires isolating those who are infected and decreasing contact with the mice.[1] Other efforts to control the spread of disease include having a cat to hunt vermin, and storing food in sealed containers.[1] Treatment is directed at addressing dehydration and improving symptoms.[1] The antiviral medication ribavirin has been recommended,[1] but evidence to support its use is weak.[4] Descriptions of the disease date from the 1950s.[1] The virus was first described in 1969 from a case in the town of Lassa, in Borno State, Nigeria.[1][5] Lassa fever is relatively common in West Africa including the countries of Nigeria, Liberia, Sierra Leone, Guinea, and Ghana.[1][2] There are about 300,000 to 500,000 cases which result in 5,000 deaths a year.[2][6] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Virology * 2.2 Spread * 3 Diagnosis * 4 Prevention * 4.1 Vaccine * 5 Treatment * 5.1 Medications * 5.2 Pregnancy * 6 Prognosis * 7 Epidemiology * 7.1 Geography * 7.2 Nigeria * 7.2.1 2018 outbreak * 7.2.2 2019 outbreak * 7.2.3 2020 outbreak * 8 Liberia * 9 History * 10 Research * 11 References * 12 External links ## Signs and symptoms[edit] Onset of symptoms is typically 7 to 21 days after exposure.[7] In 80% of those who are infected few or no symptoms occur.[7][8] These mild symptoms may include fever, tiredness, weakness, and headache.[7] In 20% of people more severe symptoms such as bleeding gums, breathing problems, vomiting, chest pain, or dangerously low blood pressure may occur.[7] Long term complications may include hearing loss.[7] In those who are pregnant, miscarriage may occur in 95%.[7] Lassa fever can be difficult to distinguish clinically from other viral hemorrhagic fevers, such as Ebola virus disease.[1] A combination of pharyngitis, pain behind the sternum, presence of excess protein in the urine and fever can indicate Lassa fever with higher specificity.[9] In cases in which death occurs, this typically occurs within 14 days of onset.[7] About 1% of all Lassa virus infections result in death.[7] Approximately 15%-20% of those who have required hospitalization for Lassa fever die.[7] The risk of death is greater in those who are pregnant.[7] A "Swollen baby syndrome" may occur in newborns, infants and toddlers with pitting edema, abdominal distension and bleeding.[10] ## Cause[edit] ### Virology[edit] A transmission electron micrograph (TEM) of a number of Lassa virus virions adjacent to some cell debris. Lassa virus is a member of the Arenaviridae, a family of negative-sense, single-stranded RNA viruses.[11] Specifically it is an old world arenavirus, which is enveloped, single-stranded, and bi-segmented RNA. This virus has both a large and a small genome section, with four lineages identified to date: Josiah (Sierra Leone), GA391 (Nigeria), LP (Nigeria) and strain AV.[12] ### Spread[edit] Mastomys natalensis, the natural reservoir of the Lassa fever virus Lassa virus commonly spreads to humans from other animals, specifically the natal multimammate mouse or African rat, also called the natal multimammate rat (Mastomys natalensis).[13] This is probably the most common mouse in equatorial Africa, common in human households and eaten as a delicacy in some areas.[13][14] The multimammate mouse can quickly produce a large number of offspring, tends to colonize human settlements increasing the risk of rodent-human contact, and is found throughout the west, central and eastern parts of the African continent.[15] Once the mouse has become a carrier, it will excrete the virus throughout the rest of its lifetime through feces and urine creating ample opportunity for exposure.[15] The virus is probably transmitted by contact with the feces or urine of animals accessing grain stores in residences.[14] No study has proven presence in breast milk, but the high level of viremia suggests it may be possible.[10] Individuals who are at a higher risk of contracting the infection are those who live in rural areas where Mastomys are discovered, and where sanitation is not prevalent. Infection typically occurs by direct or indirect exposure to animal excrement through the respiratory or gastrointestinal tracts. Inhalation of tiny particles of infectious material (aerosol) is believed to be the most significant means of exposure. It is possible to acquire the infection through broken skin or mucous membranes that are directly exposed to infectious material. Transmission from person to person has been established, presenting a disease risk for healthcare workers. The virus is present in urine for between three and nine weeks after infection, and it can be transmitted in semen for up to three months after becoming infected.[13][16][17] ## Diagnosis[edit] Liberian laboratory technicians in personal protective equipment preparing to test Lassa fever samples. A range of laboratory investigations are performed, where possible, to diagnose the disease and assess its course and complications. The confidence of a diagnosis can be compromised if laboratory tests are not available. One comprising factor is the number of febrile illnesses present in Africa, such as malaria or typhoid fever that could potentially exhibit similar symptoms, particularly for non-specific manifestations of Lassa fever.[11] In cases with abdominal pain, in countries where Lassa is common, Lassa fever is often misdiagnosed as appendicitis and intussusception which delays treatment with the antiviral ribavirin.[18] In West Africa, where Lassa is most common, it is difficult to diagnose due to the absence of proper equipment to perform testing.[19] The FDA has yet to approve a widely validated laboratory test for Lassa, but there are tests that have been able to provide definitive proof of the presence of the LASV virus.[11] These tests include cell cultures, PCR, ELISA antigen assays, plaque neutralization assays, and immunofluorescence essays. However, immunofluorescence essays provide less definitive proof of Lassa infection.[11] An ELISA test for antigen and Immunoglobulin M antibodies give 88% sensitivity and 90% specificity for the presence of the infection. Other laboratory findings in Lassa fever include lymphocytopenia (low white blood cell count), thrombocytopenia (low platelets), and elevated aspartate transaminase levels in the blood. Lassa fever virus can also be found in cerebrospinal fluid.[20] ## Prevention[edit] Main article: Prevention of viral hemorrhagic fever Community education material for Lassa fever Control of the Mastomys rodent population is impractical, so measures focus on keeping rodents out of homes and food supplies, encouraging effective personal hygiene, storing grain and other foodstuffs in rodent-proof containers, and disposing of garbage far from the home to help sustain clean households. Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person, to avoid contact with blood and body fluids. These issues in many countries are monitored by a department of public health. In less developed countries, these types of organizations may not have the necessary means to effectively control outbreaks. ### Vaccine[edit] There is no vaccine for humans as of 2019.[21] Researchers at the United States Army Medical Research Institute of Infectious Diseases facility had a promising vaccine candidate in 2002.[22] They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis virus vectors expressing the Lassa virus glycoprotein. After a single intramuscular injection, test primates have survived lethal challenge, while showing no clinical symptoms.[23] ## Treatment[edit] Treatment is directed at addressing dehydration and improving symptoms.[1] All persons suspected of Lassa fever infection should be admitted to isolation facilities and their body fluids and excreta properly disposed of. ### Medications[edit] The antiviral medication ribavirin has been recommended,[1] but evidence to support its use is weak.[4] Some evidence has found that it may worsen outcomes in certain cases.[4] Fluid replacement, blood transfusions, and medication for low blood pressure may be required. Intravenous interferon therapy has also been used. ### Pregnancy[edit] When Lassa fever infects pregnant women late in their third trimester, inducing delivery is necessary for the mother to have a good chance of survival.[24] This is because the virus has an affinity for the placenta and other highly vascular tissues. The fetus has only a one in ten chance of survival no matter what course of action is taken; hence, the focus is always on saving the life of the mother.[25] Following delivery, women should receive the same treatment as other people with Lassa fever. ## Prognosis[edit] About 15–20% of hospitalized people with Lassa fever will die from the illness. The overall case fatality rate is estimated to be 1%, but during epidemics, mortality can climb as high as 50%. The mortality rate is greater than 80% when it occurs in pregnant women during their third trimester; fetal death also occurs in nearly all those cases. Abortion decreases the risk of death to the mother.[26] Some survivors experience lasting effects of the disease,[27] and can include partial or complete deafness.[1] Because of treatment with ribavirin, fatality rates have declined.[28][29] ## Epidemiology[edit] Lassa fever distribution. Countries reporting continued spread of disease and outbreaks in blue. Countries reporting a few cases, periodic isolation of virus, or serological evidence of infection in green. Countries with unknown status in grey.[30] There are about 300,000 to 500,000 cases which result in 5,000 deaths a year.[2][6] One estimate places the number as high as 3 million cases per year.[15] Estimates of Lassa fever are complicated by the lack of easy-available diagnosis, limited public health surveillance infrastructure, and high clustering of incidence near high intensity sampling.[11] The infection affects females 1.2 times more than males. The age group predominantly infected is 21–30 years.[31] ### Geography[edit] Lassa high risk areas are near the western and eastern extremes of West Africa. As of 2018, the Lassa belt includes Guinea, Nigeria, Sierra Leone and Liberia.[10] As of 2003, 10-16% of people in Sierra Leone and Liberia admitted to hospital had the virus.[13] The case fatality rate for those who are hospitalized for the disease is about 15-20%. Research showed a twofold increase risk of infection for those living in close proximity to someone with infection symptoms within the last year. The high risk areas cannot be well defined by any known biogeographical or environmental breaks except for the multimammate rat, particularly Guinea (Kindia, Faranah and Nzerekore regions), Liberia (mostly in Lofa, Bong, and Nimba counties), Nigeria (in about 10 of 36 states) and Sierra Leone (typically from Kenema and Kailahun districts). It is less common in the Central African Republic, Mali, Senegal and other nearby countries, and less common yet in Ghana and the Democratic Republic of the Congo. Benin had its first confirmed cases in 2014, and Togo had its first confirmed cases in 2016.[16] As of 2013, the spread of Lassa outside of West Africa had been very limited. Twenty to thirty cases had been described in Europe, as being caused by importation through infected individuals.[15] These cases found outside of West Africa were found to have a high fatality risk because of the delay of diagnosis and treatment due to being unaware of the risk associated with the symptoms.[15] Imported cases have not manifested in larger epidemics outside of Africa due to a lack of human to human transmission in hospital settings. An exception had occurred in 2003 when a healthcare worker became infected before the person showed clear symptoms.[15] ### Nigeria[edit] #### 2018 outbreak[edit] An outbreak of Lassa fever occurred in Nigeria during 2018 and spread to 18 of the country's states; it was the largest outbreak of Lassa recorded.[32][33][34] On 25 February 2018, there were 1081 suspected cases and 90 reported deaths; 317 of the cases and 72 deaths were confirmed as Lassa which increased to a total of 431 reported cases in 2018.[35] #### 2019 outbreak[edit] The total cases in Nigeria in 2019 was 810 with 167 deaths, the largest case fatality rate(23.3%)till then.[36][37] #### 2020 outbreak[edit] The epidemic started from the second week of the January. By the tenth week the total number of cases has risen to 855 and deaths to 144, the case fatality rate of 16.8%.[37] ## Liberia[edit] Lassa fever is endemic in Liberia. From 1 January 2017 through 23 January 2018, 91 suspected cases were reported from six counties: Bong, Grand Bassa, Grand Kru, Lofa, Margibi, and Nimba. Thirty-three of these cases were laboratory confirmed, including 15 deaths (case fatality rate for confirmed cases = 45.4%).[38] In February 2020, a total of 24 confirmed cases with nine associated deaths has been reported from nine health districts in six counties.Grand Bossa and Bong counties account for 20 of the confirmed cases.[39] ## History[edit] The disease was identified in Nigeria in 1969.[15] It is named after the town Lassa in which it was discovered.[15] A prominent expert in the disease, Aniru Conteh, died from the disease.[40] ## Research[edit] The Lassa virus is one of several viruses identified by WHO as a likely cause of a future epidemic. They therefore list it for urgent research and development to develop new diagnostic tests, vaccines, and medicines.[41][42] In 2007, SIGA Technologies, studied a medication in guinea pig with Lassa fever.[43] Work on a vaccine is continuing, with multiple approaches showing positive results in animal trials.[44] In addition to animal models, Organ-on-a-chip models have been developed to study Lassa hemorrhagic syndrome. These microchips allow for high throughput modelling of hemorrhagic syndrome and candidate drug screening. The chip model has been used to show the therapeutic effects of FX-06 for Lassa virus disease.[45] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af "Lassa fever". WHO. March 2016. Archived from the original on 1 November 2016. Retrieved 2 November 2016. 2. ^ a b c d e Ogbu O, Ajuluchukwu E, Uneke CJ (2007). "Lassa fever in West African sub-region: an overview". Journal of Vector Borne Diseases. 44 (1): 1–11. PMID 17378212. "Lassa fever is endemic in West Africa." 3. ^ Yun, N. E.; Walker, D. H. (2012). "Pathogenesis of Lassa Fever". Viruses. 4 (12): 2031–2048. doi:10.3390/v4102031. PMC 3497040. PMID 23202452. 4. ^ a b c Eberhardt, KA; Mischlinger, J; Jordan, S; Groger, M; Günther, S; Ramharter, M (October 2019). "Ribavirin for the treatment of Lassa fever: A systematic review and meta-analysis". International Journal of Infectious Diseases. 87: 15–20. doi:10.1016/j.ijid.2019.07.015. PMID 31357056. 5. ^ Frame JD, Baldwin JM, Gocke DJ, Troup JM (1 July 1970). "Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings". Am. J. Trop. Med. Hyg. 19 (4): 670–6. doi:10.4269/ajtmh.1970.19.670. PMID 4246571. 6. ^ a b Houlihan, Catherine; Behrens, Ron (12 July 2017). "Lassa fever". BMJ. 358: j2986. doi:10.1136/bmj.j2986. PMID 28701331. S2CID 206916006. 7. ^ a b c d e f g h i j "Signs and Symptoms \| Lassa Fever \| CDC". www.cdc.gov. 6 March 2019. Retrieved 18 June 2019. 8. ^ Greenky D, Knust B, Dziuban EJ (May 2018). "What Pediatricians Should Know About Lassa Virus". JAMA Pediatrics. 172 (5): 407–408. doi:10.1001/jamapediatrics.2017.5223. PMC 5970952. PMID 29507948. 9. ^ McCormick JB, King IJ, Webb PA, Johnson KM, O'Sullivan R, Smith ES, Trippel S, Tong TC (March 1987). "A Case-Control Study of the Clinical Diagnosis and Course of Lassa Fever". The Journal of Infectious Diseases. 155 (3): 445–455. doi:10.1093/infdis/155.3.445. PMID 3805772. 10. ^ a b c David Greenky, Barbara Knust, Eric J. DziubanWhat Pediatricians Should Know About Lassa Virus. JAMA Pediatr. 2018;172(5):407-408. doi:10.1001/jamapediatrics.2017.5223 11. ^ a b c d e Peterson, A. Townsend; Moses, Lina M.; Bausch, Daniel G. (8 August 2014). "Mapping Transmission Risk of Lassa Fever in West Africa: The Importance of Quality Control, Sampling Bias, and Error Weighting". PLOS ONE. 9 (8): e100711. Bibcode:2014PLoSO...9j0711P. doi:10.1371/journal.pone.0100711. ISSN 1932-6203. PMC 4126660. PMID 25105746. 12. ^ Goeijenbier, Marco; Wagenaar, Jiri; Goris, Marga; Martina, Byron; Henttonen, Heikki; Vaheri, Antti; Reusken, Chantal; Hartskeerl, Rudy; Osterhaus, Albert (1 February 2013). "Rodent-borne hemorrhagic fevers: under-recognized, widely spread and preventable – epidemiology, diagnostics and treatment". Critical Reviews in Microbiology. 39 (1): 26–42. doi:10.3109/1040841X.2012.686481. ISSN 1040-841X. PMID 22670688. S2CID 31217913. 13. ^ a b c d Richmond, J. K.; Baglole, D. J. (2003). "Lassa fever: Epidemiology, clinical features, and social consequences". BMJ. 327 (7426): 1271–1275. doi:10.1136/bmj.327.7426.1271. PMC 286250. PMID 14644972. 14. ^ a b Werner, Dietrich, editor (2004). Biological Resources and Migration. Springer. pp. 363. ISBN 978-3-540-21470-0. 15. ^ a b c d e f g h Goeijenbier, Marco; Wagenaar, Jiri; Goris, Marga; Martina, Byron; Henttonen, Heikki; Vaheri, Antti; Reusken, Chantal; Hartskeerl, Rudy; Osterhaus, Albert; Van Gorp, Eric (7 June 2012). "Rodent-borne hemorrhagic fevers: under-recognized, widely spread and preventable – epidemiology, diagnostics and treatment". Critical Reviews in Microbiology. 39 (1): 26–42. doi:10.3109/1040841X.2012.686481. PMID 22670688. S2CID 31217913. 16. ^ a b Public Health England: Lassa fever: origins, reservoirs, transmission and guidelines Archived 2 February 2016 at the Wayback Machine First published: 5 September 2014. Last updated: 1 April 2016 17. ^ "Lassa fever". Media Centre Fact Sheet No 179. World Health Organization. Archived from the original on 5 June 2015. Retrieved 26 May 2015. 18. ^ Dongo, A. E.; Kesieme, E. B.; Iyamu, C. E.; Okokhere, P. O.; Akhuemokhan, O. C.; Akpede, G. O. (2013). "Lassa fever presenting as acute abdomen: a case series". Virology Journal. 10: 124. doi:10.1186/1743-422X-10-123. PMC 3639802. PMID 23597024. 19. ^ Asogun, D. A.; Adomeh, D. I.; Ehimuan, J.; Odia, I.; Hass, M.; Gabriel, M.; Olschläger, S.; Becker-Ziaja, B.; Folarin, O.; Phelan, E.; Ehiane, P. E.; Ifeh, V. E.; Uyigue, E. A.; Oladapo, Y. T.; Muoebonam, E. B.; Osunde, O.; Dongo, A.; Okokhere, P. O.; Okogbenin, S. A.; Momoh, M.; Alikah, S. O.; Akhuemokhan, O. C.; Imomeh, P.; Odike, M. A.; Gire, S.; Andersen, K.; Sabeti, P. C.; Happi, C. T.; Akpede, G. O.; Günther, S. (2012). Bausch, Daniel G (ed.). "Molecular Diagnostics for Lassa Fever at Irrua Specialist Teaching Hospital, Nigeria: Lessons Learnt from Two Years of Laboratory Operation". PLOS Neglected Tropical Diseases. 6 (9): e1839. doi:10.1371/journal.pntd.0001839. PMC 3459880. PMID 23029594. 20. ^ Günther, S.; Weisner, B.; Roth, A.; Grewing, T.; Asper, M.; Drosten, C.; Emmerich, P.; Petersen, J.; Wilczek, M.; Schmitz, H. (2001). "Lassa Fever Encephalopathy: Lassa Virus in Cerebrospinal Fluid but Not in Serum". The Journal of Infectious Diseases. 184 (3): 345–349. doi:10.1086/322033. PMID 11443561. 21. ^ "Lassa". Viral Hemorrhagic Fever Consortium. Retrieved 18 June 2019. 22. ^ Preston, Richard (2002). The demon in the freezer: a true story. New York: Random House. ISBN 978-0-375-50856-1. 23. ^ Geisbert TW, Jones S, Fritz EA, et al. (2005). "Development of a New Vaccine for the Prevention of Lassa Fever". PLOS Med. 2 (6): e183. doi:10.1371/journal.pmed.0020183. PMC 1160587. PMID 15971954. 24. ^ Price ME, Fisher-Hoch SP, Craven RB, McCormick JB (September 1988). "A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy". BMJ. 297 (6648): 584–7. doi:10.1136/bmj.297.6648.584. PMC 1834487. PMID 3139220. 25. ^ Samuel, Daso. "Lassa fever... What you need to know" (PDF). Archived (PDF) from the original on 25 June 2017. Retrieved 1 February 2017. 26. ^ Centers for Disease Control and Prevention, "Lassa Fever, Signs and Symptoms" Archived 9 July 2017 at the Wayback Machine 27. ^ Emond, R. T.; Bannister, B.; Lloyd, G.; Southee, T. J.; Bowen, E. T. (1982). "A case of Lassa fever: Clinical and virological findings". British Medical Journal (Clinical Research Ed.). 285 (6347): 1001–1002. doi:10.1136/bmj.285.6347.1001. PMC 1500383. PMID 6812716. 28. ^ "Lassa fever". World Health Organization. Retrieved 11 September 2017. 29. ^ McCormick, J. B.; King, I. J.; Webb, P. A.; Scribner, C. L.; Craven, R. B.; Johnson, K. M.; Elliott, L. H.; Belmont-Williams, R. (2 January 1986). "Lassa fever. Effective therapy with ribavirin". The New England Journal of Medicine. 314 (1): 20–26. doi:10.1056/NEJM198601023140104. ISSN 0028-4793. PMID 3940312. 30. ^ "Outbreak Distribution Map of Lassa Fever". www.cdc.gov. CDC. 4 March 2019. Retrieved 27 April 2019. 31. ^ Owoseye, Ayodamola (11 March 2020). "Lassa Fever: Nigeria's death toll reaches 144". Retrieved 13 March 2020. 32. ^ Maxmen, Amy (15 March 2018). "Deadly Lassa-fever outbreak tests Nigeria's revamped health agency". Nature. 555 (7697): 421–422. Bibcode:2018Natur.555..421M. doi:10.1038/d41586-018-03171-y. PMID 29565399. 33. ^ "On the frontlines of the fight against Lassa fever in Nigeria". World Health Organization. March 2018. 34. ^ Beaubien, Jason (19 March 2018). "Nigeria Faces Mystifying Spike in Deadly Lassa Fever". NPR. 35. ^ "Lassa Fever – Nigeria". World Health Organization. 1 March 2018. 36. ^ Edward-Ekpu, Uwagbale. "Nigeria is already dealing with a deadlier viral outbreak than the coronavirus epidemic". Quartz Africa. Retrieved 13 March 2020. 37. ^ a b "Lassa fever situation report" (PDF). Nigeria Centre for Disease Control. March 2020. 38. ^ "WHO \| Lassa Fever – Liberia". WHO. Retrieved 13 March 2020. 39. ^ "Liberia reports increase in Lassa fever". Outbreak News Today. 4 February 2020. Retrieved 13 March 2020. 40. ^ "Aniru Conteh". BMJ. 328 (7447): 1078.1. 1 May 2004. doi:10.1136/bmj.328.7447.1078. PMC 403863. 41. ^ Kieny, Marie-Paule. "After Ebola, a Blueprint Emerges to Jump-Start R&D". Scientific American Blog Network. Archived from the original on 20 December 2016. Retrieved 13 December 2016. 42. ^ "LIST OF PATHOGENS". World Health Organization. Archived from the original on 20 December 2016. Retrieved 13 December 2016. 43. ^ "SIGA Technologies says passes first hurdle with lassa fever..." Reuters. 15 May 2007. Retrieved 1 May 2019. 44. ^ "WHO Target Product Profiles for Lassa virus Vaccine" (PDF). World Health Organization. April 2017. Retrieved 11 September 2017. 45. ^ Lassa hemorrhagic shock syndrome‐on‐a‐chip ## External links[edit] * Viruses portal * Echioya, Deborah U.; Hass, Meike; Olshlager, Stephan; Becker-Ziaja, Beate; Chukwu, Christian O. Onyebuchi; Coker, Jide; Nasidi, Abdulsalam; Ogugua, Osi-Ogdu; Gunther, Stephan; Omilabu, Sunday A. (2010). "Lassa Fever, Nigeria, 2005-2008". Emerging Infectious Diseases. 6. 16 (6): 1040–41. doi:10.3201/eid1606.100080. PMC 3086228. PMID 20507773. * Branco, Luis M.; Grove, Jessica N.; Boisen, Matt L.; Shaffer, Jeffrey G.; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Grant, Donald S.; Garry, Robert F. (4 October 2011). "Emerging Trends in Lassa Fever: Redefining the Role of Immunoglobulin M and Inflammation in Diagnosing Acute Infection". Virology Journal. 8: 478. doi:10.1186/1743-422x-8-478. PMC 3223505. PMID 22023795. Classification D * ICD-10: A96.2 * ICD-9-CM: 078.8 * MeSH: D007835 * DiseasesDB: 7272 * v * t * e Zoonotic viral diseases (A80–B34, 042–079) Arthropod -borne Mosquito -borne Bunyavirales * Arbovirus encephalitides: La Crosse encephalitis * LACV * Batai virus * BATV * Bwamba Fever * BWAV * California encephalitis * CEV * Jamestown Canyon encephalitis * Tete virus * Tahyna virus * TAHV * Viral hemorrhagic fevers: Rift Valley fever * RVFV * Bunyamwera fever * BUNV * Ngari virus * NRIV Flaviviridae * Arbovirus encephalitides: Japanese encephalitis * JEV * Australian encephalitis * MVEV * KUNV * Saint Louis encephalitis * SLEV * Usutu virus * West Nile fever * WNV * Viral hemorrhagic fevers: Dengue fever * DENV-1-4 * Yellow fever * YFV * Zika fever * Zika virus Togaviridae * Arbovirus encephalitides: Eastern equine encephalomyelitis * EEEV * Western equine encephalomyelitis * WEEV * Venezuelan equine encephalomyelitis * VEEV * Chikungunya * CHIKV * O'nyong'nyong fever * ONNV * Pogosta disease * Sindbis virus * Ross River fever * RRV * Semliki Forest virus Reoviridae * Banna virus encephalitis Tick -borne Bunyavirales * Viral hemorrhagic fevers: Bhanja virus * Crimean–Congo hemorrhagic fever (CCHFV) * Heartland virus * Severe fever with thrombocytopenia syndrome (Huaiyangshan banyangvirus) * Tete virus Flaviviridae * Arbovirus encephalitides: Tick-borne encephalitis * TBEV * Powassan encephalitis * POWV * Viral hemorrhagic fevers: Omsk hemorrhagic fever * OHFV * Kyasanur Forest disease * KFDV * AHFV * Langat virus * LGTV Orthomyxoviridae * Bourbon virus Reoviridae * Colorado tick fever * CTFV * Kemerovo tickborne viral fever Sandfly -borne Bunyavirales * Adria virus (ADRV) * Oropouche fever * Oropouche virus * Pappataci fever * Toscana virus * Sandfly fever Naples virus Rhabdoviridae * Chandipura virus Mammal -borne Rodent -borne Arenaviridae * Viral hemorrhagic fevers: Lassa fever * LASV * Venezuelan hemorrhagic fever * GTOV * Argentine hemorrhagic fever * JUNV * Brazilian hemorrhagic fever * SABV * Bolivian hemorrhagic fever * MACV * LUJV * CHPV Bunyavirales * Hemorrhagic fever with renal syndrome * DOBV * HTNV * PUUV * SEOV * AMRV * THAIV * Hantavirus pulmonary syndrome * ANDV * SNV Herpesviridae * Murid gammaherpesvirus 4 Bat -borne Filoviridae * BDBV * SUDV * TAFV * Marburg virus disease * MARV * RAVV Rhabdoviridae * Rabies * ABLV * MOKV * DUVV * LBV * CHPV Paramyxoviridae * Henipavirus encephalitis * HeV * NiV Coronaviridae * SARS-related coronavirus * SARS-CoV * MERS-CoV * SARS-CoV-2 Primate -borne Herpesviridae * Macacine alphaherpesvirus 1 Retroviridae * Simian foamy virus * HTLV-1 * HTLV-2 Poxviridae * Tanapox * Yaba monkey tumor virus Multiple vectors Rhabdoviridae * Rabies * RABV * Mokola virus Poxviridae * Monkeypox [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Lassa fever	c0023092	26,707	wikipedia	https://en.wikipedia.org/wiki/Lassa_fever	2021-01-18T18:40:46	{"mesh": ["D007835"], "umls": ["C0023092"], "icd-9": ["078.8"], "orphanet": ["99824"], "wikidata": ["Q706845"]}
For the condition in animals, see Corneal ulcers in animals. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Corneal ulcer" – news · newspapers · books · scholar · JSTOR (August 2016) (Learn how and when to remove this template message) Corneal ulcer Other namesUlcerative keratitis SpecialtyOphthalmology Corneal ulcer is an inflammatory or, more seriously, infective condition of the cornea involving disruption of its epithelial layer with involvement of the corneal stroma. It is a common condition in humans particularly in the tropics and the agrarian societies. In developing countries, children afflicted by Vitamin A deficiency are at high risk for corneal ulcer and may become blind in both eyes, which may persist lifelong. In ophthalmology, a corneal ulcer usually refers to having an infectious cause while the term corneal abrasion refers more to physical abrasions.[1] ## Contents * 1 Signs and symptoms * 2 Types * 2.1 Superficial and deep corneal ulcers * 3 Refractory corneal ulcers * 3.1 Melting ulcers * 4 Corneal healing * 5 Diagnosis * 6 Treatment * 6.1 Refractory ulcers * 7 See also * 7.1 Seasonal corneal ulcer * 8 References * 9 External links ## Signs and symptoms[edit] Corneal ulcers are extremely painful due to nerve exposure, and can cause tearing, squinting, and vision loss of the eye. There may also be signs of anterior uveitis, such as miosis (small pupil), aqueous flare (protein in the aqueous humour), and redness of the eye. An axon reflex may be responsible for uveitis formation—stimulation of pain receptors in the cornea results in release inflammatory mediators such as prostaglandins, histamine, and acetylcholine. Sensitivity to light (photophobia) is also a common symptom of corneal ulcer. Redness of the affected eye is common. Brow ache and head ache may be present. Drooping of eye lid may be present. Slit lamp examination shows loss of epithelium. the site of the ulcer is studied and marked in case sheet.the edge of the ulcer is studied.whether satellite lesion is present or not is seen. Next, the cornea is stained with 1% fluorescein. The ulcer is stained green. ## Types[edit] ### Superficial and deep corneal ulcers[edit] Corneal ulcers are a common human eye disease. They are caused by trauma, particularly with vegetable matter, as well as chemical injury, contact lenses and infections. Other eye conditions can cause corneal ulcers, such as entropion, distichiasis, corneal dystrophy, and keratoconjunctivitis sicca (dry eye). Many micro-organisms cause infective corneal ulcer. Among them are bacteria, fungi, viruses, protozoa, and chlamydia: * Corneal Ulcer after a bacterial keratitis Bacterial keratitis is caused by Staphylococcus aureus, Streptococcus viridans, Escherichia coli, Enterococci, Pseudomonas, Nocardia, N. Gonorrhoea and many other bacteria. * Fungal keratitis causes deep and severe corneal ulcer. It is caused by Aspergillus sp., Fusarium sp., Candida sp., as also Rhizopus, Mucor, and other fungi. The typical feature of fungal keratitis is slow onset and gradual progression, where signs are much more than the symptoms. Small satellite lesions around the ulcer are a common feature of fungal keratitis and hypopyon is usually seen. * Viral keratitis causes corneal ulceration. It is caused most commonly by Herpes simplex, Herpes zoster and Adenoviruses. Also it can be caused by coronaviruses & many other viruses. Herpes virus cause a dendritic ulcer, which can recur and relapse over the lifetime of an individual. * Protozoa infection like Acanthamoeba keratitis is characterized by severe pain and is associated with contact lens users swimming in pools. * Chlamydia trachomatis can also contribute to development of corneal ulcer. Superficial ulcers involve a loss of part of the epithelium. Deep ulcers extend into or through the stroma and can result in severe scarring and corneal perforation. Descemetoceles occur when the ulcer extends through the stroma. This type of ulcer is especially dangerous and can rapidly result in corneal perforation, if not treated in time. The location of the ulcer depends somewhat on the cause. Central ulcers are typically caused by trauma, dry eye, or exposure from facial nerve paralysis or exophthalmos. Entropion, severe dry eye and trichiasis (inturning of eyelashes) may cause ulceration of the peripheral cornea. Immune-mediated eye disease can cause ulcers at the border of the cornea and sclera. These include Rheumatoid arthritis, rosacea, systemic sclerosis which lead to a special type of corneal ulcer called Mooren's ulcer. It has a circumferential crater like depression of the cornea, just inside the limbus, usually with an overhanging edge. ## Refractory corneal ulcers[edit] Main article: Recurrent corneal erosion Refractory corneal ulcers are superficial ulcers that heal poorly and tend to recur. They are also known as indolent ulcers or Boxer ulcers. They are believed to be caused by a defect in the basement membrane and a lack of hemidesmosomal attachments. They are recognized by undermined epithelium that surrounds the ulcer and easily peels back. Refractory corneal ulcers are most commonly seen in diabetics and often occur in the other eye later. They are similar to Cogan's cystic dystrophy. ### Melting ulcers[edit] Melting ulcers are a type of corneal ulcer involving progressive loss of stroma in a dissolving fashion. This is most commonly seen in Pseudomonas infection, but it can be caused by other types of bacteria or fungi. These infectious agents produce proteases and collagenases which break down the corneal stroma. Complete loss of the stroma can occur within 24 hours. Treatment includes antibiotics and collagenase inhibitors such as acetylcysteine. Surgery in the form of corneal transplantation (penetrating keratoplasty) is usually necessary to save the eye. ## Corneal healing[edit] An ulcer of the cornea heals by two methods: migration of surrounding epithelial cells followed by mitosis (dividing) of the cells, and introduction of blood vessels from the conjunctiva. Superficial small ulcers heal rapidly by the first method. However, larger or deeper ulcers often require the presence of blood vessels to supply inflammatory cells. White blood cells and fibroblasts produce granulation tissue and then scar tissue, effectively healing the cornea. ## Diagnosis[edit] Diagnosis is done by direct observation under magnified view of slit lamp revealing the ulcer on the cornea. The use of fluorescein stain, which is taken up by exposed corneal stroma and appears green, helps in defining the margins of the corneal ulcer, and can reveal additional details of the surrounding epithelium. Herpes simplex ulcers show a typical dendritic pattern of staining. Rose-Bengal dye is also used for supra-vital staining purposes, but it may be very irritating to the eyes. In descemetoceles, the Descemet's membrane will bulge forward and after staining will appear as a dark circle with a green boundary, because it does not absorb the stain. Doing a corneal scraping and examining under the microscope with stains like Gram's and KOH preparation may reveal the bacteria and fungi respectively. Microbiological culture tests may be necessary to isolate the causative organisms for some cases. Other tests that may be necessary include a Schirmer's test for keratoconjunctivitis sicca and an analysis of facial nerve function for facial nerve paralysis. ## Treatment[edit] Proper diagnosis is essential for optimal treatment. The cause of the ulcer is to be decided. Whether infective or non-infective. Bacterial corneal ulcer require intensive fortified antibiotic therapy to treat the infection. Fungal corneal ulcers require intensive application of topical anti-fungal agents. Viral corneal ulceration caused by herpes virus may respond to antivirals like topical acyclovir ointment instilled at least five times a day. Alongside, supportive therapy like pain medications are given, including topical cycloplegics like atropine or homatropine to dilate the pupil and thereby stop spasms of the ciliary muscle. Superficial ulcers may heal in less than a week. Deep ulcers and descemetoceles may require conjunctival grafts or conjunctival flaps, soft contact lenses, or corneal transplant. Proper nutrition, including protein intake and Vitamin C are usually advised. In cases of Keratomalacia, where the corneal ulceration is due to a deficiency of Vitamin A, supplementation of the Vitamin A by oral or intramuscular route is given. Drugs that are usually contraindicated in corneal ulcer are topical corticosteroids[2] and anesthetics \- these should not be used on any type of corneal ulcer because they prevent healing, may lead to superinfection with fungi and other bacteria and will often make the condition much worse. ### Refractory ulcers[edit] Topical antibiotics are used at hourly intervals to treat infectious corneal ulcers. Cycloplegic eye drops are applied to give rest to the eye. Pain medications are given as needed. Loose epithelium and ulcer base can be scraped off and sent for culture sensitivity studies to find out the pathogenic organism. This helps in choosing appropriate antibiotics. Complete healing takes anywhere from about a few weeks to several months. Refractory corneal ulcers can take a long time to heal, sometimes months. In case of progressive or non-healing ulcers, surgical intervention by an ophthalmologist with corneal transplantation may be required to save the eye. In all corneal ulcers it is important to rule out predisposing factors like diabetes mellitus and immunodeficiency. Conjunctival flap may be drawn over the ulcer as an alternative. ## See also[edit] ### Seasonal corneal ulcer[edit] * Christmas Eye, a seasonal epidemic of corneal ulceration which predominantly occurs only within a particular region of Australia * Vernal keratoconjunctivitis, a recurrent, bilateral, and self-limiting inflammation of conjunctiva, having a periodic seasonal incidence: Grade 3 ## References[edit] 1. ^ Root, Timothy (2007-12-17). "What's the difference between a corneal abrasion and an ulcer?". TimRoot.com. Retrieved 2017-06-09. 2. ^ Alhassan, M.B.; Rabiu, M.; Aqbabiaka, I.O. (2014). "Interventions for Mooren's ulcer". Cochrane Database Syst Rev. 1: CD006131. doi:10.1002/14651858.CD006131.pub3. PMID 24452998. ## External links[edit] Wikimedia Commons has media related to Corneal ulcer. Classification D * ICD-10: H16.0 * ICD-9-CM: 370.00 * MeSH: D003320 * DiseasesDB: 35065 * SNOMED CT: 91514001 External resources * MedlinePlus: 001032 * eMedicine: oph/249 * v * t * e Tests and procedures involving the eyes Eye surgery · Eye examination Adnexa Eyelids * Blepharoplasty * East Asian blepharoplasty * Epicanthoplasty * Tarsorrhaphy Lacrimal system * Dacryocystorhinostomy * Punctoplasty Globe Cornea * Radial keratotomy * LASIK * Keratomileusis * Epikeratophakia * Corneal transplantation * Photorefractive keratectomy * Intrastromal corneal ring segment * Corneal collagen cross-linking Other * Glaucoma surgery * Trabeculectomy * Iridectomy * Phacoemulsification * Cataract surgery * Capsulorhexis * Vitrectomy * Enucleation Extraocular muscles * Harada–Ito procedure * Strabismus surgery * Botulinum toxin therapy of strabismus Medical imaging * Fluorescein angiography * Indocyanine green angiography * Fundus photography * Corneal topography * Optical coherence tomography * Electrodiagnosis: Electrooculography * Electroretinography * Electronystagmography Eye examination * Gonioscopy * Dilated fundus examination * Ocular tonometry * Ophthalmoscopy * Retinoscopy * Color perception test * Visual field test/Perimetry Radiotherapy * Plaque radiotherapy * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Corneal ulcer	c0010043	26,708	wikipedia	https://en.wikipedia.org/wiki/Corneal_ulcer	2021-01-18T18:54:16	{"mesh": ["D003320"], "umls": ["C0010043"], "wikidata": ["Q1628473"]}
A number sign (#) is used with this entry because this form of disordered steroidogenesis is caused by homozygous or compound heterozygous mutations in the POR gene (124015), which encodes cytochrome p450 oxidoreductase, on chromosome 7q11.2. Mutations in this gene also result in a form of Antley-Bixler syndrome (ABS1; 201750). Description This rare variant of congenital adrenal hyperplasia, caused by mutations in the POR gene, results in apparent combined deficiency of P450C17 (609300) and P450C21 (613815) and accumulation of steroid metabolites. The most striking phenotypic feature is that affected girls are born with ambiguous genitalia, indicating intrauterine androgen excess. After birth, however, virilization does not progress and amounts of circulating androgens are low or normal. Affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, sometimes suggesting the pattern seen in patients with Antley-Bixler syndrome (see 207410) (summary by Arlt et al., 2004). Clinical Features In a 6-month-old 46,XY infant with a female phenotype and ambiguous genitalia, Peterson et al. (1985) found an unusual pattern of plasma and urinary steroids indicating that the child had multiple abnormalities of steroid-biosynthetic microsomal mixed-function oxidases: 21-hydroxylase, 17-alpha-hydroxylase, and 17,20-desmolase. Individually, each is responsible for a form of congenital adrenal hypoplasia; see 201910 and 202110. The deficit in activities of the first 2 enzymes resulted in decreased cortisol synthesis with subsequent increased ACTH secretion and adrenocortical hyperplasia. The male pseudohermaphroditism results from deficient testosterone synthesis due to deficiency of 17-alpha-hydroxylase and 17,20-desmolase. The family resided in the Dominican Republic. The mother and 2 sisters of the affected child, with normal phenotype, had mild 17-alpha-hydroxylase deficiency. The father had a normal urinary steroid profile. Peterson et al. (1985) proposed that since cytochrome P450 is the terminal oxidase for all 3 of these steroid microsomal mixed-function oxidases, impairment of translocation of P450 into the endoplasmic reticulum of the adrenocortical microsomes may represent a single defect affecting the activity of the 3 oxidases. Insertion of newly synthesized cytochrome P-450 into liver microsomes is known to require a signal-recognition particle bound to P-450 (Sakaguchi et al., 1984). Arlt et al. (2004) described 3 patients with apparent combined P450C17 and P450C21 deficiency. In 1 family an affected sister showed bony changes similar to those seen in Antley-Bixler syndrome, as well as ambiguous genitalia; her brother with congenital adrenal hyperplasia had normal male genitalia at birth and no skeletal abnormalities. In a third sporadic case, the girl showed at 13 years of age a marfanoid habitus, scoliosis, arachnodactyly, dysplastic ears, and long slim limbs. Williamson et al. (2006) reported a girl with a mild Antley-Bixler-like phenotype, ambiguous genitalia, impaired steroidogenesis, and compound heterozygosity for mutations in the POR gene. There was brachycephaly with a flat occiput, frontal bossing, and broad forehead. In addition, there was significant midface hypoplasia with a small mouth. Cranial, ovarian, uterine, and adrenal sonograms were normal. Skeletal survey at 5 weeks was normal except for advanced bone age of 6 months. There was no evidence of craniosynostosis, femoral bowing, or radiohumeral synostosis. Her ratio of pregnanediol to cortisol metabolites was more than twice normal and her other steroid ratios were higher than normal, but not as high as other published cases, demonstrating that the spectrum of biochemical severity is wider than previously suggested. The mother had undetectable serum unconjugated estriol at 18 weeks' gestation, but fetal morphology was normal on ultrasound at 20 weeks. Williamson et al. (2006) stated that a very low or negligible maternal serum unconjugated estriol is highly suspicious and warrants investigation for POR deficiency even in the presence of a normal fetal ultrasound. Hershkovitz et al. (2008) reported 4 undervirilized males of an extended Bedouin family. All 4 were 46,XY. None of the mothers became virilized during their pregnancies. Onset of puberty was normal in 2 patients, but inadequate virilization required testosterone replacement in both. One patient retained one dysfunctional testis and a small penis. No skeletal malformation, dysmorphism, or limited limb movements were found, and X-rays showed no radioulnar or radiohumeral synostosis. Biochemical Features Shackleton et al. (2004) monitored the second pregnancy of the mother of 2 children with P450 oxidoreductase deficiency reported by Arlt et al. (2004). The mother's estriol excretion failed to increase normally and she showed signs of virilization at 23 weeks of gestation, but there was no evidence for aromatase deficiency. Urine steroid analysis showed gradually increasing excretion of epiallopregnanediol, which the authors believed was the maternal urinary excretion product of fetal 5-pregnene-3-beta,20-alpha-diol, the principal metabolite of pregnenolone. Shackleton et al. (2004) proposed that excessive excretion of epiallopregnanediol together with low estriol may be diagnostic for fetal P450 oxidoreductase deficiency. Molecular Genetics In a phenotypically normal woman with amenorrhea and disordered steroidogenesis, Fluck et al. (2004) found compound heterozygosity for mutations in the POR gene (124015.0003-124015.0004). Fluck et al. (2004) hypothesized that milder mutations in POR may manifest as mild disorders of steroid synthesis, whereas severe mutations in POR without associated disorders of FGF receptors are sufficient to cause the ABS phenotype. All 3 patients with apparent combined P450C17 and P450C21 deficiency described by Arlt et al. (2004) were compound heterozygotes (see 124015.0005 and 124015.0007-124015.0009), whereas their parents and an unaffected sib were heterozygotes. Hershkovitz et al. (2008) reported 4 undervirilized males of an extended Bedouin family. One of these had been reported (Biason-Lauber et al., 1997) to carry mutations in the CYP17A1 gene (609300), encoding P450c17, causing isolated 17,20-lyase deficiency (202110). Gas chromatography-mass spectrometry (GC-MS) urinary steroid profiling and serum steroid measurements showed combined deficiencies of 17,20-lyase and 21-hydroxylase. Sequencing of exons 1 and 8 of CYP17A1 in 2 different laboratories showed no mutations. Sequencing of the POR gene showed that all 4 patients were homozygous for G539R (124015.0016), which was shown by Huang et al. (2005) to retain 46% of normal 17-alpha-hydroxylase activity but only 8% of the 17,20-lyase activity of P450c17. Hershkovitz et al. (2008) conclude that POR deficiency can masquerade clinically as isolated 17,20-lyase deficiency. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DISORDERED STEROIDOGENESIS DUE TO CYTOCHROME P450 OXIDOREDUCTASE DEFICIENCY	c0001627	26,709	omim	https://www.omim.org/entry/613571	2019-09-22T15:58:16	{"mesh": ["D000312"], "omim": ["613571"], "orphanet": ["418", "95699"], "synonyms": ["Alternative titles", "ADRENAL HYPERPLASIA, CONGENITAL, DUE TO CYTOCHROME P450 OXIDOREDUCTASE DEFICIENCY", "DISORDERED STEROIDOGENESIS DUE TO POR DEFICIENCY"], "genereviews": ["NBK1419"]}
Orgasm-induced seizures is a rare neurologic disease characterized by complex partial seizures with or without secondary generalization, or idiopathic primarily generalized epilepsy, triggered by sexual orgasm. Seizures usually start immediately, shortly after or a few hours after the achievement of orgasm, last a few seconds or minutes, and are followed, in very rare cases, by intense migraine. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Orgasm-induced seizures	None	26,710	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166421	2021-01-23T18:01:48	{"icd-10": ["G40.5"]}
A number sign (#) is used with this entry because hypogonadotropic hypogonadism-10 with or without anosmia (HH10) is caused by homozygous mutation in the TAC3 gene (162330) on chromosome 12q13. Description Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia, see 147950. Clinical Features Gianetti et al. (2010) reported a female proband with normosmic IHH from a large multiply consanguineous Asian family. She had 3 affected sisters, including 1 who was anosmic, and an unaffected sister. There was evidence for neuroendocrine recovery after discontinuation of sex steroid therapy in the affected individuals: the proband conceived a child without fertility medications but suffered an early pregnancy loss, whereas 1 of her affected sisters conceived spontaneously and carried the pregnancy to term. The third affected sister had regular menstrual cycles but had not conceived, and the unaffected sister had a positive withdrawal bleed to a progesterone challenge but did not cycle spontaneously. Molecular Genetics In a Turkish IHH family with a region of homozygosity on chromosome 12q, Topaloglu et al. (2009) analyzed the biologically plausible candidate gene TAC3 and identified homozygosity for a missense mutation in the 2 affected sisters (162330.0001). The mutation was found in heterozygosity in the unaffected parents and was not found in 100 ethnically matched Turkish or Kurdish controls. Gianetti et al. (2010) analyzed the TAC3 gene in 345 probands with normosmic IHH and identified homozygosity for a 1-bp deletion (162330.0002) in a female proband from a large multiply consanguineous Asian family who was negative for mutation in 7 other HH-associated genes. She had 3 affected sisters, including 1 who was anosmic, who were also homozygous for the deletion; an unaffected sister was a heterozygous carrier of the mutation. INHERITANCE \- Autosomal recessive HEAD & NECK Nose \- Anosmia (in some patients) CHEST Breasts \- Delayed or absent thelarche GENITOURINARY Internal Genitalia (Female) \- Primary amenorrhea NEUROLOGIC Central Nervous System \- Anosmia (in some patients) \- Mental retardation, mild (in some patients) ENDOCRINE FEATURES \- Patients have normal pituitary function \- Delayed or absent puberty \- Low estradiol levels in females \- Low or normal serum gonadotropins MISCELLANEOUS \- Neuroendocrine recovery occurs in some patients \- Only female patients reported (last curated October 2013) MOLECULAR BASIS \- Caused by mutation in the tachykinin-3 gene (TAC3, 162330.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYPOGONADOTROPIC HYPOGONADISM 10 WITH OR WITHOUT ANOSMIA	c3553843	26,711	omim	https://www.omim.org/entry/614839	2019-09-22T15:54:04	{"doid": ["0090089"], "omim": ["614839"], "orphanet": ["432"], "synonyms": ["Gonadotropic deficiency", "Isolated congenital gonadotropin deficiency", "Normosmic idiopathic hypogonadotropic hypogonadism", "nIHH"], "genereviews": ["NBK1334"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Abortion in Ghana" – news · newspapers · books · scholar · JSTOR (January 2019) (Learn how and when to remove this template message) Abortion in Ghana is legally permissible in Ghana. The abortion should also be conducted only at a Government hospital; registered private hospital, clinics registered under the Private Hospitals and Maternity Homes Act, 1958 (No. 8) and a place approved by the Minister of Health by a Legislative Instrument. Illegal Abortions are criminal offenses subject to at most five years in prison for the pregnant woman who induced said abortion, as well as for any doctor or other person who assisted this pregnant woman in accessing, or carrying out, an abortion.[1] Attempts to cause abortions are also criminal, as are the purveyance, supply, or procurement of chemicals and instruments whose intent is to induce abortions. ## Contents * 1 Terminology * 2 Exceptions * 3 Law * 4 Statistics * 5 Abortion and Contraceptives * 6 References ## Terminology[edit] The definition of abortion is quite wide. According to Act 29, section 58, article 3, of the Criminal code of 1960, “Abortion or miscarriage means premature expulsion or removal of conception from the uterus or womb before the period of gestation is completed.”[1] Thus, both words, abortion and miscarriage, can be used interchangeably to refer to the same phenomenon. The law would seem to cover induced abortions, where the pregnant woman willfully expels a viable fetus, and also spontaneous abortions, or miscarriages, which may be encouraged by the pregnant woman through various means. Medically, there have been attempts to clearly distinguish between the two,[2] but the laws in Ghana concerning this matter do not make this distinction. ## Exceptions[edit] In some situations, abortions are legal. The laws of Ghana allow abortions where (1) the pregnancy was as a result of rape, defilement, or incest, which are themselves all crimes in Ghana, and (2) where the pregnant woman requests the abortion. The pregnant woman's next of kin may request the abortion if the woman lacks the capacity to request it. For instance, if she is unconscious and in need of immediate medical attention that may entail abortion; if she is mentally incapable of making medical decisions (for example has an Intellectual disability); or if she is a minor according to the law. In Ghana, the age of minority is below eighteen years, although the legal age for consent is 16 years of age. ## Law[edit] Abortion is a criminal offence pursuant to Act 29, section 58 of the Criminal code of 1960,[1] amended by PNDCL 102 of 1985, which states that: 1. Subject to the provisions of subsection (2) of this section 1. any woman who with intent to cause abortion or miscarriage administers to herself or consent to be administered to her any poison, drug or other noxious thing or uses any instrument or other means whatsoever; or 2. any person who— 1. administers to a woman any poison, drug or other noxious thing or uses any instrument or other means whatsoever with intent to cause abortion or miscarriage, whether or not the woman is pregnant or has given her consent 2. induces a woman to cause or consent to causing abortion or miscarriage; 3. aids and abets a woman to cause abortion or miscarriage; 4. attempts to cause abortion or miscarriage; or 5. supplies or procures any poison, drug, instrument or other thing knowing that it is intended to be used or employed to cause abortion or miscarriage; shall be guilty of an offence and liable on conviction to imprisonment for a term not exceeding five years. 2. It is not an offense under section (1) if an abortion or miscarriage is caused in any of the following circumstances by a registered medical practitioner specializing in Gynaecology or any other registered medical practitioner in a government hospital or a private hospital or clinic registered under the Private Hospital and Maternity Home Act, 1958 (No. 9) or in a place approved for the purpose by legislative instrument made by the Secretary: 1. where pregnancy is the result of rape or defilement of a female idiot or incest and the abortion or miscarriage is requested by the victim or her next of kin or the person in loco parentis, if she lacks the capacity to make such request; 2. where the continuance of the pregnancy would involve risk to the life of the pregnant woman or injury to her physical or mental health and such a woman consents to it or if she lacks the capacity to give such consent it is given on her behalf by her next of kin or the person in loco parentis; 3. where there is substantial risk that if the child were born it may suffer from or later develop a serious physical abnormality or disease. 3. For the purposes of this section, abortion or miscarriage means premature expulsion or removal of conception from the uterus or womb before the period of gestation is completed. ## Statistics[edit] According to national statistical data from 2009, 7% of all pregnancies are aborted. Within the population of women between 15 and 49, 15% have had abortions.[3] For every 1,000 women in Ghana of childbearing age of 15 to 44, 15 abortions are performed. Another study carried out in the 1990s suggested that in southern Ghana, the number is marginally higher, at 17 abortions for every 1,000 women.[4] This number is lower than the statistics available for West Africa as a whole: abortions rates are at 28 per 1,000 women[5] Ghanaian women of the following demographics are more likely to have abortions: women who have never been married; women in their twenties; women with no children; wealthy women; and women from urban areas. Never-married women are twice as likely to seek the procedure as those who are married. The tendency to seek abortion decreases with number of children: women with no children are seven times more likely to seek an abortion than women with three or more children. For these women, the most prominent reason for seeking the abortion was the stigma associated with having a child out of wedlock. Women who have had previous abortions are far more likely to seek the procedure. Researchers peg this to the possibility that these women may have more knowledge, both of the legal status of abortions, and more likely, where to obtain the procedure. Women in the top 40% of the wealth distribution in the country are 67% - 80% more likely to have abortions that their poorer counterparts.[6] Younger women are more likely to seek abortions, with women between 20 and 24 years being most likely, at 25 abortions per 1,000 women, and the frequency decreasing with every successive age group.[3] Urban women are far more likely to have abortions, with 34 abortions per 1,000 women. Overall, urbanites are 110% more likely to seek abortions than their rural counterparts, at 21 abortions per 1,000 women versus 10 abortions per 1,000 women. The reasons that Ghanaian women give for seeking abortions include: the financial inability to care for a child; the pregnancy interfering with their occupation or schooling; and wanting to space out their childbearing or to limit family size.[7][8][9] Also due to limited number of legal practitioners to perform safe abortion, it is expensive therefore many women cannot afford it and they turn to have unsafe abortion by unskilled practitioners[10] Approximately 45% of abortions in Ghana are unsafe.[6] 11% of Ghanaian maternal deaths are due to unsafe abortions,[3] and maternal mortality is the second leading cause of death among Ghanaian women. Some women experience complications from these experiences. Because so few women know that abortions are legal on many grounds in Ghana, they do not seek, or demand post abortion care, even when they have legitimate reasons to obtain legal abortions.[3] According to a 2007 survey, only 3% of pregnant women, and 6% of women actively seeking abortions, knew the laws surrounding the procedure.[6] These numbers are relatively unreliable, because of how stigmatized abortions are in Ghana. Much of this data was collected based on face-to-face interviews, rendering it unlikely that they will reveal an accurate estimate of the occurrence of abortions. According to a paper, the number of abortions in Ghana is more likely to be closer to the West African rate of 28 per 1,000 women.[6] ## Abortion and Contraceptives[edit] The low rate of contraceptive use is part of the driver for abortions.[6] According to national statistical data, contraceptive use has increased over the decades, but from 13% use by married women in 1988, to just 25% by this demographic in 2003 followed by a slight decline to 24% in 2008.[8] A much higher proportion of sexually active unmarried women use modern contraceptives, but in 2008, this number was just 28% of the population. As such, 35% of married women, and 20% of sexually active unmarried married fall in the pool of people who are not seeking children, and yet are not using any modern contraceptive methods. As a consequence of this dearth, upwards of 37% of pregnancies in Ghana are unintended. A further 23% are mistimed, that is to say, do not occur at a time preferred by the individuals. 14% of all pregnancies are not wanted by the individuals pregnant. This translates to more than 300,000 children being products of unwanted pregnancies.[7] Overall, the average number of children Ghanaian women have has decreased from 6.4 to 4.0 between 1988 and 2008.[8] Nonetheless, this does not match the recorded desire of women, who wish to have less than four children. For more than a third of these women who are not looking for children nor are on contraceptives, the reason they give for not doing so are often health related, or a fear of the side effects and the risks associated with the use of contraceptives. The proportion of women in this pool rises with education and urbanity. Poorer women are overall more likely to have unplanned births, and less likely to use modern contraceptives, than their wealthier counterparts.[6] ## References[edit] 1. ^ a b c Abortion or miscarriage. Consolidation of Criminal Code of Ghana, 1960. Act 29. Section 58. 1999. Dec 10, pp. 37–38 2. ^ Moscrop, Andrew (2013-02-21). "'Miscarriage or abortion?' Understanding the medical language of pregnancy loss in Britain; a historical perspective". Medical Humanities. 39 (2): 98–104. doi:10.1136/medhum-2012-010284. ISSN 1468-215X. PMC 3841747. PMID 23429567. 3. ^ a b c d Ghana Statistical Service (GSS), Ghana Health Service (GHS) and Macro International, Ghana Maternal Health Survey 2007, Accra, Ghana: GSS and GHS; and Calverton, MD, USA: Macro International, 2009. 4. ^ Ahiadeke, Clement (June 2001). "Incidence of Induced Abortion in Southern Ghana". International Family Planning Perspectives. 27 (2): 96–108. doi:10.2307/2673822. ISSN 0190-3187. JSTOR 2673822. 5. ^ World Health Organization (WHO), Unsafe Abortion: Global and Regional Estimates of the Incidence of Unsafe Abortion and Associated Mortality in 2003, fifth ed., Geneva: WHO, 2007 6. ^ a b c d e f Sedgh, Gilda (2010). "Abortion in Ghana" (PDF). Guttmacher Institute. 7. ^ a b Aboagye PK et al., An Assessment of the Readiness to Offer Contraceptives and Comprehensive Abortion Care in the Greater Accra, Eastern, and Ashanti Regions of Ghana, Chapel Hill, NC, USA: Ipas, 2007. 8. ^ a b c Blanc AK and Grey S, Greater than expected fertility decline in Ghana: untangling a puzzle, Journal of Biosocial Science, 2002, 34(4):475-495. 9. ^ Baiden FK et al., Unmet need for essential obstetric services in a rural district in Northern Ghana: complications of unsafe abortions remain a major cause of mortality, Journal of the Royal Institute of Public Health, 2006, 120(5):421–426. 10. ^ Morhee RAS and Morhee ESK, "Overview of the law and availability of abortion services in Ghana", Ghana Medical Journal, September 2006, 40(3): 80-86 * v * t * e Abortion in Africa Sovereign states * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde (Cabo Verde) * Central African Republic * Chad * Comoros * Democratic Republic of the Congo * Republic of the Congo * Djibouti * Egypt * Equatorial Guinea * Eritrea * Eswatini (Swaziland) * Ethiopia * Gabon * The Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast (Côte d'Ivoire) * Kenya * Lesotho * Liberia * Libya * Madagascar * Malawi * Mali * Mauritania * Mauritius * Morocco * Mozambique * Namibia * Niger * Nigeria * Rwanda * São Tomé and Príncipe * Senegal * Seychelles * Sierra Leone * Somalia * South Africa * South Sudan * Sudan * Tanzania * Togo * Tunisia * Uganda * Zambia * Zimbabwe States with limited recognition * Sahrawi Arab Democratic Republic * Somaliland Dependencies and other territories * Canary Islands / Ceuta / Melilla (Spain) * Madeira (Portugal) * Mayotte / Réunion (France) * Saint Helena / Ascension Island / Tristan da Cunha (United Kingdom) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Abortion in Ghana	None	26,712	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Ghana	2021-01-18T18:30:32	{"wikidata": ["Q61002909"]}
An interstitial lung disease with a poor prognosis, that is characterized by the progressive formation of scar tissue within the lungs in the absence of any known cause. ## Epidemiology Idiopathic pulmonary fibrosis (IPF) incidence appears to be increasing. Reported incidences range from 0.2 per 100.000 per year to 94 per 100.000 per year. The prevalence is estimated to be higher in men than in women. ## Clinical description The mean age at presentation is 66 years. IPF initially usually manifests with symptoms of breathlessness on exertion and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones. Clubbing is found in approximately 50% of IPF patients typically exertional dyspnea progresses over a period of months to years. In practice patients are often misdiagnosed. ## Etiology The etiology is not yet completely understood. The current conceptual model is that environmental factors may cause microscopic damage in the lungs and that in susceptible people this may lead to a disturbed healing reaction that will result in an ongoing process of scar formation in the lung. This will ultimately lead to loss of lung function. ## Diagnostic methods IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP). The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images. If these are non-conclusive a lung biopsy can be considered, though potential implications and associated risks should always be weighed and discussed. The diagnosis of IPF can be made by defined criteria that have been published in guidelines endorsed by several professional societies. ## Differential diagnosis Differential diagnosis includes other idiopathic interstitial pneumonias, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis), forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis + and other environmental (sometimes occupational) exposures. In a subgroup of patients with pulmonary fibrosis, despite thorough investigations, no definite diagnosis can be made and this group is than labeled as unclassifiable- pulmonary fibrosis. ## Genetic counseling In patients that present one or more family members with pulmonary fibrosis, genetic counseling should be considered for; genetic testing (giving information before performing the test), familial counseling on potential implications in those forms with family aggregation that present a recognized functional gene variant, especially for telomerase or surfactant gene mutations. ## Management and treatment Pharmacological management : Two medications, pirfenidone and nintedanib, are recommended in the current international guidelines for the treatment of IPF. These medication slow down disease progression, as measured by decline in FVC by approximately 50% and are safe. Besides these, multiple new molecular therapeutic targets have been identified and several clinical trials are investigating the efficacy of novel medicat ions. These non pharmacological management approaches aim to improve or maintain quality of life and sometimes also life longer. Preventative measures as smoking cessation, influenza and pneumococcal vaccination are recommended. Supplemental oxygen is recommended for patients with an oxyhemoglobin saturation of less than 88% and reduces exertional dyspnea and improves exercise capacity for patients. Pulmonary rehabilitation and measures aimed at symptom relieve improve health related quality of life for patients. In a subgroup of patient lung transplantation may be an option. ## Prognosis The median survival without treatment is 2 to 5 years from the time of diagnosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Idiopathic pulmonary fibrosis	c1800706	26,713	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2032	2021-01-23T18:15:52	{"gard": ["8609"], "mesh": ["D054990"], "omim": ["178500", "616371", "616373"], "umls": ["C0085786", "C1800706"], "icd-10": ["J84.1"], "synonyms": ["IPF"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant mental retardation-51 (MRD51) is caused by heterozygous mutation in the KMT5B gene (610881) on chromosome 11q13. Clinical Features Stessman et al. (2017) reported 4 unrelated patients (patients 1 through 4) and reviewed 3 patients (patients 5, 6, and 7) previously reported by Iossifov et al. (2014) with a variety of cognitive neurodevelopmental disorders associated with heterozygous variants in the KMT5B gene. The patients ranged in age from 5 to 19 years. All had developmental delay with mild to moderate intellectual disability, 3 of 4 (75%) had poor or absent speech, and 3 of 5 (60%) had delayed motor development or coordination difficulties. Five of 6 (83%) had autism spectrum disorder, and 4 had behavioral abnormalities, including attention problems. Three patients had a history of febrile seizures. All had additional variable and nonspecific features, including dysmorphic facial features, cryptorchidism, foot deformities, and sleep difficulties, and some had a tendency toward tall stature. Two had mild brain anomalies on MRI, including enlarged ventricles. One patient had combined variable immunodeficiency. Faundes et al. (2018) reported 2 unrelated patients, 13 and 19 years of age, with MRD51. They had global developmental delay with mildly delayed walking, intellectual disability, and poor language. One had 'atypical autism,' and the other had learning disability, autism spectrum disorder, and hypotonia. Dysmorphic features included facial asymmetry, large head circumference (+2 to +4 SD), frontal bossing, epicanthal folds, posteriorly rotated ears, proptosis, and microtia. One patient had seizures that resolved. Molecular Genetics In 7 unrelated patients with MRD51, Iossifov et al. (2014) and Stessman et al. (2017) identified 7 different heterozygous variants in the KMT5B gene (see, e.g., 610881.0001-610881.0003). Four of the variants were categorized as 'likely gene disruptive' (LGD) events, such as nonsense or frameshift variants, and 3 were missense variants predicted to be deleterious. Five of the variants were demonstrated to have occurred de novo. One missense variant was maternally inherited without clinical information on the mother, and parental DNA was not available for another patient to determine segregation. Three of the variants were private, only identified in the affected patient (family), and 4 were classified as 'ultra-rare.' Functional studies of the variants and studies of patient cells were not performed. The first 4 patients were ascertained from a large cohort of over 11,730 patients with autism spectrum disorder, intellectual disability, and/or developmental delay involving 15 centers across 7 countries and 4 continents (Stessman et al., 2017). The authors used single-molecule molecular inversion probes (smMIPs) to sequence 208 candidate genes in these patient samples and confirmed the findings by Sanger sequencing. These results were then combined with recently reported similar data and published exome datasets, which identified 3 additional patients with KMT5B mutations. The finding of LGD and missense mutations in the KMT5B gene was statistically significant. Three of the patients (patients 5, 6, and 7) had previously been reported by Iossifov et al. (2014) as part of a large genetic study on autism. In 2 unrelated patients with MRD51, Faundes et al. (2018) identified de novo heterozygous loss-of-function variants in the KMT5B gene (610881.0004 and 610881.0005). The patients were ascertained from a cohort of 4,293 trios from the Deciphering Developmental Disorders (DDD) study who underwent exome sequencing. The KMT5B gene was chosen for study through a pathway-based approach focusing on candidate genes involved in histone lysine methylation/demethylation. The variants were filtered against several large databases, including ExAC, the 1000 Genomes Project, and the Exome Sequencing Project. Functional studies of the variants and studies of patient cells were not performed, but both variants were predicted to result in a loss of function and haploinsufficiency. Two additional unrelated patients with a similar phenotype were found to carry de novo heterozygous deletions (399 kb and 839 kb, respectively) encompassing the KMT5B gene. INHERITANCE \- Autosomal dominant GROWTH Height \- Tendency toward taller height GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism SKELETAL Feet \- Foot deformities NEUROLOGIC Central Nervous System \- Delayed development \- Intellectual disability, variable \- Speech delay \- Febrile seizures (in some patients) Behavioral Psychiatric Manifestations \- Autism spectrum disorder \- Autistic features \- Behavioral problems MISCELLANEOUS \- Highly variable phenotype \- Variable extraneurologic features \- Seven unrelated patients have been reported (last curated November 2017) \- De novo mutation (in most patients) MOLECULAR BASIS \- Caused by mutation in the lysine-specific methyltransferase 5B gene KMT5B, 610881.0001 ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MENTAL RETARDATION, AUTOSOMAL DOMINANT 51	c4540474	26,714	omim	https://www.omim.org/entry/617788	2019-09-22T15:44:46	{"omim": ["617788"]}
A rare type of autoimmune hepatitis characterized by clinical presentation as cryptogenic hepatitis, interface hepatitis on histological examination, elevated serum aminotransferase levels, hypergammaglobulinemia, and presence of circulating autoantibodies, specifically antinuclear antibodies (ANA), smooth muscle antibodies (SMA)/anti-actin antibodies, and/or anti-soluble liver antigen (SLA) antibodies. The disease predominantly develops at a post-pubertal age and most commonly takes a chronic course, although acute or acute severe presentation may also be observed. Typical concurrent autoimmune diseases are autoimmune thyroiditis, rheumatic diseases, and inflammatory bowel disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autoimmune hepatitis type 1	c4303164	26,715	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=563576	2021-01-23T18:01:03	{"synonyms": ["AIH type 1"]}
Chisa (1965) reported affected brother and sister, and Kopf et al. (1965) described affected sisters. Herd and Hunter (1998) quoted an incidence of halo nevi of 1%. They reported a family that had lived in New Zealand in which a typical halo nevus was noted below the left breast of the mother. One daughter, aged 9 years, had 2 halo nevi, and 2 older daughters had 1 or 2 halo nevi. All 4 individuals had had much sun exposure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HALO NEVI	c0474824	26,716	omim	https://www.omim.org/entry/234300	2019-09-22T16:27:17	{"mesh": ["D055882"], "omim": ["234300"], "synonyms": ["Alternative titles", "LEUKODERMA ACQUISITUM CENTRIFUGUM OF SUTTON"]}
Hepatocellular adenoma (HA) is a rare benign tumor of the liver Not to be confused with Hepatocellular carcinoma. Hepatocellular adenoma Micrograph of a hepatic adenoma (bottom of image). H&E stain SpecialtyGastroenterology, oncology Hepatocellular adenoma (also known as hepatic adenoma or hepadenoma) is a rare, benign liver tumor. It most commonly occurs in people with elevated systemic levels of estrogen, classically in women taking estrogen-containing oral contraceptive medication.[1] ## Contents * 1 Signs and symptoms * 1.1 Related Conditions * 2 Diagnosis * 2.1 Radiologic differential diagnosis * 2.2 Subtypes * 2.3 Pathologic diagnosis * 3 Treatment * 4 Epidemiology * 5 References * 6 External links ## Signs and symptoms[edit] About 25–50% of hepatic adenomas cause pain in the right upper quadrant or epigastric region of the abdomen.[2] Since hepatic adenomas can be large (8–15 cm), patients may notice a palpable mass. However, hepatic adenomas are usually asymptomatic, and may be discovered incidentally on imaging ordered for some unrelated reason.[2] Large hepatic adenomas have a tendency to rupture and bleed massively inside the abdomen. If not treated, there is a 30% risk of bleeding.[3] Bleeding may lead to hypotension, tachycardia, and sweating (diaphoresis). ### Related Conditions[edit] Hepatic adenomas are related to glycogen storage diseases, type 1 diabetes, as well as anabolic steroid use. ## Diagnosis[edit] Hepatic adenoma is usually detected by imaging, typically an ultrasound or CT, as a hyperenhancing liver nodule. Given that several liver tumors appear similarly on these imaging modalities, a multi-phase contrast-enhanced imaging study such as CT or MRI may be used to provide more information.[3][4] The significance of making a specific diagnosis is that, unlike other benign liver tumors such as hemangioma and focal nodular hyperplasia, hepatic adenomas have a small but meaningful risk of progressing into a malignancy.[3] Although imaging provides supportive information, a definitive diagnosis of hepatic adenoma requires biopsy of the tissue. ### Radiologic differential diagnosis[edit] * Echinococcal cyst * Focal fatty change * Focal nodular hyperplasia * Hepatoblastoma * Infiltrative liver disease * Inflammatory pseudotumor * Leiomyosarcoma * Lymphoma * Nodular regenerative hyperplasia ### Subtypes[edit] Hepatic adenomas may be sub-classified according to morphologic appearance by microscopy, immunohistochemical staining, and genetic mutational analysis:[5][6][7] * Inflammatory (40%–50%) * HNF1α-inactivated (35%–40%) * β-catenin–activated \- with exon 3 versus exon 7/8 mutation * β-Catenin–activated inflammatory \- with exon 3 versus exon 7/8 mutation * Unclassified Although the significance of this categorization is still under research, the subtypes may indicate differential risk of hemorrhage or malignant transformation. ### Pathologic diagnosis[edit] Micrograph of a hepatic adenoma demonstrating a regular reticulin scaffold. Reticulin stain Hepatic adenomas are, typically, well-circumscribed nodules that consist of sheets of hepatocytes with a bubbly vacuolated cytoplasm. The hepatocytes are on a regular reticulin scaffold and less or equal to three cell thick. The histologic diagnosis of hepatic adenomas can be aided by reticulin staining. In hepatic adenomas, the reticulin scaffold is preserved and hepatocytes do not form layers of four or more hepatocytes, as is seen in hepatocellular carcinoma. Cells resemble normal hepatocytes and are traversed by blood vessels but lack portal tracts or central veins. * Micrograph of hepatic adenoma. H&E stain * Micrograph of hepatic adenoma. Reticulin stain ## Treatment[edit] Some authors feel that all hepatocellular adenoma should be resected, because of the risk of rupture causing bleeding and because they may contain malignant cells.[8] Current recommendations are that all hepatic adenomas should be resected, as long as they are surgically accessible and the patient is a reasonable operative candidate.[9] Patients with adenomas should avoid oral contraceptives or hormonal replacement therapy. Pregnancy could cause the adenoma to grow faster, so patients with hepatic adenomas should avoid pregnancy.[10] ## Epidemiology[edit] Liver tumor types by relative incidence in adults in the United States, with hepatocellular adenoma at right.[11] The majority of hepatic adenomas arise in women aged 20–40, most of whom use oral contraceptives. Other medications which also alter circulating hormone levels, such as anabolic or androgenic steroids, Barbiturates, clomifene, have also been implicated as risk factors.[2] Incidence of adenomas may be increased in metabolic diseases, including tyrosinemia and type 1 diabetes mellitus, and glycogen storage diseases (types 1 and 3), as well as in beta-thalassemia and hemochromatosis.[2] ## References[edit] 1. ^ Rooks J, Ory H, Ishak K, Strauss L, Greenspan J, Hill A, Tyler C (1979). "Epidemiology of hepatocellular adenoma. The role of oral contraceptive use". JAMA. 242 (7): 644–8. doi:10.1001/jama.242.7.644. PMID 221698. 2. ^ a b c d "Hepatocellular Adenoma: eMedicine Gastroenterology". 3. ^ a b c Anthony S. Fauci; Eugene Braunwald; Dennis L. Kasper; Stephen L. Hauser; Dan L. Longo; J. Larry Jameson; Joseph Loscalzo (2008). Harrison's principles of internal medicine (17th ed.). New York: McGraw-Hill Medical. pp. Chapter 92 (benign liver tumors). ISBN 978-0071466332. 4. ^ Hussain S, van den Bos I, Dwarkasing R, Kuiper J, den Hollander J (2006). "Hepatocellular adenoma: findings at state-of-the-art magnetic resonance imaging, ultrasound, computed tomography and pathologic analysis". Eur Radiol. 16 (9): 1873–86. doi:10.1007/s00330-006-0292-4. PMID 16708218. 5. ^ Bioulac-Sage, Paulette; Sempoux, Christine; Balabaud, Charles (June 2017). "Hepatocellular Adenomas: Morphology and Genomics". Gastroenterology Clinics of North America. 46 (2): 253–272. doi:10.1016/j.gtc.2017.01.003. ISSN 1558-1942. PMID 28506364. 6. ^ Nault, JC; Couchy, G; Balabaud, C; Morcrette, G; Caruso, S; Blanc, JF; Bacq, Y; Calderaro, J; Paradis, V; Ramos, J; Scoazec, JY; Gnemmi, V; Sturm, N; Guettier, C; Fabre, M; Savier, E; Chiche, L; Labrune, P; Selves, J; Wendum, D; Pilati, C; Laurent, A; De Muret, A; Le Bail, B; Rebouissou, S; Imbeaud, S; GENTHEP, Investigators.; Bioulac-Sage, P; Letouzé, E; Zucman-Rossi, J (March 2017). "Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation" (PDF). Gastroenterology. 152 (4): 880–894.e6. doi:10.1053/j.gastro.2016.11.042. PMID 27939373. 7. ^ Larson, Brent K.; Guindi, Maha (2017). "A Limited Immunohistochemical Panel Can Subtype Hepatocellular Adenomas for Routine Practice". American Journal of Clinical Pathology. 147 (6): 557–570. doi:10.1093/ajcp/aqx010. PMID 28472207. 8. ^ Toso C, Majno P, Andres A, Rubbia-Brandt L, Berney T, Buhler L, Morel P, Mentha G (2005). "Management of hepatocellular adenoma: solitary-uncomplicated, multiple and ruptured tumors". World J Gastroenterol. 11 (36): 5691–5. doi:10.3748/wjg.v11.i36.5691. PMC 4481490. PMID 16237767.Full text Archived 2007-03-11 at the Wayback Machine 9. ^ Cho, S; Marsh J; Steel J; et al. (2008). "Surgical management of hepatocellular adenoma: take it or leave it?". Ann Surg Oncol. 15 (15): 2795–2803. doi:10.1245/s10434-008-0090-0. PMID 18696154. 10. ^ "Hepatocellular Adenoma Treatment & Management". WebMD. Medscape. Retrieved 11 July 2012. 11. ^ Table 37.2 in: Sternberg, Stephen (2012). Sternberg's diagnostic surgical pathology. Place of publication not identified: LWW. ISBN 978-1-4511-5289-0. OCLC 953861627. ## External links[edit] Classification D * ICD-O: M8170/0 * MeSH: D018248 * DiseasesDB: 5726 External resources * eMedicine: med/48 * Orphanet: 54272 * University of Utah—Pathology Images * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hepatocellular adenoma	c0206669	26,717	wikipedia	https://en.wikipedia.org/wiki/Hepatocellular_adenoma	2021-01-18T18:57:36	{"mesh": ["D018248"], "umls": ["C0206669"], "orphanet": ["54272"], "wikidata": ["Q1172076"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant spinocerebellar ataxia-42 (SCA42) is caused by heterozygous mutation in the CACNA1G gene (604065) on chromosome 17q21. Heterozygous mutation in the CACNA1G gene can also cause early-onset severe spinocerebellar ataxia-42 with neurodevelopmental deficits (SCA42ND; 618087). Description Spinocerebellar ataxia-42 is an autosomal dominant neurologic disorder characterized predominantly by gait instability and additional cerebellar signs such as dysarthria, nystagmus, and saccadic pursuits. The age at onset and severity of the disorder is highly variable; it is slowly progressive (summary by Coutelier et al., 2015). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). Clinical Features Coutelier et al. (2015) reported 10 patients from 3 unrelated French families with spinocerebellar ataxia. The age at symptom onset was highly variable, ranging from 9 to 78 years, although most had onset in mid-adulthood. Gait instability was the most common manifestation, and additional features included dysarthria, saccadic eye movements, diplopia, and nystagmus. Less common features included decreased distal vibration sense and urinary symptoms. Five patients had mild pyramidal signs, such as hyperreflexia and spasticity. Brain imaging showed cerebellar atrophy of the cerebellar vermis. The progression of the disorder was relatively slow. Three patients had depression and 2 had cognitive impairment. Neuropathologic studies, available for one 83-year-old affected individual who also had dementia, showed cerebellar atrophy with Purkinje cell loss and loss of neurons in the inferior olive. There was also microscopic evidence of Alzheimer disease (AD; 104300). Morino et al. (2015) reported 2 unrelated, large multigenerational Japanese families with slowly progressive SCA42. The age at onset ranged from 18 to 70 years, and the main features included ataxic gait, dysarthria, and gaze-evoked horizontal nystagmus. Cognitive impairment, seizures, muscle atrophy, involuntary movements, and parkinsonism were not observed. However, 2 patients in one family had prominent resting tremor. Brain imaging showed cerebellar atrophy. Inheritance The transmission pattern of SCA42 in the families reported by Coutelier et al. (2015) was consistent with autosomal dominant inheritance. Molecular Genetics In affected members of 3 unrelated French families with SCA42, Coutelier et al. (2015) identified a heterozygous missense mutation in the CACNA1G gene (R1715H; 604065.0001). The mutation in the first family was found by linkage analysis combined with whole-exome sequencing; the mutations in the other 2 families were found by screening of a large number of probands with a similar disorder. The mutation segregated with the phenotype in all families, and haplotype analysis excluded a founder effect. The substitution occurred in the voltage-sensing region. In vitro electrophysiologic studies and computer modeling simulations suggested that the mutation results in decreased neuronal excitability. In affected members of 2 unrelated Japanese families with SCA42, Morino et al. (2015) identified heterozygosity for the same R2715H mutation in the CACNA1G gene. The mutations were found by linkage analysis and exome sequencing, and there was a shared haplotype containing the mutation between these 2 families. Electrophysiologic studies showed that the mutation shifted the activation to more positive (depolarized) membrane potentials. Inactivation potentials were also shifted to more positive membrane potentials, although the slope factor was not significantly different. The findings indicated that SCA42 is a channelopathy. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Nystagmus \- Diplopia \- Saccadic pursuit ABDOMEN Gastrointestinal \- Dysphagia (in some patients) GENITOURINARY Bladder \- Urinary urgency (in some patients) NEUROLOGIC Central Nervous System \- Spinocerebellar ataxia \- Gait instability \- Dysarthria \- Tremor (in some patients) \- Pyramidal signs (in some patients) \- Hyperreflexia (in some patients) \- Spasticity (in some patients) \- Myokymia orbicularis (in some patients) \- Cerebellar atrophy Peripheral Nervous System \- Decreased distal vibratory sense (in some patients) MISCELLANEOUS \- Variable age at onset (range 9 to 78 years) \- Slow progression MOLECULAR BASIS \- Caused by mutation in the T-type voltage-dependent calcium channel, alpha-1G subunit gene (CACNA1G, 604065.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPINOCEREBELLAR ATAXIA 42	c4225205	26,718	omim	https://www.omim.org/entry/616795	2019-09-22T15:47:52	{"omim": ["616795"], "orphanet": ["458803"], "synonyms": ["SCA42"]}
Cyclosporosis is a parasitic disease caused by Cyclospora cayetanensis, a recently discovered coccidia that was initially described in Peru and then in most intertropical zones. Infection occurs through ingestion of contaminated food or water and leads to abdominal pain, anorexia and diarrhoea, which may resolve spontaneously in immunocompetent individuals but may persist in a chronic form in immunocompromised subjects, leading to a decline in their general state of health. ## Epidemiology The prevalence is unknown. ## Diagnostic methods The diagnosis is made by parasitological examination of the stools. ## Management and treatment Treatment revolves around administration of cotrimoxazole. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Cyclosporosis	c4274225	26,719	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=210	2021-01-23T16:54:30	{"gard": ["9528"], "icd-10": ["A07.3"]}
Choanal atresia (CA) is a congenital anomaly of the posterior nasal airway characterized by the obstruction of one (unilateral) or both (bilateral) choanal aperture(s), with clinical manifestations ranging from acute respiratory distress to chronic nasal obstruction. ## Epidemiology CA has a birth prevalence of approximately 1/11,630 in Europe and it follows a ''2:1'' ratio, namely female to male and unilateral to bilateral CA. ## Clinical description CA is a congenital disorder that consists of a unilateral or bilateral bony or membranous septum between the nose and nasopharynx. In bilateral CA (see this term), neonates present at birth with acute respiratory distress requiring orotracheal intubation or placement of an oropharyngeal cannula. Nasotracheal intubation is not possible. Neonates with bilateral CA can also present with a history of multiple failed extubation attempts, especially in those with secondary airway issues. Spontaneous survival with a bilateral CA is possible but exceptional. In unilateral CA (see this term), infants can be asymptomatic often until the first respiratory infection. The most common presentation is persistent unilateral nasal obstruction or persistent mucoid rhinorrhea. CA can either occur in an isolated form or associated with other congenital deformities such as in CHARGE syndrome, Crouzon disease, Down syndrome, Treacher-Collins syndrome, 22q11.2 deletion syndrome (see these terms) or polydactyly. Bilateral CA is more common in patients with other congenital anomalies while unilateral CA occurs more frequently in isolated cases. ## Etiology The following hypotheses are thought to result in developmental failure of the nasal cavity to communicate with the nasopharynx: persistence of the buccopharyngeal membrane from the fetal foregut; abnormal persistence of mesoderm forming adhesions in the nasochoanal region; abnormal persistence of the nasobuccal membrane of Hochstetter; or misdirection during neural crest cell migration. Prenatal exposure to maternal hyperthyroidism treated with methimazole may also be associated with CA development. ## Diagnostic methods Initial clinical evaluation includes introduction of a 6 or 8 French suction catheter via the nostrils, methylene blue dye test, cotton wisp test, and laryngeal mirror test. Flexible nasal endoscopy after mucous suctioning allows direct visualization of the atretic plate in the choana. Definitive evaluation is achieved with a computerized tomography scan which shows thickening of the medial portion of the pterygoid plates and enlargement of the posterior portion of the vomer, with or without membranous involvement. Tomography may also detect an associated malformation of semi-circular canals as found in CHARGE syndrome. ## Differential diagnosis Differential diagnoses include isolated pyriform aperture stenosis, nasolacrimal duct cyst (see these terms), turbinate hypertrophy, septal dislocation and deviation, antrochoanal polyp or nasal neoplasm. ## Management and treatment The goal of initial treatment for infants with bilateral CA is to maintain an adequate airway via the oral route. An oral airway or a feeding nipple with large holes to facilitate air flow can be used. If a patient still fails to maintain an adequate airway, endotracheal intubation must be performed. A tracheostomy may be required in patients with severe comorbidities but it is not necessary in cases of isolated (even bilateral) CA. Definitive surgical correction by nasal endoscopic approach is performed when appropriate and when feasible (weight >2kg). Given the relatively low morbidity of unilateral CA, definitive treatment is delayed until a later age (>18 months of age), when possible, as the chance of successful surgical repair increases with age. ## Prognosis CA (mainly the bilateral form) is a life-threatening condition and treatment cannot be delayed. In both unilateral and bilateral cases, restenosis necessitating reoperation is common. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Choanal atresia	c0008297	26,720	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137914	2021-01-23T18:01:04	{"mesh": ["D002754"], "omim": ["608911"], "umls": ["C0008297"], "icd-10": ["Q30.0"]}
A rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by severe short stature and craniofacial dysmorphism (microcephaly, narrow face with flat cheeks, ptosis, prominent nose with a convex ridge, low-set ears with small or absent lobes, high-arched/cleft palate, micrognathia), associated with premature graying and loss of scalp hair, redundant, dry and wrinkled skin of the palms, premature senility and varying degrees of intellectual disability. Cryptorchidism and skeletal anomalies may also be observed. There have been no further descriptions in the literature since 1970. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Microcephalic primordial dwarfism, Montreal type	c1859468	26,721	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2617	2021-01-23T18:50:36	{"gard": ["895"], "mesh": ["C535448"], "omim": ["210700"], "umls": ["C1859468"], "icd-10": ["Q87.1"], "synonyms": ["Bird-headed dwarfism, Montreal type"]}
Pelger-Huet anomaly (PHA) is an inherited blood condition in which the nuclei of several types of white blood cells (neutrophils and eosinophils) have unusual shape (bilobed, peanut or dumbbell-shaped instead of the normal trilobed shape) and unusual structure (coarse and lumpy). Click here to view a picture of these cells seen under the microscope. PHA is considered to be a benign disorder in most instances, as individuals with PHA are typically healthy. PHA is caused by mutations in the LBR gene. It is suspected that mutations within the LBR gene are responsible for a spectrum of disorders including isolated PHA; PHA with mild skeletal symptoms; and Hydrops, Ectopic calcification, Moth-eaten skeletal dysplasia (HEM). PHA was previously thought to be inherited in an autosomal dominant manner; however, co-dominant inheritance has been suggested as well. It is important to distinguish PHA from acquired or pseudo-Pelger-Huet anomaly, which may be found in individuals with certain types of leukemia or myelodysplastic syndromes. Diagnosis is made based on characteristic appearance of white blood cell nuclei identified by a blood smear. Most individuals with PHA do not require treatment as they do not have symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Pelger-Huet anomaly	c0030779	26,722	gard	https://rarediseases.info.nih.gov/diseases/9148/pelger-huet-anomaly	2021-01-18T17:58:24	{"mesh": ["D010381"], "omim": ["169400"], "synonyms": ["PHA", "Pelger Huet anomaly", "Pelger-Huet nuclear anomaly", "Ovoid neutrophil nuclei, developmental delay, epilepsy and skeletal abnormalities"]}
Arachnoiditis is a pain disorder caused by inflammation of the arachnoid, one of the membranes that surrounds and protects the nerves of the spinal cord. The inflammation may occur due to irritation from chemicals; infection; direct injury to the spine; chronic compression of spinal nerves; or complications from spinal surgery or other spinal procedures. It may result in scar tissue and adhesions, which cause the spinal nerves to “stick” together. If arachnoiditis affects the function of nerves, it can cause symptoms such as numbness, tingling, and a characteristic stinging and burning pain in the lower back or legs. In some people. it may affect the bladder, bowel, and sexual function. Very severe arachnoiditis can result in paralysis of the legs. Treatment aims to relieve pain and improve symptoms that impair function. Treatment may include pain medications, physical therapy, and psychotherapy. Surgical treatment is controversial because it offers only short-term relief and may increase formation of scar tissue. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Arachnoiditis	c0003708	26,723	gard	https://rarediseases.info.nih.gov/diseases/5839/arachnoiditis	2021-01-18T18:02:03	{"mesh": ["D001100"], "omim": ["182950"], "orphanet": ["137817"], "synonyms": ["Spinal arachnoiditis"]}
Congenital disorder caused by maternal warfarin administration Fetal warfarin syndrome Warfarin SpecialtyTeratology Usual onsetEmbryo CausesMaternal warfarin administration Diagnostic methodObservation of key symptoms PreventionAvoid administration of warfarin during pregnancy TreatmentAdminister Vitamin K and plasma with clotting factors. Surgical correction Fetal warfarin syndrome is a disorder of the embryo which occurs in a child whose mother took the medication warfarin (brand name: Coumadin) during pregnancy. Resulting abnormalities include low birth weight, slower growth, mental retardation, deafness, small head size, and malformed bones, cartilage, and joints.[1] Warfarin is an oral anticoagulant drug (blood thinner) used to reduce blood clots, deep vein thrombosis, and embolism in people with prosthetic heart valves, atrial fibrillation, or those who have suffered ischemic stroke.[2] Warfarin blocks the action of vitamin K, causing an inhibition of blood clotting factors and the pro-bone-building hormone osteocalcin. Warfarin is a teratogen which can cross from the mother to the developing fetus. The inhibition of clotting factors can lead to internal bleeding of the fetus while the inhibition of osteocalcin causes lower bone growth. As well as birth defects, warfarin can induce spontaneous abortion or stillbirth.[3] Because of this, warfarin is contraindicated during pregnancy. ## Contents * 1 Signs and symptoms * 1.1 Growth * 1.2 Facial features * 1.3 Bodily features * 1.4 CNS * 1.5 Physiological * 2 Cause * 3 Mechanism * 4 Prevention * 5 Management * 5.1 Medication * 5.2 Surgical correction * 6 References * 7 External links ## Signs and symptoms[edit] The key symptoms, visible at birth, vary between individuals exposed to warfarin in utero. The severity and occurrence of symptoms is dose dependent with higher doses (>5 mg warfarin daily) more likely to cause immediately noticeable defects.[4] The period of pregnancy in which warfarin is administered can affect the category of defects which develop. Warfarin taken in the first trimester of pregnancy is more likely to result in physical abnormalities while warfarin taken in the second and third trimester more commonly causes abnormalities of the central nervous system. The more extreme symptoms such as severe mental retardation, blindness and deafness occur more often when warfarin is used throughout all three trimesters.[3] ### Growth[edit] Babies born with fetal warfarin syndrome may have a below-average birth weight and do continue to grow at a reduced rate.[5] ### Facial features[edit] Children with fetal warfarin syndrome show many otolaryngological abnormalities consistent with abnormal bone and cartilage growth. Children may present with hypoplasia of the nasal ridge and a deep groove at the midline of the nose,[3] thinned or absent nasal septum,[6] choanal atresia; a narrowing the airway at the posterior nasal cavity, cleft lip and laryngomalacia;[3] large soft protrusions into the larynx. These facial defects and narrowing of the airways often lead to respiratory distress, noisy breathing and later; speech defects. Narrow airways often widen with age and allow for easier breathing.[3] Dental problems are also seen with abnormally large dental buds and late eruption of deciduous teeth.[6] Development of the eyes is also affected by warfarin. Microphthalmia; abnormally small eyes, telecanthus; abnormally far apart eyes and strabismus; misaligned or crossed eyes are common signs of fetal warfarin syndrome.[6] The appearance of an ectopic lacrimal duct, where the tear duct protrudes laterally onto the eye has also been noted.[6] ### Bodily features[edit] Whole body skeletal abnormalities are common in fetal warfarin syndrome. A generalized reduction in bone size causes rhizomelia; disproportionally short limbs, brachydactyly; short fingers and toes,[3] a shorter neck,[6] short trunk, scoliosis; abnormal curvature of the spine and stippled epiphyses; malformation of joints. Abnormalities of the chest: either pectus carinatum;[3] a protruding sternum, or pectus excavatum;[6] a sunken sternum form an immediately recognizable sign of fetal warfarin syndrome. Congenital heart defects such as a thinned atrial septum, coarctation of the aorta, patent ductus arteriosus; a connection between the pulmonary artery and aorta occur in 8% of fetal warfarin syndrome patients. Situs inversus totalis, the complete left-right mirroring of thoracic organs, has also been observed ### CNS[edit] Defects of the central nervous system can lead to profound mental challenges. Fetal warfarin syndrome can lead to microcephaly; an abnormally small head, hydrocephaly; increased ventricle size and CSF volume, and agenesis of the corpus callosum. These defects contribute to the appearance of significant mental retardation in 31% of fetal warfarin syndrome cases.[3] Hypotonia, whole body muscle relaxation, can appear in newborns with severe nervous deficits. Atrophy of the optic nerve can also cause blindness in fetal warfarin syndrome.[7] ### Physiological[edit] Inhibition of coagulation and resultant internal bleeding can cause too few red blood cells to be present in the bloodstream and low blood pressure in newborns with fetal warfarin syndrome.[5] Low hemoglobin levels can lead to partial oxygen starvation, a high level of lactic acid in the bloodstream, and acidosis. Prolonged oozing of fluid from the stump of the cut umbilical cord is common. ## Cause[edit] Fetal warfarin syndrome appears in greater than 6% of children whose mothers took warfarin during pregnancy.[3] Warfarin has a low molecular weight so can pass from the maternal to fetal bloodstream through the tight filter-like junctions of the placental barrier. As the teratogenic effects of warfarin are well known, the medication is rarely prescribed to pregnant women. However, for some patients, the risks associated with discontinuing warfarin use may outweigh the risk of embryopathy. Patients with prosthetic heart valves carry a particularly high risk of thrombus formation due to the inorganic surface and turbulent blood flow generated by a mechanical prosthesis. The risk of blood clotting is further increased by generalized hypercoagulability as concentrations of clotting factors rise during pregnancy.[8] This increased chance of blood clots leads to an increased risk of potentially fatal pulmonary or systemic emboli cutting of blood flow and oxygen to critical organs. Thus, some patients may continue taking warfarin throughout the pregnancy despite the risks to the developing child. ## Mechanism[edit] Warfarin’s ability to cause fetal warfarin syndrome in utero stems from its ability to limit vitamin K activation.[3] Warfarin binds to and blocks the enzyme Vitamin K epoxide reductase which is usually responsible for activating vitamin K during vitamin K recycling. Vitamin K, once activated, is able to add a carboxylic acid group to glutamate residues of certain proteins which assists in correct protein folding.[9] Without active vitamin K, a fetus exposed to warfarin is unable to produce large quantities of clotting and bone growth factors. Without vitamin K, clotting factors II, VII, IX and X are unable to be produced. Without these vital parts of the coagulation cascade a durable fibrin plug cannot form to block fluid escaping from damaged or permeable vasculature.[2] Anemia is common in fetuses exposed to warfarin as blood constantly seeps into the interstitial fluid or amniotic cavity.[5] High doses of warfarin and heavy bleeding lead to abortion and stillbirth. Osteocalcin is another protein dependent on vitamin K for correct folding and function. Osteocalcin is normally secreted by osteoblast cells and plays a role in aiding correct bone mineralization and bone maturation.[10] In the presence of warfarin and subsequent absence of vitamin K and active osteocalcin, bone mineralization and growth are stunted. ## Prevention[edit] Fetal warfarin syndrome is prevented by withholding prescription to pregnant women or those trying to conceive. As warfarin can remain in the mother’s body for up to five days,[11] warfarin should not be administered in the days leading up to conception. Doctors must take care to ensure women of reproductive age are aware of the risks to the baby should they get pregnant, before prescribing warfarin. For some women, such as those with prosthetic heart valves, anticoagulation medication cannot be suspended during pregnancy as the risk of thrombus and emboli is too high. In such cases an alternate anticoagulant, which cannot pass through the placental barrier to the fetus, is proscribed in place of warfarin. Heparin is one such anticoagulant medication, although its efficacy in patients with prosthetic heart valves is not well established.[12] New anticoagulant medications, which are efficacious and non-teratogenic such as ximelagatran continue to be developed.[3] ## Management[edit] ### Medication[edit] As well as the routine dose of vitamin K given to newborns after birth, babies born with fetal warfarin syndrome are given additional doses intramuscularly to overcome any remaining warfarin in the circulation and prevent further bleeding. Fresh frozen plasma is also administered to raise concentrations of active blood clotting factors. If the child is anemic from extensive bleeding in-utero, red blood cell concentrate is given to restore oxygen carrying capacity.[5] ### Surgical correction[edit] Surgical interventions can be given to improve functionality and correct cosmetic abnormalities. Osteotomy (bone cutting) and zetaplasty surgeries are used to cut away abnormal tissue growths at the piriform aperture around and pharynx to reduce airway obstruction.[6] Rhinoplasty surgery is used to restore normal appearance and function of the nose.[6] Heart surgery may also be required to close a patent ductus arteriosus. ## References[edit] 1. ^ Yurdakök, M. 2012, "Fetal and neonatal effects of anticoagulants used in pregnancy: a review", The Turkish journal of pediatrics, vol. 54, no. 3, pp. 207. 2. ^ a b Reid, A., Forrester, C. & Shwe, K. 2009, "Warfarin", Student BMJ, vol. 17. 3. ^ a b c d e f g h i j k Hou, J. 2004, "Fetal warfarin syndrome", Chang Gung medical journal, vol. 27, no. 9, pp. 691. 4. ^ Vitale, N., De Feo, M., De Santo, L.S., Pollice, A., Tedesco, N. & Cotrufo, M. 1999, "Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves", Journal of the American College of Cardiology, vol. 33, no. 6, pp. 1637-1641. 5. ^ a b c d Starling, L.D., Sinha, A., Boyd, D. & Furck, A. 2012, "Fetal warfarin syndrome", BMJ case reports, vol. 2012, no. 1, pp. 1-4 6. ^ a b c d e f g h Silveira, D.B., da Rosa, E.B., de Mattos, V.F., Goetze, T.B., Sleifer, P., Santa Maria, F.D., Rosa, R.C.M., Rosa, R.F.M. & Zen, P.R.G. 2015, "Importance of a multidisciplinary approach and monitoring in fetal warfarin syndrome", American Journal of Medical Genetics Part A, vol. 167, no. 6, pp. 1294-1299. 7. ^ Raghav, S. & Reutens, D. 2006;2007;, "Neurological sequelae of intrauterine warfarin exposure", Journal of Clinical Neuroscience, vol. 14, no. 2, pp. 99-103. 8. ^ Maiello, M., Torella, M., Caserta, L., Caserta, R., Sessa, M., Tagliaferri, A., Bernacchi, M., Napolitano, M., Nappo, C., De Lucia, D. & Panariello, S. 2006, "Hypercoagulability during pregnancy: evidences for a thrombophilic state", Minerva ginecologica, vol. 58, no. 5, pp. 417. 9. ^ Danziger, J. 2008, "Vitamin K-dependent Proteins, Warfarin, and Vascular Calcification", Clinical Journal of the American Society of Nephrology, vol. 3, no. 5, pp. 1504-1510. 10. ^ Yamauchi, M., Yamaguchi, T., Nawata, K., Takaoka, S. & Sugimoto, T. 2010, "Relationships between undercarboxylated osteocalcin and vitamin K intakes, bone turnover, and bone mineral density in healthy women", Clinical Nutrition, vol. 29, no. 6, pp. 761-765. 11. ^ Walfisch, A. & Koren, G. 2010, "The "Warfarin Window" in Pregnancy: The Importance of Half-life", Journal of obstetrics and gynaecology Canada, vol. 32, no. 10, pp. 988. 12. ^ Loftus, C. (1996). Neurosurgical aspects of pregnancy. Park Ridge, Ill.: American Association of Neurological Surgeons. ## External links[edit] Classification D * ICD-10: Q86.0 * ICD-9-CM: 760.7 * MeSH: C536683 * DiseasesDB: 33178 * Datagenno - Fetal Warfarin Syndrome * v * t * e Congenital malformation due to substance exposure * Fetal alcohol spectrum disorder * Fetal hydantoin syndrome * Fetal warfarin syndrome * Prenatal amphetamine exposure * Prenatal cannabis exposure * Prenatal cocaine exposure * Prenatal nicotine exposure Other * Substance use disorder [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Fetal warfarin syndrome	c0265374	26,724	wikipedia	https://en.wikipedia.org/wiki/Fetal_warfarin_syndrome	2021-01-18T18:29:45	{"gard": ["8580"], "mesh": ["C536683"], "umls": ["C0265374"], "icd-9": ["760.79"], "icd-10": ["Q86.2"], "orphanet": ["1914"], "wikidata": ["Q2549256"]}
Pallotta and Fusilli (1998) described a mother and her twin daughters, all of whom had severe selective tooth agenesis of the permanent teeth with persistence of the deciduous teeth, precocious calcification of the choroid plexus, dysmorphic facies, and minor digital anomalies. There was agenesis of all permanent teeth except for the upper middle incisors and the first upper and lower molars. There were bilateral and symmetric, rounded, calcified masses localized at the level of the basal ganglia, with hypoplastic greater wings of the sphenoid, narrowed cribriform of the ethmoid bone, fused clinoid processes, and hypoplastic nasal septum. All 3 had telecanthus, downslanting palpebral fissures, mild ocular proptosis, flattened, wide nasal bridge, a small nose with forward-slanting nostrils, and mild retrognathia. There was clinodactyly of the fifth finger and hypoplasia of the distal phalanx of the second toe. Karyotypes were normal. The twins were thought to be monozygous. Growth parameters were around the 90th centile in the girls and intelligence was well above average. Pallotta and Fusilli (1998) described their patients as having hypodontia, but they actually had oligodontia; see definitions in 106600. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	FACIAL DYSMORPHISM, SELECTIVE TOOTH AGENESIS, AND CHOROID CALCIFICATION	c1970343	26,725	omim	https://www.omim.org/entry/603589	2019-09-22T16:12:49	{"mesh": ["C567039"], "omim": ["603589"]}
Somatosensory disorder SpecialtyNeurology A somatosensory disorder is an impairment of the somatosensory system. ## Contents * 1 Signs and symptoms * 1.1 Seizures * 2 Mechanism * 3 Diagnosis * 4 References * 5 External links ## Signs and symptoms[edit] People may experience numbness, prickling or tingling sensations (paresthesias), or the feeling a limb has "fallen asleep" (an indicator of nerve compression), burning, cutting or other sensations.[1] ### Seizures[edit] Certain types of seizures are associated with the somatosensory system. Cortical injury may lead to loss of thermal sensation or the ability to discriminate pain. An aura involving thermal and painful sensations is a phenomenon known to precede the onset of an epileptic seizure or focal seizure. Another type of seizure, called a sensory Jacksonian seizure involves an abnormal, localizable, cutaneous sensation but does not have apparent stimulus. This sensation may progress along a limb or to adjacent cutaneous body areas, reflecting abnormal neuronal firing in the postcentral gyrus where an epileptic discharge is propagated. These episodes in which patients are consciously aware during a seizure have been useful for identifying problems associated with the somatosensory cortex. Patients can describe the nature of the seizure and how they feel during it.[2] ## Mechanism[edit] The absence of proprioception or two-point tactile discrimination on one side of the body suggests injury to the contralateral side of the primary somatosensory cortex. However, depending on the extent of the injury, damage can range in loss of proprioception of an individual limb or the entire body. A deficit known as cortical astereognosis of the receptive type describes an inability to make use of tactile sensory information for identifying objects placed in the hand. For example, if this type of injury effects the hand region in the primary somatosensory cortex for one cerebral hemisphere, a patient with closed eyes cannot perceive the position of the fingers on the contralateral hand and will not be able to identify objects such as keys or a cell phone if they are placed into that hand.[2] ## Diagnosis[edit] Evaluation of any suspected disease of the somatosensory system is included in a neurological examination of the peripheral nervous system. Modern techniques for testing somatosensory function are still quite crude compared to testing motor function.[1] Evaluation of somatosensory stimuli are limited by the patient's interpretation of sensation in response to testing. Tactile sensation is tested with a cotton wisp or light touch with a finger. Pain is assessed by pinprick or pinwheel (Wartenberg wheel). A 128 Hz tuning fork is used for testing vibrations. ## References[edit] 1. ^ a b H., Ropper, Allan (2014-05-16). Adams and Victor's principles of neurology. Samuels, Martin A.,, Klein, Joshua (Tenth ed.). New York. ISBN 9780071794794. OCLC 857402060. 2. ^ a b Augustine, James R. (2008). Human Neuroanatomy. San Diego, CA: Academic Press. p. 360. ISBN 978-0-12-068251-5. ## External links[edit] Classification D * ICD-10: R20 * ICD-9-CM: 782.0 * MeSH: D020886 * v * t * e Symptoms and signs relating to skin and subcutaneous tissue Disturbances of skin sensation * Hypoesthesia * Paresthesia * Formication * Hyperesthesia * Hypoalgesia * Hyperalgesia Circulation * Cyanosis * Pallor * Livedo * Livedo reticularis * Flushing * Petechia * Blanching Edema * Peripheral edema * Anasarca Other * Rash * Desquamation * Induration * Diaphoresis * Mass * Neck mass Skin * Asboe-Hansen sign * Auspitz's sign * Borsari's sign * Braverman's sign * Crowe sign * Dennie–Morgan fold * Darier's sign * Fitzpatrick's sign * Florid cutaneous papillomatosis * Gottron's sign * Hutchinson's sign * Janeway lesion * Kerr's sign * Koebner's phenomenon * Koplik's spots * Leser-Trelat sign * Nikolsky's sign * Pastia's sign * Russell's sign * Wickham striae * Wolf's isotopic response * Munro's microabscess Nails * Aldrich-Mees' lines * Beau's lines * Muehrcke's lines * Terry's nails This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Somatosensory disorder	c0752262	26,726	wikipedia	https://en.wikipedia.org/wiki/Somatosensory_disorder	2021-01-18T18:52:53	{"mesh": ["D020886"], "icd-9": ["782.0"], "icd-10": ["R20"], "wikidata": ["Q1641015"]}
Cutaneous mastocytoma is a form of cutaneous mastocytosis (CM, see this term) generally characterized by the presence of a solitary or multiple hyperpigmented macules, plaques or nodules associated with abnormal accumulation of mast cells in the skin. ## Epidemiology Prevalence is unknown but mastocytomas are the second most frequent form of CM in children, accounting for 10-15% of cases. ## Clinical description Patients generally present during infancy, with most presenting in the first three months of life. However, rare cases of onset in adulthood have been reported. Mastocytomas usually appear as oval lesions with red-brown, pink or yellow pigmentation. The diameter varies from around 1-4 cm and the surface may be smooth or have a ''peau d'orange'' appearance. The trunk, face, neck and extremities are the most common sites of involvement. Patients with multiple mastocytomas (up to 5) have been reported with new lesions appearing at different locations up to two months after emergence of the initial lesion. Other skin manifestations may include blistering (most frequent during infancy), pruritus and urticaria. Stroking of the lesions results in Darier's sign and generalized flushing in some cases. Additional systemic symptoms are rarely associated with cutaneous mastocytomas but a few cases with fever, gastrointestinal disturbances (nausea, colic and diarrhea), headaches and asthma-like symptoms have been reported. ## Etiology Mutations in the KIT gene (4q11-q12) have been identified in some patients with CM, however, this mutation is rare in the pediatric population and the etiology and pathogenesis of cutaneous mastocytoma remains to be determined. ## Diagnostic methods Diagnosis is made on the basis of the clinical appearance of the lesions and the presence of Darier's sign. Histopathological examinations confirm the diagnosis by revealing a dense inﬁltrate of mast cells in the upper dermis. ## Differential diagnosis The differential diagnosis generally includes melanocytic nevi, xanthomas and juvenile xanthogranuloma (see this term). ## Management and treatment Treatment is symptomatic and includes oral administration of antihistamines, topical steroids and the use of hydrocolloid dressings to cover the lesions. Trigger factors (such as rubbing of the lesions and use of nonsteroidal anti-inflammatory drugs) should be avoided. Surgical excision provides a definitive cure for patients with alarming symptomatic lesions that do not respond to other forms of treatment and has been recommended as a first-line therapy in some cases. ## Prognosis The prognosis for patients with onset during infancy is good with regression of most lesions during childhood and complete resolution by adolescence. Rare cases of persisting mastocytoma in adulthood have been reported. Spontaneous resolution is less common in patients with adult-onset. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Cutaneous mastocytoma	c0343115	26,727	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79455	2021-01-23T17:04:01	{"gard": ["12687"], "mesh": ["D054705"], "umls": ["C0343115"], "icd-10": ["Q82.2"], "synonyms": ["Cutaneous local mastocytoma", "Multiple mastocytoma", "Solitary mastocytoma"]}
Type of birthmark caused by a collection of melanocytes Café au lait spot A café au lait spot on a patient's left cheek SpecialtyDermatology Café au lait spots, or café au lait macules, are flat, hyperpigmented birthmarks.[1] The name café au lait is French for "coffee with milk" and refers to their light-brown color. Café au lait lesions with rough borders (“coast of Maine”) may be seen in McCune-Albright syndrome.[2][3] In contrast, Café au lait lesions of neurofibromatosis have smooth borders (“coast of California").[3] They are caused by a collection of pigment-producing melanocytes in the epidermis of the skin.[4] These spots are typically permanent and may grow or increase in number over time.[5] Café au lait spots are often harmless but may be associated with syndromes such as neurofibromatosis type 1 and McCune–Albright syndrome.[5] ## Contents * 1 Cause * 2 Diagnosis * 3 Prognosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Cause[edit] Neurofibromatosis type I café au lait spot Further information: List of conditions associated with café au lait macules Café au lait spots can arise from diverse and unrelated causes:[6][7] * Ataxia–telangiectasia * Basal cell nevus syndrome * Benign congenital skin lesion * Bloom syndrome * Chédiak–Higashi syndrome * Congenital melanocytic naevus * Fanconi anemia * Gaucher disease * Hunter syndrome * Jaffe–Campanacci syndrome * Legius syndrome * Maffucci syndrome * They can be caused by vitiligo in the rare McCune–Albright syndrome.[8] * Multiple mucosal neuroma syndrome * Having six or more café au lait spots greater than 5 mm in diameter before puberty, or greater than 15 mm in diameter after puberty, is a diagnostic feature of neurofibromatosis type I (NF-1), but other features are required to diagnose NF-1.[4] Familial multiple café au lait spots have been observed without an NF-1 diagnosis.[9] * Noonan syndrome * Silver–Russell syndrome * Tuberous sclerosis * Watson syndrome * Wiskott–Aldrich syndrome ## Diagnosis[edit] Diagnosis is visual with measurement of spot size. The number of spots can have clinical significance for diagnosis of associated disorders such as Neurofibromatosis type I. Six or more spots of at least 5mm in diameter in pre-pubertal children and at least 15mm in post-pubertal individuals is one of the major diagnostic criteria for NF1.[10] ## Prognosis[edit] Café au lait spots are usually present at birth, permanent, and may grow in size or increase in number over time.[5] Cafe au lait spots are themselves benign and do not cause any illness or problems. However, they may be associated with syndromes such as Neurofibromatosis Type 1 and McCune-Albright syndrome.[5] The size and shape of the spots can vary in terms of description. In Neurofibromatosis Type 1, the spots tend to be described as ovoid, with smooth borders. In other disorders, the spots can be less ovoid, with jagged borders. In Neurofibromatosis Type 1, the spots tend to resemble the "coast of California," rather than the "coast of Maine," meaning the edges are smoother and more linear. [4] ## Treatment[edit] Café au lait spots can be removed with lasers.[11] Results are variable as the spots are often not completely removed or can come back after treatment. Often, a test spot is treated first to help predict the likelihood of treatment success.[12] ## See also[edit] * Birthmark * Nevus * List of cutaneous conditions * List of conditions associated with café au lait macules ## References[edit] 1. ^ Plensdorf S, Martinez J (January 2009). "Common pigmentation disorders". American Family Physician. 79 (2): 109–16. PMID 19178061. 2. ^ coast of Maine spots - General Practice Notebook 3. ^ a b Jameson, J. Larry; Kasper, Dennis L.; Longo, Dan L.; Fauci, Anthony S.; Hauser, Stephen L.; Loscalzo, Joseph (eds.). Harrison's principles of internal medicine (20th ed.). New York. ISBN 978-1-259-64403-0. OCLC 1029074059. 4. ^ a b c Listernick, Robert; Charrow, Joel (2012). "Chapter 141: The Neurofibromatoses". In Goldsmith, Lowell; Katz, Stephen I.; Gilchrest, Barbara A.; Paller, Amy S.; Leffell, David J.; Wolff, Klaus (eds.). Fitzpatrick's dermatology in general medicine (8th ed.). New York: McGraw-Hill Medical. ISBN 978-0-07-166904-7. 5. ^ a b c d Morelli, JG (2013). CURRENT Diagnosis & Treatment: Pediatrics, 22e. New York, NY: McGraw-Hill. pp. Chapter 15: Skin. ISBN 978-0-07-182734-8. 6. ^ "Cafe Au Lait Spots", by William D James, MD 7. ^ Cafe Au Lait Spots 8. ^ Whyte, M. P.; Podgornik, M. N.; Zerega, J.; Reinus, W. R. (2000). "Café-au-lait spots caused by vitiligo in McCune-Albright syndrome". J Bone Miner Res. 15 (12): 2521–2523. doi:10.1359/jbmr.2000.15.12.2521. PMID 11127218. S2CID 43896568. 9. ^ Arnsmeier, Sheryl L.; Riccardi, Vincent M.; Paller, Amy S. (1994). "Familial Multiple Cafe au lait Spots". Archives of Dermatology. 130 (11): 1425–1426. doi:10.1001/archderm.1994.01690110091015. PMID 7979446. 10. ^ "Neurofibromatosis 1". GeneReviews. 11. ^ Scheinfeld, Noah S.; et al. (2011). "Laser Treatment of Benign Pigmented Lesions". Medscape Reference. 12. ^ al.], editors, Lowell A. Goldsmith ... [et (2012). Fitzpatrick's dermatology in general medicine (8th ed.). New York: McGraw-Hill Medical. pp. Chapter 239. ISBN 978-0-07-166904-7.CS1 maint: extra text: authors list (link) ## External links[edit] Classification D * ICD-10: L81.3 * ICD-9-CM: 709.09 * OMIM: 114030 * MeSH: D019080 * DiseasesDB: 16118 External resources * eMedicine: ped/2754 Wikimedia Commons has media related to Café au lait spot. Look up cafe au lait or macule in Wiktionary, the free dictionary. * eMedicine * v * t * e Pigmentation disorders/Dyschromia Hypo-/ leucism Loss of melanocytes Vitiligo * Quadrichrome vitiligo * Vitiligo ponctué Syndromic * Alezzandrini syndrome * Vogt–Koyanagi–Harada syndrome Melanocyte development * Piebaldism * Waardenburg syndrome * Tietz syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric dermatosis * Schamberg disease * Majocchi's disease * Gougerot–Blum syndrome * Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis * Lichen aureus * Angioma serpiginosum * Hemosiderin hyperpigmentation Other metals * Argyria * Chrysiasis * Arsenic poisoning * Lead poisoning * Titanium metallic discoloration Other * Carotenosis * Tar melanosis Dyschromia * Dyschromatosis symmetrica hereditaria * Dyschromatosis universalis hereditaria See also * Skin color * Skin whitening * Tanning * Sunless * Tattoo * removal * Depigmentation [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Café au lait spot	c0265974	26,728	wikipedia	https://en.wikipedia.org/wiki/Caf%C3%A9_au_lait_spot	2021-01-18T18:46:15	{"mesh": ["D019080"], "umls": ["C0265974", "C0221263"], "icd-9": ["709.09"], "icd-10": ["L81.3"], "wikidata": ["Q856979"]}
Chromosome 14q deletion is a chromosome abnormality that occurs when there is a missing (deleted) copy of genetic material on the long arm (q) of chromosome 14. The severity of the condition and the signs and symptoms depend on the size and location of the deletion and which genes are involved. Features that often occur in people with chromosome 14q deletion include developmental delay, intellectual disability, behavioral problems and distinctive facial features. Chromosome testing of both parents can provide more information on whether or not the deletion was inherited. In most cases, parents do not have any chromosomal anomaly. However, sometimes one parent is found to have a balanced translocation, where a piece of a chromosome has broken off and attached to another one with no gain or loss of genetic material. The balanced translocation normally does not cause any signs or symptoms, but it increases the risk for having an affected child with a chromosomal anomaly like a deletion. Treatment is based on the signs and symptoms present in each person. This page is meant to provide general information about 14q deletions. You can contact GARD if you have questions about a specific deletion on chromosome 14. To learn more about chromosomal anomalies please visit our GARD webpage on FAQs about Chromosome Disorders. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Chromosome 14q deletion	c2931701	26,729	gard	https://rarediseases.info.nih.gov/diseases/3722/chromosome-14q-deletion	2021-01-18T18:01:25	{"mesh": ["C538033"], "umls": ["C2931701"], "synonyms": ["Deletion 14q", "Monosomy 14q", "14q deletion", "14q monosomy", "Partial monosomy 14q"]}
Congenital myasthenic syndromes SpecialtyNeurology Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction. The effects of the disease are similar to Lambert-Eaton Syndrome and myasthenia gravis, the difference being that CMS is not an autoimmune disorder. There are only 600 known family cases of this disorder and it is estimated that your chance of having it is 1 in 200,000. ## Contents * 1 Types * 2 Presentation * 3 Mechanisms * 3.1 Postsynaptic CMS * 4 Diagnosis * 5 Management * 6 See also * 7 References * 8 External links ## Types[edit] The types of CMS are classified into three categories: presynaptic, postsynaptic, and synaptic.[citation needed] * Presynaptic symptoms include brief stops in breathing, weakness of the eye, mouth, and throat muscles. These symptoms often result in double vision and difficulty chewing and swallowing. * Postsynaptic symptoms in infants include severe muscle weakness, feeding and respiratory problems, and delays in the ability to sit, crawl, and walk. * Synaptic symptoms include early childhood feeding and respiratory problems, reduced mobility, curvature of the spine, and weakness, which causes a delay in motor milestones. ## Presentation[edit] Onset symptoms for all ages may include droopy eyelids. A particular form of postsynaptic CMS (slow-channel CMS) includes severe weakness beginning in infancy or childhood that progresses and leads to loss of mobility and respiratory problems in adolescence or later life.[citation needed] ## Mechanisms[edit] ### Postsynaptic CMS[edit] CMS is associated with genetic defects that affect proteins of the neuromuscular junction. Postsynaptic defects are the most frequent cause of CMS and often result in abnormalities in the acetylcholine receptor (AChR). In the neuromuscular junction there is a vital pathway that maintains synaptic structure and results in the aggregation and localization of AChR on the postsynaptic folds. This pathway consists of agrin, muscle-specific tyrosine kinase (MuSK), acetylcholine receptors (AChRs) and the AChR-clustering protein rapsyn, encoded by the RAPSN gene. The vast majority of mutations causing CMS are found in the AChR subunits and rapsyn genes.[1] Out of all mutations associated with CMS, more than half are mutations in one of the four genes encoding the adult acetylcholine receptor (AChR) subunits. Mutations of the AChR often result in endplate deficiency. Most of the mutations of the AChR are mutations of the CHRNE gene. The CHRNE gene codes for the epsilon subunit of the AChR. Most mutations are autosomal recessive loss-of-function mutations and as a result there is endplate AChR deficiency. CHRNE is associated with changing the kinetic properties of the AChR.[2] One type of mutation of the epsilon subunit of the AChR introduces an Arginine into the binding site at the α/ε subunit interface of the receptor. The addition of a cationic Arg into the anionic environment of the AChR binding site greatly reduces the kinetic properties of the receptor. The result of the newly introduced Arg is a 30-fold reduction of agonist affinity, 75-fold reduction of gating efficiency, and an extremely weakened channel opening probability. This type of mutation results in an extremely fatal form of CMS.[3] Another common underlying mechanism of CMS is the mutation of the rapsyn protein, coded by the RAPSN gene. Rapsyn interacts directly with the AChRs and plays a vital role in agrin-induced clustering of the AChR. Without rapsyn, functional synapses cannot be created as the folds do not form properly. Patients with CMS-related mutations of the rapsyn protein typically are either homozygous for N88K or heterozygous for N88K and a second mutation. The major effect of the mutation N88K in rapsyn is to reduce the stability of AChR clusters. The second mutation can be a determining factor in the severity of the disease.[1] Studies have shown that most patients with CMS that have rapsyn mutations carry the common mutation N88K on at least one allele. However, research has revealed that there is a small population of patients who do not carry the N88K mutation on either of their alleles, but instead have different mutations of the RAPSN gene that codes for rapsyn on both of their alleles. Two novel missense mutations that have been found are R164C and L283P and the result is a decrease in co-clustering of AChR with raspyn. A third mutation is the intronic base alteration IVS1-15C>A and it causes abnormal splicing of RAPSN RNA. These results show that diagnostic screening for CMS mutations of the RAPSN gene cannot be based exclusively on the detection of N88K mutations[4] Dok-7 is a postsynaptic protein that binds and activates MuSK protein, which then leads to AChR clustering and typical folding of the postsynaptic membrane. Mutations of Dok-7 are another underlying mechanism of postsynaptic CMS.[5] ## Diagnosis[edit] Congenital myasthenic syndromes (CMS) is "often difficult to diagnose because of a broad differential diagnosis and lack of specific laboratory findings. Identification of the underlying mutation is critical, as certain mutations lead to treatment-responsive conditions while others do not."[6] Whole exome sequencing (WES) is often used as a diagnostic tool that allows for the "initiation of specific treatment".[6] ## Management[edit] Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravis, treatments used in MG are not useful in CMS. MG is treated with immunosuppressants, but CMS is not an autoimmune disorder. Instead, CMS is genetic and responds to other forms of drug treatments.A form of presynaptic CMS is caused by an insufficient release of acetylcholine (ACh) and is treated with cholinesterase inhibitors.[citation needed] Postsynaptic fast-channel CMS (ACh receptors do not stay open long enough) is treated with cholinesterase inhibitors and 3,4-diaminopyridine.[7][8] In the U.S., the more stable phosphate salt formulation of 3,4-diaminopyridine (amifampyridine phosphate) is under development as an orphan drug for CMS and is available to eligible patients at no cost under an expanded access program by Catalyst Pharmaceuticals.[9][10][11][12][13] Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which plugs the ACh receptor. Ephedrine has been tested on patients in clinical trials and appears to be an effective treatment for DOK7 CMS. Most patients tolerate this type of treatment and improvements in strength can be impressive. Further research must be done in order to determine the long-term response of ephedrine as well as the most effective dosage regimen. Ephedrine can lead to a profound improvement in muscle strength and an even more impressive effect on day-to-day function. The effect of ephedrine is delayed and the improvement occurs over a period of months.[5] Ephedrine was given at doses between 15 and 90 mg/day and as a result, muscle strength improved.[14] ## See also[edit] * Congenital disorder * Myasthenia gravis * Lambert-Eaton syndrome ## References[edit] 1. ^ a b Cossins, J.; Burke, G.; Maxwell, S.; Spearman, H.; Man, S.; Kuks, J.; Vincent, A.; Palace, J.; Fuhrer, C.; Beeson, D. (2006). "Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations". Brain. 129 (10): 2773–2783. doi:10.1093/brain/awl219. PMID 16945936. 2. ^ Abicht, A.; Dusl, M.; Gallenmüller, C.; Guergueltcheva, V.; Schara, U.; Della Marina, A.; Wibbeler, E.; Almaras, S.; Mihaylova, V.; Von Der Hagen, M.; Huebner, A.; Chaouch, A.; Müller, J. S.; Lochmüller, H. (2012). "Congenital myasthenic syndromes: Achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: A study of 680 patients". Human Mutation. 33 (10): 1474–1484. doi:10.1002/humu.22130. PMID 22678886. 3. ^ Shen, X. -M.; Brengman, J. M.; Edvardson, S.; Sine, S. M.; Engel, A. G. (2012). "Highly fatal fast-channel syndrome caused by AChR subunit mutation at the agonist binding site". Neurology. 79 (5): 449–454. doi:10.1212/WNL.0b013e31825b5bda. PMC 3405251. PMID 22592360. 4. ^ Muller, J. S.; Baumeister, S. K.; Rasic, V. M.; Krause, S.; Todorovic, S.; Kugler, K.; Müller-Felber, W.; Abicht, A.; Lochmüller, H. (2006). "Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations". Neurology. 67 (7): 1159–1164. doi:10.1212/01.wnl.0000233837.79459.40. PMID 16931511. 5. ^ a b Palace, J. (2012). "DOK7 congenital myasthenic syndrome". Annals of the New York Academy of Sciences. 1275 (1): 49–53. Bibcode:2012NYASA1275...49P. doi:10.1111/j.1749-6632.2012.06779.x. PMID 23278577. 6. ^ a b Alvin Das; Dimitri Agamanolis; Bruce Cohen (8 April 2014). "Use of Next-Generation Sequencing as a Diagnostic Tool for Congenital Myasthenic Syndrome". Neurology. 51 (10): 717–20. doi:10.1016/j.pediatrneurol.2014.07.032. PMID 25194721. "As with other rare childhood neurological conditions, CMS is often difficult to diagnose because of a broad differential diagnosis and lack of specific laboratory findings. Identification of the underlying mutation is critical, as certain mutations lead to treatment-responsive conditions while others do not. This case serves to highlight the importance of WES as a diagnostic tool that will assist in proper diagnosis, and in some circumstances, allow for initiation of specific treatment." 7. ^ Engel AG, et al. (April 2015). "Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment". Lancet Neurol. 14 (4): 420–34. doi:10.1016/S1474-4422(14)70201-7. PMC 4520251. PMID 25792100. 8. ^ Engel AG, et al. (2012). "New horizons for congenital myasthenic syndromes". Ann N Y Acad Sci. 1275 (1): 1275:54–62. Bibcode:2012NYASA1275...54E. doi:10.1111/j.1749-6632.2012.06803.x. PMC 3546605. PMID 23278578. 9. ^ Raust, JA; et al. (2007). "Stability studies of ionised and non-ionised 3,4-diaminopyridine: hypothesis of degradation pathways and chemical structure of degradation products". J Pharm Biomed Anal. 43 (1): 83–8. doi:10.1016/j.jpba.2006.06.007. PMID 16844337. 10. ^ http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001032/WC500069918.pdf 11. ^ [1] 12. ^ [2], Muscular Dystrophy Association Press Release 13. ^ [3] Archived 2015-07-25 at the Wayback Machine, Rare Disease Report 14. ^ Lashley, D.; Palace, J.; Jayawant, S.; Robb, S.; Beeson, D. (2010). "Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7". Neurology. 74 (19): 1517–1523. doi:10.1212/WNL.0b013e3181dd43bf. PMC 2875925. PMID 20458068. * About Congenital Myasthenic Syndrome From the Mayo Clinic * Treatment for Congenital Myasthenic Syndromes From the Mayo Clinic ## External links[edit] * Congenital Myasthenic Syndromes Classification D * ICD-10: G70.2 * MeSH: D020294 External resources * Orphanet: 590 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Congenital myasthenic syndrome	c0751882	26,730	wikipedia	https://en.wikipedia.org/wiki/Congenital_myasthenic_syndrome	2021-01-18T19:07:36	{"gard": ["11902"], "mesh": ["D020294"], "umls": ["C0751882"], "orphanet": ["590"], "wikidata": ["Q3508800"]}
Enlargement of the heart muscle Hypertrophic cardiomyopathy Other namesAsymmetric septal hypertrophy; idiopathic hypertrophic subaortic stenosis;[1] hypertrophic obstructive cardiomyopathy (HOCM) SpecialtyCardiology SymptomsFeeling tired, leg swelling, shortness of breath, chest pain, fainting[2] ComplicationsHeart failure, irregular heartbeat, sudden cardiac death[3][4] CausesGenetics, Fabry disease, Friedreich's ataxia, certain medications[5][6] Diagnostic methodElectrocardiogram, echocardiogram, stress testing, genetic testing[7] Differential diagnosisHypertensive heart disease, aortic stenosis, athlete's heart[5] TreatmentMedications, implantable cardiac defibrillator, surgery[7] MedicationBeta blockers, diuretics, disopyramide[7] PrognosisLess than 1% per year risk of death (with treatment)[8] Frequency1 in 500 people[9] Hypertrophic cardiomyopathy (HCM) is a condition in which the heart becomes thickened without an obvious cause.[9] The parts of the heart most commonly affected are the interventricular septum and the ventricles.[10] This results in the heart being less able to pump blood effectively and also may cause electrical conduction problems.[3] People who have HCM may have a range of symptoms. People may be asymptomatic, or may have fatigue, leg swelling, and shortness of breath.[2] It may also result in chest pain or fainting.[2] Symptoms may be worse when the person is dehydrated.[10] Complications may include heart failure, an irregular heartbeat, and sudden cardiac death.[3][4] HCM is most commonly inherited from a person's parents[6] in an autosomal dominant pattern.[10] It is often due to mutations in certain genes involved with making heart muscle proteins.[6] Other inherited causes of left ventricular hypertrophy may include Fabry disease, Friedreich's ataxia, and certain medications such as tacrolimus.[5] Other considerations for causes of enlarged heart are athlete's heart and hypertension (high blood pressure).[10] Making the diagnosis of HCM often involves a family history or pedigree, an electrocardiogram, echocardiogram, and stress testing.[7] Genetic testing may also be done.[7] HCM can be distinguished from other inherited causes of cardiomyopathy by its autosomal dominant pattern, whereas Fabry disease and Friedreich Ataxia are inherited in an autosomal recessive pattern.[10] Treatment may depend on symptoms and other risk factors. Medications may include the use of beta blockers or disopyramide.[7] An implantable cardiac defibrillator may be recommended in those with certain types of irregular heartbeat.[7] Surgery, in the form of a septal myectomy or heart transplant, may be done in those who do not improve with other measures.[7] With treatment, the risk of death from the disease is less than one percent per year.[8] HCM affects about one in 500 people.[9] Rates in men and women are about equal.[9] People of all ages may be affected.[9] The first modern description of the disease was by Donald Teare in 1958.[11][12] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 3.1 Obstructive or non-obstructive * 3.2 Cardiac catheterization * 4 Screening * 4.1 United States * 4.2 Canada * 4.3 UK * 5 Treatment * 5.1 Asymptomatic people * 5.2 Medications * 5.3 Surgical septal myectomy * 5.4 Alcohol septal ablation * 5.5 Mitral clip * 5.6 Implantable pacemaker or defibrillator * 5.7 Cardiac transplantation * 6 Prognosis * 7 Children * 8 Other animals * 8.1 Cats * 8.2 Gorillas * 9 References * 10 External links ## Signs and symptoms[edit] The course of HCM is variable. Many people are asymptomatic or mildly symptomatic, and many of those carrying disease genes for HCM do not have clinically detectable disease.[13] The symptoms of HCM include shortness of breath due to stiffening and decreased blood filling of the ventricles, exertional chest pain (sometimes known as angina) due to reduced blood flow to the coronary arteries, uncomfortable awareness of the heart beat (palpitations), as well as disruption of the electrical system running through the abnormal heart muscle, lightheadedness, weakness, fainting and sudden cardiac death.[14] Shortness of breath is largely due to increased stiffness of the left ventricle (LV), which impairs filling of the ventricles, but also leads to elevated pressure in the left ventricle and left atrium, causing back pressure and interstitial congestion in the lungs. Symptoms are not closely related to the presence or severity of an outflow tract gradient.[15] Often, symptoms mimic those of congestive heart failure (esp. activity intolerance and dyspnea), but treatment of each is different. Beta blockers are used in both cases, but treatment with diuretics, a mainstay of CHF treatment, will exacerbate symptoms in hypertrophic obstructive cardiomyopathy by decreasing ventricular preload volume and thereby increasing outflow resistance (less blood to push aside the thickened obstructing tissue).[16] Major risk factors for sudden death in individuals with HCM include prior history of cardiac arrest or ventricular fibrillation, spontaneous sustained ventricular tachycardia, abnormal exercise blood pressure and non-sustained ventricular tachycardia,[17][18] unexplained syncope, family history of premature sudden death, and LVW thickness greater than 15 mm to 30 mm, on ECHO cardiogram. "Spike and dome" pulse and "triple ripple apical impulse" are two other signs that can be discovered in physical examination.[19] ## Genetics[edit] Genetic basis Gene Locus Type MYH7 14q12 CMH1 ( 192600) TNNT2 1q32 CMH2 ( 115195) TPM1 15q22.1 CMH3 ( 115196) MYBPC3 11p11.2 CMH4 ( 115197) ? ? CMH5 PRKAG2 7q36 CMH6 ( 600858) TNNI3 19q13.4 CMH7 ( 613690) MYL3 3p CMH8 ( 608751) TTN 2q24.3 CMH9 ( 613765) MYL2 12q23-q24 CMH10 ( 608758) ACTC1 15q14 CMH11 ( 612098) CSRP3 11p15.1 CMH12 ( 612124) Familial hypertrophic cardiomyopathy is inherited as an autosomal dominant trait and is attributed to mutations in one of a number of genes that encode for the sarcomere proteins.[10] Currently, about 50–60% of people with a high index of clinical suspicion for HCM will have a mutation identified in at least one of nine sarcomeric genes. Approximately 40% of these mutations occur in the β-myosin heavy chain gene on chromosome 14 q11.2-3, and approximately 40% involve the cardiac myosin-binding protein C gene. Since HCM is typically an autosomal dominant trait, children of a single HCM parent have 50% chance of inheriting the disease-causing mutation. Whenever such a mutation is identified, family-specific genetic testing can be used to identify relatives at-risk for the disease, although clinical severity and age of onset cannot be predicted.[20] In individuals without a family history of HCM, the most common cause of the disease is a de novo mutation of the gene that produces the β-myosin heavy chain. An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype of the disease. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of adverse outcomes.[21][22] Some mutations could have more harmful potential compared to others (β-myosin heavy chain). For example, troponin T mutations were originally associated with a 50% mortality before the age of 40. However, a more recent and larger study found a similar risk to other sarcomeric protein mutations.[23] The age at disease onset of HCM with MYH7 is earlier and leads to more severe symptoms.[24] Moreover, mutations on troponin C can alter Ca+2 sensibility on force development in cardiac muscle, these mutations are named after the amino acid that was changed after the location in which it happened, such as A8V, A31S, C84Y and D145E.[25] ## Diagnosis[edit] An ECG showing HOCM A diagnosis of hypertrophic cardiomyopathy is based upon a number of features of the disease process. While there is use of echocardiography, cardiac catheterization, or cardiac MRI in the diagnosis of the disease, other important considerations include ECG, genetic testing (although not primarily used for diagnosis),[26] and any family history of HCM or unexplained sudden death in otherwise healthy individuals. In about 60 to 70% of the cases, cardiac MRI shows thickening of more than 15 mm of the lower part of the ventricular septum. T1-weighted imaging may identify scarring of cardiac tissues while T2-weighted imaging may identify oedema and inflammation of cardiac tissue which is associated with acute clinical signs of chest pain and fainting episodes.[27] Pulsus bisferiens may occasional be found during examination.[28] ### Obstructive or non-obstructive [edit] Depending on whether the distortion of normal heart anatomy causes an obstruction of the outflow of blood from the left ventricle of the heart, HCM can be classified as obstructive or non-obstructive. * The obstructive variant of HCM, hypertrophic obstructive cardiomyopathy (HOCM), has also historically been known as idiopathic hypertrophic subaortic stenosis (IHSS) and asymmetric septal hypertrophy (ASH). * Another, non-obstructive variant of HCM is apical hypertrophic cardiomyopathy,[29] also called Yamaguchi Syndrome or Yamaguchi Hypertrophy, first described in individuals of Japanese descent. ### Cardiac catheterization[edit] Pressure tracings demonstrating the Brockenbrough–Braunwald–Morrow sign AO = Descending aorta; LV = Left ventricle; ECG = Electrocardiogram. After the third QRS complex, the ventricle has more time to fill. Since there is more time to fill, the left ventricle will have more volume at the end of diastole (increased preload). Due to the Frank–Starling law of the heart, the contraction of the left ventricle (and pressure generated by the left ventricle) will be greater on the subsequent beat (beat #4 in this picture). Because of the dynamic nature of the outflow obstruction in HCM, the obstruction increases more than the left ventricular pressure increase. This causes a fall in the aortic pressure as the left ventricular pressure rises (seen as the yellow shaded area in the picture). Upon cardiac catheterization, catheters can be placed in the left ventricle and the ascending aorta, to measure the pressure difference between these structures. In normal individuals, during ventricular systole, the pressure in the ascending aorta and the left ventricle will equalize, and the aortic valve is open. In individuals with aortic stenosis or with HCM with an outflow tract gradient, there will be a pressure gradient (difference) between the left ventricle and the aorta, with the left ventricular pressure higher than the aortic pressure. This gradient represents the degree of obstruction that has to be overcome in order to eject blood from the left ventricle. The Brockenbrough–Braunwald–Morrow sign is observed in individuals with HCM with outflow tract gradient. This sign can be used to differentiate HCM from aortic stenosis. In individuals with aortic stenosis, after a premature ventricular contraction (PVC), the following ventricular contraction will be more forceful, and the pressure generated in the left ventricle will be higher. Because of the fixed obstruction that the stenotic aortic valve represents, the post-PVC ascending aortic pressure will increase as well. In individuals with HCM, however, the degree of obstruction will increase more than the force of contraction will increase in the post-PVC beat. The result of this is that the left ventricular pressure increases and the ascending aortic pressure decreases, with an increase in the LVOT gradient. While the Brockenbrough–Braunwald–Morrow sign is most dramatically demonstrated using simultaneous intra-cardiac and intra-aortic catheters, it can be seen on routine physical examination as a decrease in the pulse pressure in the post-PVC beat in individuals with HCM. ## Screening[edit] Main article: Hypertrophic cardiomyopathy screening Although HCM may be asymptomatic, affected individuals may present with symptoms ranging from mild to critical heart failure and sudden cardiac death at any point from early childhood to seniority.[13][30] HCM is the leading cause of sudden cardiac death in young athletes in the United States, and the most common genetic cardiovascular disorder.[4] One study found that the incidence of sudden cardiac death in young competitive athletes declined in the Veneto region of Italy by 89% since the 1982 introduction of routine cardiac screening for athletes, from an unusually high starting rate.[31] As of 2010, however, studies have shown that the incidence of sudden cardiac death, among all people with HCM, has declined to one percent or less.[32] Screen-positive individuals who are diagnosed with cardiac disease are usually told to avoid competitive athletics. HCM can be detected with an echocardiogram (ECHO) with 80%+ accuracy,[citation needed] which can be preceded by screening with an electrocardiogram (ECG) to test for heart abnormalities. Cardiac magnetic resonance imaging (CMR), considered the gold standard for determining the physical properties of the left ventricular wall, can serve as an alternative screening tool when an echocardiogram provides inconclusive results.[33] For example, the identification of segmental lateral ventricular hypertrophy cannot be accomplished with echocardiography alone. Also, left ventricular hypertrophy may be absent in children under thirteen years of age. This undermines the results of pre-adolescents’ echocardiograms.[13] Researchers, however, have studied asymptomatic carriers of an HCM-causing mutation through the use of CMR and have been able to identify crypts in the interventricular septal tissue in these people. It has been proposed that the formation of these crypts is an indication of myocyte disarray and altered vessel walls that may later result in the clinical expression of HCM.[33] A possible explanation for this is that the typical gathering of family history only focuses on whether sudden death occurred or not. It fails to acknowledge the age at which relatives suffered sudden cardiac death, as well as the frequency of the cardiac events. Furthermore, given the several factors necessary to be considered at risk for sudden cardiac death, while most of the factors do not have strong predictive value individually, there exists ambiguity regarding when to implement special treatment.[34] ### United States[edit] There are several potential challenges associated with routine screening for HCM in the United States.[35] First, the U.S. athlete population of 15 million is almost twice as large as Italy's estimated athlete population.[35] Second, these events are rare, with fewer than 100 deaths in the U.S. due to HCM in competitive athletes per year,[36] or about 1 death per 220,000 athletes.[37] Lastly, genetic testing would provide a definitive diagnosis; however, due to the numerous HCM-causing mutations, this method of screening is complex and is not cost-effective.[13] Therefore, genetic testing in the United States is limited to individuals who exhibit clear symptoms of HCM, and their family members. This ensures that the test is not wasted on detecting other causes of ventricular hypertrophy (due to its low sensitivity), and that family members of the individual are educated on the potential risk of being carriers of the mutant gene(s).[38] ### Canada[edit] Canadian genetic testing guidelines and recommendations for individuals diagnosed with HCM are as follows:[26] * The main purpose of genetic testing is for screening family members. * According to the results, at-risk relatives may be encouraged to undergo extensive testing. * Genetic testing is not meant for confirming a diagnosis. * If the diagnosed individual has no relatives that are at risk, then genetic testing is not required. * Genetic testing is not intended for risk assessment or treatment decisions. * Evidence only supports clinical testing in predicting the progression and risk of developing complications of HCM. For individuals suspected of having HCM: * Genetic testing is not recommended for determining other causes of left ventricular hypertrophy (such as "athlete's heart", hypertension, and cardiac amyloidosis). * HCM may be differentiated from other hypertrophy-causing conditions using clinical history and clinical testing. ### UK[edit] A post-mortem following the death of TV presenter David Frost in 2013 found he had HCM, though it did not contribute to his death and his family was not informed. The sudden cardiac death of his 31-year-old son in 2015 led the family to collaborate with the British Heart Foundation to raise funds for better screening.[39] ## Treatment[edit] ### Asymptomatic people[edit] A significant number of people with hypertrophic cardiomyopathy do not have any symptoms and will have a normal life expectancy, although they should avoid particularly strenuous activities or competitive athletics. Asymptomatic people should be screened for risk factors for sudden cardiac death. In people with resting or inducible outflow obstructions, situations that will cause dehydration or vasodilation (such as the use of vasodilatory or diuretic blood pressure medications) should be avoided. Septal reduction therapy is not recommended in asymptomatic people.[7] ### Medications[edit] The primary goal of medications is to relieve symptoms such as chest pain, shortness of breath, and palpitations. Beta blockers are considered first-line agents, as they can slow down the heart rate and decrease the likelihood of ectopic beats. For people who cannot tolerate beta blockers, nondihydropyridine calcium channel blockers such as verapamil can be used, but are potentially harmful in people who also have low blood pressure or severe shortness of breath at rest. These medications also decrease the heart rate, though their use in people with severe outflow obstruction, elevated pulmonary artery wedge pressure, and low blood pressures should be done with caution. Dihydropyridine calcium channel blockers should be avoided in people with evidence of obstruction. For people whose symptoms are not relieved by the above treatments, disopyramide can be considered for further symptom relief. Diuretics can be considered for people with evidence of fluid overload, though cautiously used in those with evidence of obstruction. People who continue to have symptoms despite drug therapy can consider more invasive therapies. Intravenous phenylephrine (or another pure vasoconstricting agent) can be used in the acute setting of low blood pressure in those with obstructive hypertrophic cardiomyopathy who do not respond to fluid administration.[7] ### Surgical septal myectomy[edit] Main article: Septal myectomy Surgical septal myectomy is an open-heart operation done to relieve symptoms in people who remain severely symptomatic despite medical therapy. It has been performed successfully since the early 1960s.[17] Surgical septal myectomy uniformly decreases left ventricular outflow tract obstruction and improves symptoms, and in experienced centers has a surgical mortality of less than 1%, as well as 85% success rate.[30] It involves a median sternotomy (general anesthesia, opening the chest, and cardiopulmonary bypass) and removing a portion of the interventricular septum.[13] Surgical myectomy resection that focuses just on the subaortic septum, to increase the size of the outflow tract to reduce Venturi forces, may be inadequate to abolish systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. With this limited resection, the residual mid-septal bulge still redirects flow posteriorly; SAM persists because flow still gets behind the mitral valve. It is only when the deeper portion of the septal bulge is resected that flow is redirected anteriorly away from the mitral valve, abolishing SAM. With this in mind, a modification of the Morrow myectomy termed extended myectomy, mobilization and partial excision of the papillary muscles has become the excision of choice.[40][41][42][43] In people with particularly large redundant mitral valves, anterior leaflet plication may be added to complete separation of the mitral valve and outflow.[43] Complications of septal myectomy surgery include possible death, arrhythmias, infection, incessant bleeding, septal perforation/defect, and stroke.[30] ### Alcohol septal ablation[edit] Main article: Alcohol septal ablation Alcohol septal ablation, introduced by Ulrich Sigwart in 1994, is a percutaneous technique that involves injection of alcohol into one or more septal branches of the left anterior descending artery. This is a catheter technique with results similar to the surgical septal myectomy procedure but is less invasive, since it does not involve general anaesthesia and opening of the chest wall and pericardium (which are done in a septal myectomy). In a select population with symptoms secondary to a high outflow tract gradient, alcohol septal ablation can reduce the symptoms of HCM. In addition, older individuals and those with other medical problems, for whom surgical myectomy would pose increased procedural risk, would likely benefit from the less-invasive septal ablation procedure.[13][44] When performed properly, an alcohol septal ablation induces a controlled heart attack, in which the portion of the interventricular septum that involves the left ventricular outflow tract is infarcted and will contract into a scar. There is debate over which people are best served by surgical myectomy, alcohol septal ablation, or medical therapy.[45] ### Mitral clip[edit] Main article: MitraClip Since 2013, mitral clips have been implanted via catheter as a new strategy to correct the motion of the mitral valve in people with severe obstructive HCM. The device fastens together the mitral valve leaflets to improve the heart's blood outflow. The mitral clip has not yet established the long-term reliability of septal myectomy or alcohol septal ablation, but HCM specialists are increasingly offering the clip as a less-invasive treatment option.[46][47] ### Implantable pacemaker or defibrillator[edit] Further information: Pacemaker and ICD device The use of a pacemaker has been advocated in a subset of individuals, in order to cause asynchronous contraction of the left ventricle. Since the pacemaker activates the interventricular septum before the left ventricular free wall, the gradient across the left ventricular outflow tract may decrease. This form of treatment has been shown to provide less relief of symptoms and less of a reduction in the left ventricular outflow tract gradient when compared to surgical myectomy.[48] Technological advancements have also led to the development of a dual-chamber pacemaker, which is only turned on when needed (in contrast to a regular pacemaker which provides a constant stimulus). Although the dual-chamber pacemaker has shown to decrease ventricular outflow tract obstruction, experimental trials have found only a few individuals with improved symptoms.[34] Researchers suspect that these reports of improved symptoms are due to a placebo effect.[30] The procedure includes an incision on the anterolateral area below the clavicle. Two leads are then inserted; one into the right atrium and the other into the right ventricular apex via the subclavian veins. Once in place, they are secured and attached to the generator which will remain inside the fascia, anterior to the pectoral muscle.[30] Complications of this procedure include infection, electrical lead and generator malfunction which will require replacement.[30] For people with HCM who exhibit one or more of the major risk factors for sudden cardiac death, an implantable cardioverter-defibrillator (ICD) or a combination pacemaker/ICD all-in-one unit may be recommended as an appropriate precaution.[7][17][49][50] In 2014, European Society of Cardiology suggested a practical risk score to calculate that risk.[51] ### Cardiac transplantation[edit] Further information: Cardiac transplantation In cases that are unresponsive to all other forms of treatment, cardiac transplantation is one option. It is also the only treatment available for end-stage heart failure.[34] However, transplantation must occur before the onset of symptoms such as pulmonary vessel hypertension, kidney malfunction, and thromboembolism in order for it to be successful. Studies have indicated a seven-year survival rate of 94% in people with HCM after transplantation.[34] ## Prognosis[edit] A systematic review from 2002 concluded that: "Overall, HCM confers an annual mortality rate of about 1%... HCM may be associated with important symptoms and premature death but more frequently with no or relatively mild disability and normal life expectancy."[13] ## Children[edit] Even though hypertrophic cardiomyopathy (HCM) may be present early in life and is most likely congenital, it is one of the most-uncommon cardiac malformations encountered in pediatric cardiology, largely because the presentation of symptoms is usually absent, incomplete, or delayed into adulthood. Most of the current information pertaining to HCM arises from studies in adult populations, and the implication of these observations for pediatric population is often uncertain.[52] Nonetheless, recent studies in pediatric cardiology have revealed that HCM accounts for 42% of childhood cardiomyopathies, with an annual incidence rate of 0.47/100,000 in children.[53] Further, in asymptomatic cases, sudden death is considered one of the most-feared complications associated with the disease in select pediatric populations. Consequently, the recommended practice is to screen children of affected individuals throughout childhood to detect cardiac abnormalities at an early stage, in the hope of preventing further complications of the disease.[52] Generally, the diagnosis of HCM in a pediatric population is made during assessment for murmur, congestive heart failure, physical exhaustion, and genetic testing of children of affected individuals.[52] Specifically, echocardiogram (ECHO) has been used as a definitive noninvasive diagnostic tool in nearly all children. ECHO assesses cardiac ventricular size, wall thickness, systolic and diastolic function, and outflow obstruction. Thus, ECHO has been chosen as an ideal means to detect excessive wall thickening of cardiac muscle in HCM.[52] For children with HCM, treatment strategies aim to reduce disease symptoms and lower the risk of sudden death.[54] Due to the heterogeneity of the disease, treatment is usually modified according to individual's needs.[54] β-blockers improve left ventricular filling and relaxation and thereby improve symptoms. In some children, β–blockers (e.g., propranolol) were shown effective to reduce the risk of sudden death.[54] Further, calcium channel blockers (verapamil) and antiarrhythmic drugs may be used as an adjunct therapy to β-blockers in symptomatic children. Nonetheless, further testing is needed to determine their definitive benefits.[54] ## Other animals[edit] Echocardiography of hypertrophic-obstructive cardiomyopathy (HOCM) in a cat. ### Cats[edit] Feline hypertrophic cardiomyopathy (HCM) is the most common heart disease in domestic cats;[55][56][57] the disease process and genetics are believed to be similar to the disease in humans.[58] In Maine Coon cats, HCM has been confirmed as an autosomal dominant inherited trait.[59] Numerous cat breeds have HCM as a problem in the breed.[60] The first genetic mutation (in cardiac myosin binding protein C) responsible for feline HCM was discovered in 2005 in Maine Coon cats.[61] A test for this mutation (A31P) is available.[62] About one-third of Maine Coon cats tested for the mutation are either heterozygous or homozygous for the mutation, although many of the cats that are heterozygous have no overt evidence of the disease on an echocardiogram (low penetrance). Some Maine Coon cats with clinical evidence of hypertrophic cardiomyopathy test negative for this mutation, strongly suggesting that another cause exists in the breed. The cardiac myosin binding protein C mutation identified in Maine Coon cats has not been found in any other breed of cat with HCM, but more recently another myosin binding protein C mutation has been identified in Ragdoll cats with HCM.[63][64] As in humans, feline HCM is not present at birth but develops over time. It has been identified for the first time in cats as young as 6 months of age and at least as old as 7 years of age. Clinically, cats with hypertrophic cardiomyopathy commonly have a systolic anterior motion (SAM) of the mitral valve (see graphic).[65] Cats with severe HCM often develop left heart failure (pulmonary edema; pleural effusion) because of severe diastolic dysfunction of the left ventricle. They may also develop a left atrial thrombus that embolizes, most commonly, to the terminal aorta creating acute pain and rear limb paralysis (see below). Sudden death can also occur but appears to be uncommon.[66][67] Ultrasound of the heart (echocardiography) is necessary to diagnose HCM in cats.[68][69][70] Measurement of circulating cardiac biomarkers, like N‐terminal‐proBNP (NT‐proBNP)[71][72] and troponin I (TnI) may be used in cats to strengthen the suspicion of cardiac disease.[73] There is a Point-of-care test for feline NT-proBNP available which can be used at the veterinary clinic when echocardiography is not possible to perform.[74][75][76] There is no cure for feline HCM. Many but not all cats have a heart murmur. Many cats that have a heart murmur do not have HCM. Frequently the first signs that a cat has HCM are tachypnea/dyspnea due to heart failure or acute pain and paralysis due to systemic thromboembolism. While medication is commonly given to cats with HCM that have no clinical signs, no medication has been shown to be helpful at this stage and it has been shown that an ACE inhibitor is not beneficial until heart failure is present[77] (at which time a diuretic is most beneficial). Diltiazem generally produces no demonstrable benefit. Atenolol is commonly administered when a severe systolic anterior motion of the mitral valve is present. Feline arterial thromboembolism (FATE) is a relatively common and devastating complication of feline HCM and other feline cardiomyopathies. The thrombus generally forms in the left atrium, most commonly the left auricle. The formation is thought to be primarily due to blood flow stasis. Classically, the thromboembolism lodges at the iliac trifurcation of the aorta, occluding either one or both of the common iliac arteries. Because this split is called the saddle, and is the most frequent location for the thrombus, FATE is commonly known as saddle thrombus.[78] Clinically this presents as a cat with complete loss of function in one or both hind limbs. The hind limbs are cold and the cat is in considerable pain. Emboli may, rarely, lodge in other locations, most commonly the right front limb and the renal arteries. Clopidogrel is used to try to prevent left atrial thrombus formation in cats with HCM and a large left atrium. The FATCAT study at Purdue University demonstrated that it is superior to aspirin for the prevention of a second thrombus from forming in cats that have already experienced a clot. Thrombolytic agents (e.g., tissue plasminogen activator) have been used with some success to break down an existing aortic thromboembolism, but their cost is high and outcome appears to be no better than giving a cat time (48–72 hours) to break down its own clot. Pain management is extremely important. The prognosis for cats with FATE is often poor as they are likely to have significant HCM already and a recurrent bout of FATE is likely.[79] For this reason, euthanasia is often a valid consideration. ### Gorillas[edit] In July 2013, Rigo, a 42-year-old western lowland gorilla, resident in Melbourne Zoo and father of Mzuri, the first gorilla born by artificial insemination, died unexpectedly as a result of HCM. The condition is not uncommon in male gorillas over the age of 30, and in many cases, there is no sign of the disease until the individual's sudden death.[80] ## References[edit] 1. ^ "Other Names for Cardiomyopathy". NHLBI. June 22, 2016. Archived from the original on 28 July 2016. Retrieved 31 August 2016. 2. ^ a b c "What Are the Signs and Symptoms of Cardiomyopathy?". NHLBI. 22 June 2016. Archived from the original on 28 July 2016. Retrieved 10 November 2017. 3. ^ a b c "What Is Cardiomyopathy?". NHLBI. 22 June 2016. Archived from the original on 10 November 2017. 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Retrieved 2013-07-26. ## External links[edit] Classification D * ICD-10: I42.1–I42.2 * ICD-9-CM: 425.1 * OMIM: 192600 * MeSH: D002312 * DiseasesDB: 6373 External resources * MedlinePlus: 000192 * eMedicine: med/290 ped/1102 radio/129 * Patient UK: Hypertrophic cardiomyopathy * Orphanet: 217569 * Hypertrophic cardiomyopathy at Curlie * GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview * National Heart, Blood, and Lung Institute Cardiomyopathy Page * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular 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Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hypertrophic cardiomyopathy	c0949658	26,731	wikipedia	https://en.wikipedia.org/wiki/Hypertrophic_cardiomyopathy	2021-01-18T18:31:41	{"mesh": ["D002312", "D024741"], "umls": ["C0949658", "C0007194"], "orphanet": ["217568", "99739"], "wikidata": ["Q1364270"]}
A congenital respiratory tract anomaly characterized by a cleft extending below the vocal folds into the cricoid cartilage, with swallowing disorders and lung infections. ## Epidemiology Prevalence of this form of LC is unknown, but it is thought to be rare. ## Clinical description Patients most often have aspirations and severe respiratory and swallowing disorders. Dyspnea and stridor are also possible. ## Etiology The causes underlying development of this anomaly are unknown. ## Management and treatment Management includes anti-reflux treatment and nasogastric tube feeding. Treatment involves surgical correction of the cleft, often using an endoscopic treatment approach. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Laryngotracheoesophageal cleft type 2	None	26,732	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93939	2021-01-23T18:19:27	{"icd-10": ["Q32.1"], "synonyms": ["LTEC II", "LTEC2", "Laryngo-tracheo-esophageal cleft type 2"]}
A number sign (#) is used with this entry because of evidence that X-linked mental retardation-99 (MRX99) is caused by mutation in the USP9X gene (300072) on chromosome Xp11. Heterozygous mutation in the USP9X gene can also cause female-restricted X-linked syndromic mental retardation-99 (MRXS99F; 300968). Clinical Features Homan et al. (2014) reported 4 patients from 3 unrelated families with X-linked recessive mental retardation. The families were previously ascertained by Tarpey et al. (2009) in a large-scale study that resequenced coding exons of the X chromosome in patients with mental retardation. The patients showed developmental delay, hypotonia, and some behavioral abnormalities, such as aggression. Two patients had broad thumbs and short stature; information on the other 2 patients was unavailable. One patient had relative macrocephaly, facial dysmorphism, constipation, and hyperextensible joints and skin. Brain MRI of 1 patient was normal. Inheritance The transmission pattern in 1 of the families with MRX99 reported by Homan et al. (2014) was consistent with X-linked recessive inheritance. Molecular Genetics In affected male members of 2 unrelated families with X-linked recessive nonsyndromic mental retardation-99, Homan et al. (2014) identified 2 different hemizygous mutations in the USP9X gene (L2093H; 300072.0001 and c.7574delA; 300072.0003). In 1 family, unaffected females were found to be heterozygous for the mutation. A patient from a third family carried a heterozygous USP9X variant (L2157I; 300072.0002), but he also carried a deletion including the ARID1B gene (614556), which is known to cause MRD12 (135900). None of the USP9X variants affected the catalytic activity of USP9X. Isolated hippocampal neurons from Usp9x-knockout male mice (-/Y) showed a 43% reduction in axonal length and arborization compared to wildtype. The 3 USP9X variants were unable to rescue the defect, consistent with a loss of function in axonal growth. Loss of Usp9x also caused a 42% decrease in neuronal migration, which was partially rescued by the L2093H variant, but not by L2157I or c.7574delA. The variants coimmunoprecipitated normally with DCX (300121) in nonpolarized HEK293 cells, but did not localize properly to the axonal growth cone in immature polarized neurons. Overall, the findings suggested that the USP9X variants caused changes in the neuronal cytoskeleton, which may affect neuronal migration and axonal growth, resulting in intellectual disability. INHERITANCE \- X-linked recessive GROWTH Height \- Short stature HEAD & NECK Head \- Prominent forehead Face \- Dysmorphic features SKELETAL Hands \- Broad thumbs MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation Behavioral Psychiatric Manifestations \- Aggressive behavior (in some patients) \- Obsessive behaviour (in some patients) MISCELLANEOUS \- Variable features \- Two families have been reported (as of curation date April 2014) MOLECULAR BASIS \- Caused by mutation in the ubiquitin-specific protease 9, X chromosome gene (USP9X, 300072.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MENTAL RETARDATION, X-LINKED 99	c2931498	26,733	omim	https://www.omim.org/entry/300919	2019-09-22T16:19:12	{"doid": ["0050776"], "mesh": ["C567906"], "omim": ["300919"], "orphanet": ["777"]}
A number sign (#) is used with this entry because generalized epilepsy with febrile seizures plus, type 2 (GEFSP2) and familial febrile seizures-3A (FEB3A) are both caused by heterozygous mutation in the SCN1A gene (182389) on chromosome 2q24. See also GEFS+, type 7 (613863) and FEB3B (613863), which are both caused by mutation in the SCN9A gene (603415) on chromosome 2q24. Description Mutations in the SCN1A gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures to generalized epilepsy with febrile seizures plus, type 2, which represents a more severe phenotype. Patients with isolated febrile seizures usually have onset between ages 6 months and 4 years and show spontaneous remission by age 6 years (summary by Mantegazza et al., 2005), whereas patients with GEFS+ continue to have various types of febrile and afebrile seizures later in life (summary by Singh et al., 2009). Dravet syndrome (607208), or severe myoclonic epilepsy of infancy, is the most severe phenotype associated with SCN1A mutations. Mutations in certain genes can cause a phenotypic spectrum of overlap between the isolated febrile phenotype and the GEFS+ phenotype. For a general phenotypic description and a discussion of genetic heterogeneity of GEFS+, see 604233. For a phenotypic description and a discussion of genetic heterogeneity of familial febrile seizures, see 121210. Clinical Features ### GEFS+ Type 2 Baulac et al. (1999) studied a family in which affected individuals in 3 successive generations presented clinical similarities with families with GEFS+. Patients expressed a variable phenotype combining febrile seizures, generalized seizures often precipitated by fever at age greater than 6 years, myoclonic seizures, absence seizures, hemiclonic seizures, and partial seizures, with a variable degree of severity. Moulard et al. (1999) reported a family in which 6 individuals had isolated typical febrile seizures, and 5 had typical febrile seizures associated with generalized epilepsy. Afebrile seizures occurred in childhood until the teenage years. ### Familial Febrile Seizures 3A Mantegazza et al. (2005) reported a large Italian family in which at least 12 members spanning 4 generations had simple febrile seizures. The age at onset ranged from 5 months to 4 years, and none had seizures beyond age 6 years. Most seizures were brief, lasting 1 to 5 minutes, although 1 patient had seizures lasting up to 15 minutes. Three affected individuals developed afebrile partial seizures of mesial temporal lobe origin with vegetative or experiential phenomena at the ages of 10, 13, and 11 years. Very rare partial complex seizures or nocturnal secondary generalized tonic-clonic seizures also occurred in all 3 of them. Two of these patients had MRI evidence of unilateral mesial temporal sclerosis. Mantegazza et al. (2005) noted that febrile convulsions had been identified as a risk factor for temporal lobe epilepsy with hippocampal sclerosis (Briellmann et al., 2001). Mantegazza et al. (2005) concluded that the phenotype was distinct from GEFS+ and was most consistent with simple febrile seizures. Mapping By genomewide linkage analysis of a family with GEFS+ using semiautomated fluorescent genotyping, Baulac et al. (1999) identified a GEFS+ locus on chromosome 2q21-q33. The maximum pairwise lod score was 3.00 with a recombination fraction 0.0 for marker D2S2330. Haplotype reconstruction defined a 22-cM candidate interval flanked by markers D2S156 and D2S2314. Moulard et al. (1999) also found linkage of GEFS+ to chromosome 2q24-q33. By linkage analysis of an Italian family with simple febrile seizures, Mantegazza et al. (2005) found linkage to the FEB3 locus on chromosome 2q24 (see Peiffer et al. (1999) and NOMENCLATURE). Molecular Genetics Escayg et al. (2000) demonstrated that the 2 GEFS+ families reported by Baulac et al. (1999) and Moulard et al. (1999) each carried a different heterozygous mutation in the SCN1A gene (R1648H, 182389.0001 and T875M, 182389.0002, respectively). In 2 unrelated Japanese families with GEFS+2 associated with development of partial epilepsy, Sugawara et al. (2001) identified 2 novel mutations in the SCN1A gene. One of these mutations, val1428-to-ala (182389.0011), was a missense mutation in the pore-forming region of the sodium channel, which the authors hypothesized may affect ion selectivity. Orrico et al. (2009) identified 21 mutations, including 14 novel mutations, in the SCN1A gene in 22 (14.66%) of 150 Italian pediatric probands with epilepsy. SCN1A mutations were found in 21.2% of patients with GEFS+ and in 75% of patients with Dravet syndrome (607208) from the overall patient cohort. ### Familial Febrile Seizures 3A In 12 affected members of an Italian family with simple febrile seizures mapping to 2q24, Mantegazza et al. (2005) identified a heterozygous mutation in the SCN1A gene (182389.0015). This disorder is designated FEB3A. In a 2-stage case-control study including a total of 234 patients with febrile seizures, Schlachter et al. (2009) found a significant association between the major A allele of SNP rs3812718 in the SCN1A gene (182389.0016) and febrile seizures (first stage p value of 0.000017; replication p value of 0.00069). The data suggested that homozygosity for the A allele confers a 3-fold increased relative risk of febrile seizures and may account for a population attributable risk factor of up to 50%. The data were consistent with the hypothesis that low-risk variants with a high population frequency contribute to the risk of common and genetically complex diseases such as epilepsy. Cytogenetics Suls et al. (2010) reported a 4-generation Bulgarian family with epilepsy transmitting a heterozygous 400-kb deletion on chromosome 2q24 encompassing the SCN1A and TTC21B (612014) genes. The phenotype was variable, but all had onset of generalized tonic-clonic seizures around the first year of life (range, 8 to 14 months), and some had myoclonic or absence seizures. Three of 4 patients had febrile seizures in infancy. One patient had mild mental retardation, 1 had psychomotor slowing, and 1 had mental retardation from early infancy; all had reduced seizures on medication. The fourth patient died of status epilepticus at age 13 months. Thus, 2 patients had a phenotype reminiscent of Dravet syndrome, whereas the phenotype in the other 2 was more consistent with GEFS+2. The unaffected father in the first generation was found to be somatic mosaic for the deletion. Suls et al. (2010) noted that deletions involving SCN1A usually result in the much more severe Dravet syndrome, in which affected individuals cannot raise a family and thus do not transmit the mutation. The report of this family with a deletion of SCN1A in which 2 affected individuals were able to raise a family suggested the presence of genetic modifiers and showed intrafamilial variability. Nomenclature Two different genes, SCN1A (182389) and SCN9A (603415), map to the FEB3 locus on chromosome 2q24, first identified by Peiffer et al. (1999) in a large Utah family with febrile seizures. This family was later found by Singh et al. (2009) to have GEFS+7 (613863) caused by mutation in the SCN9A gene (603415). In an Italian family with isolated febrile seizures, Mantegazza et al. (2005) found linkage to the FEB3 locus and identified a pathogenic mutation in the SCN1A gene; this form of febrile seizures is designated FEB3A. In 2 unrelated probands with isolated febrile seizures, Singh et al. (2009) identified pathogenic mutations in the SCN9A (603415) gene on chromosome 2q24; this form of febrile seizures is designated FEB3B (see 613863). INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, generalized, associated with fever \- Febrile seizures \- Generalized tonic-clonic seizures \- Absence seizures \- Myoclonic seizures \- Hemiclonic seizures \- Partial seizures \- Patients show normal psychomotor development MISCELLANEOUS \- Onset of febrile seizures typically between 6 months and 6 years of age \- Simple febrile seizures usually remit by age 6 years \- Variable severity \- Some patients have a more severe phenotype and have febrile and afebrile seizures after childhood (GEFS+) \- Seizures recur in 33% of patients \- Between 2 and 7% of children will develop afebrile seizure disorders later in life MOLECULAR BASIS \- Caused by mutation in the voltage-gated sodium channel type I, alpha polypeptide gene (SCN1A, 182389.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 2	c3502809	26,734	omim	https://www.omim.org/entry/604403	2019-09-22T16:11:58	{"doid": ["0060170", "0111294"], "mesh": ["C565808"], "omim": ["604403"], "orphanet": ["36387"], "synonyms": ["Alternative titles", "GEFS+, TYPE 2"], "genereviews": ["NBK1318"]}
A number sign (#) is used with this entry because susceptibility to the development of colorectal cancer-12 (CRCS12) is conferred by heterozygous mutation in the POLE gene (174762) on chromosome 12q24. Description Colorectal cancer-12 is an autosomal dominant disorder characterized by a high-penetrance predisposition to the development of colorectal adenomas and carcinomas, with a variable tendency to develop multiple and large tumors. Onset usually occurs before age 40 years. The histologic features of the tumors may be unremarkable (Palles et al., 2013) or show microsatellite instability (MSI) (Elsayed et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of colorectal cancer, see 114500. Clinical Features Palles et al. (2013) reported a large 3-generation family in which 8 individuals had various manifestations of a colorectal adenoma syndrome with predisposition to colorectal carcinoma. Affected individuals developed multiple adenomas or colorectal cancer as adults, between ages 23 and 61 years. Twelve additional pedigrees with the same disorder were subsequently identified. All showed autosomal dominant inheritance of a predisposition of multiple adenomas and/or colorectal cancer with onset usually before age 40 years. Histologic features of the tumors were unremarkable, but all were microsatellite stable. Elsayed et al. (2015) reported 2 Dutch families and an unrelated Dutch patient with CRCS12 confirmed by genetic analysis. In the first family, a mother was diagnosed with an MSI colorectal tumor and 2 adenomas at age 40 years. She later developed multiple colorectal polyps as well as microsatellite-stable endometrial cancer at age 50. Her son was diagnosed with MSI adenocarcinoma at age 30. Tumor tissue from these patients showed loss of MSH2 (609309) and/or MSH6 (600678) protein expression, suggestive of Lynch syndrome (see, e.g., 120435), although there were no germline mutations in these genes. The mother's tumor showed a hypermutator phenotype, with multiple somatic mutations in several genes. In the second family, the proband was diagnosed with multiple polyps at age 34. An adenoma with cancer showed MSI associated with immunohistochemical loss of MSH2 and MSH6 protein staining, also in the absence of germline variants in these genes. The patient had a family history of colorectal and other forms of cancer, but DNA and tumor tissue samples from her relatives were not available. The unrelated Dutch patient was diagnosed with a microsatellite-stable colon cancer and polyposis at age 33. No tumor tissue was available for analysis. The MSI observed in some of these patients was in contrast to the microsatellite stability observed in the tumors from the family reported by Palles et al. (2013). Bellido et al. (2016) reviewed phenotypic data on 47 patients from 20 families with the POLE L424V mutation, including a new case with a de novo occurrence. The mean number of colonic adenomas among 23 carriers available for ascertainment was 19.3, with a range of 1 to 68; 82% had 2 or more adenomas, and 74% had 5 or more. Colorectal cancer was diagnosed in 30 of 47 (64%) mutation carriers with mean age at first diagnosis 40.7 years. Brain tumors were present in 3 of 47 (6%) of carriers with a mean age at diagnosis of 30.6 years. Duodenal adenomas were present in 7 of 14 (50%). The authors recommended testing for mutations in POLE in patients with attenuated adenomatous polyposis and in other forms of CRC with or without oligopolyposis. Inheritance The transmission pattern of CRCS12 in the families reported by Palles et al. (2013) was consistent with autosomal dominant inheritance. Molecular Genetics In affected members of a family with susceptibility to colorectal cancer-12, Palles et al. (2013) identified a heterozygous missense mutation in the POLE gene (L424V; 174762.0001) affecting a highly conserved residue in the exonuclease (proofreading) domain. The mutation was identified by whole-genome sequencing. The L424V mutation was subsequently identified in 12 more families with early-onset colorectal adenomas and carcinomas. Some tumors had additional somatic mutations, for example, in the APC (611731) or KRAS (190070) genes. In addition to germline POLE mutations, Palles et al. (2013) identified somatic POLE mutations, many affecting the exonuclease domain, in 15 colorectal cancers from a large database. All of these tumors had additional somatic mutations, most commonly in the APC gene. These findings suggested that the mechanism of tumorigenesis in POLE-mutated tumors is decreased fidelity of replication-associated polymerase proofreading, leading to an increased mutation rate. Valle et al. (2014) identified a de novo heterozygous L424V mutation in the POLE gene in a 28-year-old woman with polyposis and colorectal cancer. No loss of heterozygosity at the POLE chromosomal region was found in tumor DNA. This patient was ascertained from a cohort of 858 Spanish probands with familial/early-onset CRC who underwent screening of the POLE gene, thus accounting for 0.12% of the total. Elsayed et al. (2015) identified heterozygosity for the L424V mutation in the POLE gene in 3 (0.25%) of 1,188 Dutch index patients with polyposis or familial colorectal cancer. In 1 patient, the mutation occurred de novo. Tumor tissue samples available from 3 patients from 2 families showed microsatellite instability and were found to have somatic mutations in the MSH2 and/or MSH6 genes. The findings indicated that POLE DNA analysis is warranted in MSI colorectal cancer, especially in the absence of a germline variant in DNA mismatch repair genes. INHERITANCE \- Autosomal dominant ABDOMEN Gastrointestinal \- Colorectal adenomas \- Colorectal polyps \- Colorectal carcinoma NEOPLASIA \- Colorectal carcinoma \- Endometrial cancer MISCELLANEOUS \- Tumors are microsatellite stable \- Some tumors may be microsatellite instable and carry somatic mutations in MSH mismatch repair genes \- Onset before age 40 years \- Patients develop multiple tumors MOLECULAR BASIS \- Caused by mutation in the DNA polymerase, epsilon gene (POLE, 174762.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	COLORECTAL CANCER, SUSCEPTIBILITY TO, 12	c2674616	26,735	omim	https://www.omim.org/entry/615083	2019-09-22T15:53:14	{"mesh": ["C538265"], "omim": ["615083"], "orphanet": ["220460", "447877"], "synonyms": ["Alternative titles", "COLORECTAL CANCER, SUSCEPTIBILITY TO, ON CHROMOSOME 12q24"]}
Mowat–Wilson syndrome Other namesHirschsprung disease-intellectual disability syndrome Mowat–Wilson syndrome, clinical features of Patient 2 at age: (A) 1 year and 6 months; (B–C) 3 years and 5 months; (D–E) 8 years and 1 month. Mowat–Wilson syndrome is a rare genetic disorder that was clinically delineated by Dr. David R. Mowat and Dr. Meredith J. Wilson in 1998.[1][2] ## Contents * 1 Presentation * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 References * 7 Further reading * 8 External links ## Presentation[edit] This autosomal dominant disorder is characterized by a number of health defects including Hirschsprung's disease, intellectual disability, epilepsy,[3] delayed growth and motor development, congenital heart disease, genitourinary anomalies and absence of the corpus callosum. However, Hirschsprung's disease is not present in all infants with Mowat–Wilson syndrome and therefore it is not a required diagnostic criterion.[4] Distinctive physical features include microcephaly, narrow chin, cupped ears with uplifted lobes with central depression, deep and widely set eyes, open mouth, wide nasal bridge and a shortened philtrum.[citation needed] ## Causes[edit] The disorder is expressed in an autosomal dominant fashion and may result from a de novo loss of function mutation or total deletion of the ZEB2 gene located on chromosome 2q22.[5] ## Diagnosis[edit] This section is empty. You can help by adding to it. (July 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (July 2017) ## Prognosis[edit] There is no cure for this syndrome. Treatment is supportive and symptomatic. All children with Mowat–Wilson syndrome required early intervention with speech therapy, occupational therapy and physical therapy.[4] ## References[edit] 1. ^ Mowat, DR; Croaker, GD; Cass, DT; Kerr, BA; Chaitow, J; Adès, LC; Chia, NL; Wilson, MJ (1998). "Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: Delineation of a new syndrome and identification of a locus at chromosome 2q22-q23". Journal of Medical Genetics. 35 (8): 617–23. doi:10.1136/jmg.35.8.617. PMC 1051383. PMID 9719364. 2. ^ "Medical Advisory Board". Mowat-Wilson Syndrome Foundation. Retrieved 12 May 2020. 3. ^ Cordelli, DM; Garavelli, L; Savasta, S; Guerra, A; Pellicciari, A; Giordano, L; Bonetti, S; Cecconi, I; et al. (2013). "Epilepsy in Mowat-Wilson syndrome: Delineation of the electroclinical phenotype". American Journal of Medical Genetics Part A. 161A (2): 273–84. doi:10.1002/ajmg.a.35717. PMID 23322667. 4. ^ a b Todo A, Harrington JW. New-onset seizures in infant with square facies, hypospadias, and Hirschsprung disease. Consultant for Pediatricians. 2010;9:103-107. 5. ^ "ZEB2 - zinc finger E-box binding homeobox 2". HUGO Gene Nomenclature Committee. 29 August 2019. Retrieved 30 August 2019. ## Further reading[edit] * Cerruti Mainardi, P; Pastore, G; Zweier, C; Rauch, A (2004). "Mowat-Wilson syndrome and mutation in the zinc finger homeo box 1B gene: A well defined clinical entity". Journal of Medical Genetics. 41 (2): e16. doi:10.1136/jmg.2003.009548. PMC 1735678. PMID 14757866. * Mowat, DR; Wilson, MJ; Goossens, M (2003). "Mowat-Wilson syndrome". Journal of Medical Genetics. 40 (5): 305–10. doi:10.1136/jmg.40.5.305. PMC 1735450. PMID 12746390. ## External links[edit] Classification D * ICD-10: Q43.1 * OMIM: 235730 * MeSH: C536990 * DiseasesDB: 32975 External resources * Orphanet: 2152 Wikimedia Commons has media related to Mowat–Wilson syndrome. * Centre for Genetics Education in Sydney, Australia (PDF Information Sheet) * GeneReview of Mowat–Wilson syndrome * Mowat-Wilson Syndrome Foundation * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mowat–Wilson syndrome	c1856113	26,736	wikipedia	https://en.wikipedia.org/wiki/Mowat%E2%80%93Wilson_syndrome	2021-01-18T19:07:55	{"gard": ["9673"], "mesh": ["C536990"], "umls": ["C1856113"], "orphanet": ["2152"], "wikidata": ["Q2757585"]}
A rare pancreatic disease characterized by chronic non-alcoholic pancreatitis that presents with abdominal pain, steatorrhea, obstructive jaundice and responds well to steroid therapy and is seen in two subforms: type which affects elderly males, involves other organs and has increased immunoglobin G4 (IgG4) levels and type 2 which affects both sexes equally but presents at a younger age and has no other organ involvement or increased IgG4 levels. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autoimmune pancreatitis	c2609129	26,737	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=103919	2021-01-23T18:01:10	{"gard": ["10911"], "umls": ["C2609129"], "icd-10": ["K86.1"], "synonyms": ["AIP"]}
Overview of obesity in India States and union territories of India ordered by * Area * Population * GDP (per capita) * * * * Abbreviations * Access to safe drinking water * Availability of toilets * Capitals * Child nutrition * Crime rate * Ease of doing business * Electricity penetration * Fertility rate * Forest cover * Highest point * HDI * Home ownership * Household size * Human trafficking * Institutional delivery * Life expectancy at birth * Literacy rate * Media exposure * Number of vehicles * Number of voters * Open defecation * Origin of name * Places of worship * Poverty rate * Power capacity * Safety of women * School enrollment rate * Sex ratio * Suicide rate * Tax revenues * TV ownership * Transport network * Underweight people * Unemployment rate * Vaccination coverage * v * t * e Obesity in India has reached epidemic proportions in the 21st century, with morbid obesity affecting 5% of the country's population.[1] India is following a trend of other developing countries that are steadily becoming more obese. Unhealthy, processed food has become much more accessible following India's continued integration in global food markets. This, combined with rising middle class incomes, is increasing the average caloric intake per individual among middle class and high income households.[2] Obesity is a major risk factor for cardiovascular disease, and NGOs such as the Indian Heart Association have been raising awareness about this issue.[3] While studying 22 different SNPs near to MC4-R gene, scientists have identified a SNP (single nucleotide polymorphism) named rs12970134 to be mostly associated with waist circumference. In this study more than two thousand individuals of Indian origin participated and the aforementioned SNP is highly prevalent in this group.[4] Internationally, a BMI over 25 kg/m2 is considered overweight. Due to genetic tendency of Indians towards abdominal obesity and its associated risk of related lifestyle diseases such as diabetes and heart disease, guidelines for diagnosis of obesity and abdominal obesity for India have been published in JAPI (2009) that a BMI over 23 kg/m2 is considered overweight.[5] Further definitions: Normal BMI: 18.0-22.9 kg/m2, Overweight: 23.0-24.9 kg/m2, Obesity: >25 kg/m2.[5] ## Contents * 1 NFHS data * 2 See also * 3 References * 4 Further reading ## NFHS data[edit] This is a list of the states of India ranked in order of percentage of people who are overweight or obese, based on data from the 2007 National Family Health Survey.[6] States Males (%) Males rank Females (%) Females rank India 12.1 14 16 15 Delhi 45.5 - 49.8 \- Punjab 30.3 1 37.5 1 Kerala 24.3 2 34 2 Goa 20.8 3 27 3 Tamil Nadu 19.8 4 24.4 4 Andhra Pradesh 17.6 5 22.7 5 Sikkim 17.3 6 21 6 Mizoram 16.9 7 20.3 7 Himachal Pradesh 16 8 19.5 8 Maharashtra 15.9 9 18.1 9 Gujarat 15.4 10 17.7 10 Haryana 14.4 11 17.6 11 Karnataka 14 12 17.3 12 Manipur 13.4 13 17.1 13 Uttarakhand 11.4 15 14.8 14 Arunachal Pradesh 10.6 16 12.5 15 Uttar Pradesh 4.9 17 12 16 Jammu and Kashmir 8.7 18 11.1 17 Bihar 8.5 19 10.5 18 Nagaland 8.4 20 10.2 19 Rajasthan 8.4 20 9 20 Meghalaya 8.2 22 8.9 21 Odisha 6.9 23 8.6 21 Assam 6.7 24 7.8 23 Chhattisgarh 6.5 25 7.6 27 West Bengal 6.1 26 7.1 25 Madhya Pradesh 5.4 27 6.7 26 Jharkhand 5.3 28 5.9 27 Telangana 5.2 29 5.3 28 Tripura 5.1 30 5.2 29 ## See also[edit] * Malnutrition in India ## References[edit] 1. ^ "India facing obesity epidemic: experts". The Hindu. 2007-10-12. 2. ^ Gulati, S; Misra, A (2017). "Abdominal obesity and type 2 diabetes in Asian Indians: Dietary strategies including edible oils, cooking practices and sugar intake". European Journal of Clinical Nutrition. 71 (7): 850–857. doi:10.1038/ejcn.2017.92. PMID 28612831. S2CID 23766777. 3. ^ Indian Heart Association Webpage 26 April 2015. <http://indianheartassociation.org/> 4. ^ Chambers, John C; Elliott, Paul; Zabaneh, Delilah; Zhang, Weihua; Li, Yun; Froguel, Philippe; Balding, David; Scott, James; Kooner, Jaspal S (2008). "Common genetic variation near MC4R is associated with waist circumference and insulin resistance". Nature Genetics. 40 (6): 716–8. doi:10.1038/ng.156. PMID 18454146. S2CID 12331736. 5. ^ a b Misra, A; Chowbey, P; Makkar, B. M; Vikram, N. K; Wasir, J. S; Chadha, D; Joshi, S. R; Sadikot, S; Gupta, R; Gulati, S; Munjal, Y. P (2009). "Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management". The Journal of the Association of Physicians of India. 57: 163–70. PMID 19582986. 6. ^ "National Family Health Survey, 2005-06". Mumbai: International Institute for Population Sciences. 2007. Cite journal requires `\|journal=` (help) ## Further reading[edit] * Praween Kumar Agrawal (2002-05-23). "Emerging Obesity in Northern Indian States: A Serious threat for Health" (PDF). IUSSP Conference, Bankik, June 10–12 2002. * Yajnik, C. S (2007). "Obesity epidemic in India: Intrauterine origins?". Proceedings of the Nutrition Society. 63 (3): 387–96. doi:10.1079/PNS2004365. PMID 15373948. * Misra, A (2002). "Erratum: High prevalence of diabetes, obesity and dyslipidemia in urban slum population of northern India". International Journal of Obesity. 26 (9): 1281. doi:10.1038/sj.ijo.0802030. * Yoon, Kun-Ho; Lee, Jin-Hee; Kim, Ji-Won; Cho, Jae Hyoung; Choi, Yoon-Hee; Ko, Seung-Hyun; Zimmet, Paul; Son, Ho-Young (2006). "Epidemic obesity and type 2 diabetes in Asia". The Lancet. 368 (9548): 1681–8. doi:10.1016/S0140-6736(06)69703-1. PMID 17098087. 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[v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Obesity in India	None	26,738	wikipedia	https://en.wikipedia.org/wiki/Obesity_in_India	2021-01-18T19:00:19	{"wikidata": ["Q7074856"]}
Angiofibroma SpecialtyOncology Angiofibromas are small, reddish brown or even flesh-colored, smooth, shiny, 0.1 to 0.3 cm papules present over the sides of the nose and the medial portions of the cheeks.[1] They contain fibrous tissue. ## See also[edit] * List of cutaneous conditions * Nasopharyngeal angiofibroma * Tuberous sclerosis ## References[edit] 1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). Page 994. McGraw-Hill. ISBN 0-07-138076-0. ## External links[edit] Classification D * ICD-10: D10.6 (ILDS D23.L75) * ICD-O: M9160/0 * MeSH: D018322 * DiseasesDB: 32229 * v * t * e Tumours of blood vessels Blood vessel * Hemangiosarcoma * Blue rubber bleb nevus syndrome * Hemangioendothelioma * Composite * Endovascular papillary * Epithelioid * Kaposiform * Infantile * Retiform) * Spindle cell * Proliferating angioendotheliomatosis * Hemangiopericytoma * Venous lake * Kaposi's sarcoma * African cutaneous * African lymphadenopathic * AIDS-associated * Classic * Immunosuppression-associated * Hemangioblastoma * Hemangioma * Capillary * Cavernous * Glomeruloid * Microvenular * Targeted hemosiderotic * Angioma * Cherry * Seriginosum * Spider * Tufted * Universal angiomatosis * Angiokeratoma * of Mibelli * Angiolipoma * Pyogenic granuloma Lymphatic * Lymphangioma/lymphangiosarcoma * Lymphangioma circumscriptum * Acquired progressive lymphangioma * PEComa * Lymphangioleiomyomatosis * Cystic hygroma * Multifocal lymphangioendotheliomatosis * Lymphangiomatosis Either * Angioma/angiosarcoma * Angiofibroma This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Angiofibroma	c0206731	26,739	wikipedia	https://en.wikipedia.org/wiki/Angiofibroma	2021-01-18T18:32:46	{"mesh": ["D018322"], "umls": ["C0206731"], "icd-10": ["D10.6"], "wikidata": ["Q4763256"]}
Retiform parapsoriasis SpecialtyDermatology Retiform parapsoriasis is a cutaneous condition, considered to be a type of large-plaque parapsoriasis.[1] It is characterized by widespread, ill-defined plaques on the skin, that have a net-like or zebra-striped pattern.[2] Skin atrophy, a wasting away of the cutaneous tissue, usually occurs within the area of these plaques.[1] ## See also[edit] * Parapsoriasis * Poikiloderma vasculare atrophicans * List of cutaneous conditions ## References[edit] 1. ^ a b Lambert WC, Everett MA (Oct 1981). "The nosology of parapsoriasis". J. Am. Acad. Dermatol. 5 (4): 373–95. doi:10.1016/S0190-9622(81)70100-2. PMID 7026622. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. ## External links[edit] Classification D * ICD-10: L41.5 * ICD-9-CM: 696.2 * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Retiform parapsoriasis	c0263369	26,740	wikipedia	https://en.wikipedia.org/wiki/Retiform_parapsoriasis	2021-01-18T18:46:38	{"umls": ["C0263369"], "icd-9": ["696.2"], "icd-10": ["L41.5"], "wikidata": ["Q7316746"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-68 (DFNA68) is caused by heterozygous mutation in the HOMER2 gene (604799) on chromosome 15q25. One such family has been reported. Clinical Features Azaiez et al. (2015) studied a multigenerational kindred of European descent segregating autosomal dominant deafness. Pure tone audiometric evaluation of affected individuals revealed postlingual progressive bilateral hearing loss; bone conduction thresholds excluded conductive hearing impairment. Onset of hearing loss typically occurred in the first decade of life and involved the high frequencies; there was significant subsequent progression of hearing loss over all frequencies, with an annual threshold deterioration of 1.2 to 1.6 dB per year. No syndromic features or autoimmune phenotypes were found on clinical examination. Molecular Genetics In a multigenerational kindred segregating autosomal dominant postlingual progressive sensorineural hearing loss, in which plausible pathogenic variants in known deafness-associated genes had been excluded, Azaiez et al. (2015) performed whole-exome sequencing and identified a heterozygous missense mutation in the HOMER2 gene (R185P; 604799.0001) that segregated with disease. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural, postlingual progressive MISCELLANEOUS \- Onset of symptoms in the first decade of life \- Based on report of 1 family (last curated December 2015) MOLECULAR BASIS \- Caused by mutation in the homolog 2 of Drosophila Homer gene (HOMER2, 604799.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DEAFNESS, AUTOSOMAL DOMINANT 68	c4225240	26,741	omim	https://www.omim.org/entry/616707	2019-09-22T15:48:08	{"doid": ["0110589"], "omim": ["616707"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"]}
Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury,[1] toxic metabolites, or autoimmunity.[2] In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues.[2] The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood–brain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells.[3] However, circulating peripheral immune cells may surpass a compromised BBB and encounter neurons and glial cells expressing major histocompatibility complex molecules, perpetuating the immune response.[4] Although the response is initiated to protect the central nervous system from the infectious agent, the effect may be toxic and widespread inflammation as well as further migration of leukocytes through the blood–brain barrier.[2] ## Contents * 1 Causes * 2 Neuroimmune response * 2.1 Glial cells * 2.2 Cytokines * 3 Peripheral immune response * 4 Traumatic brain injury * 5 Spinal cord injury * 6 Aging * 7 Role in neurodegenerative disease * 7.1 Alzheimer's disease * 7.2 Parkinson's disease * 7.3 Multiple sclerosis * 8 Role as a therapeutic target * 8.1 Drug therapy * 8.2 Exercise * 9 References * 10 Further reading ## Causes[edit] Neuroinflammation is widely regarded as chronic, as opposed to acute, inflammation of the central nervous system.[5] Acute inflammation usually follows injury to the central nervous system immediately, and is characterized by inflammatory molecules, endothelial cell activation, platelet deposition, and tissue edema.[6] Chronic inflammation is the sustained activation of glial cells and recruitment of other immune cells into the brain. It is chronic inflammation that is typically associated with neurodegenerative diseases. Common causes of chronic neuroinflammation include: * Toxic metabolites * Autoimmunity * Aging * Microbes * Viruses * Traumatic brain injury * Spinal cord injury * Air pollution * Passive smoke ## Neuroimmune response[edit] See also: Neuroimmune system ### Glial cells[edit] Microglia are recognized as the innate immune cells of the central nervous system.[2] Microglia actively survey their environment through, and change their cell morphology significantly in response to neural injury.[7] Acute inflammation in the brain is typically characterized by rapid activation of microglia.[5] During this period, there is no peripheral immune response. Over time, however, chronic inflammation causes the degradation of tissue and of the blood–brain barrier. During this time, microglia generate reactive oxygen species and release signals to recruit peripheral immune cells for an inflammatory response.[7] Astrocytes are glial cells that are the most abundant cells in the brain. They are involved in maintenance and support of neurons and compose a significant component of the blood–brain barrier. After insult to the brain, such as traumatic brain injury, astrocytes may become activated in response to signals released by injured neurons or activated microglia.[6][1] Once activated, astrocytes may release various growth factors and undergo morphological changes. For example, after injury astrocytes form the glial scar composed of a proteoglycan matrix that hinders axonal regeneration.[6] However more recent studies revealed that glia scar is not detrimental but beneficial for axonal regeneration. [8] ### Cytokines[edit] Cytokines are a class of proteins that regulates inflammation, cell signaling, and various cell processes such as growth and survival.[9] Chemokines are a subset of cytokines that regulate cell migration, such as attracting immune cells to a site of infection or injury.[9] Various cell types in the brain may produce cytokines and chemokines such as microglia, astrocytes, endothelial cells, and other glial cells. Physiologically, chemokines and cytokines function as neuromodulators that regulate inflammation and development. In the healthy brain, cells secrete cytokines to produce a local inflammatory environment to recruit microglia and clear the infection or injury. However, in neuroinflammation, cells may have sustained release of cytokines and chemokines which may compromise the blood–brain barrier.[10] Peripheral immune cells are called to the site of injury via these cytokines and may now migrate across the compromised blood brain barrier into the brain. Common cytokines produced in response to brain injury include: interleukin-6 (IL-6), which is produced during astrogliosis, and interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), which can induce neuronal cytotoxicity. Although the pro-inflammatory cytokines may cause cell death and secondary tissue damage, they are necessary to repair the damaged tissue.[11] For example, TNF-α causes neurotoxicity at early stages of neuroinflammation, but contributes to tissue growth at later stages of inflammation. ## Peripheral immune response[edit] The blood–brain barrier is a structure composed of endothelial cells and astrocytes that forms a barrier between the brain and circulating blood. Physiologically, this enables the brain to be protected from potentially toxic molecules and cells in the blood. Astrocytes form tight junctions and therefore may strictly regulate what may pass the blood–brain barrier and enter the interstitial space.[6] After injury and sustained release of inflammatory factors such as chemokines, the blood–brain barrier may be compromised, becoming permeable to circulating blood components and peripheral immune cells. Cells involved in the innate and adaptive immune responses, such as macrophages, T Cells, and B Cells, may then enter into the brain. This exacerbates the inflammatory environment of the brain and contributes to chronic neuroinflammation and neurodegeneration. ## Traumatic brain injury[edit] Traumatic brain injury (TBI) is brain trauma caused by significant force to the head.[6] Following TBI, there are both reparative and degenerative mechanisms that lead to an inflammatory environment. Within minutes of injury, pro-inflammatory cytokines are released. The pro-inflammatory cytokine Il-1β is one such cytokine that exacerbates the tissue damage caused by TBI. TBI may cause significant damage to vital components to the brain, including the blood–brain barrier. Il-1β causes DNA fragmentation and apoptosis, and together with TNF-α may cause damage to the blood–brain barrier and infiltration of leukocytes. (). Increased density of activated immune cells have been found in the human brain after concussion.[1] ## Spinal cord injury[edit] Spinal Cord Injury (SCI) can be divided into three separate phases. The primary or acute phase occurs from seconds to minutes post injury, the secondary phase occurs from minutes to weeks after injury, and the chronic phase occurs from months to years following injury.[12] A primary SCI is caused by spinal cord compression or transection, leading to glutamate excitotoxicity, sodium and calcium ion imbalances, and free radical damage.[13] Neurodegeneration via apoptosis and demyelination of neuronal cells causes inflammation at the injury site.[12] This leads to a secondary SCI, whose symptoms include edema, cavitation of spinal parenchyma, reactive gliosis, and potentially permanent loss of function.[12] During the SCI induced inflammatory response, several pro-inflammatory cytokines including interleukin 1β (IL-1β), inducible Nitric Oxide Synthase (iNOS), Interferon-γ (IFN-γ), IL-6, IL-23, and tumor necrosis factor α (TNFα) are secreted, activating local microglia and attracting various immune cells such as naive bone-marrow derived macrophages.[14] These activated microglia and macrophages play a role in the pathogenesis of SCI. Upon infiltration of the injury site's epicenter, macrophages will undergo phenotype switching from an M2 phenotype to an M1-like phenotype. The M2 phenotype is associated with anti-inflammatory factors such as IL-10, IL-4, and IL-13 and contributes to wound healing and tissue repair. However, the M1-like phenotype is associated with pro-inflammatory cytokines and reactive oxygen species that contribute to increased damage and inflammation.[15] Factors such as myelin debris, which is formed by the injury at the damage site, has been shown to induce the phenotype shift from M2 to M1.[16] A decreased population of M2 macrophages and an increased population of M1 macrophages is associated with chronic inflammation.[16] Short term inflammation is important in clearing cell debris from the site of injury, but it is this chronic, long-term inflammation that will lead to further cell death and damage radiating from the site of injury.[17] ## Aging[edit] Aging is often associated with cognitive impairment and increased propensity for developing neurodegenerative diseases, such as Alzheimer's disease.[18] Elevated inflammatory markers seemed to accelerate the brain aging process[19] In the aged brain alone, without any evident disease, there are chronically increased levels of pro-inflammatory cytokines and reduced levels of anti-inflammatory cytokines. The homeostatic imbalance between anti-inflammatory and pro-inflammatory cytokines in aging is one factor that increases the risk for neurodegenerative disease. Additionally, there is an increased number of activated microglia in aged brains, which have increased expression of major histocompatibility complex II (MHC II), ionized calcium binding adaptor-1 (IBA1), CD86, ED1 macrophage antigen, CD4, and leukocyte common antigen.[20] These activated microglia decrease the ability for neurons to undergo long term potentiation (LTP) in the hippocampus and thereby reduce the ability to form memories.[21] ## Role in neurodegenerative disease[edit] ### Alzheimer's disease[edit] Alzheimer's disease (AD) has historically been characterized by two major hallmarks: neurofibrillary tangles and amyloid-beta plaques.[22] Neurofibrillary tangles are insoluble aggregates of tau proteins, and amyloid-beta plaques are extracellular deposits of the amyloid-beta protein. Current thinking in AD pathology goes beyond these two typical hallmarks to suggest that a significant portion of neurodegeneration in Alzheimer's is due to neuroinflammation.[22][23] Activated microglia are seen in abundance in post-mortem AD brains. Current thought is that inflammatory cytokine-activated microglia cannot phagocytose amyloid-beta, which may contribute to plaque accumulation as opposed to clearance.[24] Additionally, the inflammatory cytokine IL-1β is upregulated in AD and is associated with decreases of synaptophysin and consequent synaptic loss. Further evidence that inflammation is associated with disease progression in AD is that persons that take non-steroidal anti-inflammatory drugs (NSAIDs) regularly have been associated with reduced AD later in life.[citation needed] Elevated inflammatory markers showed an association with accelerated brain aging, which might explain the link to neurodegeneration in AD-related brain regions.[19] ### Parkinson's disease[edit] The leading hypothesis of Parkinson's disease progression includes neuroinflammation as a major component.[25] This hypothesis stipulates that Stage 1 of Parkinson's disease begins in the gut, as evidenced by a large number of cases that begin with constipation[citation needed]. The inflammatory response in the gut may play a role[citation needed] in alpha-synuclein (α-Syn) aggregation and misfolding, a characteristic of Parkinson's disease pathology. If there is a balance between good bacteria and bad bacteria in the gut, the bacteria may remain contained to the gut. However, dysbiosis of good bacteria and bad bacteria may cause a “leaky” gut, creating an inflammatory response. This response aids α-Syn misfolding and transfer across neurons, as the protein works its way up to the CNS.[citation needed] The brainstem is vulnerable to inflammation, which would explain Stage 2, including sleep disturbances and depression. In Stage 3 of the hypothesis, the inflammation affects the substantia nigra, the dopamine producing cells of the brain, beginning the characteristic motor deficits of Parkinson's disease. Stage 4 of Parkinson's disease includes deficits caused by inflammation in key regions of the brain that regulate executive function and memory. As evidence supporting this hypothesis, patients in Stage 3 (motor deficits) that are not experiencing cognitive deficits already show that there is neuroinflammation of the cortex. This suggests that neuroinflammation may be a precursor to the deficits seen in Parkinson's disease.[25] ### Multiple sclerosis[edit] Multiple sclerosis is the most common disabling neurological disease of young adults.[26] It is characterized by demyelination and neurodegeneration, which contribute to the common symptoms of cognitive deficits, limb weakness, and fatigue.[27] In multiple sclerosis, inflammatory cytokines disrupt the blood–brain barrier and allow for the migration of peripheral immune cells into the central nervous system. When they have migrated into the central nervous system, B cells and plasma cells produce antibodies against the myelin sheath that insulates neurons, degrading the myelin and slowing conduction in the neurons. Additionally, T cells may enter through the blood–brain barrier, be activated by local antigen presenting cells, and attack the myelin sheath. This has the same effect of degrading the myelin and slowing conduction. As in other neurodegenerative diseases, activated microglia produce inflammatory cytokines that contribute to widespread inflammation. It has been shown that inhibiting microglia decreases the severity of multiple sclerosis.[25] ## Role as a therapeutic target[edit] ### Drug therapy[edit] Because neuroinflammation has been associated with a variety of neurodegenerative diseases, there is increasing interest to determine whether reducing inflammation will reverse neurodegeneration. Inhibiting inflammatory cytokines, such as IL-1β, decreases neuronal loss seen in neurodegenerative diseases. Current treatments for multiple sclerosis include interferon-B, Glatiramer acetate, and Mitoxantrone, which function by reducing or inhibiting T Cell activation, but have the side effect of systemic immunosuppression [28] In Alzheimer's disease, the use of non-steroidal anti-inflammatory drugs decreases the risk of developing the disease. Current treatments for Alzheimer's disease include NSAIDs and glucocorticoids. NSAIDs function by blocking conversion of prostaglandin H2 into other prostaglandins (PGs) and thromboxane (TX). Prostoglandins and thromboxane act as inflammatory mediators and increase microvascular permeability. ### Exercise[edit] Exercise is a promising mechanism of prevention and treatment for various diseases characterized by neuroinflammation.[20] Aerobic exercise is used widely to reduce inflammation in the periphery. Exercise has been shown to decrease proliferation of microglia in the brain, decrease hippocampal expression of immune-related genes, and reduce expression of inflammatory cytokines such as TNF-α. ## References[edit] 1. ^ a b c Ebert SE, Jensen P, Ozenne B, Armand S, Svarer C, Stenbaek DS et al. Molecular imaging of neuroinflammation in patients after mild traumatic brain injury: a longitudinal 123 I-CLINDE SPECT study. Eur J Neurol 2019\. doi:10.1111/ene.13971. 2. ^ a b c d Gendelman HE (December 2002). "Neural immunity: Friend or foe?". Journal of Neurovirology. 8 (6): 474–9. doi:10.1080/13550280290168631. PMID 12476342. 3. ^ Das Sarma J (April 2014). "Microglia-mediated neuroinflammation is an amplifier of virus-induced neuropathology". Journal of Neurovirology. 20 (2): 122–36. doi:10.1007/s13365-013-0188-4. PMID 23979705. 4. ^ 't Hart BA, den Dunnen WF (September 2013). "Commentary on special issue: CNS diseases and the immune system". Journal of Neuroimmune Pharmacology. 8 (4): 757–9. doi:10.1007/s11481-013-9486-0. PMID 23754135. 5. ^ a b Streit WJ, Mrak RE, Griffin WS (July 2004). "Microglia and neuroinflammation: a pathological perspective". Journal of Neuroinflammation. 1 (1): 14. doi:10.1186/1742-2094-1-14. PMC 509427. PMID 15285801. 6. ^ a b c d e Mayer CL, Huber BR, Peskind E (October 2013). "Traumatic brain injury, neuroinflammation, and post-traumatic headaches". Headache. 53 (9): 1523–30. doi:10.1111/head.12173. PMC 4089888. PMID 24090534. 7. ^ a b Garden GA (October 2013). "Epigenetics and the modulation of neuroinflammation". Neurotherapeutics. 10 (4): 782–8. doi:10.1007/s13311-013-0207-4. PMC 3805872. PMID 23963788. 8. ^ Anderson MA, Burda JE, Sofroniew MV (April 2016). "Astrocyte scar formation aids central nervous system axon regeneration". Nature. 1 (1): 20. doi:10.1038/nature17623. PMC 5243141. PMID 27027288. 9. ^ a b Ramesh G, MacLean AG, Philipp MT (July 2013). "Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain". Mediators of Inflammation. 2013: 480739. doi:10.1155/2013/480739. PMC 3753746. PMID 23997430. 10. ^ Ren H, Han R, Chen X, Liu X, Wan J, Wang L, Yang X, Wang J (May 2020). "Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update". J Cereb Blood Flow Metab. doi:10.1177/0271678X20923551. PMID 32423330. 11. ^ Zhu H, Wang Z, Yu J, Yang X, He F, Liu Z, Che F, Chen X, Ren H, Hong M, Wang J (March 2019). "Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage". Prog. Neurobiol. 178: 101610. doi:10.1016/j.pneurobio.2019.03.003. PMID 30923023. 12. ^ a b c Zhou X, He X, Ren Y (October 2014). "Function of microglia and macrophages in secondary damage after spinal cord injury". Neural Regeneration Research. 9 (20): 1787–95. doi:10.4103/1673-5374.143423. PMC 4239768. PMID 25422640. 13. ^ Garcia E, Aguilar-Cevallos J, Silva-Garcia R, Ibarra A (2016). "Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury". Mediators of Inflammation. 2016: 9476020. doi:10.1155/2016/9476020. PMC 4935915. PMID 27418745. 14. ^ Cameron MJ, Kelvin DJ (2013). Cytokines, Chemokines and Their Receptors. Landes Bioscience. 15. ^ Martinez FO, Gordon S (2014-03-03). "The M1 and M2 paradigm of macrophage activation: time for reassessment". F1000Prime Reports. 6 (13): 13. doi:10.12703/p6-13. PMC 3944738. PMID 24669294. 16. ^ a b Wang X, Cao K, Sun X, Chen Y, Duan Z, Sun L, Guo L, Bai P, Sun D, Fan J, He X, Young W, Ren Y (April 2015). "Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris". Glia. 63 (4): 635–51. doi:10.1002/glia.22774. PMC 4331228. PMID 25452166. 17. ^ Fehlings MG, Nguyen DH (May 2010). "Immunoglobulin G: a potential treatment to attenuate neuroinflammation following spinal cord injury". Journal of Clinical Immunology. 30 Suppl 1 (1): S109–12. doi:10.1007/s10875-010-9404-7. PMC 2883090. PMID 20437085. 18. ^ Gomes da Silva, Sergio (2013). "Exercise-induced hippocampal anti-inflammatory response in aged rats". Journal of Neuroinflammation. 10: 61. doi:10.1186/1742-2094-10-61. PMC 3657539. PMID 23663962. 19. ^ a b Janowitz D, Habes M, Toledo JB, Hannemann A, Frenzel S, Terock J, Davatzikos C, Hoffmann W, Grabe HJ (2019). "Inflammatory markers and imaging patterns of advanced brain aging in the general population". Brain Imaging and Behavior. doi:10.1007/s11682-019-00058-y. PMID 30820858. 20. ^ a b Kohman RA, Bhattacharya TK, Wojcik E, Rhodes JS (September 2013). "Exercise reduces activation of microglia isolated from hippocampus and brain of aged mice". Journal of Neuroinflammation. 10: 114. doi:10.1186/1742-2094-10-114. PMC 3848770. PMID 24044641. 21. ^ Lynch MA (2010). "Age-related neuroinflammatory changes negatively impact on neuronal function". Frontiers in Aging Neuroscience. 1: 6. doi:10.3389/neuro.24.006.2009. PMC 2874409. PMID 20552057. 22. ^ a b Meraz-Ríos MA, Toral-Rios D, Franco-Bocanegra D, Villeda-Hernández J, Campos-Peña V (August 2013). "Inflammatory process in Alzheimer's Disease". Frontiers in Integrative Neuroscience. 7: 59. doi:10.3389/fnint.2013.00059. PMC 3741576. PMID 23964211. 23. ^ Culibrk RA, Hahn MS (2020). "The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease". Frontiers in Aging Neuroscience. 12: 583884. doi:10.3389/fnagi.2020.583884. PMC 7750365. PMID 33364931. 24. ^ Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG (November 2009). "Does neuroinflammation fan the flame in neurodegenerative diseases?". Molecular Neurodegeneration. 4: 47. doi:10.1186/1750-1326-4-47. PMC 2784760. PMID 19917131. 25. ^ a b c Barnum CJ, Tansey MG (August 2012). "Neuroinflammation and non-motor symptoms: the dark passenger of Parkinson's disease?". Current Neurology and Neuroscience Reports. 12 (4): 350–8. doi:10.1007/s11910-012-0283-6. PMID 22580742. 26. ^ "Multiple Sclerosis: Hope Through Research". The National Institute of Neurological Disorders and Stroke. Retrieved 2016-08-22. 27. ^ Zindler E, Zipp F (December 2010). "Neuronal injury in chronic CNS inflammation". Best Practice & Research. Clinical Anaesthesiology. 24 (4): 551–62. doi:10.1016/j.bpa.2010.11.001. PMID 21619866. 28. ^ McPherson RC, Anderton SM (September 2013). "Adaptive immune responses in CNS autoimmune disease: mechanisms and therapeutic opportunities". Journal of Neuroimmune Pharmacology. 8 (4): 774–90. doi:10.1007/s11481-013-9453-9. PMID 23568718. ## Further reading[edit] * Maggi P, Macri SM, Gaitán MI, Leibovitch E, Wholer JE, Knight HL, Ellis M, Wu T, Silva AC, Massacesi L, Jacobson S, Westmoreland S, Reich DS (October 2014). "The formation of inflammatory demyelinated lesions in cerebral white matter". Annals of Neurology. 76 (4): 594–608. doi:10.1002/ana.24242. PMC 4723108. PMID 25088017. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Neuroinflammation	c0027881	26,742	wikipedia	https://en.wikipedia.org/wiki/Neuroinflammation	2021-01-18T19:05:34	{"umls": ["C0027881"], "wikidata": ["Q17157137"]}
Main article: hypertension Benign hypertension or benign essential hypertension are historical terms that are considered misleading,[1] as hypertension is never benign, and consequently they have fallen out of use (see history of hypertension). The terminology persisted in the International Classification of Disease (ICD9), but is not included in the current ICD10. [2] ## References[edit] 1. ^ McIver C (September 1964). "Blood pressure; a consideration of terminology". Can Med Assoc J. 91: 578–80. PMC 1927435. PMID 14175874. 2. ^ Beckman, Kenneth D. (March 2014). "How to document and code for hypertensive diseases in ICD-10". Family Practice Management. 21 (2): 5–9. ISSN 1531-1929. PMID 24693838. * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension This medical article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Benign hypertension	c0155583	26,743	wikipedia	https://en.wikipedia.org/wiki/Benign_hypertension	2021-01-18T18:45:12	{"umls": ["C0155583"], "wikidata": ["Q4887962"]}
A number sign (#) is used with this entry because of evidence that catecholaminergic polymorphic ventricular tachycardia-3 (CPVT3) is caused by homozygous mutation in the TECRL gene (617242) on chromosome 4q13. Description Catecholaminergic polymorphic ventricular tachycardia-3 (CPVT3) is characterized by overlapping features of long QT syndrome (see 192500) and CPVT. Affected individuals exhibit adrenergic ventricular tachycardia associated with a high prevalence of cardiac arrest and sudden cardiac death, with recurrent atrial tachycardia sometimes triggering the ventricular arrhythmias. In addition, affected individuals have a normal or mildly prolonged QTc on baseline electrocardiography, with a paradoxical QT increase during adrenergic simulation (summary by Devalla et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of CPVT, see 604772. Clinical Features Bhuiyan et al. (2007) studied a large consanguineous family of Sudanese origin in which 3 sibs died suddenly during physical activity. The first death occurred in a 10-year-old girl who died while playing in a fun park; no evaluation was performed. The second death involved her younger brother, who collapsed at 12 years of age while skating; during resuscitation he was noted to have several episodes of ventricular tachycardia. Electrocardiography (ECG) revealed a mildly prolonged QTc (450 to 490 ms) and premature ventricular contractions (PVCs) with a right bundle branch block (RBBB) morphology and superior axis, indicating a left ventricular origin. ECG showed no structural cardiac anomaly. He remained in a vegetative state until his death from pneumonia 2 years later. The third sib was a younger sister who underwent palliative surgery for tetralogy of Fallot in infancy, at which time ECG revealed a QTc of 440 ms; ECG at 14 months of age showed QTc of 480 to 490 ms. After corrective cardiac surgery at 3 years of age, ECG showed RBBB with QRS duration of 110 ms and QTc of 470 to 490 ms (uncorrected for widened QRS complex). She collapsed and died while playing sports at 8 years of age. A 7-year-old male cousin, also born of consanguineous parents, was the only surviving patient. ECG after a syncopal episode while playing outdoors showed borderline prolonged QTc of 480 ms; echocardiogram was normal. Exercise stress testing revealed isolated PVCs at a heart rate of 144 bpm, with couplets appearing at a heart rate of 170 bpm after exercising for 6 minutes, at which time the test was terminated. He was put on a beta-blocker and restricted from exercise and was still alive at follow-up 18 months later. The parents were all asymptomatic, and the parents of the surviving patient had normal ECGs; 3 asymptomatic sibs of the deceased sibs had no PVCs on 24-hour ECG monitoring. Devalla et al. (2016) studied 2 unrelated French Canadian women who were successfully rescuscitated from cardiac arrest. The first presented with ventricular fibrillation and cardiac arrest while walking at age 22 years, without prior history of syncope or documented arrhythmia. Coronary angiography, echocardiography, and invasive electrophysiologic (EP) testing were normal. Resting ECG showed a normal QT interval, but isoproterenol infusion resulted in QT prolongation. During follow-up the patient had recurrent episodes of exercise- or emotion-induced atrial and ventricular arrhythmias, resulting in multiple shocks from an implantable cardioverter-defibrillator (ICD). In addition, significant repolarization abnormalities with QT prolongation (QTc range, 451-494 ms) were occasionally seen on resting ECGs, and the patient was given a diagnosis of long QT syndrome (LQTS). Family history was negative for sudden cardiac death except for a paternal cousin who died suddenly at age 34 years; no details were available. The second French Canadian woman presented at age 18 with numerous syncopal episodes triggered by emotional stress and documentation of nonsustained ventricular tachycardia (VT) during exercise stress testing. Despite beta-blocker therapy, she experienced aborted cardiac arrest at age 31 years. QTc at rest was 437 ms with repolarization abnormalities. Isoproterenol infusion induced sustained polymorphic VT, and epinephrine challenge resulted in a 57-ms paradoxical QT prolongation with ventricular bigeminy, suggesting a low repolarization reserve consistent with LQTS. During follow-up, the patient had multiple episodes of adrenergic atrial and ventricular arrhythmias, provoked by either exercise or emotion, resulting in numerous ICD shocks. EP mapping revealed an extensive low-voltage area along the interatrial septum, as well as multiple foci of atrial tachycardia that were successfully ablated. Family history was negative for arrhythmias, and the proband's 2 sons were asymptomatic with normal baseline ECGs and 24-hour Holter monitoring. In addition, her father was asymptomatic, with a normal ECG and negative epinephrine test. Devalla et al. (2016) also restudied the consanguineous Sudanese family originally reported by Bhuiyan et al. (2007), noting that 7 of 13 children had experienced exertion-induced arrhythmias and/or sudden cardiac death in early childhood; 5 of the 7 children had undergone a fatal arrhythmic episode. Mapping In a large consanguineous family of Sudanese origin with a history of sudden death following exercise, negative for mutation in 11 genes involved in cardiac electric impulse propagation, including RYR2 (180902) and CASQ2 (114251), Bhuiyan et al. (2007) performed whole genome scanning and identified a homozygous region on chromosome 7p22-p14 that was shared by the 2 deceased sibs from whom DNA was available and their affected cousin. Mapping with additional markers revealed a 25-Mb interval flanked by D7S526 distally and D7S481 proximally that showed complete cosegregation with disease. A maximum multipoint lod score of 3.17 was obtained with marker D7S493. No significant sequence alterations were detected in coding exons or exon-intron boundaries of screened candidate genes in that region. Devalla et al. (2016) restudied the Sudanese family originally reported by Bhuiyan et al. (2007) and noted that reanalysis with inclusion of a young family member who was only later identified as affected indicated that the consensus homozygous locus in all affected individuals was on chromosome 4. Molecular Genetics In a consanguineous Sudanese family with CPVT and QT prolongation, previously studied by Bhuiyan et al. (2007), Devalla et al. (2016) performed whole-exome sequencing and identified homozygosity for a splice site mutation in the TECRL gene (617242.0001) that segregated fully with disease in the family. By whole-exome sequencing in 2 unrelated French Canadian women with CPVT and prolongation of the QT interval, who were negative for mutation in the 5 genes most commonly associated with LQT, they identified homozygosity for the same missense mutation in TECRL (R196Q; 617242.0002). INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Polymorphic ventricular tachycardia induced by emotion or physical activity \- Borderline prolonged QT interval \- Syncope \- Sudden death MISCELLANEOUS \- Onset at early age, associated with sudden death in childhood ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 3	c1631597	26,744	omim	https://www.omim.org/entry/614021	2019-09-22T15:56:46	{"doid": ["0060677"], "mesh": ["C536334"], "omim": ["614021"], "orphanet": ["3286"], "genereviews": ["NBK1289"]}
A number sign (#) is used with this entry because of evidence that Lamb-Shaffer syndrome (LAMSHF) is caused by heterozygous mutation in the SOX5 gene (604975) on chromosome 12p12. Some patients with a similar phenotype may have deletions of chromosome 12p12 including several genes in addition to SOX5. Description Lamb-Shaffer syndrome is a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, and mild dysmorphic facial features. Additional variable skeletal abnormalities may also be present (summary by Nesbitt et al., 2015). Clinical Features Lamb et al. (2012) reported 9 unrelated patients with developmental delay and intellectual disability associated with haploinsufficiency of the SOX5 gene. Other common features included speech delay and dysmorphisms such as strabismus, frontal bossing, ear abnormalities, and low nasal bridge. Several patients had behavioral problems, including stereotypic behavior or pervasive developmental delay. Only 2 had seizures. More variable features included hypotonia, clumsiness, poor balance, articulation difficulties, and scoliosis. Schanze et al. (2013) reported a 9-year-old boy (patient 2) with global developmental delay, poor early speech development, and dysmorphic features, including high forehead, downslanting palpebral fissures, thin upper lip, open mouth, and pointed chin. He had some ritualistic behavior and constipation. Lee et al. (2013) reported a 32-month-old boy with global developmental delay and severe expressive language delay. Dysmorphic features included frontal bossing, depressed nasal bridge with bulbous nasal tip, epicanthal folds, strabismus, prominent philtral ridges, underdeveloped helices, and mild facial hypoplasia. Additional multisystem anomalies included right renal agenesis, ureteral stenosis, optic nerve hypoplasia, laryngotracheomalacia, and vertebral clefts. Lee et al. (2013) noted that the pregnancy was complicated by gestational diabetes that was controlled with glyburide; it was unknown whether this had a teratogenic effect. Nesbitt et al. (2015) reported a 17-year-old girl with delayed psychomotor development, intellectual disability (IQ of 50), and mild dysmorphic features, including blepharoptosis, low-set and posteriorly rotated ears, retrognathia, prominent maxilla, midline tongue groove, and narrow palate with overcrowded teeth. She developed nonprogressive optic atrophy at age 10, and also had exotropia and mild myopia. Additional features included mild mitral regurgitation, thoracic kyphoscoliosis, lumbar lordosis, pectus carinatum, long fingers, and long halluces reminiscent of a marfanoid habitus. She also had anxiety. Cytogenetics By use of oligonucleotide-based array comparative genomic hybridization (array CGH) to test 24,081 probands referred for developmental delay or intellectual disability, Lamb et al. (2012) identified 10 patients with large deletions of chromosome 12p12 that involved all or part of the SOX5 gene and additional genes. Patients with larger deletions tended to have more dysmorphic features and more musculoskeletal anomalies compared to those with smaller deletions. Lamb et al. (2012) suggested that haploinsufficiency for the SOX5 may contribute to neurodevelopmental delay. Schanze et al. (2013) reported 2 unrelated children (patients 1 and 3) with global developmental delay associated with heterozygous deletions of chromosome 12p21 including the SOX5 gene: the deletion in 1 patient encompassed 4 genes, whereas the deletion in the other patient encompassed 23 genes. The deletion was confirmed to be de novo in 1 of the patients. The patient with the shorter deletion had mild dysmorphic features, including downslanting palpebral fissures, epicanthal folds, strabismus, broad nasal bridge with upturned and bulbous tip, and open mouth. Molecular Genetics By use of oligonucleotide-based array comparative genomic hybridization (array CGH) to test 24,081 probands referred for developmental delay or intellectual disability, Lamb et al. (2012) identified 9 unrelated patients with variable deletions of chromosome 12p12 that involved only the SOX5 gene, including 1 patient with a translocation. The deletions ranged in size from 72 to 466 kb (see, e.g., 604975.0001 and 604975.0002). Depending on the size and location, the deletions were predicted to impact the different SOX5 protein isoforms to varying degrees. In 1 case, the deletion was inherited from an affected mother and was present in an affected sister. Two additional patients had deletions involving noncoding regions of the SOX5 gene; 1 of these patients had a milder phenotype and inherited the deletion from an unaffected father and paternal grandmother. In comparison, Lamb et al. (2012) identified 4 exonic deletions and 58 smaller intronic deletions in the SOX5 gene among the 8,329 controls in the dataset of Cooper et al. (2011). Lamb et al. (2012) suggested that haploinsufficiency for the SOX5 gene may contribute to neurodevelopmental delay. In a boy with LAMSHF, Schanze et al. (2013) identified a de novo heterozygous intragenic deletion in the SOX5 gene (604975.0003). The deletion was found by array CGH. The results were confirmed by FISH. Functional studies and studies on patient cells were not performed. In a boy with LAMSHF, Lee et al. (2013) identified a de novo heterozygous intragenic deletion in the SOX5 gene (604975.0004). The deletion was found by array CGH. The results were confirmed by FISH. Functional studies and studies on patient cells were not performed. In a 17-year-old girl with LAMSHF, Nesbitt et al. (2015) identified a de novo heterozygous nonsense mutation in the SOX5 gene (G341X; 604975.0005). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies and studies on patient cells were not performed, but the molecular findings were consistent with SOX5 haploinsufficiency. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Frontal bossing \- Facial asymmetry Ears \- Low-set ears \- Posteriorly rotated ears Eyes \- Downslanting palpebral fissures \- Epicanthal folds \- Strabismus \- Myopia Nose \- Depressed nasal bridge \- Broad nasal bridge \- Bulbous nasal tip Mouth \- Open mouth Teeth \- Crowded teeth SKELETAL Spine \- Scoliosis (in some patients) \- Vertebral clefts (in some patients) Hands \- Clinodactyly \- Long fingers (in some patients) Feet \- Flat feet (in some patients) \- Long halluces (in some patients) \- Overlapping toes (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Poor speech development Behavioral Psychiatric Manifestations \- Stereotypic features MISCELLANEOUS \- Highly variable phenotype MOLECULAR BASIS \- Caused by mutation in the SRY-BOX 5 gene (SOX5, 604975.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LAMB-SHAFFER SYNDROME	c4225202	26,745	omim	https://www.omim.org/entry/616803	2019-09-22T15:47:51	{"omim": ["616803"], "orphanet": ["313892", "313884"], "synonyms": ["Del(12)(p12.1)", "Monosomy 12p12.1"]}
A number sign (#) is used with this entry because of evidence that linear skin defects with multiple congenital anomalies-3 (LSDMCA3) is caused by heterozygous mutation in the NDUFB11 gene (300403) on chromosome Xp11. For a discussion of genetic heterogeneity of linear skin defects with multiple congenital anomalies, see LSDMCA1 (309801). A hemizygous missense mutation in the NDUFB11 gene (300403.0003) has been found in 1 male patient with mitochondrial complex I deficiency (see 252010). That patient died in infancy (Kohda et al., 2016). Clinical Features Van Rahden et al. (2015) reported 2 unrelated girls with linear skin defects of the face and neck at birth, cardiomyopathy, and various other congenital anomalies. In 1 patient, the skin defects disappeared within the first few months of life; she also exhibited axial hypotonia and failure to thrive. Ocular examination showed lacrimal duct atresia. At 6 months of age, she was hospitalized after cardiac arrest and underwent repeated treatment of ventricular fibrillation and tachycardia, but died within a few weeks. Autopsy revealed histiocytoid cardiomyopathy and thyroid abnormalities, including sites of oncocytic metaplasia and C-cell hyperplasia. The other patient had corpus callosum agenesis and dilated lateral ventricles diagnosed on prenatal ultrasound. At 2 months of age, she had seizures and also developed dilated cardiomyopathy, for which she underwent cardiac transplantation at age 6 months. Eye examination at age 15 months showed myopia, nystagmus, and strabismus. Severe psychomotor delay became evident over time; she started walking at age 3 years and could speak simple sentences and had sphincter control by age 7 years. Severe muscular hypotonia and delayed dentition were also present. Neither patient exhibited microphthalmia or sclerocornea, and blood lactate levels were normal in both. In the second family, ultrasound in the next pregnancy showed thickened myocardium, pericardial effusion, corpus callosum dysgenesis, small cerebellum, connection between a lateral ventricle and the cavum septum pellucidum, and intrauterine growth retardation; the pregnancy was terminated. Molecular Genetics In 2 unrelated girls with linear skin defects, cardiomyopathy, and various other congenital anomalies, van Rahden et al. (2015) identified heterozygosity for truncating mutations in the NDUFB11 gene (R88X, 300403.0001 and c.402delG, 300403.0002). In 1 family, the proband's unaffected mother was also heterozygous for the c.402delG mutation, as was an aborted affected female fetus. Both the mother and the proband had complete skewing of X-chromosome inactivation (XCI, 100:0) in peripheral blood cells, whereas the ratio in the fetus was 99:1. The affected girl in the other family showed a highly skewed pattern in leukocyte-derived DNA (10:90), whereas her healthy mother, who did not carry the R88X mutation, had a less skewed XCI ratio of 20:80. By shRNA-mediated NDUFB11 knockdown in HeLa cells, van Rahden et al. (2015) demonstrated that NDUFB11 is essential for assembly and activity of complex I in the mitochondrial respiratory chain, as well as for cell growth and survival. INHERITANCE \- X-linked dominant GROWTH Other \- Failure to thrive HEAD & NECK Face \- Linear skin defects on face at birth (in both patients) Eyes \- Lacrimal duct atresia \- Myopia \- Nystagmus \- Strabismus Teeth \- Delayed dentition Neck \- Linear skin defects on neck at birth (in both patients) CARDIOVASCULAR Heart \- Cardiomyopathy, histiocytoid \- Cardiomyopathy, dilated \- Ventricular tachycardia \- Ventricular fibrillation \- Cardiac arrest SKIN, NAILS, & HAIR Skin \- Linear skin defects on face and neck (in both patients) \- Atrophic hyperpigmented streaks on face and neck \- Linear atrophic hyperpigmented streak on left index finger MUSCLE, SOFT TISSUES \- Muscular hypotonia, severe NEUROLOGIC Central Nervous System \- Axial hypotonia \- Seizures \- Corpus callosum agenesis \- Dilation of lateral ventricles METABOLIC FEATURES \- Normal blood lactate levels (in both patients) ENDOCRINE FEATURES \- Thyroid oncocytic metaplasia \- C-cell hyperplasia MISCELLANEOUS \- Based on report of 2 unrelated patients (last curated May 2015) \- Skewed X-inactivation, with complete skewing in some individuals \- Congenital linear skin defects may disappear within a few months of life MOLECULAR BASIS \- Caused by mutation in the NADH dehydrogenase-1 beta subcomplex-11 gene (NDUFB11, 300403.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LINEAR SKIN DEFECTS WITH MULTIPLE CONGENITAL ANOMALIES 3	c0796070	26,746	omim	https://www.omim.org/entry/300952	2019-09-22T16:19:08	{"mesh": ["C537466"], "omim": ["300952"], "orphanet": ["2556"], "synonyms": ["Alternative titles", "LINEAR SKIN DEFECTS WITH CARDIOMYOPATHY AND OTHER CONGENITAL ANOMALIES"], "genereviews": ["NBK7041"]}
Glycogen storage disease type 5 (GSDV) is a genetic disorder that prevents the body from breaking down glycogen. Glycogen is an important source of energy that is stored in muscle tissue. People with GSDV typically experience fatigue, muscle pain, and cramps during the first few minutes of exercise (exercise intolerance). Usually, when people with this disease rest after brief exercise they can resume exercising with little or no discomfort (a characteristic phenomenon known as "second wind"). The signs and symptoms can vary significantly and may include burgundy-colored urine, fatigue, exercise intolerance, muscle cramps, muscle pain, muscle stiffness, and muscle weakness. It is caused by mutations in the PYGM gene and is inherited in an autosomal recessive fashion. There is no cure or specific treatment but the disease can be managed with moderate-intensity aerobic training (e.g., walking or brisk walking, bicycling) and diet. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Glycogen storage disease type 5	c0017924	26,747	gard	https://rarediseases.info.nih.gov/diseases/6528/glycogen-storage-disease-type-5	2021-01-18T18:00:16	{"mesh": ["D006012"], "omim": ["232600"], "orphanet": ["368"], "synonyms": ["GSD 5", "McArdle disease", "McArdle type glycogen storage disease", "PYGM deficiency", "Muscle glycogen phosphorylase deficiency", "Myophosphorylase deficiency"]}
Benign neonatal seizures include two disorders: benign idiopathic neonatal seizures and benign familial neonatal seizures.[1] They are not classified as epilepsy.[2] Anticonvulsants are not needed.[1] And those affected do not develop epilepsy when they grow up.[1] ## References[edit] 1. ^ a b c Jerome Engel; Timothy A. Pedley; Jean Aicardi, eds. (2008). Epilepsy: A Comprehensive Textbook, Volume 3. Lippincott Williams & Wilkins. p. 2287. ISBN 9780781757775. 2. ^ National Institute for Health and Clinical Excellence (January 2012). "9". The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care (PDF). National Clinical Guideline Centre. pp. 119–129. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Benign neonatal seizures	c0270851	26,748	wikipedia	https://en.wikipedia.org/wiki/Benign_neonatal_seizures	2021-01-18T19:05:03	{"mesh": ["D020936"], "umls": ["C0270851"], "orphanet": ["1949"], "wikidata": ["Q15975183"]}
Sphincter of Oddi dysfunction A diagram of the biliary tree showing the sphincter of Oddi. Note that part of the gall bladder has been removed, and the liver has been lifted off the tree. SpecialtyGastroenterology, general surgery Sphincter of Oddi dysfunction refers to a group of functional disorders leading to abdominal pain due to dysfunction of the Sphincter of Oddi: functional biliary sphincter of Oddi and functional pancreatic sphincter of Oddi disorder. The sphincter of Oddi is a sphincter muscle, a circular band of muscle at the bottom of the biliary tree which controls the flow of pancreatic juices and bile into the second part of the duodenum. The pathogenesis of this condition is recognized to encompass stenosis or dyskinesia of the sphincter of Oddi (especially after cholecystectomy); consequently the terms biliary dyskinesia, papillary stenosis, and postcholecystectomy syndrome have all been used to describe this condition. Both stenosis and dyskinesia can obstruct flow through the sphincter of Oddi and can therefore cause retention of bile in the biliary tree and pancreatic juice in the pancreatic duct. Individuals with sphincter of Oddi dysfunction present with abdominal pain resembling that of structural or inflammatory disorders of the gallbladder, biliary tree or pancreas. Among other characteristics, the pain is typically in the upper part of the abdomen or in the right upper quadrant of the abdomen, lasts 30 minutes or longer, and is not associated with a structural abnormality that could lead to these symptoms. The disorder is classified into two subtypes: functional biliary sphincter of Oddi disorder, where there is no disturbance in pancreatic enzyme measurements, such as amylase and lipase; and, functional pancreatic sphincter of Oddi disorder, where pancreatic enzyme measurements are elevated. Attacks can be precipitated by opioid analgesics,[1] particularly in patients having undergone a cholecystectomy or bariatric surgery. ## Contents * 1 Classification * 1.1 Functional gallbladder disorder * 1.2 Functional biliary sphincter of Oddi disorder * 2 Characteristics * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Classification[edit] Functional disorders of the gallbladder, bile duct and pancreas have been defined and classified by the Rome criteria for functional gastrointestinal disorders.[2] The criteria outline three variants of functional disorders of the gallbladder, bile duct and pancreas, termed functional gallbladder disorder, functional biliary sphincter of Oddi disorder and functional pancreatic sphincter of Oddi disorder. All of the following criteria need to be met for as part of the definition of a functional disorder of the gallbladder:[2] * the pain must be located in the upper part of the abdomen and/or the right upper quadrant of the abdomen * episodes of pain must last at least 30 minutes * the symptoms must be recurrent, and occur at differing intervals * the pain must incrementally increase to a "steady level" * the pain must be severe enough the patient's daily activities are affected, or that the patient must attend the emergency department * the pain must not be relieved by any of bowel movements, change in posture, or antacids; and, * other structural disorders that could explain the symptoms must be excluded. ### Functional gallbladder disorder[edit] Individuals are classified as having a functional gallbladder disorder if the above criteria are met, if the gallbladder is present, and if the testing of liver enzymes, conjugated bilirubin, and pancreatic enzymes (amylase and lipase) are normal.[2] ### Functional biliary sphincter of Oddi disorder[edit] If all of the above criteria are met, individuals are classified as having a functional biliary sphincter of Oddi disorder, if the testing of pancreatic enzymes (amylase and lipase) is normal.[2] The old Milwaukee classification of biliary sphincter of Oddi dysfunction (SOD) used to divide the condition into three subtypes:[3] but it is no longer in use. Type I included patients with biliary-type abdominal pain, with all of altered liver enzymes on blood testing, dilated biliary ducts on ultrasound or ERCP, and delayed bile clearance on HIDA scan. Type II included patients with biliary-type abdominal pain associated with at least one of the following: altered liver enzymes on blood testing, dilated biliary ducts on imaging tests, and delayed bile clearance on HIDA scan. Biliary-type pain in the absence of any sign of biliary or pancreatic alteration was the so-called Type III biliary SOD. The hypothesis that this pain could be linked to SOD has been studied in a large trial published in JAMA (2014) [4] where patients were randomized to sphincterotomy or sham surgery. Contrary to expectations, patients who were not subjected to sphincterotomy fared better. Overall, the investigators found that only 23% of the patients who underwent sphincterotomy improved versus 37% of the control group. The EPISOD trial has substantiated the ineffectiveness of endoscopic sphincterotomy in patients with these symptoms and SOD Type III is no longer considered to be a clinical entity. ## Characteristics[edit] Sphincter of Oddi dysfunction may be suggested by pain which seems to come from a biliary origin, which may or may not be associated with transient increases of liver or pancreatic enzymes. Common bile duct dilation and episodes of pancreatitis are also signs.[5] ## Pathophysiology[edit] Two mechanisms are involved in the development of sphincter of Oddi dysfunction, either or both of which may be contributory to the condition: stenosis, or narrowing of the sphincter of Oddi (also termed papillary stenosis), and dyskinesia, or alteration in the function of the sphincter of Oddi (also termed biliary dyskinesia).[5] Individuals with stenosis of the sphincter of Oddi typically have an elevated baseline pressure of the sphincter of Oddi, due to an anatomical problem that leads to narrowing of the sphincter, such as recurrent passage of gallstones through the ampulla of Vater, trauma to the sphincter from procedures such as endoscopic retrograde cholangiopancreatography or biliary surgery, or infections of the common bile duct. In contrast, dyskinesia of the sphincter of Oddi is a purely functional disorder, wherein there is intermittent obstruction of the bile duct due to inappropriate spasms. The reasons for dyskinesia of the sphincter of Oddi are not completely understood, but believed to be due to alteration in local gut hormones and peptides, such as cholecystokinin, which act on the sphincter or to altered neuronal control of the sphincter.[6] ## Diagnosis[edit] For diagnosis, measures of liver biochemistry and pancreatic enzymes are performed. Along with ruling out structural abnormalities, normally by performing an abdominal ultrasound and endoscopic retrograde cholangiopancreatography (ERCP). Measurements of bile transit when performing ERCP are taken to help evaluate different treatment options.[5] Sphincter of Oddi dysfunction is best diagnosed using manometry-an internal test done to measure the pressures within surrounding ducts to determine whether or not the muscle is functioning normally. ## Treatment[edit] Medication (to prevent spasms) or Sphincterotomy (surgical procedure to cut the muscle) are the standard treatments for sphincter of Oddi dysfunction. One or the other may be better based on the classification of the condition. ## See also[edit] * Stenosis * Dyskinesia * Bile ## References[edit] 1. ^ https://web.archive.org/web/20080731060352/http://www.anzca.edu.au/fpm/events/fpm-events/1-CBell.pdf[full citation needed] 2. ^ a b c d Rome Foundation. "Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders" (PDF). Rome Foundation. Retrieved March 16, 2014. 3. ^ Prajapati, D. N.; Hogan, W. J. (2003). "Sphincter of Oddi dysfunction and other functional biliary disorders: Evaluation and treatment". Gastroenterology Clinics of North America. 32 (2): 601–18. doi:10.1016/s0889-8553(03)00025-6. PMID 12858608. 4. ^ Cotton PB, Durkalski V, Romagnuolo J, Pauls Q, Fogel E, Tarnasky P, Aliperti G, Freeman M, Kozarek R, Jamidar P, Wilcox M, Serrano J, Brawman-Mintzer O, Elta G, Mauldin P, Thornhill A, Hawes R, Wood-Williams A, Orrell K, Drossman D, Robuck P (2014). "Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial". JAMA. 311: 2101–2109. doi:10.1001/jama.2014.5220. PMC 4428324. PMID 24867013.CS1 maint: multiple names: authors list (link) 5. ^ a b c Corazziari, E (2003). "Sphincter of Oddi dysfunction". Digestive and Liver Disease. 35 Suppl 3: S26–9. doi:10.1016/s1590-8658(03)00090-2. PMID 12974506. 6. ^ Toouli, J (2009). "Sphincter of Oddi: Function, dysfunction, and its management". Journal of Gastroenterology and Hepatology. 24 Suppl 3: S57–62. doi:10.1111/j.1440-1746.2009.06072.x. PMID 19799700. ## External links[edit] Classification D * ICD-10: K83.8 * ICD-9-CM: 576.5 * MeSH: D046628 * DiseasesDB: 12297 * http://www.ddc.musc.edu/public/symptomsDiseases/diseases/pancreas/SOD.html * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Sphincter of Oddi dysfunction	c0878588	26,749	wikipedia	https://en.wikipedia.org/wiki/Sphincter_of_Oddi_dysfunction	2021-01-18T18:53:45	{"mesh": ["D046628"], "umls": ["C0878588", "C4048750"], "icd-9": ["576.5"], "wikidata": ["Q4162400"]}
Premenstrual dysphoric disorder Other namesLate luteal phase dysphoric disorder SpecialtyPsychiatry SymptomsMood swings, depression, irritability, uneasiness, change in appetite, feeling tired, anxiety Causesunknown Risk factorsFamily history Diagnostic methodbased on symptoms Differential diagnosisPremenstrual syndrome, depression, anxiety disorder Treatmentcounselling, lifestyle change, medication Frequency1.8–5.8% of menstruating women Premenstrual dysphoric disorder (PMDD) is a severe and disabling form of premenstrual syndrome affecting 1.8–5.8% of menstruating women.[1] The disorder consists of a variety of affective, behavioral and somatic symptoms that recur monthly during the luteal phase of the menstrual cycle.[2][3] It affects women from their early teens up until menopause, excluding those with hypothalamic amenorrhea or during pregnancy and breastfeeding.[4] Women with PMDD are at higher risk of suicide, with rates of suicidal thoughts 2.8 times higher, history of suicidal planning 4.15 times, and suicide attempts 3.3 times.[5] The emotional effects of premenstrual dysphoric disorder are theorized to be the result of severe gonadal steroid fluctuations, as they cause dysregulation of serotonin uptake and transmission, and potentially calcium regulation, circadian rhythm, BDNF, the HPA-axis and immune function as well.[6] Some studies have suggested that those with PMDD are more at risk of developing postpartum depression after pregnancy, but other evidence has been found to suggest against that notion.[7] PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders in 2013.[1] It has 11 main symptoms, and a woman has to exhibit at least five to qualify for PMDD.[6] Roughly 20% of menstruating women have some symptoms of PMDD, but either have less than five or do not have functional impairment.[8] Treatment is often with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) as well as ovulation suppression using birth control pills and GnRH analogues.[3] SSRIs are the most common treatment, as they tend to improve both the physical and emotional symptoms as well as the general behavior and functionality of the woman.[3] ## Contents * 1 Signs and symptoms * 1.1 Associated conditions * 2 Cause * 2.1 Relationship to pregnancy * 3 Diagnosis * 3.1 DSM-5 * 3.2 ICD 11 * 3.3 Other * 3.4 Differential diagnosis * 4 Treatment * 4.1 Medication * 4.2 Psychotherapy * 4.3 Surgery * 5 Epidemiology * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). Like PMS, premenstrual dysphoric disorder follows a predictable, cyclic pattern. Symptoms begin in the late luteal phase of the menstrual cycle (after ovulation) and end shortly after menstruation begins.[9] On average, the symptoms last six days but can start up to two weeks before menses, meaning symptoms can be felt for up to three weeks out of a cycle. Severe symptoms can begin and worsen until the onset of menstruation, with many not feeling relief until a few days after menstruation ends. The most intense symptoms occurring in the week and days leading up to the first day of menstrual blood flow.[2] The symptoms usually cease shortly after the start of the menstrual period or a few days after it ending.[3][10] The onset of symptoms only during or around the luteal phase is key for diagnosing a woman with PMDD rather than any other mood disorders.[4] The symptoms can be physical or emotional, but mood symptoms must be present for the diagnosis.[9] Women with PMDD may have thoughts of suicide.[11] A mood log in which a woman records mood patterns over time may help direct.[4] The International Society for the Study of Premenstrual Disorders (ISPMD) defines two categories of premenstrual disorders: core PMD and variant PMD.[4] Core PMD has six characteristics, all mainly focusing on the cyclical nature of PMDD and its typical onset pre-menses tracked over the course of more than two menstrual cycles. The four classified Variant PMDs involve more unexpected variables that cause the onset of premenstrual distress; such as, PMD with absent menstruation or premenstrual exacerbation, wherein the symptoms of another preexisting psychological disorder may be heightened as a result of PMDD onset.[4] ### Associated conditions[edit] Bipolar depression, anxiety disorders, and other Axis I disorders are more common in those with PMDD.[12] In women with PMDD, there is a 50-78% lifetime incidence of various psychiatric disorders such as generalized anxiety disorder, seasonal affective disorder, and major depressive disorder.[3] ## Cause[edit] PMDD mood symptoms are only present in menstruating women. Thus, symptoms do not occur during pregnancy and after menopause. Other mood disorders typically persist across all reproductive life events and are independent of a woman's menstrual cycle or lack thereof.[13] The most agreed-upon possibilities for what causes PMDD currently are heightened sensitivity to fluctuating levels of certain hormones (i.e. the reproductive hormones), environmental stress, and genetic predisposition.[4] The sex steroids—estrogen and progesterone—are neuroactive; they have been noted in rat models to be involved in serotonin pathways.[4] Serotonin is involved in mood regulation alongside estrogen, whose receptors are found in the prefrontal cortex and hippocampus—the regions most known for their involvement in regulating one's mood and cognition overall.[2][4] While the timing of symptoms suggests hormonal fluctuations as the cause of PMDD, a demonstrable hormonal imbalance in women with PMDD has not been identified. In fact, levels of reproductive hormones and their metabolites in women with and without PMDD are indistinguishable.[14][15][16] It is instead hypothesized that women with PMDD are more sensitive to normal levels of hormone fluctuations, predominantly estrogen and progesterone, which produces biochemical events in the nervous system that cause the premenstrual symptoms.[16] These symptoms are more predominant in women who have a predisposition to the disorder.[9] It is apparent that the premenstrual disorders are biologically driven and are not only psychological or cultural phenomena. PMDD has been reported by menstruating women worldwide, indicating a biological basis that is not geographically selective.[2] Most psychologists infer that this disorder is caused by both a reaction to hormone flux and also genetic components. There is evidence of heritability of (retrospectively-reported) premenstrual symptoms from several twin and family studies done in the 1990s, with the heritability of PMDD proving to be about 56%.[17][18][19] Disorders of this nature are often caused by a mix of both environmental and biological factors. Environmental stressors have also been found to prospectively increase risk for PMDD symptoms.[20][21] Genetics do not operate in a vacuum: environmental components such as stress, hormonal fluctuation, and epigenetics play a key role in the pathology and onset of the disorder.[22] Some studies have noted evidence of interpersonal trauma (domestic violence, physical or emotional trauma, or substance abuse) or seasonal changes (making PMDD potentially comorbid with Seasonal Affective Disorder) having an impact on PMDD risk.[3][23] But the most common pre-existing disorder found in those diagnosed with PMDD is major depression, wherein they either actually had it or were misdiagnosed when they should have only been diagnosed with PMDD.[23] The last environmental factor is primarily sociological: the sociocultural aspects of being female, performing female gender roles, and stress from engaging in female sexual activity.[1] ### Relationship to pregnancy[edit] Women with PMDD usually see their symptoms disappear while they are pregnant. Premenstrual dysphoric disorder is primarily a mood disorder that is associated with onset of menstruation; pregnancy, menopause, and hysterectomies all cause menstruation to cease, thereby stopping the proposed sex steroid-/serotonin-caused symptoms from occurring.[24][25] Although one might expect a higher rate of postpartum depression among those with PMDD, a large study of women with prospectively-confirmed PMDD did not find a higher prevalence of postpartum depression than in controls.[7][25] If a woman had experienced PPD beforehand, there was found to be a less-than 12% chance of PMDD pathology emerging—hardly any differentiation from the regular population of those who have never experienced postpartum depression.[25] However, PMDD symptoms can get worse following pregnancy, or other associated events such as birth and miscarriage.[11] Menopause launches a woman into an associated mood disorder called climacteric depression.[7] The permanent stopping of the menstrual cycle causes a myriad of physiological and psychological symptoms and issues, all associated with the natural estrogen deficiency post-menopause.[7] ## Diagnosis[edit] Diagnostic criteria for PMDD are provided by a number of expert medical guides. Diagnosis can be supported by having women who are seeking treatment for PMDD use a daily charting method to record their symptoms.[4] Daily charting helps to distinguish when mood disturbances are experienced and allows PMDD to be more easily distinguished from other mood disorders. With PMDD, mood symptoms are present only during the luteal phase, or last two weeks, of the menstrual cycle.[9] While PMDD mood symptoms are of a cyclical nature, other mood disorders are variable or constant over time. Although there is a lack of consensus on the most efficient instrument by which to confirm a PMDD diagnosis, several validated scales for recording premenstrual symptoms include the Calendar of Premenstrual Experiences (COPE), Daily Record of Severity of Problems (DRSP), and Prospective Record of the Severity of Menstruation (PRISM).[26][27] In the context of research, standardized numerical cutoffs are often applied to verify the diagnosis.[26] The difficulty of diagnosing PMDD is one reason that it can be challenging for lawyers to cite the disorder as a defence of crime, in the very rare cases where PMDD is allegedly associated with criminal violence.[28] ### DSM-5[edit] The DSM-5 which established seven criteria (A through G) for the diagnosis of PMDD.[1] There is overlap between the criteria for PMDD in the DSM-5 and the criteria found in the Daily Record of Severity of Problems (DRSP).[26][27] According to the DSM-5, a diagnosis of PMDD requires the presence of at least five of these symptoms with one of the symptoms being numbers 1-4.[1] These symptoms should occur during the week before menses and remit after initiation of menses. In order to meet criteria for the diagnosis, the symptoms should be charted prospectively for two consecutive ovulation cycles in order to confirm a temporal and cyclical nature of the symptoms. The symptoms should also be severe enough to affect normal work, school, social activities, and/or relationships with others.[1] The symptoms of Criteria A-C must have been met for most menstrual cycles that occurred in the preceding year, and have to have affected normal functioning to some degree (Criterion D). Criterion A: During most menstrual cycles throughout the past year, at least 5 of the following 11 symptoms (especially including at least 1 of the first 4 listed) must be present in the final week before the onset of menses, must start to improve within a few days after the onset of menses, and become minimal or absent in the week post-menses:[1] 1. Marked lability (e.g., mood swings) 2. Marked irritability or anger 3. Markedly depressed mood 4. Marked anxiety and tension 5. Decreased interest in usual activities 6. Difficulty in concentration 7. Lethargy and marked lack of energy 8. Marked change in appetite (e.g., overeating or specific food cravings) 9. Hypersomnia or insomnia 10. Feeling overwhelmed or out of control 11. Physical symptoms (e.g., breast tenderness or swelling, joint or muscle pain, a sensation of bloating and weight gain)[1][3] Criterion B: One (or more) of the following symptoms must be present:[1] 1. Marked affective lability (e.g., mood swings, feeling suddenly sad or tearful, or increased sensitivity to rejection) 2. Marked irritability or anger or increased interpersonal conflicts 3. Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts 4. Marked anxiety, tension, and/or feelings of being keyed up or on edge Criterion C: One (or more) of the following symptoms must be present additionally, to reach a total of 5 symptoms when combined with present symptoms from Criterion B above:[1] 1. Decreased interest in usual activities (e.g., work, school, friends, hobbies). 2. Subjective difficulty in concentration. 3. Lethargy, easy fatigability, or marked lack of energy. 4. Marked change in appetite; overeating; or specific food cravings. 5. Hypersomnia or insomnia. 6. A sense of being overwhelmed or out of control. 7. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of "bloating," or weight gain. Criterion D: The symptoms observed in Criteria A-C are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).[1] * Clinically significant distress is not defined explicitly by the DSM-IV, where it has been critiqued by multiple scholars as being too vague, and potentially detrimental for those who have symptoms of depression, anxiety, or other mood disorders because they do not meet the clinical significance requirement.[29][30] Criterion E: The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder (Dysthymia), or a personality disorder—although it may co-occur with any of these disorders.[1] Criterion F: Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. The diagnosis may be made provisionally prior to this confirmation.[1] Criterion G The symptoms are not attributable to the physiological effects of a substance (e.g., drug abuse, a medication, other treatments) or another medical condition (e.g., hyperthyroidism).[1] ### ICD 11[edit] Diagnostic criteria for PMDD are also provided by the 2016 World Health Organization's International Classification of Diseases (ICD-11-CM):[31][32] > GA34.41 Premenstrual dysphoric disorder > > Description > > During a majority of menstrual cycles within the past year, a pattern of mood symptoms (depressed mood, irritability), somatic symptoms (lethargy, joint pain, overeating), or cognitive symptoms (concentration difficulties, forgetfulness) that begin several days before the onset of menses, start to improve within a few days after the onset of menses, and then become minimal or absent within approximately 1 week following the onset of menses. The temporal relationship of the symptoms and luteal and menstrual phases of the cycle may be confirmed by a prospective symptom diary. The symptoms are severe enough to cause significant distress or significant impairment in personal, family, social, educational, occupational or other important areas of functioning and do not represent the exacerbation of a mental disorder. Early drafts of the ICD did not recognize PMDD as a separate condition.[33] In the World Health Organisation's classification system, the International Classification of Diseases (ICD-11), PMDD is listed as a "disease of the genitourinary system".[34] ### Other[edit] Other organizations that have published diagnostic criteria for PMDD include the Royal College of Obstetricians and Gynecologists and the International Society for the Study of Premenstrual Disorders (ISPMD).[35][31] The ISPMD was a consensus group established by an international multidisciplinary group of experts. The group's diagnostic criteria for PMDD focuses on the cyclic nature of the symptoms occurring during the luteal phase of the menstrual cycle, as well as the symptoms being absent after menstruation and before ovulation and causing significant impairment. The ISPMD diagnostic criteria for PMDD do not specify symptom characteristics or number of symptoms.[35] In 2003 the Committee for Proprietary Medicinal Products required the manufacturer of fluoxetine to remove PMDD from the list of indications in Europe.[36] In Australia, PMDD is recognized by the Therapeutic Goods Administration. However, antidepressants are not reimbursed for PMDD under the Pharmaceutical Benefits Scheme.[37] ### Differential diagnosis[edit] In addition to Axis I disorders, several other medical illnesses such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and migraine disorder may present symptoms similar or identical to those of PMDD. The symptoms which coincide with mood disorders, i.e. major depressive disorder or bipolar disorder, may worsen during the premenstrual period and thus may mimic PMDD. This phenomenon is known as premenstrual exacerbation (PME) and refers to the worsening of mood disorder symptoms during the premenstrual phase. An estimated 40% of those who seek treatment for PMDD are found to not have PMDD, but rather a PME of an underlying mood disorder.[38] ## Treatment[edit] ### Medication[edit] Several medications have received empirical support for the treatment of PMDD. Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication.[9][39][40] The U.S. Food and Drug Administration (FDA) has approved four SSRIs for the treatment of PMDD: Fluoxetine (available as generic or as Prozac or Sarafem), sertraline (Zoloft), paroxetine (Paxil), and escitalopram oxalate (Lexapro).[41] Unlike treatments for depressive disorders, SSRIs do not need to be taken daily but instead can be taken only in the luteal phase or during PMDD symptoms.[3] This is because those who respond to SSRIs usually experience symptoms relief within 1–2 days.[42] Studies in rats suggest this rapid response to SSRIs is due to the elevation of the neuroactive progesterone metabolite allopregnanolone in the brain, rather than serotonin.[43][44] Luteal phase dosing can be started 14 days before menses and subsequently discontinued after start of menstrual flow.[41] Women taking SSRIs to ease PMDD generally report >50% alleviation in symptoms, which was significant improvement compared to placebo.[42] Although less studied, SNRIs have also shown benefits for those with PMDD. In a randomized, controlled clinical trial of women with PMDD, 60% of the subjects taking venlafaxine (Effexor) improved, versus 35% on placebo. Improvement was noticed during the first treatment cycle with 80% symptom reduction.[45] Another FDA approved treatment for PMDD is the oral contraceptive with ethinylestradiol and drospirenone (a novel progestin) taken on a 24-4 schedule (24 active pills, 4 inactive pills).[41] It has been shown that hormonal birth control containing drospirenone and low levels of estrogen helps relieve severe PMDD symptoms, for at least the first three months that it is used.[46] The idea behind using oral contraceptives is to suppress ovulation, therefore suppressing sex hormone fluctuations. Another treatment, typically used when other options have failed, is injection of a gonadotropin-releasing hormone agonist.[47] These drugs create a temporary, drug-induced menopause-like condition. Addback of estradiol is recommended to prevent bone loss long-term; this generally necessitates the concurrent addback of progesterone to prevent estradiol-induced endometrial hyperplasia. Two landmark studies have demonstrated that the addback of estradiol or progesterone on top of GnRH agonists can cause a resurgence of PMDD symptoms but that this resurgence of symptoms remits after one month of stable addback.[48][49][50] ### Psychotherapy[edit] Cognitive behavioral therapy (CBT) has been shown to be effective for reducing premenstrual symptoms in women with (retrospectively-reported) PMS.[51] CBT is an evidence-based approach for treating depression and focuses on the link between mood, thoughts, and actions to help people address current issues and symptoms. When CBT was compared to SSRI alone or in combination with SSRI, groups receiving CBT had significant improvement of PMS symptoms.[51] Through the practice of CBT, people are better able to recognize and modify recurrent issues as well as thought and behavior patterns that interfere with functioning well or that make depressive symptoms worse. However, a recent meta-analysis suggests that existing psychotherapies may be primarily useful for reducing impairment (rather than symptom severity) in PMDD.[51] ### Surgery[edit] When drug-based treatments are ineffective or produce significant side effects, then removing the ovaries through oophorectomy can produce an immediate and permanent cure.[24] Typically, the uterus is removed during the same surgery, and the woman is prescribed a low-dose estrogen patch to reduce the symptoms produced by surgically induced menopause.[24] ## Epidemiology[edit] A majority of menstruating women have feeling of premenstrual symptoms to some degree, with 20-30% feeling enough symptoms to qualify for diagnosis of PMS and 3-8% of that group qualifying for the diagnosis of PMDD.[2][3] With only a small fraction feeling such intense distress linked to the onset of menstruation, any fear of social pathologizing of normal emotional and physical symptoms as a result of menstruation is unnecessary; PMDD is distinct, and having it included in the DSM-5 works to affirm that.[23] ## History[edit] In the 18th century, there were early accounts of weeping and other symptoms recurring almost every month,[52] and in 1822 Prichard gave this description: “Many women … display a degree of excitement and irritation … at the period of menstruation; these are chiefly females of very irritable habits. In such instances, … an unusual vehemence of feeling and expression is observed … or there is torpor and dejection of mind with a despondent disposition”. [53] In 1827 a German mother was acquitted of infanticide on the grounds of menstrual mood disorder.[54] Premenstrual tension was also described in the French literature of the early 19th century.[55] Nearly one hundred years later, there were American descriptions of a cyclic personality change appearing 10-14 days before, and ending dramatically at the menses.[56] The diagnostic category was discussed in the DSM-IIIR (1987), in which the proposed condition was named "Late Luteal Phase Dysphoric Disorder" and was included in the appendix as a proposed diagnostic category needing further study.[57] Preparations for the DSM-IV led to debate about whether to keep the category at all, only keep it in the appendix, or remove it entirely; the reviewers determined that the condition was still too poorly studied and defined, so it was kept in the appendix but elaborated with diagnostic criteria to aid further study.[25][58] As preparations were underway in 1998 for the DSM-IV-TR, the conversation changed, as Eli Lilly and Company paid for a large clinical trial of fluoxetine as a potential treatment for the condition that was then conducted by Canadian academics and published in the New England Journal of Medicine in 1995.[59] Other studies have been conducted as well, wherein all found that approximately 60% of women with PMDD in the trials improved with the drug; representatives from Lilly & Co. and the FDA participated in the discussion.[25][58] Various strong stances were taken in said discussion. Sally Severino, a psychiatrist, argued that because symptoms were more prevalent in the United States, PMDD was a culture-bound syndrome and not a biological condition; she also claimed it unnecessarily pathologized the hormonal changes of the menstrual cycle.[25] Jean Endicott, another psychiatrist and chair of the committee, has argued that it was a valid condition from which women suffer and should be diagnosed and treated, and has claimed that if the symptoms were felt by males, far more effort and research would have been done by that moment. In the end the committee kept PMDD in the appendix.[25] The decision has been criticized as being driven by Lilly's financial interests, and possibly by financial interests of members of the committee who had received funding from Lilly.[25] Paula Caplan, a psychologist who had served on the committee for the DSM-IV, noted at the time of the DSM-IV-TR decision that there was evidence that calcium supplements could treat PMDD but the committee gave it no attention. She had also claimed that the diagnostic category is harmful to women with PMDD, leading them to believe they are mentally ill, and potentially leading others to mistrust them in situations as important as job promotions or child custody cases.[25] She has called PMDD a fake disorder.[60] Nada Stotland has expressed concern that women with PMDD may actually have a more serious condition like major depressive disorder or may be facing difficult circumstances—such domestic abuse—and therefore may have their true issues remain undiagnosed and mismanaged if their gynecologist diagnoses them with PMDD and gives them drugs to treat it.[25] The validity of PMDD was once more heavily debated when it came time to create the DSM-5 in 2008.[61][62] In the end it was moved out of the appendix and into the main text as a formal category. A review in the Journal of Clinical Psychiatry published in 2014 examined the arguments against inclusion, which it summarized as: 1. the PMDD label will harm women economically, politically, legally, and domestically; 2. there is no equivalent hormone-based medical label for males; 3. the research on PMDD is faulty; 4. PMDD is a culture-bound condition; 5. PMDD is due to situational, rather than biological, factors; and 6. PMDD was fabricated by pharmaceutical companies for financial gain.[63] Each argument was addressed and researchers found: 1. No evidence of harm; 2. no equivalent hormone-driven disorder has been discovered in men despite research seeking it; 3. the research base has matured and many more reputable studies have been performed; 4. several cases of PMDD have been reported or identified; 5. a small minority of women do have the condition; and 6. while there has been financial conflict of interest, it has not made the available research unusable.[2][63] It concluded that women have historically been under-treated and told that they were making their symptoms up, and that the formal diagnostic criteria would spur more funding, research, diagnosis and treatment for women with PMDD.[63] ## References[edit] 1. ^ a b c d e f g h i j k l m n Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA: American Psychiatric Association. 2013. p. 625.4. Code: 625.4 (N94.3) 2. ^ a b c d e f Yonkers, Kimberly Ann; O'Brien, Shaughn; Eriksson, Elias (April 2008). "Premenstrual syndrome". 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S2CID 21181483. 25. ^ a b c d e f g h i j Kepple, AL; Lee, EE; Haq, N; Rubinow, DR; Schmidt, PJ (April 2016). "History of postpartum depression in a clinic-based sample of women with premenstrual dysphoric disorder". Journal of Clinical Psychiatry. 77 (4): 415–420. doi:10.4088/JCP.15m09779. PMC 6328311. PMID 27035701. 26. ^ a b c Eisenlohr-Moul, Tory A; Girdler, Susan S; Schmalenberger, Katja M; Dawson, Danyelle N; Surana, Pallavi; Johnson, Jacqueline L; Rubinow, David R (August 2016). "Toward the Reliable Diagnosis of DSM-5 Premenstrual Dysphoric Disorder: The Carolina Premenstrual Assessment Scoring System (C-PASS)". The American Journal of Psychiatry. 174 (1): 51–59. doi:10.1176/appi.ajp.2016.15121510. PMC 5205545. PMID 27523500. 27. ^ a b Endicott, J; Nee, J; Harrison, W (2006). "Daily Record of Severity of Problems (DRSP): reliability and validity". Archives of Women's Mental Health. 9 (1): 41–49. doi:10.1007/s00737-005-0103-y. PMID 16172836. S2CID 25479566. 28. ^ Ro, Christine. "The overlooked condition that can trigger extreme behaviour". www.bbc.com. Retrieved 2020-01-04. 29. ^ Spitzer, RL; Wakefield, JC (December 1999). "DSM-IV diagnostic criterion for clinical significance: does it help solve the false positives problem?". The American Journal of Psychiatry. 156 (12): 1856–64. doi:10.1176/ajp.156.12.1856 (inactive 2020-12-22). PMID 10588397.CS1 maint: DOI inactive as of December 2020 (link) 30. ^ Grenier, Sébastien; Préville, Michel; Boyer, Richard; O'Connor, Kieron; Béland, Sarah-Gabrielle; Potvin, Olivier; Hudon, Carol; Brassard, Joëlle (April 2011). "The Impact of DSM-IV Symptom and Clinical Significance Criteria on the Prevalence Estimates of Subthreshold and Threshold Anxiety in the Older Adult Population". The American Journal of Geriatric Psychiatry. 19 (4): 316–326. doi:10.1097/JGP.0b013e3181ff416c. PMC 3682986. PMID 21427640. 31. ^ a b "Premenstrual Syndrome, Management (Green-top Guideline No. 48)". Royal College of Obstetricians and Gynaecologists. December 2016. 32. ^ ICD-11: GA34.41 Premenstrual dysphoric disorder 33. ^ Worcester, Nancy; Whatley, Marianne N (2000). Women's Health: Readings on Social, Economic, and Political Issues. Sage Publications. p. 613. 34. ^ "ICD-11 - Mortality and Morbidity Statistics". icd.who.int. Retrieved 2019-08-26. 35. ^ a b O'Brien, PM; Bäckström, T; Brown, C; Dennerstein, L; Endicott, J; Epperson, CN; Eriksson, E; Freeman, E; Halbreich, U (February 2011). "Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders: the ISPMD Montreal consensus". Archives of Women's Mental Health. 14 (1): 13–21. doi:10.1007/s00737-010-0201-3. PMC 4134928. PMID 21225438. 36. ^ Moynihan, R (February 2004). "Controversial disease dropped from Prozac product information". BMJ. 328 (7436): 365. doi:10.1136/bmj.328.7436.365. PMC 341379. PMID 14962861. 37. ^ "Sertraline (Zoloft), fluoxetine (Lovan, Prozac) for premenstrual dysphoric disorder (PMDD)". National Prescribing Service Limited. 38. ^ "PMDD/PMS". MGH Center for Women's Mental Health. January 2019. 39. ^ Agyemang, Amma A (2018). Kreutzer, Jeffrey S; DeLuca, John; Caplan, Bruce (eds.). Encyclopedia of Clinical Neuropsychology. Switzerland: Springer, Cham. doi:10.1007/978-3-319-57111-9. ISBN 978-3-319-57111-9. 40. ^ Eriksson, E; Endicott, J; Andersch, B; Angst, J; Demyttenaere, K; Facchinetti, F; Lancznik, M; Montgomery, S; Muscettola, G (2002). "New perspectives on the treatment of premenstrual syndrome and premenstrual dysphoric disorder". Archives of Women's Mental Health. 4 (4): 111–119. doi:10.1007/s007370200009. S2CID 10427915. 41. ^ a b c Ward S (2016). Maternal-Child Nursing Care. Philadelphia, PA, USA: F.A. Davis Company. p. 32. ISBN 978-0-8036-3665-1. 42. ^ a b Rapkin AJ, Winer SA (February 2008). "The pharmacologic management of premenstrual dysphoric disorder". Expert Opinion on Pharmacotherapy. 9 (3): 429–45. doi:10.1517/14656566.9.3.429. PMID 18220493. S2CID 72888643. 43. ^ Fry JP, Li KY, Devall AJ, Cockcroft S, Honour JW, Lovick TA (December 2014). "Fluoxetine elevates allopregnanolone in female rat brain but inhibits a steroid microsomal dehydrogenase rather than activating an aldo-keto reductase". British Journal of Pharmacology. 171 (24): 5870–80. doi:10.1111/bph.12891. PMC 4290723. PMID 25161074. 44. ^ Devall AJ, Santos JM, Fry JP, Honour JW, Brandão ML, Lovick TA (January 2015). "Elevation of brain allopregnanolone rather than 5-HT release by short term, low dose fluoxetine treatment prevents the estrous cycle-linked increase in stress sensitivity in female rats". European Neuropsychopharmacology. 25 (1): 113–23. doi:10.1016/j.euroneuro.2014.11.017. PMID 25498416. S2CID 21493779. 45. ^ Freeman EW, Rickels K, Yonkers KA, Kunz NR, McPherson M, Upton GV (November 2001). "Venlafaxine in the treatment of premenstrual dysphoric disorder". Obstetrics and Gynecology. 98 (5 Pt 1): 737–44. doi:10.1016/s0029-7844(01)01530-7. PMID 11704162. S2CID 42597741. 46. ^ Lopez LM, Kaptein AA, Helmerhorst FM (February 2012). "Oral contraceptives containing drospirenone for premenstrual syndrome". The Cochrane Database of Systematic Reviews. 2 (2): CD006586. doi:10.1002/14651858.CD006586.pub4. PMID 22336820. 47. ^ Yonkers KA, Simoni MK (January 2018). "Premenstrual disorders". American Journal of Obstetrics and Gynecology. 218 (1): 68–74. doi:10.1016/j.ajog.2017.05.045. PMID 28571724. S2CID 21125434. 48. ^ Yonkers, KA; Simoni, MK (January 2018). "Premenstrual disorders". American Journal of Obstetrics and Gynecology. 218 (1): 68–74. doi:10.1016/j.ajog.2017.05.045. PMID 28571724. S2CID 21125434. 49. ^ Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR (January 1998). "Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome". The New England Journal of Medicine. 338 (4): 209–16. doi:10.1056/NEJM199801223380401. PMID 9435325. 50. ^ Schmidt PJ, Martinez PE, Nieman LK, Koziol DE, Thompson KD, Schenkel L, Wakim PG, Rubinow DR (October 2017). "Premenstrual Dysphoric Disorder Symptoms Following Ovarian Suppression: Triggered by Change in Ovarian Steroid Levels But Not Continuous Stable Levels". The American Journal of Psychiatry. 174 (10): 980–989. doi:10.1176/appi.ajp.2017.16101113. PMC 5624833. PMID 28427285. 51. ^ a b c Kleinstäuber M, Witthöft M, Hiller W (September 2012). "Cognitive-behavioral and pharmacological interventions for premenstrual syndrome or premenstrual dysphoric disorder: a meta-analysis". Journal of Clinical Psychology in Medical Settings. 19 (3): 308–19. doi:10.1007/s10880-012-9299-y. PMID 22426857. 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Archived from the original on 2018-06-17. 59. ^ Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. American Psychiatric Association. 2000. doi:10.1176/appi.books.9780890420249.dsm-iv-tr (inactive 2020-12-22).CS1 maint: DOI inactive as of December 2020 (link) 60. ^ Steiner, M; Steinberg, S; Stewart, D; Carter, D; Berger, C; Reid, R; Grover, D; Streiner, D (June 1995). "Fluoxetine in the treatment of premenstrual dysphoria. Canadian Fluoxetine/Premenstrual Dysphoria Collaborative Study Group". New England Journal of Medicine. 332 (23): 1529–34. doi:10.1056/NEJM199506083322301. PMID 7739706. 61. ^ Caplan, Paula J (2004). "The Debate About PMDD and Sarafem". Women & Therapy. 27 (3–4): 55–67. doi:10.1300/J015v27n03_05. S2CID 141754567. 62. ^ Chen, Ingfei (18 December 2008). "A Clash of Science and Politics Over PMS". The New York Times. Archived from the original on 2011-01-23. Retrieved 27 April 2019. 63. ^ a b c Hartlage, S. Ann; Breaux, Cynthia A; Yonkers, Kimberly A (2014). "Addressing Concerns About the Inclusion of Premenstrual Dysphoric Disorder in DSM-5". The Journal of Clinical Psychiatry. 75 (1): 70–76. doi:10.4088/JCP.13cs08368. PMID 24345853. ## External links[edit] * Premenstrual dysphoric disorder at Curlie * Bhatia SC, Bhatia SK (October 2002). "Diagnosis and treatment of premenstrual dysphoric disorder". American Family Physician. 66 (7): 1239–48. PMID 12387436. * International Association for Premenstrual Disorders (IAPMD) Classification D * ICD-10: F38.8 * ICD-9-CM: 311 * MeSH: D065446 External resources * MedlinePlus: 007193 * eMedicine: article/293257 * v * t * e Menstrual cycle Events and phases * Menstruation * Follicular phase * Ovulation * Luteal phase Life stages * Menarche * Menopause Tracking Signs * Basal body temperature * Cervical mucus * Mittelschmerz Systems * Fertility awareness * Calendar-based methods * Billings Ovulation Method * Creighton Model Suppression * Extended cycle combined hormonal contraceptive * Lactational amenorrhea Disorders * Amenorrhea * Anovulation * Dysmenorrhea * Hypomenorrhea * Irregular menstruation * Menometrorrhagia * Menorrhagia * Metrorrhagia * Oligomenorrhea Related events * Folliculogenesis * Menstrual synchrony * Premenstrual syndrome / Premenstrual dysphoric disorder / Menstrual psychosis * Sexual activity In culture and religion * Chhaupadi * Feminine hygiene * Sanitary napkin * Tampon * Menstrual cup * Menstrual Hygiene Day * Menstrual taboo * Menstruation hut * Niddah [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Premenstrual dysphoric disorder	c0520676	26,750	wikipedia	https://en.wikipedia.org/wiki/Premenstrual_dysphoric_disorder	2021-01-18T19:09:22	{"mesh": ["D065446"], "umls": ["C0520676"], "icd-9": ["311"], "wikidata": ["Q2728811"]}
Robinow syndrome is a rare disorder that affects the development of many parts of the body, particularly the skeleton. The types of Robinow syndrome can be distinguished by the severity of their signs and symptoms and by their pattern of inheritance: autosomal recessive or autosomal dominant. Autosomal recessive Robinow syndrome is characterized by skeletal abnormalities including shortening of the long bones in the arms and legs, particularly the forearms; abnormally short fingers and toes (brachydactyly); wedge-shaped spinal bones (hemivertebrae) leading to an abnormal curvature of the spine (kyphoscoliosis); fused or missing ribs; and short stature. Affected individuals also have distinctive facial features, such as a broad forehead, prominent and widely spaced eyes, a short nose with an upturned tip, a wide nasal bridge, and a broad and triangle-shaped mouth. Together, these facial features are sometimes described as "fetal facies" because they resemble the facial structure of a developing fetus. Other common features of autosomal recessive Robinow syndrome include underdeveloped genitalia in both males and females, and dental problems such as crowded teeth and overgrowth of the gums. Kidney and heart defects are also possible. Development is delayed in 10 to 15 percent of people with this condition, although intelligence is usually normal. Autosomal dominant Robinow syndrome has signs and symptoms that are similar to, but tend to be milder than, those of the autosomal recessive form. Abnormalities of the spine and ribs are rarely seen in the autosomal dominant form, and short stature is less pronounced. A variant form of autosomal dominant Robinow syndrome includes increased bone mineral density (osteosclerosis) affecting the bones of the skull in addition to the signs and symptoms listed above. This variant is called the osteosclerotic form of Robinow syndrome. ## Frequency Both the autosomal recessive and autosomal dominant forms of Robinow syndrome are rare. Fewer than 200 people with autosomal recessive Robinow syndrome have been described in the medical literature. This form of the condition has been identified in families from several countries, including Turkey, Oman, Pakistan, and Brazil. Autosomal dominant Robinow syndrome has been diagnosed in fewer than 50 families; about 10 of these families have had the osteosclerotic form. ## Causes Autosomal recessive Robinow syndrome results from mutations in the ROR2 gene. This gene provides instructions for making a protein whose function is not well understood, although it is involved in chemical signaling pathways that are essential for normal development before birth. In particular, the ROR2 protein appears to play a critical role in the formation of the skeleton, heart, and genitals. Mutations in the ROR2 gene prevent cells from making any functional ROR2 protein, which disrupts development starting before birth and leads to the characteristic features of Robinow syndrome. Autosomal dominant Robinow syndrome can be caused by mutations in several genes, including FZD2, WNT5A, DVL1, and DVL3. The osteosclerotic form of the condition results from DVL1 gene mutations. The proteins produced from the genes associated with autosomal dominant Robinow syndrome appear to be part of the same chemical signaling pathways as the ROR2 protein. Mutations in any of these genes alter the production or function of their respective proteins, which impairs chemical signaling that is important for early development. Some people with the characteristic signs and symptoms of Robinow syndrome do not have an identified mutation in any of the known genes. In these cases, the cause of the condition is unknown. ### Learn more about the genes associated with Robinow syndrome * DVL1 * DVL3 * FZD2 * ROR2 * WNT5A Additional Information from NCBI Gene: * GPC4 * NXN * RAC3 ## Inheritance Pattern As discussed above, Robinow syndrome can have either an autosomal recessive or an autosomal dominant pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. In some cases of Robinow syndrome, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Robinow syndrome	c0265205	26,751	medlineplus	https://medlineplus.gov/genetics/condition/robinow-syndrome/	2021-01-27T08:24:51	{"gard": ["312"], "mesh": ["C562492"], "omim": ["180700", "616331", "616894", "268310"], "synonyms": []}
## Description Sebaceous gland hyperplasia presents as one or more elevated, soft, yellow papules with central umbilication on the face, particularly the forehead. Lesions may spread to the neck and upper part of the thorax. Sebaceous gland hyperplasia occurs frequently in older individuals, particularly in men past middle age (Nomland, 1930). A premature form has its appearance during puberty or just afterwards, male predominance, and excessive sebaceous secretion. Most cases are sporadic (summary by Boonchai and Leenutaphong, 1997). Clinical Features Dupre et al. (1980) described 2 brothers with premature sebaceous gland hyperplasia of the face with onset during puberty. The disorder showed slow progression and a confluence of lesions resulted in the formation of large plaques on the face with excessive sebaceous secretion. De Villez and Roberts (1982) and Bhawan and Calhoun (1983) described sporadic cases of presenile sebaceous gland hyperplasia. Boonchai and Leenutaphong (1997) described a Thai family with premature sebaceous gland hyperplasia similar to that reported by Dupre et al. (1980) in 5 consecutive generations. There were 6 instances of male-to-male transmission. Weisshaar et al. (1999) described a family with familial nevoid sebaceous gland hyperplasia in 3 consecutive generations. All the patients were successfully treated with oral isotretinoin. Inheritance Male-to-male transmission of presenile sebaceous gland hyperplasia in a Thai family by Boonchai and Leenutaphong (1997) suggested autosomal dominant inheritance. The pedigree reported by Weisshaar et al. (1999) suggested autosomal dominant inheritance with incomplete penetrance. Inheritance \- Autosomal dominant Misc \- Onset about puberty \- Male predominance \- Most cases sporadic Skin \- Sebaceous gland hyperplasia \- Soft, yellow, umbilicated facial papules ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SEBACEOUS GLAND HYPERPLASIA, FAMILIAL PRESENILE	c1866428	26,752	omim	https://www.omim.org/entry/601700	2019-09-22T16:14:24	{"mesh": ["C537530"], "omim": ["601700"]}
Distressing thought or behavior pattern Mental disorder Other namesPsychiatric disorder, psychological disorder, mental illness, mental disease, mental breakdown, nervous breakdown, mental health conditions[1] SpecialtyPsychiatry, clinical psychology SymptomsAgitation, anxiety, depression, mania, paranoia, psychosis ComplicationsCognitive impairment, social problems, suicide TypesAnxiety disorders, eating disorders, mood disorders, neurodevelopmental disorders, personality disorders, psychotic disorders, substance use disorders CausesGenetic and environmental factors TreatmentPsychotherapy, medications MedicationAntidepressants, antipsychotics, anxiolytics, mood stabilizers, stimulants Frequency18% per year (United States)[2] A mental disorder, also called a mental illness[3] or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning.[4] Such features may be persistent, relapsing and remitting, or occur as a single episode. Many disorders have been described, with signs and symptoms that vary widely between specific disorders.[5][6] Such disorders may be diagnosed by a mental health professional. The causes of mental disorders are often unclear. Theories may incorporate findings from a range of fields. Mental disorders are usually defined by a combination of how a person behaves, feels, perceives, or thinks.[7] This may be associated with particular regions or functions of the brain, often in a social context. A mental disorder is one aspect of mental health. Cultural and religious beliefs, as well as social norms, should be taken into account when making a diagnosis.[8] Services are based in psychiatric hospitals or in the community, and assessments are carried out by mental health professionals such as psychiatrists, psychologists, psychiatric nurses and clinical social workers, using various methods such as psychometric tests but often relying on observation and questioning. Treatments are provided by various mental health professionals. Psychotherapy and psychiatric medication are two major treatment options. Other treatments include lifestyle changes, social interventions, peer support, and self-help. In a minority of cases, there might be involuntary detention or treatment. Prevention programs have been shown to reduce depression.[7][9] In 2019, common mental disorders around the globe include depression, which affects about 264 million, bipolar disorder, which affects about 45 million, dementia, which affects about 50 million, and schizophrenia and other psychoses, which affects about 20 million people.[10] Developmental disorders include intellectual disability and pervasive developmental disorders which usually arise in infancy or childhood.[10] Stigma and discrimination can add to the suffering and disability associated with mental disorders, leading to various social movements attempting to increase understanding and challenge social exclusion. ## Contents * 1 Definition * 1.1 Nervous illness * 2 Classifications * 2.1 Dimensional models * 2.2 Disorders * 2.2.1 Anxiety disorder * 2.2.2 Mood disorder * 2.2.3 Psychotic disorder * 2.2.4 Personality disorder * 2.2.5 Eating disorder * 2.2.6 Sleep disorder * 2.2.7 Sexuality related * 2.2.8 Other * 3 Signs and symptoms * 3.1 Course * 3.2 Disability * 4 Risk factors * 4.1 Genetics * 4.2 Environment * 4.3 Drug use * 4.4 Chronic disease * 4.5 Personality traits * 4.6 Causal models * 5 Diagnosis * 5.1 Criticism * 6 Prevention * 7 Management * 7.1 Lifestyle * 7.2 Therapy * 7.3 Medication * 7.4 Other * 8 Epidemiology * 9 History * 9.1 Ancient civilizations * 9.2 Europe * 9.2.1 Middle Ages * 9.2.2 Eighteenth century * 9.2.3 Nineteenth century * 9.2.4 Twentieth century * 9.3 Europe and the United States * 10 Society and culture * 10.1 Religion * 10.2 Movements * 10.3 Cultural bias * 10.4 Laws and policies * 10.5 Perception and discrimination * 10.5.1 Stigma * 10.5.2 Media and general public * 10.5.3 Violence * 11 Mental health * 12 Other animals * 13 See also * 14 Notes * 15 Further reading * 16 External links ## Definition "Nervous breakdown" redirects here. For other uses, see Nervous breakdown (disambiguation). The definition and classification of mental disorders are key issues for researchers as well as service providers and those who may be diagnosed. For a mental state to classify as a disorder, it generally needs to cause dysfunction.[11] Most international clinical documents use the term mental "disorder", while "illness" is also common. It has been noted that using the term "mental" (i.e., of the mind) is not necessarily meant to imply separateness from brain or body. According to DSM-IV, a mental disorder is a psychological syndrome or pattern which is associated with distress (e.g. via a painful symptom), disability (impairment in one or more important areas of functioning), increased risk of death, or causes a significant loss of autonomy; however it excludes normal responses such as grief from loss of a loved one, and also excludes deviant behavior for political, religious, or societal reasons not arising from a dysfunction in the individual.[12][13] DSM-IV precedes the definition with caveats, stating that, as in the case with many medical terms, mental disorder "lacks a consistent operational definition that covers all situations", noting that different levels of abstraction can be used for medical definitions, including pathology, symptomology, deviance from a normal range, or etiology, and that the same is true for mental disorders, so that sometimes one type of definition is appropriate, and sometimes another, depending on the situation.[14] In 2013, the American Psychiatric Association (APA) redefined mental disorders in the DSM-5 as "a syndrome characterized by clinically significant disturbance in an individual's cognition, emotion regulation, or behavior that reflects a dysfunction in the psychological, biological, or developmental processes underlying mental functioning."[15] The final draft of ICD-11 contains a very similar definition.[16] The terms "mental breakdown" or "nervous breakdown" may be used by the general population to mean a mental disorder.[17] The terms "nervous breakdown" and "mental breakdown" have not been formally defined through a medical diagnostic system such as the DSM-5 or ICD-10, and are nearly absent from scientific literature regarding mental illness.[18][19] Although "nervous breakdown" is not rigorously defined, surveys of laypersons suggest that the term refers to a specific acute time-limited reactive disorder, involving symptoms such as anxiety or depression, usually precipitated by external stressors.[18] Many health experts today refer to a nervous breakdown as a "mental-health crisis".[20] ### Nervous illness Additionally to the concept of mental disorder, some people have argued for a return to the old-fashioned concept of nervous illness. In How Everyone Became Depressed: The Rise and Fall of the Nervous Breakdown (2013), Edward Shorter, a professor of psychiatry and the history of medicine, says: > About half of them are depressed. Or at least that is the diagnosis that they got when they were put on antidepressants. ... They go to work but they are unhappy and uncomfortable; they are somewhat anxious; they are tired; they have various physical pains—and they tend to obsess about the whole business. There is a term for what they have, and it is a good old-fashioned term that has gone out of use. They have nerves or a nervous illness. It is an illness not just of mind or brain, but a disorder of the entire body. ... We have a package here of five symptoms—mild depression, some anxiety, fatigue, somatic pains, and obsessive thinking. ... We have had nervous illness for centuries. When you are too nervous to function ... it is a nervous breakdown. But that term has vanished from medicine, although not from the way we speak. ... The nervous patients of yesteryear are the depressives of today. That is the bad news. ... There is a deeper illness that drives depression and the symptoms of mood. We can call this deeper illness something else, or invent a neologism, but we need to get the discussion off depression and onto this deeper disorder in the brain and body. That is the point. > > — Edward Shorter, Faculty of Medicine, University of Toronto.[21] > "In eliminating the nervous breakdown, psychiatry has come close to having its own nervous breakdown." > > — David Healy, MD, FRCPsych, Professor of Psychiatry, University of Cardiff, Wales.[22] > "Nerves stand at the core of common mental illness, no matter how much we try to forget them." > > — Peter J. Tyrer, FMedSci, Professor of Community Psychiatry, Imperial College, London[23] > "Nervous breakdown" is a pseudo-medical term to describe a wealth of stress-related feelings and they are often made worse by the belief that there is a real phenomenon called "nervous breakdown". > > — Richard E. Vatz, co-author of explication of views of Thomas Szasz in "Thomas Szasz: Primary Values and Major Contentions" ## Classifications Main article: Classification of mental disorders There are currently two widely established systems that classify mental disorders: * ICD-10 Chapter V: Mental and behavioural disorders, since 1949 part of the International Classification of Diseases produced by the WHO, * the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) produced by the American Psychiatric Association (APA) since 1952. Both of these list categories of disorder and provide standardized criteria for diagnosis. They have deliberately converged their codes in recent revisions so that the manuals are often broadly comparable, although significant differences remain. Other classification schemes may be used in non-western cultures, for example the Chinese Classification of Mental Disorders, and other manuals may be used by those of alternative theoretical persuasions, for example the Psychodynamic Diagnostic Manual. In general, mental disorders are classified separately from neurological disorders, learning disabilities or intellectual disability. Unlike the DSM and ICD, some approaches are not based on identifying distinct categories of disorder using dichotomous symptom profiles intended to separate the abnormal from the normal. There is significant scientific debate about the relative merits of categorical versus such non-categorical (or hybrid) schemes, also known as continuum or dimensional models. A spectrum approach may incorporate elements of both. In the scientific and academic literature on the definition or classification of mental disorder, one extreme argues that it is entirely a matter of value judgements (including of what is normal) while another proposes that it is or could be entirely objective and scientific (including by reference to statistical norms).[24] Common hybrid views argue that the concept of mental disorder is objective even if only a "fuzzy prototype" that can never be precisely defined, or conversely that the concept always involves a mixture of scientific facts and subjective value judgments.[25] Although the diagnostic categories are referred to as 'disorders', they are presented as medical diseases, but are not validated in the same way as most medical diagnoses. Some neurologists argue that classification will only be reliable and valid when based on neurobiological features rather than clinical interview, while others suggest that the differing ideological and practical perspectives need to be better integrated.[26][27] The DSM and ICD approach remains under attack both because of the implied causality model[28] and because some researchers believe it better to aim at underlying brain differences which can precede symptoms by many years.[29] ### Dimensional models The high degree of comorbidity between disorders in categorical models such as the DSM and ICD have led some to propose dimensional models. Studying comorbidity between disorders have demonstrated two latent (unobserved) factors or dimensions in the structure of mental disorders that are thought to possibly reflect etiological processes. These two dimensions reflect a distinction between internalizing disorders, such as mood or anxiety symptoms, and externalizing disorders such as behavioral or substance abuse symptoms.[30] A single general factor of psychopathology, similar to the g factor for intelligence, has been empirically supported. The p factor model supports the internalizing-externalizing distinction, but also supports the formation of a third dimension of thought disorders such as schizophrenia.[31] Biological evidence also supports the validity of the internalizing-externalizing structure of mental disorders, with twin and adoption studies supporting heritable factors for externalizing and internalizing disorders.[32][33][34] ### Disorders See also: List of mental disorders as defined by the DSM and ICD There are many different categories of mental disorder, and many different facets of human behavior and personality that can become disordered.[35][36][37][38] #### Anxiety disorder Anxiety disorder: Anxiety or fear that interferes with normal functioning may be classified as an anxiety disorder.[36] Commonly recognized categories include specific phobias, generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, obsessive-compulsive disorder and post-traumatic stress disorder. #### Mood disorder Mood disorder: Other affective (emotion/mood) processes can also become disordered. Mood disorder involving unusually intense and sustained sadness, melancholia, or despair is known as major depression (also known as unipolar or clinical depression). Milder but still prolonged depression can be diagnosed as dysthymia. Bipolar disorder (also known as manic depression) involves abnormally "high" or pressured mood states, known as mania or hypomania, alternating with normal or depressed moods. The extent to which unipolar and bipolar mood phenomena represent distinct categories of disorder, or mix and merge along a dimension or spectrum of mood, is subject to some scientific debate.[39][40] #### Psychotic disorder Psychotic disorder: Patterns of belief, language use and perception of reality can become dysregulated (e.g., delusions, thought disorder, hallucinations). Psychotic disorders in this domain include schizophrenia, and delusional disorder. Schizoaffective disorder is a category used for individuals showing aspects of both schizophrenia and affective disorders. Schizotypy is a category used for individuals showing some of the characteristics associated with schizophrenia but without meeting cutoff criteria. #### Personality disorder Personality disorder: Personality—the fundamental characteristics of a person that influence thoughts and behaviors across situations and time—may be considered disordered if judged to be abnormally rigid and maladaptive. Although treated separately by some, the commonly used categorical schemes include them as mental disorders, albeit on a separate "axis II" in the case of the DSM-IV. A number of different personality disorders are listed, including those sometimes classed as "eccentric", such as paranoid, schizoid and schizotypal personality disorders; types that have described as "dramatic" or "emotional", such as antisocial, borderline, histrionic or narcissistic personality disorders; and those sometimes classed as fear-related, such as anxious-avoidant, dependent, or obsessive-compulsive personality disorders. The personality disorders, in general, are defined as emerging in childhood, or at least by adolescence or early adulthood. The ICD also has a category for enduring personality change after a catastrophic experience or psychiatric illness. If an inability to sufficiently adjust to life circumstances begins within three months of a particular event or situation, and ends within six months after the stressor stops or is eliminated, it may instead be classed as an adjustment disorder. There is an emerging consensus that so-called "personality disorders", like personality traits in general, actually incorporate a mixture of acute dysfunctional behaviors that may resolve in short periods, and maladaptive temperamental traits that are more enduring.[41] Furthermore, there are also non-categorical schemes that rate all individuals via a profile of different dimensions of personality without a symptom-based cutoff from normal personality variation, for example through schemes based on dimensional models.[42][non-primary source needed] #### Eating disorder Eating disorder: These disorders involve disproportionate concern in matters of food and weight.[36] Categories of disorder in this area include anorexia nervosa, bulimia nervosa, exercise bulimia or binge eating disorder.[43][44] #### Sleep disorder Sleep disorder: These conditions are associated with disruption to normal sleep patterns. A common sleep disorder is insomnia, which is described as difficulty falling and/or staying asleep. #### Sexuality related Sexual disorders and gender dysphoria: These disorders include dyspareunia and various kinds of paraphilia (sexual arousal to objects, situations, or individuals that are considered abnormal or harmful to the person or others). #### Other Impulse control disorder: People who are abnormally unable to resist certain urges or impulses that could be harmful to themselves or others, may be classified as having an impulse control disorder, and disorders such as kleptomania (stealing) or pyromania (fire-setting). Various behavioral addictions, such as gambling addiction, may be classed as a disorder. Obsessive-compulsive disorder can sometimes involve an inability to resist certain acts but is classed separately as being primarily an anxiety disorder. Substance use disorder: This disorder refers to the use of drugs (legal or illegal, including alcohol) that persists despite significant problems or harm related to its use. Substance dependence and substance abuse fall under this umbrella category in the DSM. Substance use disorder may be due to a pattern of compulsive and repetitive use of a drug that results in tolerance to its effects and withdrawal symptoms when use is reduced or stopped. Dissociative disorder: People who suffer severe disturbances of their self-identity, memory and general awareness of themselves and their surroundings may be classified as having these types of disorders, including depersonalization disorder or dissociative identity disorder (which was previously referred to as multiple personality disorder or "split personality"). Cognitive disorder: These affect cognitive abilities, including learning and memory. This category includes delirium and mild and major neurocognitive disorder (previously termed dementia). Developmental disorder: These disorders initially occur in childhood. Some examples include autism spectrum disorders, oppositional defiant disorder and conduct disorder, and attention deficit hyperactivity disorder (ADHD), which may continue into adulthood. Conduct disorder, if continuing into adulthood, may be diagnosed as antisocial personality disorder (dissocial personality disorder in the ICD). Popularist labels such as psychopath (or sociopath) do not appear in the DSM or ICD but are linked by some to these diagnoses. Somatoform disorders may be diagnosed when there are problems that appear to originate in the body that are thought to be manifestations of a mental disorder. This includes somatization disorder and conversion disorder. There are also disorders of how a person perceives their body, such as body dysmorphic disorder. Neurasthenia is an old diagnosis involving somatic complaints as well as fatigue and low spirits/depression, which is officially recognized by the ICD-10 but no longer by the DSM-IV.[45][non-primary source needed] Factitious disorders, such as Munchausen syndrome, are diagnosed where symptoms are thought to be experienced (deliberately produced) and/or reported (feigned) for personal gain. There are attempts to introduce a category of relational disorder, where the diagnosis is of a relationship rather than on any one individual in that relationship. The relationship may be between children and their parents, between couples, or others. There already exists, under the category of psychosis, a diagnosis of shared psychotic disorder where two or more individuals share a particular delusion because of their close relationship with each other. There are a number of uncommon psychiatric syndromes, which are often named after the person who first described them, such as Capgras syndrome, De Clerambault syndrome, Othello syndrome, Ganser syndrome, Cotard delusion, and Ekbom syndrome, and additional disorders such as the Couvade syndrome and Geschwind syndrome.[46] Various new types of mental disorder diagnosis are occasionally proposed. Among those controversially considered by the official committees of the diagnostic manuals include self-defeating personality disorder, sadistic personality disorder, passive-aggressive personality disorder and premenstrual dysphoric disorder. ## Signs and symptoms ### Course The onset of psychiatric disorders usually occurs from childhood to early adulthood.[47] Impulse-control disorders and a few anxiety disorders tend to appear in childhood. Some other anxiety disorders, substance disorders and mood disorders emerge later in the mid-teens.[48] Symptoms of schizophrenia typically manifest from late adolescence to early twenties.[49] The likely course and outcome of mental disorders vary and are dependent on numerous factors related to the disorder itself, the individual as a whole, and the social environment. Some disorders may last a brief period of time, while others may be long term in nature. All disorders can have a varied course. Long-term international studies of schizophrenia have found that over a half of individuals recover in terms of symptoms, and around a fifth to a third in terms of symptoms and functioning, with many requiring no medication. While some have serious difficulties and support needs for many years, "late" recovery is still plausible. The World Health Organization concluded that the long-term studies' findings converged with others in "relieving patients, carers and clinicians of the chronicity paradigm which dominated thinking throughout much of the 20th century."[50][non-primary source needed][51] Around half of people initially diagnosed with bipolar disorder achieve symptomatic recovery (no longer meeting criteria for the diagnosis) within six weeks, and nearly all achieve it within two years, with nearly half regaining their prior occupational and residential status in that period. Less than half go on to experience a new episode of mania or major depression within the next two years.[52][non-primary source needed] Functioning has been found to vary, being poor during periods of major depression or mania but otherwise fair to good, and possibly superior during periods of hypomania in Bipolar II.[53][non-primary source needed] ### Disability Disorder Disability-adjusted life years[54] Major depressive disorder 65.5 million Alcohol-use disorder 23.7 million Schizophrenia 16.8 million Bipolar disorder 14.4 million Other drug-use disorders 8.4 million Panic disorder 7.0 million Obsessive-compulsive disorder 5.1 million Primary insomnia 3.6 million Post-traumatic stress disorder 3.5 million Some disorders may be very limited in their functional effects, while others may involve substantial disability and support needs. The degree of ability or disability may vary over time and across different life domains. Furthermore, continued disability has been linked to institutionalization, discrimination and social exclusion as well as to the inherent effects of disorders. Alternatively, functioning may be affected by the stress of having to hide a condition in work or school etc., by adverse effects of medications or other substances, or by mismatches between illness-related variations and demands for regularity.[55] It is also the case that, while often being characterized in purely negative terms, some mental traits or states labeled as disorders can also involve above-average creativity, non-conformity, goal-striving, meticulousness, or empathy.[56] In addition, the public perception of the level of disability associated with mental disorders can change.[57] Nevertheless, internationally, people report equal or greater disability from commonly occurring mental conditions than from commonly occurring physical conditions, particularly in their social roles and personal relationships. The proportion with access to professional help for mental disorders is far lower, however, even among those assessed as having a severely disabling condition.[58] Disability in this context may or may not involve such things as: * Basic activities of daily living. Including looking after the self (health care, grooming, dressing, shopping, cooking etc.) or looking after accommodation (chores, DIY tasks, etc.) * Interpersonal relationships. Including communication skills, ability to form relationships and sustain them, ability to leave the home or mix in crowds or particular settings * Occupational functioning. Ability to acquire an employment and hold it, cognitive and social skills required for the job, dealing with workplace culture, or studying as a student. In terms of total disability-adjusted life years (DALYs), which is an estimate of how many years of life are lost due to premature death or to being in a state of poor health and disability, mental disorders rank amongst the most disabling conditions. Unipolar (also known as Major) depressive disorder is the third leading cause of disability worldwide, of any condition mental or physical, accounting for 65.5 million years lost. The first systematic description of global disability arising in youth, in 2011, found that among 10- to 24-year-olds nearly half of all disability (current and as estimated to continue) was due to mental and neurological conditions, including substance use disorders and conditions involving self-harm. Second to this were accidental injuries (mainly traffic collisions) accounting for 12 percent of disability, followed by communicable diseases at 10 percent. The disorders associated with most disability in high income countries were unipolar major depression (20%) and alcohol use disorder (11%). In the eastern Mediterranean region, it was unipolar major depression (12%) and schizophrenia (7%), and in Africa it was unipolar major depression (7%) and bipolar disorder (5%).[59] Suicide, which is often attributed to some underlying mental disorder, is a leading cause of death among teenagers and adults under 35.[60][61] There are an estimated 10 to 20 million non-fatal attempted suicides every year worldwide.[62] ## Risk factors Main article: Causes of mental disorders The predominant view as of 2018 is that genetic, psychological, and environmental factors all contribute to the development or progression of mental disorders.[63] Different risk factors may be present at different ages, with risk occurring as early as during prenatal period.[64] ### Genetics Main article: Psychiatric genetics A number of psychiatric disorders are linked to a family history (including depression, narcissistic personality disorder[65][66] and anxiety).[67] Twin studies have also revealed a very high heritability for many mental disorders (especially autism and schizophrenia).[68] Although researchers have been looking for decades for clear linkages between genetics and mental disorders, that work has not yielded specific genetic biomarkers yet that might lead to better diagnosis and better treatments.[69] Statistical research looking at eleven disorders found widespread assortative mating between people with mental illness. That means that individuals with one of these disorders were two to three times more likely than the general population to have a partner with a mental disorder. Sometimes people seemed to have preferred partners with the same mental illness. Thus, people with schizophrenia or ADHD are seven times more likely to have affected partners with the same disorder. This is even more pronounced for people with autism spectrum disorders who are 10 times more likely to have a spouse with the same disorder.[70] ### Environment The prevalence of mental illness is higher in more economically unequal countries During the prenatal stage, factors like unwanted pregnancy, lack of adaptation to pregnancy or substance abuse during pregnancy increases the risk of developing a mental disorder.[64] Maternal stress and birth complications including prematurity and infections have also been implicated in increasing susceptibility for mental illness.[71] Infants neglected or not provided optimal nutrition have a higher risk of developing cognitive impairment.[64] Social influences have also been found to be important,[72] including abuse, neglect, bullying, social stress, traumatic events, and other negative or overwhelming life experiences. Aspects of the wider community have also been implicated,[73] including employment problems, socioeconomic inequality, lack of social cohesion, problems linked to migration, and features of particular societies and cultures. The specific risks and pathways to particular disorders are less clear, however. Nutrition also plays a role in mental disorders.[7][74] In schizophrenia and psychosis, risk factors include migration and discrimination, childhood trauma, bereavement or separation in families, abuse of drugs,[75] and urbanicity.[73] In anxiety, risk factors may include parenting factors including parental rejection, lack of parental warmth, high hostility, harsh discipline, high maternal negative affect, anxious childrearing, modelling of dysfunctional and drug-abusing behaviour, and child abuse (emotional, physical and sexual).[76] Adults with imbalance work to life are at higher risk for developing anxiety.[64] For bipolar disorder, stress (such as childhood adversity) is not a specific cause, but does place genetically and biologically vulnerable individuals at risk for a more severe course of illness.[77] ### Drug use Mental disorders are associated with drug use including: cannabis,[78] alcohol[79] and caffeine,[80] use of which appears to promote anxiety.[81] For psychosis and schizophrenia, usage of a number of drugs has been associated with development of the disorder, including cannabis, cocaine, and amphetamines.[82][78] There has been debate regarding the relationship between usage of cannabis and bipolar disorder.[83] Cannabis has also been associated with depression.[78] Adolescents are at increased risk for tobacco, alcohol and drug use; Peer pressure is the main reason why adolescents start using substances. At this age, the use of substances could be detrimental to the development of the brain and place them at higher risk of developing a mental disorder.[64] ### Chronic disease People living with chronic conditions like HIV and diabetes are at higher risk for developing a mental disorder. People living with diabetes experience significant stress from biological impact of the disease, which places them at risk for developing anxiety and depression. Diabetic patients also have to deal with emotional stress trying to manage the disease. Conditions like heart disease, stroke, respiratory conditions, cancer and arthritis increase the risk of developing a mental disorder when compared to the general population.[84] ### Personality traits Risk factors for mental illness include a propensity for high neuroticism[85][86] or "emotional instability". In anxiety, risk factors may include temperament and attitudes (e.g. pessimism).[67] ### Causal models Mental disorders can arise from multiple sources, and in many cases there is no single accepted or consistent cause currently established. An eclectic or pluralistic mix of models may be used to explain particular disorders.[86][87] The primary paradigm of contemporary mainstream Western psychiatry is said to be the biopsychosocial model which incorporates biological, psychological and social factors, although this may not always be applied in practice. Biological psychiatry follows a biomedical model where many mental disorders are conceptualized as disorders of brain circuits likely caused by developmental processes shaped by a complex interplay of genetics and experience. A common assumption is that disorders may have resulted from genetic and developmental vulnerabilities, exposed by stress in life (for example in a diathesis–stress model), although there are various views on what causes differences between individuals. Some types of mental disorders may be viewed as primarily neurodevelopmental disorders. Evolutionary psychology may be used as an overall explanatory theory, while attachment theory is another kind of evolutionary-psychological approach sometimes applied in the context of mental disorders. Psychoanalytic theories have continued to evolve alongside and cognitive-behavioral and systemic-family approaches. A distinction is sometimes made between a "medical model" or a "social model" of disorder and disability. ## Diagnosis Psychiatrists seek to provide a medical diagnosis of individuals by an assessment of symptoms, signs and impairment associated with particular types of mental disorder. Other mental health professionals, such as clinical psychologists, may or may not apply the same diagnostic categories to their clinical formulation of a client's difficulties and circumstances.[88] The majority of mental health problems are, at least initially, assessed and treated by family physicians (in the UK general practitioners) during consultations, who may refer a patient on for more specialist diagnosis in acute or chronic cases. Routine diagnostic practice in mental health services typically involves an interview known as a mental status examination, where evaluations are made of appearance and behavior, self-reported symptoms, mental health history, and current life circumstances. The views of other professionals, relatives or other third parties may be taken into account. A physical examination to check for ill health or the effects of medications or other drugs may be conducted. Psychological testing is sometimes used via paper-and-pen or computerized questionnaires, which may include algorithms based on ticking off standardized diagnostic criteria, and in rare specialist cases neuroimaging tests may be requested, but such methods are more commonly found in research studies than routine clinical practice.[89][90] Time and budgetary constraints often limit practicing psychiatrists from conducting more thorough diagnostic evaluations.[91] It has been found that most clinicians evaluate patients using an unstructured, open-ended approach, with limited training in evidence-based assessment methods, and that inaccurate diagnosis may be common in routine practice.[92] In addition, comorbidity is very common in psychiatric diagnosis, where the same person meets the criteria for more than one disorder. On the other hand, a person may have several different difficulties only some of which meet the criteria for being diagnosed. There may be specific problems with accurate diagnosis in developing countries. More structured approaches are being increasingly used to measure levels of mental illness. * HoNOS is the most widely used measure in English mental health services, being used by at least 61 trusts.[93] In HoNOS a score of 0–4 is given for each of 12 factors, based on functional living capacity.[94] Research has been supportive of HoNOS,[95] although some questions have been asked about whether it provides adequate coverage of the range and complexity of mental illness problems, and whether the fact that often only 3 of the 12 scales vary over time gives enough subtlety to accurately measure outcomes of treatment.[96] ### Criticism Since the 1980s, Paula Caplan has been concerned about the subjectivity of psychiatric diagnosis, and people being arbitrarily "slapped with a psychiatric label." Caplan says because psychiatric diagnosis is unregulated, doctors are not required to spend much time interviewing patients or to seek a second opinion. The Diagnostic and Statistical Manual of Mental Disorders can lead a psychiatrist to focus on narrow checklists of symptoms, with little consideration of what is actually causing the person's problems. So, according to Caplan, getting a psychiatric diagnosis and label often stands in the way of recovery.[97][unreliable medical source] In 2013, psychiatrist Allen Frances wrote a paper entitled "The New Crisis of Confidence in Psychiatric Diagnosis", which said that "psychiatric diagnosis... still relies exclusively on fallible subjective judgments rather than objective biological tests." Frances was also concerned about "unpredictable overdiagnosis."[98] For many years, marginalized psychiatrists (such as Peter Breggin, Thomas Szasz) and outside critics (such as Stuart A. Kirk) have "been accusing psychiatry of engaging in the systematic medicalization of normality." More recently these concerns have come from insiders who have worked for and promoted the American Psychiatric Association (e.g., Robert Spitzer, Allen Frances).[99] A 2002 editorial in the British Medical Journal warned of inappropriate medicalization leading to disease mongering, where the boundaries of the definition of illnesses are expanded to include personal problems as medical problems or risks of diseases are emphasized to broaden the market for medications.[100] ## Prevention Main article: Prevention of mental disorders The 2004 WHO report "Prevention of Mental Disorders" stated that "Prevention of these disorders is obviously one of the most effective ways to reduce the [disease] burden."[101] The 2011 European Psychiatric Association (EPA) guidance on prevention of mental disorders states "There is considerable evidence that various psychiatric conditions can be prevented through the implementation of effective evidence-based interventions."[102] A 2011 UK Department of Health report on the economic case for mental health promotion and mental illness prevention found that "many interventions are outstandingly good value for money, low in cost and often become self-financing over time, saving public expenditure".[103] In 2016, the National Institute of Mental Health re-affirmed prevention as a research priority area.[104] Parenting may affect the child's mental health, and evidence suggests that helping parents to be more effective with their children can address mental health needs.[105][106] Universal prevention (aimed at a population that has no increased risk for developing a mental disorder, such as school programs or mass media campaigns) need very high numbers of people to show effect (sometimes known as the "power" problem). Approaches to overcome this are (1) focus on high-incidence groups (e.g. by targeting groups with high risk factors), (2) use multiple interventions to achieve greater, and thus more statistically valid, effects, (3) use cumulative meta-analyses of many trials, and (4) run very large trials.[107][108] ## Management Main articles: Treatment of mental disorders, Services for mental disorders, and Mental health professional "Haus Tornow am See" (former manor house), Germany from 1912 is today separated into a special education school and a hotel with integrated work/job- and rehabilitation-training for people with mental disorders Treatment and support for mental disorders is provided in psychiatric hospitals, clinics or a range of community mental health services. In some countries services are increasingly based on a recovery approach, intended to support individual's personal journey to gain the kind of life they want. There are a range of different types of treatment and what is most suitable depends on the disorder and the individual. Many things have been found to help at least some people, and a placebo effect may play a role in any intervention or medication. In a minority of cases, individuals may be treated against their will, which can cause particular difficulties depending on how it is carried out and perceived. Compulsory treatment while in the community versus non-compulsory treatment does not appear to make much of a difference except by maybe decreasing victimization.[109] ### Lifestyle Lifestyle strategies, including dietary changes, exercise and quitting smoking may be of benefit.[9][74][110] ### Therapy There is also a wide range of psychotherapists (including family therapy), counselors, and public health professionals. In addition, there are peer support roles where personal experience of similar issues is the primary source of expertise.[111][112][113][114] A major option for many mental disorders is psychotherapy. There are several main types. Cognitive behavioral therapy (CBT) is widely used and is based on modifying the patterns of thought and behavior associated with a particular disorder. Other psychotherapy include dialectic behavioral therapy (DBT) and interpersonal psychotherapy (IPT). Psychoanalysis, addressing underlying psychic conflicts and defenses, has been a dominant school of psychotherapy and is still in use. Systemic therapy or family therapy is sometimes used, addressing a network of significant others as well as an individual. Some psychotherapies are based on a humanistic approach. There are a number of specific therapies used for particular disorders, which may be offshoots or hybrids of the above types. Mental health professionals often employ an eclectic or integrative approach. Much may depend on the therapeutic relationship, and there may be problems with trust, confidentiality and engagement. ### Medication A major option for many mental disorders is psychiatric medication and there are several main groups. Antidepressants are used for the treatment of clinical depression, as well as often for anxiety and a range of other disorders. Anxiolytics (including sedatives) are used for anxiety disorders and related problems such as insomnia. Mood stabilizers are used primarily in bipolar disorder. Antipsychotics are used for psychotic disorders, notably for positive symptoms in schizophrenia, and also increasingly for a range of other disorders. Stimulants are commonly used, notably for ADHD.[115] Despite the different conventional names of the drug groups, there may be considerable overlap in the disorders for which they are actually indicated, and there may also be off-label use of medications. There can be problems with adverse effects of medication and adherence to them, and there is also criticism of pharmaceutical marketing and professional conflicts of interest. However, these medications in combination with non-pharmacological methods, such as cognitive behavioral therapy (CBT) are seen to be most effective in treating mental disorders. ### Other Electroconvulsive therapy (ECT) is sometimes used in severe cases when other interventions for severe intractable depression have failed. ECT is usually indicated for treatment resistant depression, severe vegetative symptoms, psychotic depression, intense suicidal ideation, depression during pregnancy, and catonia. Psychosurgery is considered experimental but is advocated by some neurologists in certain rare cases.[116][117] Counseling (professional) and co-counseling (between peers) may be used. Psychoeducation programs may provide people with the information to understand and manage their problems. Creative therapies are sometimes used, including music therapy, art therapy or drama therapy. Lifestyle adjustments and supportive measures are often used, including peer support, self-help groups for mental health and supported housing or supported employment (including social firms). Some advocate dietary supplements.[118] Reasonable accommodations (adjustments and supports) might be put in place to help an individual cope and succeed in environments despite potential disability related to mental health problems. This could include an emotional support animal or specifically trained psychiatric service dog. As of 2019 cannabis is specifically not recommended as a treatment.[119] ## Epidemiology Main article: Prevalence of mental disorders Deaths from mental and behavioral disorders per million persons in 2012 0–6 7–9 10–15 16–24 25–31 32–39 40–53 54–70 71–99 100–356 Disability-adjusted life year for neuropsychiatric conditions per 100,000 inhabitants in 2004. <2,200 2,200–2,400 2,400–2,600 2,600–2,800 2,800–3,000 3,000–3,200 3,200–3,400 3,400–3,600 3,600–3,800 3,800–4,000 4,000–4,200 >4,200 Mental disorders are common. Worldwide, more than one in three people in most countries report sufficient criteria for at least one at some point in their life.[120] In the United States, 46% qualify for a mental illness at some point.[121] An ongoing survey indicates that anxiety disorders are the most common in all but one country, followed by mood disorders in all but two countries, while substance disorders and impulse-control disorders were consistently less prevalent.[122] Rates varied by region.[123] A review of anxiety disorder surveys in different countries found average lifetime prevalence estimates of 16.6%, with women having higher rates on average.[124] A review of mood disorder surveys in different countries found lifetime rates of 6.7% for major depressive disorder (higher in some studies, and in women) and 0.8% for Bipolar I disorder.[125] In the United States the frequency of disorder is: anxiety disorder (28.8%), mood disorder (20.8%), impulse-control disorder (24.8%) or substance use disorder (14.6%).[121][126][127] A 2004 cross-Europe study found that approximately one in four people reported meeting criteria at some point in their life for at least one of the DSM-IV disorders assessed, which included mood disorders (13.9%), anxiety disorders (13.6%) or alcohol disorder (5.2%). Approximately one in ten met criteria within a 12-month period. Women and younger people of either gender showed more cases of disorder.[128] A 2005 review of surveys in 16 European countries found that 27% of adult Europeans are affected by at least one mental disorder in a 12-month period.[129] An international review of studies on the prevalence of schizophrenia found an average (median) figure of 0.4% for lifetime prevalence; it was consistently lower in poorer countries.[130] Studies of the prevalence of personality disorders (PDs) have been fewer and smaller-scale, but one broad Norwegian survey found a five-year prevalence of almost 1 in 7 (13.4%). Rates for specific disorders ranged from 0.8% to 2.8%, differing across countries, and by gender, educational level and other factors.[131] A US survey that incidentally screened for personality disorder found a rate of 14.79%.[132] Approximately 7% of a preschool pediatric sample were given a psychiatric diagnosis in one clinical study, and approximately 10% of 1- and 2-year-olds receiving developmental screening have been assessed as having significant emotional/behavioral problems based on parent and pediatrician reports.[133] While rates of psychological disorders are often the same for men and women, women tend to have a higher rate of depression. Each year 73 million women are affected by major depression, and suicide is ranked 7th as the cause of death for women between the ages of 20–59. Depressive disorders account for close to 41.9% of the disability from neuropsychiatric disorders among women compared to 29.3% among men.[134] ## History Main article: History of mental disorders ### Ancient civilizations Ancient civilizations described and treated a number of mental disorders. Mental illnesses were well known in ancient Mesopotamia,[135] where diseases and mental disorders were believed to be caused by specific deities.[136] Because hands symbolized control over a person, mental illnesses were known as "hands" of certain deities.[136] One psychological illness was known as Qāt Ištar, meaning "Hand of Ishtar".[136] Others were known as "Hand of Shamash", "Hand of the Ghost", and "Hand of the God".[136] Descriptions of these illnesses, however, are so vague that it is usually impossible to determine which illnesses they correspond to in modern terminology.[136] Mesopotamian doctors kept detailed record of their patients' hallucinations and assigned spiritual meanings to them.[135] The royal family of Elam was notorious for its members frequently suffering from insanity.[135] The Greeks coined terms for melancholy, hysteria and phobia and developed the humorism theory. Mental disorders were described, and treatments developed, in Persia, Arabia and in the medieval Islamic world. ### Europe #### Middle Ages Conceptions of madness in the Middle Ages in Christian Europe were a mixture of the divine, diabolical, magical and humoral and transcendental.[137] In the early modern period, some people with mental disorders may have been victims of the witch-hunts. While not every witch and sorcerer accused were mentally ill, all mentally ill were considered to be witches or sorcerers.[138] Many terms for mental disorder that found their way into everyday use first became popular in the 16th and 17th centuries. #### Eighteenth century Eight patients representing mental diagnoses as of the 19th century at the Salpêtrière, Paris. By the end of the 17th century and into the Enlightenment, madness was increasingly seen as an organic physical phenomenon with no connection to the soul or moral responsibility. Asylum care was often harsh and treated people like wild animals, but towards the end of the 18th century a moral treatment movement gradually developed. Clear descriptions of some syndromes may be rare prior to the 19th century. #### Nineteenth century Industrialization and population growth led to a massive expansion of the number and size of insane asylums in every Western country in the 19th century. Numerous different classification schemes and diagnostic terms were developed by different authorities, and the term psychiatry was coined (1808), though medical superintendents were still known as alienists. #### Twentieth century A patient in a strait-jacket and barrel contraption, 1908 The turn of the 20th century saw the development of psychoanalysis, which would later come to the fore, along with Kraepelin's classification scheme. Asylum "inmates" were increasingly referred to as "patients", and asylums renamed as hospitals. ### Europe and the United States Insulin shock procedure, 1950s Early in the 20th century in the United States, a mental hygiene movement developed, aiming to prevent mental disorders. Clinical psychology and social work developed as professions. World War I saw a massive increase of conditions that came to be termed "shell shock". World War II saw the development in the U.S. of a new psychiatric manual for categorizing mental disorders, which along with existing systems for collecting census and hospital statistics led to the first Diagnostic and Statistical Manual of Mental Disorders (DSM). The International Classification of Diseases (ICD) also developed a section on mental disorders. The term stress, having emerged from endocrinology work in the 1930s, was increasingly applied to mental disorders. Electroconvulsive therapy, insulin shock therapy, lobotomies and the "neuroleptic" chlorpromazine came to be used by mid-century.[139] In the 1960s there were many challenges to the concept of mental illness itself. These challenges came from psychiatrists like Thomas Szasz who argued that mental illness was a myth used to disguise moral conflicts; from sociologists such as Erving Goffman who said that mental illness was merely another example of how society labels and controls non-conformists; from behavioral psychologists who challenged psychiatry's fundamental reliance on unobservable phenomena; and from gay rights activists who criticised the APA's listing of homosexuality as a mental disorder. A study published in Science by Rosenhan received much publicity and was viewed as an attack on the efficacy of psychiatric diagnosis.[140] Deinstitutionalization gradually occurred in the West, with isolated psychiatric hospitals being closed down in favor of community mental health services. A consumer/survivor movement gained momentum. Other kinds of psychiatric medication gradually came into use, such as "psychic energizers" (later antidepressants) and lithium. Benzodiazepines gained widespread use in the 1970s for anxiety and depression, until dependency problems curtailed their popularity. Advances in neuroscience, genetics and psychology led to new research agendas. Cognitive behavioral therapy and other psychotherapies developed. The DSM and then ICD adopted new criteria-based classifications, and the number of "official" diagnoses saw a large expansion. Through the 1990s, new SSRI-type antidepressants became some of the most widely prescribed drugs in the world, as later did antipsychotics. Also during the 1990s, a recovery approach developed. ## Society and culture Different societies or cultures, even different individuals in a subculture, can disagree as to what constitutes optimal versus pathological biological and psychological functioning. Research has demonstrated that cultures vary in the relative importance placed on, for example, happiness, autonomy, or social relationships for pleasure. Likewise, the fact that a behavior pattern is valued, accepted, encouraged, or even statistically normative in a culture does not necessarily mean that it is conducive to optimal psychological functioning. People in all cultures find some behaviors bizarre or even incomprehensible. But just what they feel is bizarre or incomprehensible is ambiguous and subjective.[141] These differences in determination can become highly contentious. The process by which conditions and difficulties come to be defined and treated as medical conditions and problems, and thus come under the authority of doctors and other health professionals, is known as medicalization or pathologization. ### Religion See also: Psychology of religion Religious, spiritual, or transpersonal experiences and beliefs meet many criteria of delusional or psychotic disorders.[142][143] A belief or experience can sometimes be shown to produce distress or disability—the ordinary standard for judging mental disorders.[144] There is a link between religion and schizophrenia,[145] a complex mental disorder characterized by a difficulty in recognizing reality, regulating emotional responses, and thinking in a clear and logical manner. Those with schizophrenia commonly report some type of religious delusion,[145][146][147] and religion itself may be a trigger for schizophrenia.[148] ### Movements Giorgio Antonucci Thomas Szasz Controversy has often surrounded psychiatry, and the term anti-psychiatry was coined by psychiatrist David Cooper in 1967. The anti-psychiatry message is that psychiatric treatments are ultimately more damaging than helpful to patients, and psychiatry's history involves what may now be seen as dangerous treatments.[149] Electroconvulsive therapy was one of these, which was used widely between the 1930s and 1960s. Lobotomy was another practice that was ultimately seen as too invasive and brutal. Diazepam and other sedatives were sometimes over-prescribed, which led to an epidemic of dependence. There was also concern about the large increase in prescribing psychiatric drugs for children. Some charismatic psychiatrists came to personify the movement against psychiatry. The most influential of these was R.D. Laing who wrote a series of best-selling books, including The Divided Self. Thomas Szasz wrote The Myth of Mental Illness. Some ex-patient groups have become militantly anti-psychiatric, often referring to themselves as "survivors".[149] Giorgio Antonucci has questioned the basis of psychiatry through his work on the dismantling of two psychiatric hospitals (in the city of Imola), carried out from 1973 to 1996. The consumer/survivor movement (also known as user/survivor movement) is made up of individuals (and organizations representing them) who are clients of mental health services or who consider themselves survivors of psychiatric interventions. Activists campaign for improved mental health services and for more involvement and empowerment within mental health services, policies and wider society.[150][151][152] Patient advocacy organizations have expanded with increasing deinstitutionalization in developed countries, working to challenge the stereotypes, stigma and exclusion associated with psychiatric conditions. There is also a carers rights movement of people who help and support people with mental health conditions, who may be relatives, and who often work in difficult and time-consuming circumstances with little acknowledgement and without pay. An anti-psychiatry movement fundamentally challenges mainstream psychiatric theory and practice, including in some cases asserting that psychiatric concepts and diagnoses of 'mental illness' are neither real nor useful.[153][154][155] Alternatively, a movement for global mental health has emerged, defined as 'the area of study, research and practice that places a priority on improving mental health and achieving equity in mental health for all people worldwide'.[156] ### Cultural bias See also: Depression and culture and Cultural competence in healthcare Current diagnostic guidelines, namely the DSM and to some extent the ICD, have been criticized as having a fundamentally Euro-American outlook. Opponents argue that even when diagnostic criteria are used across different cultures, it does not mean that the underlying constructs have validity within those cultures, as even reliable application can prove only consistency, not legitimacy.[157] Advocating a more culturally sensitive approach, critics such as Carl Bell and Marcello Maviglia contend that the cultural and ethnic diversity of individuals is often discounted by researchers and service providers.[158] Cross-cultural psychiatrist Arthur Kleinman contends that the Western bias is ironically illustrated in the introduction of cultural factors to the DSM-IV. Disorders or concepts from non-Western or non-mainstream cultures are described as "culture-bound", whereas standard psychiatric diagnoses are given no cultural qualification whatsoever, revealing to Kleinman an underlying assumption that Western cultural phenomena are universal.[159] Kleinman's negative view towards the culture-bound syndrome is largely shared by other cross-cultural critics. Common responses included both disappointment over the large number of documented non-Western mental disorders still left out and frustration that even those included are often misinterpreted or misrepresented.[160] Many mainstream psychiatrists are dissatisfied with the new culture-bound diagnoses, although for partly different reasons. Robert Spitzer, a lead architect of the DSM-III, has argued that adding cultural formulations was an attempt to appease cultural critics, and has stated that they lack any scientific rationale or support. Spitzer also posits that the new culture-bound diagnoses are rarely used, maintaining that the standard diagnoses apply regardless of the culture involved. In general, mainstream psychiatric opinion remains that if a diagnostic category is valid, cross-cultural factors are either irrelevant or are significant only to specific symptom presentations.[157] Clinical conceptions of mental illness also overlap with personal and cultural values in the domain of morality, so much so that it is sometimes argued that separating the two is impossible without fundamentally redefining the essence of being a particular person in a society.[161] In clinical psychiatry, persistent distress and disability indicate an internal disorder requiring treatment; but in another context, that same distress and disability can be seen as an indicator of emotional struggle and the need to address social and structural problems.[162][163] This dichotomy has led some academics and clinicians to advocate a postmodernist conceptualization of mental distress and well-being.[164][165] Such approaches, along with cross-cultural and "heretical" psychologies centered on alternative cultural and ethnic and race-based identities and experiences, stand in contrast to the mainstream psychiatric community's alleged avoidance of any explicit involvement with either morality or culture.[166] In many countries there are attempts to challenge perceived prejudice against minority groups, including alleged institutional racism within psychiatric services.[167] There are also ongoing attempts to improve professional cross cultural sensitivity. ### Laws and policies See also: Mental health law Three quarters of countries around the world have mental health legislation. Compulsory admission to mental health facilities (also known as involuntary commitment) is a controversial topic. It can impinge on personal liberty and the right to choose, and carry the risk of abuse for political, social and other reasons; yet it can potentially prevent harm to self and others, and assist some people in attaining their right to healthcare when they may be unable to decide in their own interests.[168] All human rights oriented mental health laws require proof of the presence of a mental disorder as defined by internationally accepted standards, but the type and severity of disorder that counts can vary in different jurisdictions. The two most often utilized grounds for involuntary admission are said to be serious likelihood of immediate or imminent danger to self or others, and the need for treatment. Applications for someone to be involuntarily admitted usually come from a mental health practitioner, a family member, a close relative, or a guardian. Human-rights-oriented laws usually stipulate that independent medical practitioners or other accredited mental health practitioners must examine the patient separately and that there should be regular, time-bound review by an independent review body.[168] The individual should also have personal access to independent advocacy. In order for involuntary treatment to be administered (by force if necessary), it should be shown that an individual lacks the mental capacity for informed consent (i.e. to understand treatment information and its implications, and therefore be able to make an informed choice to either accept or refuse). Legal challenges in some areas have resulted in supreme court decisions that a person does not have to agree with a psychiatrist's characterization of the issues as constituting an "illness", nor agree with a psychiatrist's conviction in medication, but only recognize the issues and the information about treatment options.[169] Proxy consent (also known as surrogate or substituted decision-making) may be transferred to a personal representative, a family member or a legally appointed guardian. Moreover, patients may be able to make, when they are considered well, an advance directive stipulating how they wish to be treated should they be deemed to lack mental capacity in future.[168] The right to supported decision-making, where a person is helped to understand and choose treatment options before they can be declared to lack capacity, may also be included in legislation.[170] There should at the very least be shared decision-making as far as possible. Involuntary treatment laws are increasingly extended to those living in the community, for example outpatient commitment laws (known by different names) are used in New Zealand, Australia, the United Kingdom and most of the United States. The World Health Organization reports that in many instances national mental health legislation takes away the rights of persons with mental disorders rather than protecting rights, and is often outdated.[168] In 1991, the United Nations adopted the Principles for the Protection of Persons with Mental Illness and the Improvement of Mental Health Care, which established minimum human rights standards of practice in the mental health field. In 2006, the UN formally agreed the Convention on the Rights of Persons with Disabilities to protect and enhance the rights and opportunities of disabled people, including those with psychosocial disabilities.[171] The term insanity, sometimes used colloquially as a synonym for mental illness, is often used technically as a legal term. The insanity defense may be used in a legal trial (known as the mental disorder defence in some countries). ### Perception and discrimination Further information: Schizophrenogenic parents, Refrigerator mother, and Mentalism (discrimination) #### Stigma The social stigma associated with mental disorders is a widespread problem. The US Surgeon General stated in 1999 that: "Powerful and pervasive, stigma prevents people from acknowledging their own mental health problems, much less disclosing them to others."[172] In the United States, racial and ethnic minorities are more likely to experience mental health disorders often due to low socioeconomic status, and discrimination.[173][174] In Taiwan, those with mental disorders are subject to general public's misperception that the root causes of the mental disorders are "over-thinking", "having a lot of time and nothing better to do", "stagnant", "not serious in life", "not paying enough attention to the real life affairs", "mentally weak", "refusing to be resilient", "turning back to perfectionistic strivings", "not bravery" and so forth.[175] Employment discrimination is reported to play a significant part in the high rate of unemployment among those with a diagnosis of mental illness.[176] An Australian study found that having a mental illness is a bigger barrier to employment than a physical disability.[177][better source needed] The mentally ill are stigmatized in Chinese society and can not legally marry.[178] Efforts are being undertaken worldwide to eliminate the stigma of mental illness,[179] although the methods and outcomes used have sometimes been criticized.[180] #### Media and general public Main article: Mental disorders in art and literature Media coverage of mental illness comprises predominantly negative and pejorative depictions, for example, of incompetence, violence or criminality, with far less coverage of positive issues such as accomplishments or human rights issues.[181][182][183] Such negative depictions, including in children's cartoons, are thought to contribute to stigma and negative attitudes in the public and in those with mental health problems themselves, although more sensitive or serious cinematic portrayals have increased in prevalence.[184][185] In the United States, the Carter Center has created fellowships for journalists in South Africa, the U.S., and Romania, to enable reporters to research and write stories on mental health topics.[186] Former US First Lady Rosalynn Carter began the fellowships not only to train reporters in how to sensitively and accurately discuss mental health and mental illness, but also to increase the number of stories on these topics in the news media.[187][188] There is also a World Mental Health Day, which in the US and Canada falls within a Mental Illness Awareness Week. The general public have been found to hold a strong stereotype of dangerousness and desire for social distance from individuals described as mentally ill.[189] A US national survey found that a higher percentage of people rate individuals described as displaying the characteristics of a mental disorder as "likely to do something violent to others", compared to the percentage of people who are rating individuals described as being "troubled".[190] Recent depictions in media have included leading characters successfully living with and managing a mental illness, including in bipolar disorder in Homeland (2011) and posttraumatic stress disorder in Iron Man 3 (2013).[original research?] #### Violence Despite public or media opinion, national studies have indicated that severe mental illness does not independently predict future violent behavior, on average, and is not a leading cause of violence in society. There is a statistical association with various factors that do relate to violence (in anyone), such as substance abuse and various personal, social and economic factors.[191] A 2015 review found that in the United States, about 4% of violence is attributable to people diagnosed with mental illness,[192] and a 2014 study found that 7.5% of crimes committed by mentally ill people were directly related to the symptoms of their mental illness.[193] The majority of people with serious mental illness are never violent.[194] In fact, findings consistently indicate that it is many times more likely that people diagnosed with a serious mental illness living in the community will be the victims rather than the perpetrators of violence.[195][196] In a study of individuals diagnosed with "severe mental illness" living in a US inner-city area, a quarter were found to have been victims of at least one violent crime over the course of a year, a proportion eleven times higher than the inner-city average, and higher in every category of crime including violent assaults and theft.[197] People with a diagnosis may find it more difficult to secure prosecutions, however, due in part to prejudice and being seen as less credible.[198] However, there are some specific diagnoses, such as childhood conduct disorder or adult antisocial personality disorder or psychopathy, which are defined by, or are inherently associated with, conduct problems and violence. There are conflicting findings about the extent to which certain specific symptoms, notably some kinds of psychosis (hallucinations or delusions) that can occur in disorders such as schizophrenia, delusional disorder or mood disorder, are linked to an increased risk of serious violence on average. The mediating factors of violent acts, however, are most consistently found to be mainly socio-demographic and socio-economic factors such as being young, male, of lower socioeconomic status and, in particular, substance abuse (including alcoholism) to which some people may be particularly vulnerable.[56][195][199][200] High-profile cases have led to fears that serious crimes, such as homicide, have increased due to deinstitutionalization, but the evidence does not support this conclusion.[200][201] Violence that does occur in relation to mental disorder (against the mentally ill or by the mentally ill) typically occurs in the context of complex social interactions, often in a family setting rather than between strangers.[202] It is also an issue in health care settings[203] and the wider community.[204] ## Mental health Main article: Mental health The recognition and understanding of mental health conditions have changed over time and across cultures and there are still variations in definition, assessment and classification, although standard guideline criteria are widely used. In many cases, there appears to be a continuum between mental health and mental illness, making diagnosis complex.[37]:39 According to the World Health Organization (WHO), over a third of people in most countries report problems at some time in their life which meet criteria for diagnosis of one or more of the common types of mental disorder.[120] Corey M Keyes has created a two continua model of mental illness and health which holds that both are related, but distinct dimensions: one continuum indicates the presence or absence of mental health, the other the presence or absence of mental illness.[205] For example, people with optimal mental health can also have a mental illness, and people who have no mental illness can also have poor mental health.[206] ## Other animals Main article: Animal psychopathology Psychopathology in non-human primates has been studied since the mid-20th century. Over 20 behavioral patterns in captive chimpanzees have been documented as (statistically) abnormal for frequency, severity or oddness—some of which have also been observed in the wild. Captive great apes show gross behavioral abnormalities such as stereotypy of movements, self-mutilation, disturbed emotional reactions (mainly fear or aggression) towards companions, lack of species-typical communications, and generalized learned helplessness. In some cases such behaviors are hypothesized to be equivalent to symptoms associated with psychiatric disorders in humans such as depression, anxiety disorders, eating disorders and post-traumatic stress disorder. Concepts of antisocial, borderline and schizoid personality disorders have also been applied to non-human great apes.[207][208] The risk of anthropomorphism is often raised with regard to such comparisons, and assessment of non-human animals cannot incorporate evidence from linguistic communication. However, available evidence may range from nonverbal behaviors—including physiological responses and homologous facial displays and acoustic utterances—to neurochemical studies. It is pointed out that human psychiatric classification is often based on statistical description and judgment of behaviors (especially when speech or language is impaired) and that the use of verbal self-report is itself problematic and unreliable.[207][209] Psychopathology has generally been traced, at least in captivity, to adverse rearing conditions such as early separation of infants from mothers; early sensory deprivation; and extended periods of social isolation. Studies have also indicated individual variation in temperament, such as sociability or impulsiveness. Particular causes of problems in captivity have included integration of strangers into existing groups and a lack of individual space, in which context some pathological behaviors have also been seen as coping mechanisms. Remedial interventions have included careful individually tailored re-socialization programs, behavior therapy, environment enrichment, and on rare occasions psychiatric drugs. Socialization has been found to work 90% of the time in disturbed chimpanzees, although restoration of functional sexuality and care-giving is often not achieved.[207][210] Laboratory researchers sometimes try to develop animal models of human mental disorders, including by inducing or treating symptoms in animals through genetic, neurological, chemical or behavioral manipulation,[211][212] but this has been criticized on empirical grounds[213] and opposed on animal rights grounds. ## See also * Philosophy portal * Psychiatry portal * Psychology portal * Society portal * Mental illness portrayed in media * Mental disorders in film * Mental illness in fiction * Mental illness in American prisons * Parity of esteem * Psychological evaluation ## Notes 1. ^ "Mental illness - Symptoms and causes". 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"In DSM-IV, each of the mental disorders is conceptualized as a clinically significant behavioral or psychological syndrome or pattern that occurs in an individual and that is associated with present distress (e.g., a painful symptom) or disability (i.e., impairment in one or more important areas of functioning) or with a significantly increased risk of suffering death, pain, disability, or an important loss of freedom. In addition, this syndrome or pattern must not be merely an expectable and culturally sanctioned response to a particular event, for example, the death of a loved one. Whatever its original cause, it must currently be considered a manifestation of a behavioral, psychological, or biological dysfunction in the individual. 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"Animal models of depression: navigating through the clinical fog". Neuroscience and Biobehavioral Reviews. 29 (4–5): 503–13. doi:10.1016/j.neubiorev.2005.03.005. PMID 15925695. S2CID 23468566. ## Further reading * Atkinson J (2006). Private and Public Protection: Civil Mental Health Legislation. Edinburgh: Dunedin Academic Press. ISBN 978-1-903765-61-6. * Hockenbury D, Hockenbury S (2004). Discovering Psychology. Worth Publishers. ISBN 978-0-7167-5704-7. * Fried Y, Agassi J (1976). Paranoia: A Study in Diagnosis. Boston Studies in the Philosophy of Science. 50. ISBN 978-90-277-0704-8.[publisher missing] * Fried Y, Agassi J (1983). Psychiatry as Medicine. The Hague: Nijhoff. ISBN 978-90-247-2837-4. * National Academies of Sciences, Engineering, and Medicine (2016). Ending Discrimination Against People with Mental and Substance Use Disorders: The Evidence for Stigma Change. Washington, DC: National Academies Press. doi:10.17226/23442. ISBN 978-0-309-43912-1. PMID 27631043. * Porter R (2002). Madness: a brief history. Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-280266-8. * Weller MP, Eysenck M (1992). The Scientific Basis of Psychiatry. London: W.B. Saunders.[ISBN missing] * Wiencke M (2006). "Schizophrenie als Ergebnis von Wechselwirkungen: Georg Simmels Individualitätskonzept in der Klinischen Psychologie". In Kim D (ed.). Georg Simmel in Translation: Interdisciplinary Border-Crossings in Culture and Modernity. Cambridge: Cambridge Scholars Press. pp. 123–55. ISBN 978-1-84718-060-5. * Radden J (20 February 2019). "Mental Disorder (Illness)". Stanford Encyclopedia of Philosophy. * Management of physical health conditions in adults with severe mental disorders (PDF). WHO. 2018. ISBN 978-92-4-155038-3. ## External links Classification D * ICD-10: F99 * ICD-9-CM: 290-319 * MeSH: D001523 * DiseasesDB: 28852 Wikimedia Commons has media related to Mental and behavioural diseases and disorders. Wikivoyage has a travel guide for Travelling with a mental health condition. Listen to this article (7.4 megabytes) This audio file was created from a revision of this article dated 20 August 2005 (2005-08-20), and does not reflect subsequent edits. (Audio help · More spoken articles) * NIMH.NIH.gov – National Institute of Mental Health * International Committee of Women Leaders on Mental Health * Adverse Childhood Experiences: Risk Factors for Substance Misuse and Mental Health U.S. Centers for Disease Control describes the relation between childhood adversity and mental health (video) Library resources about Mental illness * * * * Resources in your library * Resources in other libraries * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement 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somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy Authority control * GND: 4047686-8 * LCCN: sh85083643 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mental disorder	c0029516	26,753	wikipedia	https://en.wikipedia.org/wiki/Mental_disorder	2021-01-18T19:04:24	{"mesh": ["D001523"], "umls": ["C0029516"], "icd-10": ["F00-F99"], "wikidata": ["Q12135"]}
The antiestrogen withdrawal response is a paradoxical improvement in breast cancer caused by discontinuation of antiestrogen therapy for breast cancer.[1][2][3][4][5] It has been documented rarely with the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene.[1][2][3][4][5] The phenomenon indicates that these agents can somehow result in stimulation of breast cancer tumor progression under certain circumstances.[1][2][3][4][5] One proposed theory for the mechanism is that the sensitivity of breast cells to estrogens shifts with estrogen deprivation, and upon antiestrogen withdrawal, endogenous estrogen acts in the manner of high-dose estrogen therapy in the breast to inhibit breast cancer growth and induce breast cancer cell death.[1] The antiestrogen withdrawal syndrome is analogous to but less common and well-known than the antiandrogen withdrawal syndrome, a phenomenon in which paradoxical improvement in prostate cancer occurs upon discontinuation of antiandrogen therapy.[4] ## References[edit] 1. ^ a b c d Jordan VC (September 2016). "A Raloxifene Withdrawal Response: Translational Research, Definitions, and Clinical Applications". Integr Cancer Ther. 15 (3): 242–4. doi:10.1177/1534735416651329. PMC 5739192. PMID 27271771. 2. ^ a b c Dosik M, Kaufman R (2004). "Raloxifene rebound regression". Cancer Invest. 22 (5): 718–22. doi:10.1081/cnv-200032978. PMID 15581053. 3. ^ a b c Lemmo W (September 2016). "Anti-Estrogen Withdrawal Effect With Raloxifene? A Case Report". Integr Cancer Ther. 15 (3): 245–9. doi:10.1177/1534735416658954. PMC 5739193. PMID 27411856. 4. ^ a b c d Maximov PY, Abderrahman B, Curpan RF, Hawsawi YM, Fan P, Jordan VC (February 2018). "A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers". Endocr. Relat. Cancer. 25 (2): R83–R113. doi:10.1530/ERC-17-0416. PMC 5771961. PMID 29162647. 5. ^ a b c Ariazi EA, Ariazi JL, Cordera F, Jordan VC (2006). "Estrogen receptors as therapeutic targets in breast cancer". Curr Top Med Chem. 6 (3): 181–202. doi:10.2174/156802606776173474. PMID 16515478. This medical article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Antiestrogen withdrawal response	None	26,754	wikipedia	https://en.wikipedia.org/wiki/Antiestrogen_withdrawal_response	2021-01-18T18:46:21	{"wikidata": ["Q97959683"]}
Not to be confused with AV nodal reentrant tachycardia. Atrioventricular reentrant tachycardia Conduction pathway in atrioventricular reentrant tachycardia, a form of supraventricular tachycardia SpecialtyCardiology Atrioventricular reentrant tachycardia (AVRT), or atrioventricular reciprocating tachycardia, is a type of abnormal fast heart rhythm and is classified as a type of supraventricular tachycardia (SVT). AVRT is most commonly associated with Wolff–Parkinson–White syndrome, but is also seen in permanent junctional reentrant tachycardia (PJRT). In AVRT, an accessory pathway allows electrical signals from the heart's ventricles to enter the atria and cause earlier than normal contraction, which leads to repeated stimulation of the atrioventricular node.[1] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Treatment * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] 12 lead electrocardiogram of an individual with Wolff–Parkinson–White syndrome exhibiting 'slurred upstrokes' or 'delta waves' before the QRS complexes An episode of SVT may present with palpitations, dizziness, shortness of breath, or losing consciousness (fainting). The electrocardiogram (ECG) would appear as a narrow-complex SVT. Between episodes of tachycardia the affected person is likely to be asymptomatic; however, the ECG would demonstrate the classic delta wave in Wolff–Parkinson–White syndrome.[2] ## Pathophysiology[edit] Mechanism of AVRT compared with other supraventricular arrhythmias Two distinct pathways are involved: the normal atrioventricular conduction system, and an accessory pathway. During AVRT, the electrical signal passes in the normal manner from the AV node into the ventricles. Then, the electrical impulse pathologically passes back into the atria via the accessory pathway, causing atrial contraction, and returns to the AV node to complete the reentrant circuit (see figure). Once initiated, the cycle may continue causing the heart to beat faster than usual. Initiation of AVRT may be through a premature impulse of atrial, junctional, or ventricular origin.[3] ## Treatment[edit] Acute management is as for SVT in general. The aim is to interrupt the circuit. In the shocked patient, DC cardioversion may be necessary. In the absence of shock, inhibition at the AV node is attempted. This is achieved first by a trial of specific physical maneuvers such as holding a breath in or bearing down. If these maneuvers fail, using intravenous adenosine[4] causes complete electrical blockade at the AV node and interrupts the reentrant electrical circuit. Long-term management includes beta blocker therapy and radiofrequency ablation of the accessory pathway. ## See also[edit] * AV nodal reentrant tachycardia * Electrical conduction system of the heart * Wolff-Parkinson-White syndrome * Permanent junctional reentrant tachycardia (PJRT) ## References[edit] 1. ^ Josephson ME. Preexcitation syndromes. In: Clinical Cardiac Electrophysiology, 4th, Lippincott Williams & Wilkins, Philadelphia 2008. p.339 2. ^ Hampton J. The ECG Made Easy. Elsevier 2008 3. ^ UpToDate: Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway 4. ^ UK Resuscitation Council. Adult tachycardia algorithm. 2010. ## External links[edit] Classification D * ICD-10: I47.1 * ICD-9-CM: 427.89, 427.0 * MeSH: D013617 * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Atrioventricular reentrant tachycardia	c0340477	26,755	wikipedia	https://en.wikipedia.org/wiki/Atrioventricular_reentrant_tachycardia	2021-01-18T18:41:44	{"mesh": ["D013611"], "umls": ["C0340477"], "wikidata": ["Q10859019"]}
## Clinical Features Cherstvoy et al. (1980) referred to a case reported by workers in Kiel and described an apparently identical case of a syndrome of phocomelia, thrombocytopenia, encephalocele and urogenital abnormalities. They called it the 'DK phocomelia syndrome' from the surname of the 2 patients. Bird et al. (1994) described a female fetus with manifestations of DK phocomelia syndrome (occipital encephalocele, cleft palate, absence of the left radius and digits 1 and 2 of the left hand, single horseshoe kidney, anal atresia, abnormal branching of coronary arteries, abnormal lobation of the lungs) and diaphragmatic agenesis. Her brother had diaphragmatic agenesis, omphalocele, accessory spleen, abnormal lobation of the lungs, and absence of papillary muscles in one leaflet of the tricuspid valve. Diaphragmatic agenesis was the only primary defect common to both sibs. Bird et al. (1994) suggested that this family provides evidence for an autosomal gene controlling the morphogenesis of midline structures. Brunetti-Pierri et al. (2004) reported a 16-month-old patient with meningoencephalocele, absence of the radii, ambiguous genitalia, and transient neonatal thrombocytopenia. Thrombocytopenia was present during the first 2 weeks of life but not found on subsequent testing. Despite the neonatal complications and meningoencephalocele, the patient later had normal psychomotor development. Cytogenetics Bamforth and Lin (1997) reported a case in which the patient had normal lymphocyte chromosomes but was mosaic in fibroblasts for deletion of 13q12. All previously reported cases of DK phocomelia had been reported as having a normal chromosomal constitution. The proposita was an 8-year-old girl who had a small parietooccipital encephalocele in the midline at birth as well as asymmetry of the face with flattening of the right side and elevation of the right ear. There was absence of the right fifth finger, hypoplasia of the thumb, and a single, palmar crease. On the other side there was hypoplasia of the fifth finger with dislocation and normal-sized thumb. The hips were dislocated. By 15 months of age, the facial asymmetry had resolved. Renal pelviureteric junction obstruction required surgical relief. When her hair started to grow, she had bald patches. At the age of 9 years, the child developed seizures. There was a wide gap between the central incisors. Population Genetics Bermejo-Sanchez et al. (2011) reported epidemiologic data on phocomelia from 19 birth defect surveillance programs, all members of the International Clearinghouse for Birth Defects Surveillance and Research. Depending on the program, data corresponded to a period from 1968 through 2006. A total of 22,740,933 live births, stillbirths, and, for some programs, elective terminations of pregnancy for fetal anomaly were monitored. After a detailed review of clinical data, only true phocomelia cases were included. Descriptive data were presented and additional analyses compared isolated cases with those with multiple congenital anomalies (MCA), excluding syndromes. Bermejo-Sanchez et al. (2011) also briefly compared congenital anomalies associated with nonsyndromic phocomelia with those presented with amelia (see 601360), another rare severe congenital limb defect. A total of 141 phocomelia cases registered gave an overall total prevalence of 0.62 per 100,000 births (95% confidence interval 0.52-0.73). Three programs, Australia Victoria, South America ECLAMC, and Italy North East, had significantly different prevalence estimates. Most cases (53.2%) had isolated phocomelia, while 9.9% had syndromes. Most nonsyndromic cases were monomelic (55.9%), with an excess of left (64.9%) and upper limb (64.9%) involvement. Most nonsyndromic cases (66.9%) were live births; most isolated cases (57.9%) weighed more than 2,499 grams; most MCA (60.7%) weighed less than 2,500 grams and were more likely stillbirths (30.8%) or terminations (15.4%) than isolated cases. The most common associated defects were musculoskeletal, cardiac, and intestinal. Limbs \- Phocomelia Inheritance \- Autosomal recessive Neuro \- Encephalocele GU \- Urogenital abnormalities Heme \- Thrombocytopenia ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DK PHOCOMELIA SYNDROME	c1857226	26,756	omim	https://www.omim.org/entry/223340	2019-09-22T16:28:40	{"mesh": ["C565618"], "omim": ["223340"], "orphanet": ["3439"], "synonyms": ["Alternative titles", "PHOCOMELIA, THROMBOCYTOPENIA, ENCEPHALOCELE, UROGENITAL MALFORMATIONS", "VON VOSS-CHERSTVOY SYNDROME"]}
Mucinous tubular and spindle cell renal carcinoma is a rare subtype of renal cell carcinoma characterized, histologically, by tubular architecture and sheets of spindle cells embedded in a mucinous/myxoid stroma and, macroscopically, by a solid, generally well-circumscribed, partially encapsulated tumor of variable size, with a homogenously colored, bulging cut surface, occassionally containing areas of hemorrhage or necrosis, usually located in the cortex. Patients can present abdominal/flank pain, adbominal mass and/or hematuria, however most are asymptomatic and tumor is discovered incidentally. Indolent behavior is frequent and association with nephrolithiasis and end-stage kidney disease has been noted. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mucinous tubular and spindle cell renal carcinoma	c4707257	26,757	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319322	2021-01-23T17:04:53	{"icd-10": ["C64"]}
## Clinical Features Ippel et al. (1994) reported 2 sisters and a brother, born to consanguineous Moroccan parents, with sutural cataract, microcephaly, and mental retardation. Retinitis pigmentosa was found in one of sisters at the age of 12 years. Funduscopy was not possible in the 2 other sibs. The same constellation of findings was found in an unrelated Dutch girl. Normal height and the absence of facial dysmorphism and optic atrophy distinguished this syndrome from Cockayne syndrome (216400), infantile Refsum syndrome (see 601539), Mirhosseini Holmes-Walton syndrome (268050), and micro syndrome (600118). Inheritance Ippel et al. (1994) suggested autosomal recessive inheritance of this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MICROCEPHALY, RETINITIS PIGMENTOSA, AND SUTURAL CATARACT	c1832214	26,758	omim	https://www.omim.org/entry/601537	2019-09-22T16:14:39	{"mesh": ["C563296"], "omim": ["601537"]}
A number sign (#) is used with this entry because of evidence that HELIX syndrome (HELIX) is caused by homozygous mutation in the CLDN10 gene (617579) on chromosome 13q32. Clinical Features Klar et al. (2017) studied 13 patients from 2 distantly related consanguineous Pakistani families segregating congenital heat intolerance and generalized anhidrosis. In all patients, the anhidrosis was associated with the inability to produce tears (alacrima) and dry mouth (xerostomia). Several affected individuals developed nephrolithiasis in adolescence, with recurrent bouts of pain. Serum electrolyte analysis revealed increased Mg(2+) levels, and abnormal renal reabsorption of cations was reflected in urine spot samples that showed low concentrations of Mg(2+) and Ca(2+). Parathyroid hormone (PTH; 168450) levels were increased 2- to 3-fold above normal in 2 patients, who also had reduced 25-hydroxy vitamin D levels. These observations suggested secondary hyperparathyroidism and renal damage, further supported by an estimated glomerular filtration rate (eGFR) in the low normal range. Serum creatinine, urea, and bicarbonate were normal, as were CT scans of the kidneys. Pancreatic and lung function were normal. Histologic analysis of patient sweat glands showed normal morphology and number. Hadj-Rabia et al. (2018) reported 6 patients from 2 unrelated consanguineous families with hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia, which the authors designated 'HELIX syndrome.' Dental examination showed severe enamel wear; panoramic dental x-rays of patients from both families showed that enamel formed but eroded quickly after tooth eruption. In both families, affected individuals had dry skin with fine white scaling, predominantly on the arms and knees. Histologic examination of patient skin specimens showed epidermal changes consistent with ichthyosis, including a slightly thickened stratum corneum with follicular ostial dilation and basket-weave keratin, and an increased number of dilated eccrine sweat glands, the epithelial cells of which showed an acantholytic appearance. All 6 patients had high plasma renin levels with normal to high plasma aldosterone and normal to low blood pressure. Plasma potassium was low in adults but normal in children, and 5 of the 6 patients had elevated plasma magnesium levels. All had normal eGFR at first visit, but eGFR decreased in the oldest patient (age 46 years) to less than half the normal value; percutaneous kidney biopsy in that patient showed extensive fibrosis but no specific damage. None of the adult patients had nephrocalcinosis. Analysis of the renal response to furosemide in 3 adult patients showed higher baseline fractional excretion (FE) of sodium and chloride than found in controls, with the FEs increasing to similar values in patients and controls during furosemide infusion. The FE of calcium increased significantly with furosemide, but less in patients than in controls, whereas the FE of magnesium increased more in patients than in controls. Hadj-Rabia et al. (2018) suggested that the renal NaCl wasting syndrome observed in these patients was primarily due to electrolyte transport disturbances in the thick ascending limb of the loop of Henle. Mapping In 2 distantly related consanguineous Pakistani families with generalized anhidrosis, severe heat intolerance, and mild renal failure, Klar et al. (2017) performed autozygosity mapping and identified a homozygous region of 235 consecutive SNPs spanning a 2-Mb interval on chromosome 13q32. Fine mapping with microsatellite markers confirmed homozygosity, and linkage analysis yielded a 2-point lod score of 4.25. Molecular Genetics In 13 affected members of 2 distantly related consanguineous Pakistani families with generalized anhidrosis, severe heat intolerance, and mild renal failure mapping to chromosome 13q32, Klar et al. (2017) identified homozygosity for a missense mutation in the CLDN10 gene (N48K; 617579.0001). The mutation segregated fully with disease in both families and was not found in 600 Pakistani control chromosomes or in the ExAC database. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Alacrima Mouth \- Xerostomia Teeth \- Enamel wear, severe CARDIOVASCULAR Vascular \- Low to low-normal blood pressure ABDOMEN Gastrointestinal \- Polydipsia GENITOURINARY Kidneys \- Polyuria \- Renal NaCl wasting \- Renal failure, mild \- Nephrolithiasis (in some patients) \- Extensive nonspecific fibrosis seen on renal biopsy (in 1 patient) \- Estimated glomerular filtration rate (eGFR) in low-normal range \- Decreased eGFR in the oldest patient SKIN, NAILS, & HAIR Skin \- Generalized hypohidrosis or anhidrosis \- Heat intolerance \- Dry skin \- Fine scaling (predominantly on arms and knees) Skin Histology \- Slightly thickened stratum corneum \- Follicular ostial dilation \- Basket-weave keratin \- Increased number of dilated eccrine sweat glands \- Acantholytic appearance of epithelial cells of eccrine sweat glands ENDOCRINE FEATURES \- Normal to high plasma aldosterone \- Elevated plasma renin levels \- Elevated parathyroid hormone levels LABORATORY ABNORMALITIES \- Hypokalemia (in adults) \- Hypermagnesemia \- Low urinary magnesium \- Hypocalciuria \- Reduced 25-hydroxy vitamin D levels MOLECULAR BASIS \- Caused by mutation in the claudin 10 gene (CLDN10, 617579.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HELIX SYNDROME	c4522164	26,759	omim	https://www.omim.org/entry/617671	2019-09-22T15:45:13	{"omim": ["617671"], "synonyms": ["Alternative titles", "HYPOHIDROSIS, ELECTROLYTE IMBALANCE, LACRIMAL GLAND DYSFUNCTION, ICHTHYOSIS, AND XEROSTOMIA"]}
Punctate palmoplantar keratoderma type I (PPKP1), also known as Buschke-Fischer-Brauer syndrome, is a very rare hereditary skin disease characterized by irregularly distributed epidermal hyperkeratosis of the palms and soles with wide variation among patients.. ## Epidemiology The prevalence of PPK1 has been estimated at 1.17/100,000 in Croatia and 3.3/100,000 in Slovenia. PPK1 has been reported 35 families worldwide to date. ## Clinical description Typical clinical characteristics are multiple hyperkeratotic papules and central indentations that are irregularly distributed on the palms and soles. The lesions usually start to develop in early adolescence but can also present later in life. Sometimes additional confluent thickening of the soles can be observed. Depending on the clinical presentation, PPKP1 can be associated with pain at pressure points, especially on the soles. The lesions may coalesce over pressure points. ## Etiology Mutations in the AAGAB gene (15q22.33-q23) have recently been identified as one of the causes of PPKP1. This gene encodes for the alpha- and gamma-adaptin-binding protein p34 which is involved in the clathrin-mediated pathway and when disrupted causes an increase in the half-life of several receptor tyrosine kinases in basal keratinocytes, leading to hyperproliferation and hyperkeratosis. Mutations in the COL14A1 gene (8q23) have also been identified as causal in some cases in Asia that seem to have a similar phenotype. ## Diagnostic methods Mutational analysis of the AAGAB gene and the COL14A1 gene confirms the clinical diagnosis. Although not specific for PPKP1, histological examination of papules reveals hypergranulosis and hyperkeratosis with a well-defined central epidermal depression. ## Differential diagnosis Differential diagnosis includes Verrucae vulgares and any other form of palmoplantar keratoderma (see this term). ## Genetic counseling PPKP1 is mostly inherited in an autosomal-dominant manner. Genetic counseling is possible. ## Management and treatment Mechanical removal of the hyperkeratosis is the most effective symptomatic treatment. Keratolytic creams can support the effect. In some patients with a severe phenotype, oral retinoids have been shown to reduce the symptoms. ## Prognosis Although the clinical appearance can worsen over time, the general prognosis is good. Depending on the clinical severity and pain sensitivity of patients, quality of life can be affected. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Punctate palmoplantar keratoderma type 1	c1835662	26,760	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79501	2021-01-23T18:34:30	{"gard": ["3103"], "mesh": ["C536161"], "omim": ["148600", "614936"], "icd-10": ["Q82.8"], "synonyms": ["Buschke-Fischer-Brauer syndrome", "Keratodermia palmoplantaris papulosa, Buschke-Fischer-Brauer type", "PPKP1"]}
An X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies). ## Epidemiology Prevalence is unknown but the syndrome was first described in 1984 in three males from two generations of the same family. ## Clinical description The syndrome is characterised by microcephaly, a large anterior fontanel, a characteristic facies (short nose, anteverted nares, epicanthal folds), club foot deformity and delayed psychomotor development. One of the affected males also had renal hypoplasia/dysplasia. All three patients died during infancy. ## Etiology The syndrome is caused by mutations in the ATRX gene (Xq13.3). ## Genetic counseling Inheritance is X-linked recessive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Holmes-Gang syndrome	c0796003	26,761	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93970	2021-01-23T17:33:24	{"mesh": ["C537457"], "omim": ["309580"], "icd-10": ["Q87.0"]}
Not to be confused with Cutaneous lymphoid hyperplasia. Pseudolymphoma SpecialtyAngiology Pseudolymphoma is a benign lymphocytic infiltrate that resembles cutaneous lymphoma histologically, clinically, or both. Lymphoma cutis is the most important type of pseudolymphoma.[1] ## Contents * 1 Presentation * 2 Cause * 3 Diagnosis * 4 References * 5 External links ## Presentation[edit] It manifests with diarrhoea, hepatosplenomegaly, moderate lymph node enlargement without histopathological changes and evidence of the reticulo-endothelial system involvement.[2] ## Cause[edit] This section is empty. You can help by adding to it. (July 2018) It is an adverse effect of phenytoin. ## Diagnosis[edit] This section is empty. You can help by adding to it. (July 2018) ## References[edit] 1. ^ Venkataram (1 January 2007). Fundamental of Pathology of Skin, 3/ed. BI Publications Pvt Ltd. p. 233. ISBN 978-81-7225-303-5. 2. ^ Halevy, S; Feuerman, EJ (1977). "Pseudolymphoma syndrome". Dermatologica. 155 (6): 321–7. PMID 144619. ## External links[edit] Classification D * MeSH: D019310 External resources * eMedicine: article/1099188 article/1098583 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Pseudolymphoma	c0221269	26,762	wikipedia	https://en.wikipedia.org/wiki/Pseudolymphoma	2021-01-18T18:35:31	{"mesh": ["D019310"], "umls": ["C0221269"], "wikidata": ["Q1592207"]}
## Clinical Features Mirkinson and Mirkinson (1975) reported this combination in a boy, his father, and his paternal grandmother. In the grandmother, bilateral cataracts and glaucoma complicated the aniridia. The patella was either hypoplastic or aplastic. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Aniridia \- Cataracts \- Glaucoma SKELETAL Limbs \- Hypoplastic patella ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ANIRIDIA AND ABSENT PATELLA	c1862868	26,763	omim	https://www.omim.org/entry/106220	2019-09-22T16:45:01	{"mesh": ["C566281"], "omim": ["106220"], "orphanet": ["1069"]}
## Clinical Features Sorgo et al. (1991) reported agonadism associated with multiple internal malformations in a 46,XY female and her 46,XX sister. In a later study of this family, Kennerknecht et al. (1993) interpreted the family as representing a gene mutation that led to the regression of midline structures including the gonadal anlage. Kennerknecht et al. (1993) noted that the 2 girls had similar internal malformations, including agonadism, hypoplasia of the right pulmonary artery, hypoplasia of the right lung, isolated dextrocardia with complex cardiac malformation, and diaphragmatic hernia or omphalocele (each in 1 sib only). They suggested that the disorder be called PAGOD syndrome for pulmonary hypoplasia, hypoplasia of the pulmonary artery, agonadism, omphalocele/diaphragmatic defect, and dextrocardia. The different sex chromosome status excluded the Y chromosome as the responsible factor. The finding of a 46,XX sex chromosome constitution combined with agonadism and an intact urogenital tract emphasized the concept of secondary regression of wolffian and mullerian structures. Kennerknecht et al. (1993) pointed to a similar situation of familial XY and XX agonadism in 2 sisters (600171) reported by Mendonca et al. (1993). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PAGOD SYNDROME	c1859967	26,764	omim	https://www.omim.org/entry/202660	2019-09-22T16:31:23	{"mesh": ["C537018"], "omim": ["202660"], "orphanet": ["991"], "synonyms": ["Alternative titles", "Pulmonary hypoplasia-agonadism-dextrocardia-diaphragmatic hernia syndrome", "AGONADISM WITH MULTIPLE INTERNAL MALFORMATIONS"]}
Bagassosis SpecialtyPulmonology Bagassosis, an interstitial lung disease, is a type of hypersensitivity pneumonitis attributed to exposure to moldy molasses (bagasse).[1][2] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Prevention * 4 History * 5 References * 6 External links ## Signs and symptoms[edit] Some symptoms and signs of Bagassosis include breathlessness, cough, haemoptysis, slight fever. Acute diffuse bronchiolitis may also occur. An xray may show mottling of lungs or a shadow. ## Cause[edit] Bagassosis has been shown to be due to a thermophilic actinomycetes for which the name thermoactinomycetes sacchari was suggested. ## Prevention[edit] The following are precautionary measures that can be taken to avoid the spread of bagassosis: 1. Dust control-prevention /suppression of dust such as wet process, enclosed apparatus, exhaust ventilation etc. should be used 2. Personal protection- masks/ respirators 3. Medical control- initial medical examination & periodical checkups of workers 4. Bagasse control- keep moisture content above 20% and spray bagasse with 2% propionic acid[3] ## History[edit] Bagassosis was first reported in India by Ganguly and Pal in 1955, in a cardboard manufacturing plant near Kolkata. India has a large cane sugar industry. The sugarcane fibre which, until recently, went to waste, is now utilised in the manufacture of cardboard, paper and rayon. ## References[edit] 1. ^ Hur, T; Cheng KC; Yang GY (October 1994). "Hypersensitivity pneumonitis: bagassosis". Gaoxiong Yi Xue Ke Xue Za Zhi. 10 (10): 558–564. PMID 7807612. 2. ^ Ueda A, Aoyama K, Ueda T, et al. (July 1992). "Recent trends in bagassosis in Japan". Br J Ind Med. 49 (7): 499–506. doi:10.1136/oem.49.7.499. PMC 1039272. PMID 1637710. 3. ^ Park's textbook of preventive & social medicine 21st edition page-747 ## External links[edit] Classification D * ICD-10: J67.1 * ICD-9-CM: 495.1 * MeSH: D011009 * DiseasesDB: 29637 * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Bagassosis	c0004681	26,765	wikipedia	https://en.wikipedia.org/wiki/Bagassosis	2021-01-18T19:09:45	{"mesh": ["D011009"], "umls": ["C0004681"], "wikidata": ["Q4841462"]}
Mental Disorder For other uses, see SAD (disambiguation). Schizoaffective disorder SpecialtyPsychiatry SymptomsHallucinations, delusions, disorganized thinking, depressed mood, manic behavior[1] ComplicationsSocial isolation, suicide Usual onset16-30 TypesBipolar type,[2] depressive type[3] CausesUnknown[4] Risk factorsGenetics, brain chemistry and structure, stress, drug use, trauma from abuse[4] Differential diagnosisPsychotic depression, bipolar disorder with psychotic features, schizophreniform disorder, schizophrenia MedicationAntipsychotics, mood stabilizers PrognosisDepends on the individual, medication response, and therapeutic support available Frequency0.5 - 0.8% Schizoaffective disorder (SZA, SZD or SAD) is a mental disorder characterized by abnormal thought processes and an unstable mood.[5][6] The diagnosis is made when the person has symptoms of both schizophrenia (usually psychosis) and a mood disorder—either bipolar disorder or depression—but does not meet the diagnostic criteria for schizophrenia or a mood disorder individually.[5][6] The main criterion for the schizoaffective disorder diagnosis is the presence of psychotic symptoms for at least two weeks without any mood symptoms present.[6] Schizoaffective disorder can often be misdiagnosed[6] when the correct diagnosis may be psychotic depression, psychotic bipolar disorder, schizophreniform disorder, or schizophrenia. It is imperative for providers to accurately diagnose patients, as treatment and prognosis differs greatly for each of these diagnoses.[6][7] There are two types of schizoaffective disorder: the bipolar type, which is distinguished by symptoms of mania, hypomania, or mixed episode; and the depressive type, which is distinguished by symptoms of depression only.[5][6] Common symptoms of the disorder include hallucinations, delusions, and disorganized speech and thinking.[8] Auditory hallucinations, or "hearing voices," are most common.[9] The onset of symptoms usually begins in young adulthood. Genetics (researched in the field of genomics); problems with neural circuits; chronic early, and chronic or short-term current environmental stress appear to be important causal factors. No single isolated organic cause has been found, but extensive evidence exists for abnormalities in the metabolism of tetrahydrobiopterin (BH4), dopamine, and glutamic acid in people with schizophrenia, psychotic mood disorders, and schizoaffective disorder. People with schizoaffective disorder are likely to have co-occurring conditions, including anxiety disorders and substance use disorders. The mainstay of current treatment is antipsychotic medication combined with mood stabilizer medication or antidepressant medication, or both. There is growing concern by some researchers that antidepressants may increase psychosis, mania, and long-term mood episode cycling in the disorder.[citation needed] When there is risk to self or others, usually early in treatment, hospitalization may be necessary.[10] Psychiatric rehabilitation, psychotherapy, and vocational rehabilitation are very important for recovery of higher psychosocial function. As a group, people with schizoaffective disorder that were diagnosed using DSM-IV and ICD-10 criteria (which have since been updated) have a better outcome,[5][6] but have variable individual psychosocial functional outcomes compared to people with mood disorders, from worse to the same.[6][11][non-primary source needed] Outcomes for people with DSM-5 diagnosed schizoaffective disorder depend on data from prospective cohort studies, which have not been completed yet.[6] The DSM-5 diagnosis was updated because DSM-IV criteria resulted in overuse of the diagnosis;[10] that is, DSM-IV criteria led to many patients being misdiagnosed with the disorder. DSM-IV prevalence estimates were less than one percent of the population, in the range of 0.5–0.8 percent;[12] newer DSM-5 prevalence estimates are not yet available. ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Substance abuse * 3 Diagnosis * 3.1 DSM-5 criteria * 3.1.1 Types * 3.1.2 Problems with DSM-IV schizoaffective disorder * 3.1.3 DSM-5 research directions * 4 Treatment * 4.1 Therapy * 4.2 Medication * 4.3 Electroconvulsive therapy * 5 Epidemiology * 6 History * 7 Research * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Schizoaffective disorder is defined by mood disorder-free psychosis in the context of a long-term psychotic and mood disorder.[6] Psychosis must meet criterion A for schizophrenia which may include delusions, hallucinations, disorganized speech or behavior and negative symptoms.[6] Both delusions and hallucinations are classic symptoms of psychosis.[13] Delusions are false beliefs which are strongly held despite evidence to the contrary.[13] Beliefs should not be considered delusional if they are in keeping with cultural beliefs. Delusional beliefs may or may not reflect mood symptoms (for example, someone experiencing depression may or may not experience delusions of guilt). Hallucinations are disturbances in perception involving any of the five senses, although auditory hallucinations (or "hearing voices") are the most common. Negative symptoms include asociality (lack of desire to form relationship), alogia (lack of speech), blunted affect (reduced intensity of outward emotional expression), avolition (lack of motivation), and anhedonia (inability to experience pleasure).[13] Negative symptoms can be more lasting and more debilitating than positive symptoms of psychosis. Mood symptoms are of mania, hypomania, mixed episode, or depression, and tend to be episodic rather than continuous. A mixed episode represents a combination of symptoms of mania and depression at the same time. Symptoms of mania include elevated or irritable mood, grandiosity (inflated self-esteem), agitation, risk-taking behavior, decreased need for sleep, poor concentration, rapid speech, and racing thoughts.[13] Symptoms of depression include low mood, apathy, changes in appetite or weight, disturbances in sleep, changes in motor activity, fatigue, guilt or feelings of worthlessness, and suicidal thinking. DSM-5 states that if a patient only experiences psychotic symptoms during a mood episode, their diagnosis is Mood Disorder with Psychotic Features and not Schizophrenia or Schizoaffective Disorder. If the patient experiences psychotic symptoms without mood symptoms for longer than a two-week period, their diagnosis is either Schizophrenia or Schizoaffective Disorder. If mood disorder episodes are present for the majority and residual course of the illness and up until the diagnosis, the patient can be diagnosed with Schizoaffective Disorder.[5] ## Causes[edit] A combination of genetic and environmental factors are believed to play a role in the development of schizoaffective disorder.[14][15] > Genetic studies do not support the view that schizophrenia, psychotic mood disorders and schizoaffective disorder are distinct etiological entities, but rather the evidence suggests the existence of common inherited vulnerability that increases the risks for all these syndromes. Some susceptibility pathways may be specific for schizophrenia, others for bipolar disorder, and yet other mechanisms and genes may confer risk for mixed schizophrenic and affective [or mood disorder] psychoses, but there is no support from genetics for the view that these are distinct disorders with distinct etiologies and pathogenesis. Laboratory studies of putative endophenotypes, brain imaging studies, and post mortem studies shed little additional light on the validity of the schizoaffective disorder diagnosis, as most studies combine subjects with different chronic psychoses in comparison to healthy subjects. > > — According to William T. Carpenter the head of the University of Maryland, Baltimore School of Medicine DSM-5 psychotic disorders workgroup, and others.[6] Viewed broadly then, biological and environmental factors interact with a person's genes in ways which may increase or decrease the risk for developing schizoaffective disorder; exactly how this happens (the biological mechanism) is not yet known. Schizophrenia spectrum disorders, of which schizoaffective disorder is a part, have been increasingly linked to advanced paternal age at the time of conception, a known cause of genetic mutations.[16] The physiology of people diagnosed with schizoaffective disorder appears to be similar, but not identical, to that of those diagnosed with schizophrenia and bipolar disorder; however, human neurophysiological function in normal brain and mental disorder syndromes is not fully understood.[9] ### Substance abuse[edit] A clear causal connection between drug use and psychotic spectrum disorders, including schizoaffective disorder, has been difficult to prove. In the specific case of cannabis (marijuana), however, evidence supports a link between earlier onset of psychotic illness and cannabis use.[17] The more often cannabis is used, particularly in early adolescence, the more likely a person is to develop a psychotic illness,[18][19][20] with frequent use being correlated with double the risk of psychosis and schizoaffective disorder.[21] A 2009 Yale review stated that in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness.[22] While cannabis use is accepted as a contributory cause of schizoaffective disorder by many,[23] it remains controversial,[24][25] since not all young people who use cannabis later develop psychosis, but those who do use cannabis have an increased odds ratio of about 3.[26] Certain drugs can imitate symptoms of schizophrenia (which we know has similar symptoms to schizoaffective disorder). This is important to note when including that substance-induced psychosis should be ruled out when diagnosing patients so that patients are not misdiagnosed.[6] ## Diagnosis[edit] Psychosis as a symptom of a psychiatric disorder is first and foremost a diagnosis of exclusion.[27] So a new-onset episode of psychosis cannot be considered to be a symptom of a psychiatric disorder until other relevant and known medical causes of psychosis are excluded, or ruled out.[27] Many clinicians improperly perform, or entirely miss this step, introducing avoidable diagnostic error and misdiagnosis.[27] An initial assessment includes a comprehensive history and physical examination. Although no biological laboratory tests exist which confirm schizoaffective disorder, biological tests should be performed to exclude psychosis associated with or caused by substance use, medications, toxins or poisons, surgical complications, or other medical illnesses. Since non-medical mental health practitioners are not trained to exclude medical causes of psychosis, people experiencing psychosis should be referred to an emergency department or hospital. Delirium should be ruled out, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, indicating other underlying factors which includes medical illnesses.[27] Excluding medical illnesses associated with psychosis is performed by using blood tests to measure: * Thyroid-stimulating hormone to exclude hypo- or hyperthyroidism, * Basic electrolytes and serum calcium to rule out a metabolic disturbance, * Full blood count including ESR to rule out a systemic infection or chronic disease, and * Serology to exclude syphilis or HIV infection. Other investigations which may be performed include: * EEG to exclude epilepsy, and an * MRI or CT scan of the head to exclude brain lesions. Blood tests are not usually repeated for relapse in people with an established diagnosis of schizoaffective disorder, unless there is a specific medical indication. These may include serum BSL if olanzapine has previously been prescribed, thyroid function if lithium has previously been taken to rule out hypothyroidism, liver function tests if chlorpromazine has been prescribed, CPK levels to exclude neuroleptic malignant syndrome, and a urinalysis and serum toxicology screening if substance use is suspected. Assessment and treatment may be done on an outpatient basis; admission to an inpatient facility is considered if there is a risk to self or others. Because psychosis may be precipitated or exacerbated by common classes of psychiatric medications, such as antidepressants,[28][29][30][31][32] ADHD stimulant medications,[33][34][35] and sleep medications,[36][37] prescribed medication-induced psychosis should be ruled out, particularly for first-episode psychosis.[27] This is an essential step to reduce diagnostic error and to evaluate potential medication sources of further patient harm.[27] Regarding prescribed medication sources of patient harm, Yale School of Medicine Professor of Psychiatry Malcolm B. Bowers, Jr, MD wrote:[38][self-published source] > Illicit drugs aren't the only ones that precipitate psychosis or mania—prescribed drugs can too, and in particular, some psychiatric drugs. We investigated this and found that about 1 in 12 psychotic or manic patients in an inpatient psychiatric facility are there due to antidepressant-induced psychosis or mania. That's unfortunate for the field [of psychiatry] and disastrous for some of our patients. > It is important to be understood here. I want to call attention to the fact that some persons with a family history of even the subtler forms of bipolar disorder or psychosis are more vulnerable than others to the mania- or psychosis-inducing potential of antidepressants, stimulants and sleeping medications. While I'm not making a blanket statement against these medications, I am urging caution in their use. I believe [clinicians] should ask patients and their families whether there is a family history of bipolar disorder or psychosis before prescribing these medications. Most patients and their families don't know the answer when they are first asked, so time should be allowed for the patient to ask family or relatives, between the session when asked by [the clinician] and a follow-up session. This may increase the wait for a medication slightly, but because some patients are vulnerable, this is a necessary step for [the clinician] to take. I believe that psychiatry as a field has not emphasized this point sufficiently. As a result, some patients have been harmed by the very treatments that were supposed to help them; or to the disgrace of psychiatry, harmed and then misdiagnosed.[28][29][30][31][34][35][36][37] Substance-induced psychosis should also be ruled out. Both substance- and medication-induced psychosis can be excluded to a high level of certainty while the person is psychotic, typically in an emergency department, using both a * Broad spectrum urine toxicology screening, and a * Full serum toxicology screening (of the blood). Some dietary supplements may also induce psychosis or mania, but cannot be ruled out with laboratory tests. So a psychotic person's family, partner, or friends should be asked whether he or she is currently taking any dietary supplements.[39] Common mistakes made when diagnosing psychotic patients include:[27] * Not properly excluding delirium, * Missing a toxic psychosis by not screening for substances and medications, * Not appreciating medical abnormalities (e.g., vital signs), * Not obtaining a medical history and family history, * Indiscriminate screening without an organizing framework, * Not asking family or others about dietary supplements, * Premature diagnostic closure, and * Not revisiting or questioning the initial diagnostic impression of primary psychiatric disorder. Only after these relevant and known causes of psychosis have been ruled out can a psychiatric differential diagnosis be made. A mental health clinician will incorporate family history, observation of a psychotic person's behavior while the person is experiencing active symptoms, to begin a psychiatric differential diagnosis. Diagnosis also includes self-reported experiences, as well as behavioral abnormalities reported by family members, friends, or significant others. Mistakes in this stage include: * Not screening for dissociative disorders. Dissociative identity disorder and psychotic symptoms in schizoaffective disorder have considerable overlap, yet a different overall treatment approach.[40] ### DSM-5 criteria[edit] The most widely used criteria for diagnosing schizoaffective disorder are from the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders-5.[6] The DSM-IV schizoaffective disorder definition was plagued by problems of being inconsistently (or unreliably) used on patients;[6] when the diagnosis is made, it doesn't stay with most patients over time;[6] and it has questionable diagnostic validity (that is, it doesn't describe a distinct disorder, nor predict any particular outcome).[6] These problems have been slightly reduced (or "modestly improved") in the DSM-5 according to Carpenter.[6] When psychotic symptoms are confined to an episode of mania or depression (with or without mixed features), the diagnosis is that of a “psychotic” mood disorder, namely either psychotic bipolar disorder or psychotic major depression. Only when psychotic states persist in a sustained fashion for two weeks or longer without concurrent affective symptoms is the diagnosis schizoaffective disorder, schizophreniform disorder or schizophrenia.[6] The second cardinal guideline in the DSM-5 diagnosis of schizoaffective disorder is one of timeframe. DSM-5 requires two episodes of psychosis (whereas DSM-IV needed only one) to qualify for the schizoaffective disorder diagnosis.[6] As such, it is no longer an "episode diagnosis."[6] The new schizoaffective framework looks at the time from "the [first episode of] psychosis up to the current episode [of psychosis], rather than only defining a single episode with [co-occurring] psychotic and mood syndromes."[6] Specifically, one of the episodes of psychosis must last a minimum of two weeks without mood disorder symptoms, but the person may be mildly to moderately depressed while psychotic.[6] The other period of psychosis "requires the overlap of mood [disorder] symptoms with psychotic symptoms to be conspicuous" and last for a greater portion of the disorder.[41] These two changes are intended by the DSM-5 workgroup to accomplish two goals:[6] * Increase the diagnosis' consistency (or reliability) when it is used; * Significantly decrease the overall use of the schizoaffective disorder diagnosis. If the schizoaffective diagnosis is used less often, other diagnoses (like psychotic mood disorders and schizophrenia) are likely to be used more often; but this is hypothetical until real-world data arrive. Validity problems with the diagnosis remain and await further work in the fields of psychiatric genetics, neuroimaging, and cognitive science that includes the overlapping fields of cognitive, affective, and social neuroscience, which may change the way schizoaffective disorder is conceptualized and defined in future versions of the DSM and ICD.[6][42] #### Types[edit] One of two types of schizoaffective disorder may be noted in a diagnosis based on the mood component of the disorder:[5][6] * Bipolar type, when the disturbance includes manic episodes, hypomania, or mixed episodes—major depressive episodes also typically occur; * Depressive type, when the disturbance includes major depressive episodes exclusively—that is, without manic, hypomanic, or mixed episodes. #### Problems with DSM-IV schizoaffective disorder[edit] The American Psychiatric Association's DSM-IV criteria for schizoaffective disorder persisted for 19 years (1994–2013). Clinicians adequately trained in diagnosis used the schizoaffective diagnosis too often,[6] largely because the criteria were poorly defined, ambiguous, and hard to use (or poorly operationalized).[6][43] Poorly trained clinicians used the diagnosis without making necessary exclusions of common causes of psychosis, including some prescribed psychiatric medications.[6] Specialty books written by experts on schizoaffective disorder have existed for over eight years before DSM-5 describing the overuse of the diagnosis.[44][45][46][47] Carpenter and the DSM-5 schizoaffective disorders workgroup analyzed data made available to them in 2009, and reported in May 2013 that:[6] > a recent review of psychotic disorders from large private insurance and Medicare databases in the U.S. found that the diagnosis of DSM-IV schizoaffective disorder was used for about a third of cases with non-affective psychotic disorders. Hence, this unreliable and poorly defined diagnosis is clearly overused. As stated above, the DSM-IV schizoaffective disorder diagnosis is very inconsistently used or unreliable.[6] A diagnosis is unreliable when several different mental health professionals observing the same individual make different diagnoses excessively.[6] Even when a structured DSM-IV diagnostic interview and best estimate procedures were made by experts in the field that included information from family informants and prior clinical records, reliability was still poor for the DSM-IV schizoaffective diagnosis.[6] The DSM-IV schizoaffective diagnosis isn't stable over time either.[6] An initial diagnosis of schizoaffective disorder during time spent at a psychiatric inpatient facility was stable at 6-month and 24-month follow ups for only 36% of patients.[6] By comparison, diagnostic stability was 92% for schizophrenia, 83% for bipolar disorder and 74% for major depression.[6] Most patients diagnosed with DSM-IV schizoaffective disorder are later diagnosed with a different disorder, and that disorder is more stable over time than the DSM-IV schizoaffective disorder diagnosis.[6] In April 2009, Carpenter and the DSM-5 schizoaffective disorder workgroup reported that they were "developing new criteria for schizoaffective disorder to improve reliability and face validity," and were "determining whether the dimensional assessment of mood [would] justify a recommendation to drop schizoaffective disorder as a diagnostic category."[12] Speaking to an audience at the May 2009 annual conference of the American Psychiatric Association, Carpenter said:[12] > We had hoped to get rid of schizoaffective [disorder] as a diagnostic category [in the DSM-5] because we don't think it's [a] valid [scientific entity] and we don't think it's reliable. On the other hand, we think it's absolutely indispensable to clinical practice. A major reason why DSM-IV schizoaffective disorder was indispensable to clinical practice is because it offered clinicians a diagnosis for patients with psychosis in the context of mood disorder whose clinical picture, at the time diagnosed, appeared different from DSM-IV "schizophrenia" or "mood disorder with psychotic features." But DSM-IV schizoaffective disorder carries an unnecessarily worse prognosis than a "mood disorder with psychotic features" diagnosis,[6] because long-term data revealed that a significant proportion of DSM-IV schizoaffective disorder patients had 15-year outcomes indistinguishable from patients with mood disorders with or without psychotic features,[6][11] even though the clinical picture at the time of first diagnosis looked different from both schizophrenia and mood disorders.[6][11] These problems with the DSM-IV schizoaffective disorder definition result in most people the diagnosis is used on being misdiagnosed;[6] furthermore, outcome studies done 10 years after the diagnosis was released showed that the group of patients defined by the DSM-IV and ICD-10 schizoaffective diagnosis had significantly better outcomes than predicted, so the diagnosis carries a misleading and unnecessarily poor prognosis.[6] The DSM-IV criteria for schizoaffective disorder will continue to be used on U.S. board examinations in psychiatry through the end of 2014; established practitioners may continue to use the problematic DSM-IV definition much further into the future also. #### DSM-5 research directions[edit] The new schizoaffective disorder criteria continue to have questionable diagnostic validity.[6] Questionable diagnostic validity does not doubt that people with symptoms of psychosis and mood disorder need treatment—psychosis and mood disorder must be treated. Instead, questionable diagnostic validity means there are unresolved problems with the way the DSM-5 categorizes and defines schizoaffective disorder. Emil Kraepelin's dichotomy (c. 1898) continues to influence classification and diagnosis in psychiatry A core concept in modern psychiatry since DSM-III was released in 1980, is the categorical separation of mood disorders from schizophrenia, known as the Kraepelinian dichotomy. Emil Kraepelin introduced the idea that schizophrenia was separate from mood disorders after observing patients with symptoms of psychosis and mood disorder, over a century ago, in 1898. This was a time before genetics were known and before any treatments existed for mental illness.[48] The Kraepelinian dichotomy wasn't used for DSM-I and DSM-II because both manuals were influenced by the dominant psychodynamic psychiatry of the time,[49] but the designers of DSM-III wanted to use more scientific and biological definitions.[49] Consequently, they looked to psychiatry's history and decided to use the Kraepelinian dichotomy as a foundation for the classification system. The Kraepelinian dichotomy continues to be used in DSM-5 despite having been challenged by data from modern psychiatric genetics for over eight years,[50] and there is now evidence of a significant overlap in the genetics of schizophrenia and bipolar disorder.[48] According to this genetic evidence, the Kraepelinian categorical separation of mood disorders from schizophrenia at the foundation of the current classification and diagnostic system is a mistaken false dichotomy.[48][51] The dichotomy at the foundation of the current system forms the basis for a convoluted schizoaffective disorder definition in DSM-IV that resulted in excessive misdiagnosis.[6] Real life schizoaffective disorder patients have significant and enduring symptoms that bridge what are incorrectly assumed to be categorically separate disorders, schizophrenia and bipolar disorder.[52] People with psychotic depression, bipolar disorder with a history of psychosis, and schizophrenia with mood symptoms also have symptoms that bridge psychosis and mood disorders.[48][51] The categorical diagnostic manuals don't reflect reality in their separation of psychosis (via the schizophrenia diagnosis) from mood disorder, nor do they currently emphasize the actual overlap found in real-life patients.[48][51] Thus, they are likely to continue to introduce either-or conceptual and diagnostic error, by way of confirmation bias into clinicians' mindsets, hindering accurate assessment and treatment.[48][51] The new definition continues the lack of parsimony of the old definition.[6][52] Simpler, clearer, and more usable definitions of the diagnosis were supported by certain members of the DSM-5 workgroup (see next paragraph); these were debated but deemed premature, because more "research [is] needed to establish a new classification system of equal or greater validity"[52] to the existing system.[6][52] Because of DSM-5's continuing problematic categorical foundation, schizoaffective disorder's conceptual and diagnostic validity remains doubtful.[48][51] After enough research is completed and data exists, future diagnostic advances will need to either eliminate and replace, or soften and bridge, the hard categorical separation of mood disorders from schizophrenia; most likely using a spectrum or dimensional approach to diagnosis.[6][51] More parsimonious definitions than the current one were considered by Carpenter and the DSM-5 workgroup:[6] > One option for the DSM-5 would have been to remove the schizoaffective disorder category and to add affective [or mood] symptoms [that is, mania, hypomania, mixed episode, or depression] as a dimension to schizophrenia and schizophreniform disorder or to define a single category for the co-occurrence of psychosis and mood symptoms. This option was extensively debated but ultimately deemed to be premature in the absence of sufficient clinical and theoretical validating data justifying such a … reconceptualization. Additionally, there appeared to be no practical way to introduce affect [or mood] dimensions covering the entire course of illness, that would capture the current concept of periods of psychosis related and unrelated to mood episodes. > [N]o valid biomarkers or laboratory measures have emerged to distinguish between affective psychosis [or psychotic mood disorders] and schizophrenia. To the contrary, the idea of a dichotomy between these types of conditions has proven naïve. [T]he admixture of “schizophrenic” and affective [or mood] symptoms is a feature of many, or even most, cases with severe mental illness. Most presenting symptoms of psychosis have little validity in determining diagnosis, prognosis, or treatment response in psychosis. [U]ltimately a more … dimensional approach [to assessment and treatment] will be required. The field of psychiatry has begun to question its assumptions and analyze its data in order to merge closer with evidence-based medicine.[51] The removal of the "episode diagnosis," and the addition of two episodes of psychosis, as qualifications for the DSM-5 schizoaffective diagnosis, may improve the diagnosis' consistency over DSM-IV for research purposes, where diagnostic criteria are by necessity followed exactingly.[41] But the new definition remains long, unwieldy, and perhaps still not very useful for community clinicians—with two psychoses, one for two weeks minimum and without mood disorder (but the person can be mildly or moderately depressed) and the other with significant mood disorder and psychosis lasting for most of the time, and with lasting mood symptoms for most of the residual portion of the illness.[6][41] Community clinicians used the previous definition "for about a third of cases with non-affective psychotic disorders."[6] Non-affective psychotic disorders are, by definition, not schizoaffective disorder. For clinicians to make such sizeable errors of misdiagnosis may imply systemic problems with the schizoaffective disorder diagnosis itself. Already, at least one expert believes the new schizoaffective definition hasn't gone far enough to solve the previous definition's problems.[41] From a scientific standpoint, modern clinical psychiatry is still a very young, underdeveloped medical specialty because its target organ, the human brain, is not yet well understood. The human brain's neural circuits, for example, are just beginning to be mapped by modern neuroscience in the Human Connectome Project and CLARITY. Clinical psychiatry, furthermore, has begun to understand and acknowledge its current limitations—but further steps by the field are required to significantly reduce misdiagnosis and patient harm; this is crucial both for responsible patient care and to retain public trust. Looking forward, a paradigm shift is needed in psychiatric research to address unanswered questions about schizoaffective disorder. The dimensional Research Domain Criteria project currently being developed by the U.S. National Institutes of Mental Health, may be the specific problem solving framework psychiatry needs to develop a more scientifically mature understanding of schizoaffective disorder as well as all other mental disorders.[53] ## Treatment[edit] The primary treatment of schizoaffective disorder is medication, with improved outcomes using combined long-term psychological and social supports.[14] Hospitalization may occur for severe episodes either voluntarily or (if mental health legislation allows it) involuntarily. Long-term hospitalization is uncommon since deinstitutionalization started in the 1950s, although it still occurs.[10] Community support services including drop-in centers, visits by members of a community mental health team, supported employment[54] and support groups are common. Evidence indicates that regular exercise has a positive effect on the physical and mental health of those with schizoaffective disorder.[55] Participating in internet forums is sometimes used by people with schizoaffective disorder in addition to outpatient medication treatment.[citation needed] ### Therapy[edit] Skillfully delivered psychosocial treatments are perhaps the most important component of pushing for and encouraging improved overall functioning in schizoaffective disorder. Supportive psychotherapy and cognitive behavioral therapy are both helpful.[56] Intensive case management (ICM) has been shown to reduce hospitalizations, improve adherence to treatment, and improve social functioning.[57] With ICM, clients are assigned a case manager responsible for coordination of care and assisting clients to access supports to address needs in multiple areas related to well-being, including housing. High quality psychosocial or psychiatric rehabilitation is very important for recovery from schizoaffective disorder. Psychiatric or psychosocial rehabilitation focuses on solving community integration problems such as obtaining and keeping housing and increasing involvement in positive social groups. It also focuses on improving and increasing activities of daily living; increasing daily healthy habits (such as normalizing sleep-wake cycles; increasing early morning natural light exposure; increasing moderate exercise [such as 20–30 minutes of moderate to brisk early morning to pre-afternoon walking daily, in order to help normalize circadian rhythms]; helping individuals understand the specific benefits of healthy food choices; increasing stress-reduction activities such as yoga, tai chi, or meditation); and decreasing unhealthy behaviors (such as substance abuse and smoking); thereby significantly improving quality of life. High quality psychiatric rehabilitation may also focus on vocational rehabilitation including preparing the client for volunteer, part-time paid work, returning to school for further education, job skills training for full-time flexible or supported employment, and other client self-improvement efforts. Core principles of effective psychiatric rehabilitation must include providing hope when the client lacks it, respect for the client wherever they are in the recovery process, empowering the client, teaching the client wellness planning, and emphasizing the importance for the client to develop social support networks.[58] A long-term goal of psychiatric and vocational rehabilitation is that the client learn and actively engage in active stress management while in education or employment, while receiving treatment. Psychiatric rehabilitation consists of eight main areas: * Psychiatric (symptom reduction and management) * Health and Medical (maintaining consistency of care) * Housing (safe environments) * Basic living skills (hygiene, meals [including increasing healthy food intake and reducing processed food intake], safety, planning and chores) * Social (relationships, family boundaries, communication and integration of client into the community) * Education and vocation (coping skills, motivation and suitable goals chosen by client) * Finance (personal budget) * Community and legal (resources) ### Medication[edit] Antipsychotic medication is usually required both for acute treatment and the prevention of relapse.[13][59] There is no single antipsychotic of choice in treating schizoaffective disorder, but atypical antipsychotics should be considered because they have mood-stabilizing activity.[13][56] Paliperidone is an antipsychotic with FDA approval for the treatment of schizoaffective disorder.[60] Antipsychotics should be used at the minimum dose necessary to control symptoms.[56] Potential side effects include extrapyramidal symptoms, including tremor, muscle stiffness, and restlessness or akathisia.[61] Atypical antipsychotics carry a risk of metabolic syndrome, including weight gain, increased blood sugar, and increased blood cholesterol, so regular monitoring of weight and blood work should be carried out.[61] Some atypical antipsychotics, such as ziprasidone and aripiprazole, are associated with less risk than others, such as olanzapine.[56][61] Medication choice is based on how effectively it reduces symptoms, how few side effects it causes, and cost. In people with treatment-refractory psychosis, a clozapine trial should be considered.[13] Clozapine is an atypical antipsychotic that is recognized as being particularly effective when other antipsychotic agents have failed.[61] Clozapine should also be considered in people with chronic and persistent suicidal thinking and behaviour, as it has been shown to reduce the risk of suicide in patients with schizoaffective disorder and a history of suicidality.[59] Between 0.5 and 2% of patients taking clozapine may develop a life-threatening complication called agranulocytosis, which is a significant drop in a type of white blood cell.[62] Because of this risk, people taking clozapine must have regular monitoring of blood cell counts.[62] The management of the bipolar type of schizoaffective disorder is similar to the treatment of bipolar disorder, with the goal of preventing mood episodes and cycling.[61] Lithium or anticonvulsant mood stabilizers such as valproic acid, carbamazepine, and lamotrigine are prescribed in combination with an antipsychotic.[56] For depression, if an antidepressant is prescribed, extra attentiveness must be given by the prescribing clinician due its risk for long-term mood cycle acceleration (that is, inducing more frequent episodes of depression per unit of time) and medication-induced psychosis or mania.[28][29][30][31] For individuals who show emerging psychosis, mania, mixed episode symptoms, or mood cycle acceleration, switching to an antipsychotic plus lithium or lamotrigine is preferable to antidepressants. For individuals who experience anxiety, anti-anxiety medications can be used, usually on a short-term basis.[56] Benzodiazepines, including lorazepam, clonazepam and diazepam, are types of anti-anxiety medications. Care must be taken when prescribing benzodiazepines due to the risk of the person developing tolerance and dependence.[61] ### Electroconvulsive therapy[edit] Electroconvulsive therapy, or ECT, may be considered for patients with schizoaffective disorder experiencing severe depression or severe psychotic symptoms that have not responded to treatment with antipsychotics.[59] ## Epidemiology[edit] Schizoaffective disorder is estimated to occur in 0.5 to 0.8 percent of people at some point in their life.[63] 30% of cases occur between the ages of 25 and 35.[64] It is more common in women than men; however, this is because of the high concentration of women in the depressive subcategory, whereas the bipolar subtype has a more or less even gender distribution.[citation needed] ## History[edit] The term schizoaffective psychosis was introduced by the American psychiatrist Jacob Kasanin in 1933[65] to describe an episodic psychotic illness with predominant affective symptoms, that was thought at the time to be a good-prognosis schizophrenia.[66] Kasanin's concept of the illness was influenced by the psychoanalytic teachings of Adolf Meyer and Kasanin postulated that schizoaffective psychosis was caused by "emotional conflicts" of a "mainly sexual nature" and that psychoanalysis "would help prevent the recurrence of such attacks."[67] He based his description on a case study of nine individuals.[67] Karl Kahlbaum (1828–1899) Other psychiatrists, before and after Kasanin, have made scientific observations of schizoaffective disorder based on assumptions of a biological and genetic cause of the illness. In 1863, German psychiatrist Karl Kahlbaum (1828–1899) described schizoaffective disorders as a separate group in his vesania typica circularis.[68] Kahlbaum distinguished between cross-sectional and longitudinal observations. (Cross-sectional refers to observation of a single, specific episode of the illness, for example, one episode of psychotic depression; while longitudinal refers to long-term observation of many distinct episodes [similar or different] often occurring over the span of years.) In 1920, psychiatrist Emil Kraepelin (1856–1926), the founder of contemporary scientific psychiatry, observed a "great number" of cases that had characteristics of both groups of psychoses that he originally posited were two distinct and separate illnesses, dementia praecox (now called schizophrenia) and manic depressive insanity (now called bipolar disorders [plural since there are more than one type of bipolar disorder] and recurrent depression).[67] Kraepelin acknowledged that "there are many overlaps in this area," that is, the area between schizophrenia and mood disorders.[69] In 1959, psychiatrist Kurt Schneider (1887–1967) began to further refine conceptualizations of the different forms that schizoaffective disorders can take since he observed "concurrent and sequential types".[67] (The concurrent type of illness he referred to is a longitudinal course of illness with episodes of mood disorder and psychosis occurring predominantly at the same time [now called psychotic mood disorders or affective psychosis]; while his sequential type refers to a longitudinal course predominantly marked by alternating mood and psychotic episodes.)[68] Schneider described schizoaffective disorders as "cases in-between" the traditional Kraepelinian dichotomy of schizophrenia and mood disorders.[68] The historical clinical observation that schizoaffective disorder is an overlap of schizophrenia and mood disorders is explained by genes for both illnesses being present in individuals with schizoaffective disorder; specifically, recent research shows that schizophrenia and mood disorders share common genes and polygenic variations.[70][71][72][73] Emil Kraepelin (1856–1926) Embracing the Kraepelinian dichotomy in DSM-III in 1980, while a step forward from psychodynamic explanations of the disorder, introduced significant problems in schizoaffective disorder diagnosis, as explained recently by the DSM-5 workgroup Schizoaffective disorder was included as a subtype of schizophrenia in DSM-I and DSM-II, though research showed a schizophrenic cluster of symptoms in individuals with a family history of mood disorders whose illness course, other symptoms and treatment outcome were otherwise more akin to bipolar disorder than to schizophrenia. DSM-III placed schizoaffective disorder in "Psychotic Disorders Not Otherwise Specified" before being formally recognized in DSM-III-R.[74] DSM-III-R included its own diagnostic criteria as well as the subtypes, bipolar and depressive.[74] In DSM-IV, published in 1994, schizoaffective disorders belonged to the category "Other Psychotic Disorders" and included almost the same criteria and the same subtypes of illness as DSM-III-R, with the addition of mixed bipolar symptomatology.[75] DSM-IV and DSM-IV-TR (published in 2000) criteria for schizoaffective disorder were poorly defined and poorly operationalized.[6] These ambiguous and unreliable criteria lasted 19 years and led clinicians to significantly overuse the schizoaffective disorder diagnosis.[6] Patients commonly diagnosed with DSM-IV schizoaffective disorder showed a clinical picture at time of diagnosis that appeared different from schizophrenia or psychotic mood disorders using DSM-IV criteria, but who as a group, were longitudinally determined to have outcomes indistinguishable from those with mood disorders with or without psychotic features.[6] A poor prognosis was assumed to apply to these patients by most clinicians, and this poor prognosis was harmful to many patients.[6][76] The poor prognosis for DSM-IV schizoaffective disorder was not based on patient outcomes research, but was caused by poorly defined criteria interacting with clinical tradition and belief; clinician enculturation with unscientific assumptions from the diagnosis' history (discussed above), including the invalid Kraepelinian dichotomy;[48][51] and by clinicians being unfamiliar with the scientific limitations of the diagnostic and classification system.[6] The DSM-5 schizoaffective disorder workgroup analyzed all of the available research evidence on schizoaffective disorder, and concluded that "presenting symptoms of psychosis have little validity in determining diagnosis, prognosis, or treatment response."[6] Given our understanding of overlapping genetics in bipolar disorders, schizoaffective disorder, and schizophrenia, as well as the overlap in treatments for these disorders; but given the lack of specificity of presenting symptoms for determining diagnosis, prognosis or treatment response in these psychotic illness syndromes, the limits of our knowledge are clearer: Presenting symptoms of psychosis describe only presenting symptoms to be treated, and not much more.[6] Schizoaffective disorder was changed to a longitudinal or life course diagnosis in DSM-5 for this reason.[6] ## Research[edit] Evidence is lacking about schizoaffective disorder's (likely multiple) causes and mechanisms (knowing these leads to specific and consistently effective treatments), and about how exactly mood episodes and psychosis are related (knowing this may lead to a simpler, clearer, and more usable behavioral definition of the disorder; as well as a better diagnostic system).[41][51] Whether schizoaffective disorder is a variant of schizophrenia (as in DSM-5 and ICD-10 classification systems), a variant of bipolar disorder, or part of a dimensional continuum between psychotic depression, bipolar disorders and schizophrenia is currently being investigated.[51] Research into the assessment and treatment of schizoaffective disorder will rely less on DSM and ICD criteria as time progresses, and more on the dimensional Research Domain Criteria currently being developed by the U.S. National Institute of Mental Health (NIMH). The Research Domain Criteria initiative, led by Bruce Cuthbert, Ph.D., of NIMH, is the inspiration for the Roadmap for Mental Health Research in Europe (ROAMER).[51][77][78] The purpose of the Research Domain Criteria initiative is to address the marked variability and overlap within and among the disorder categories, and to foster development of more effective assessment and treatment for each individual patient.[51][77][78] Over the coming decades, advances resulting from the Research Domain Criteria in the U.S. and ROAMER in Europe will be incorporated into future versions of the DSM and ICD, with the hope of eventually leading to personalized mental health of greater diagnostic accuracy and with more targeted and useful treatments, including biomedical, psychosocial, and possibly preventive approaches.[77] ## References[edit] 1. ^ "Schizoaffective Disorder Overview - Symptoms". www.nami.org. 2. ^ "Schizoaffective disorder, bipolar type". www.icd10data.com. 3. ^ "Schizoaffective disorder, depressive type". www.icd10data.com. 4. ^ a b "Schizoaffective Disorder Overview - Causes". www.nami.org. 5. ^ a b c d e f "F25 Schizoaffective disorders". 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Schizoaffective Disorders: New Research. New York: Nova Science Publishers, Inc. ISBN 978-1-60021-030-3. 48. ^ a b c d e f g h Craddock N, Owen MJ (2010). "The Kraepelinian dichotomy – going, going... But still not gone". The British Journal of Psychiatry. 196 (2): 92–95. doi:10.1192/bjp.bp.109.073429. PMC 2815936. PMID 20118450. 49. ^ a b Mayes R, Horwitz AV (2005). "DSM-III and the revolution in the classification of mental illness". J Hist Behav Sci. 41 (3): 249–67. doi:10.1002/jhbs.20103. PMID 15981242. 50. ^ Craddock N, Owen MJ (May 2005). "The beginning of the end for the Kraepelinian dichotomy". Br J Psychiatry. 186 (5): 364–6. doi:10.1192/bjp.186.5.364. PMID 15863738. 51. ^ a b c d e f g h i j k l "Mental Health on the Spectrum". Nature. Retrieved 17 September 2013. 52. ^ a b c d Heckers S, Barch DM, Bustillo J, Gaebel W, Gur R, Malaspina D, Owen MJ, Schultz S, Tandon R, Tsuang M, Van Os J, Carpenter W (2013). "Structure of the psychotic disorders classification in DSM-5". Schizophrenia Research. 150 (1): 11–4. doi:10.1016/j.schres.2013.04.039. PMID 23707641. S2CID 14580469.CS1 maint: multiple names: authors list (link) 53. ^ "Introduction to RDoC". NIMH. Retrieved 25 February 2016. 54. ^ McGurk SR, Mueser KT, Feldman K, Wolfe R, Pascaris A (March 2007). "Cognitive training for supported employment: 2–3 year outcomes of a randomized controlled trial". American Journal of Psychiatry. 164 (3): 437–41. doi:10.1176/appi.ajp.164.3.437. PMID 17329468. 55. ^ Gorczynski P, Faulkner G (2010). "Exercise therapy for schizophrenia". Cochrane Database Syst Rev (5): CD004412. doi:10.1002/14651858.CD004412.pub2. PMC 4164954. PMID 20464730. 56. ^ a b c d e f BMJ Group, "Schizoaffective disorders: Treatment", 2012 57. ^ Dieterich M, Irving CB, Park B, et al. (6 January 2017). Dieterich M (ed.). "Intensive Case Management for Severe Mental Illness". Cochrane Database of Systematic Reviews. 1 (CD007906): CD007906. doi:10.1002/14651858.CD007906.pub3. PMC 6472672. PMID 28067944. 58. ^ PSR/RPS Canada, [1], "PSR/RPS Canada Core Principles and Values"Archived 24 March 2010 at the Wayback Machine 59. ^ a b c American Psychiatric Association, "Practice Guideline for the Treatment of Patients with Schizophrenia, Second Edition", 2004 Archived 6 March 2014 at Archive.today 60. ^ Paliperidone, "Schizoaffective disorders: Treatment", 2013 61. ^ a b c d e f Stahl SM, Stahl's Essential Psychopharmacology: Neuroscientific basis and practical applications, New York: Cambridge University Press, 2008 62. ^ a b Stahl, Stephen M. (2002). Essential Psychopharmacology of Antipsychotics and Mood Stabilizers. Cambridge University Press. p. 70. ISBN 978-0-521-89074-8. 63. ^ Kaplan, HI; Saddock, VA (2007). Synopsis of Psychiatry. New York: Lippincott, Williams & Wilkins. pp. 501–502. ISBN 978-0-7817-7327-0. 64. ^ Wy, T. J. P., Saadabadi, A. (2019). "Schizoaffective Disorder". StatPearls [Internet] Treasue Island (FL). 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"Common polygenic variation contributes to risk of schizophrenia and bipolar disorder". Nature. 460 (7256): 748–52. Bibcode:2009Natur.460..748P. doi:10.1038/nature08185. PMC 3912837. PMID 19571811. 73. ^ Potash JB, Bienvenu OJ (June 2009). "Neuropsychiatric disorders: Shared genetics of bipolar disorder and schizophrenia". Nature Reviews Neurology. 5 (6): 299–300. doi:10.1038/nrneurol.2009.71. PMID 19498428. S2CID 21986987. 74. ^ a b Goodwin & Jamison 2007, p. 96. 75. ^ Goodwin & Marneros 2005, p. 192. 76. ^ Lake CR, Hurwitz N (2007). "Schizoaffective disorder merges schizophrenia and bipolar disorders as one disease". Current Opinion in Psychiatry. 20 (4): 365–79. doi:10.1097/YCO.0b013e3281a305ab. PMID 17551352. S2CID 37664803. 77. ^ a b c "No One Is Abandoning the DSM, but it is Almost Time to Transform It". Scientific American. Retrieved 20 October 2013. 78. ^ a b "Roadmap for Mental Health Research in Europe". ROAMER. Retrieved 18 October 2013. ## Further reading[edit] * Moore DP, Jefferson JW (2004). Handbook of medical psychiatry (2nd ed.). Philadelphia: Elsevier/Mosby. pp. 126–127. ISBN 978-0-323-02911-7. * Goetzt CG (2003). Textbook of clinical neurology (2nd ed.). Philadelphia: W.B. Saunders. p. 48. ISBN 978-0-7216-3800-3. ## External links[edit] Classification D * ICD-10: F25 * ICD-9-CM: 295.70 * OMIM: 181500 * MeSH: D011618 * DiseasesDB: 33444 * SNOMED CT: 68890003 External resources * MedlinePlus: 000930 * eMedicine: article/294763 * Patient UK: Schizoaffective disorder * Medicine portal * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy * v * t * e Mood disorder History * Emil Kraepelin * Karl Leonhard * John Cade * Mogens Schou * Frederick K. Goodwin * Kay Redfield Jamison Symptoms * Hallucination * Delusion * Emotional dysregulation * Anhedonia * Dysphoria * Suicidal ideation * Mood swing * Sleep disorder * Hypersomnia * Insomnia * Psychosis * Racing thoughts * Reduced affect display * Depression (differential diagnoses) Spectrum * Bipolar disorder * Bipolar I * Bipolar II * Cyclothymia * Bipolar NOS * Depression * Major depressive disorder * Dysthymia * Seasonal affective disorder * Atypical depression * Melancholic depression * Schizoaffective disorder * Mania * Mixed affective state * Hypomania * Major depressive episode * Rapid cycling Treatment Anticonvulsants * Carbamazepine * Lamotrigine * Oxcarbazepine * Valproate * Sodium valproate * Valproate semisodium Sympathomimetics, SSRIs and similar * Dextroamphetamine * Methylphenidate * Bupropion * Sertraline * Fluoxetine * Escitalopram Other mood stabilizers * Antipsychotics * Lithium * Lithium carbonate * Lithium citrate * Lithium sulfate * Lithium toxicity * Atypical antipsychotics Non-pharmaceutical * Clinical psychology * Electroconvulsive therapy * Involuntary commitment * Light therapy * Psychotherapy * Transcranial magnetic stimulation * Cognitive behavioral therapy * Dialectical behavior therapy Authority control * NDL: 01175908 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Schizoaffective disorder	c0036337	26,766	wikipedia	https://en.wikipedia.org/wiki/Schizoaffective_disorder	2021-01-18T18:51:08	{"mesh": ["D011618"], "umls": ["C0036337"], "wikidata": ["Q834047"]}
Anaplastic oligoastrocytoma is a brain tumor that forms when two types of cells in the brain, called oligodendrocytes and astrocytes, rapidly increase in number to form a mass. These brain cells are known as glial cells, which normally protect and support nerve cells in the brain. Because an oligoastrocytoma is made up of a combination of two cell types, it is known as a mixed glioma. An oligoastrocytoma is described as anaplastic when the tumor grows quickly and the cancer cells within the tumor have the potential to spread into surrounding brain tissue or to more distant parts of the body. Oligoastrocytomas usually occur in a part of the brain called the cerebrum and are diagnosed in adults between the ages of 30 and 50. The exact cause of this condition is unknown. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Anaplastic oligoastrocytoma	c0431108	26,767	gard	https://rarediseases.info.nih.gov/diseases/10637/anaplastic-oligoastrocytoma	2021-01-18T18:02:08	{"umls": ["C0431108"], "synonyms": []}
Mycosis fungoides is a disease in which T-cell lymphocytes (a type of white blood cell) become malignant (cancerous) and affect the skin. This condition is one of the most common types of T-cell lymphoma. Mycosis fungoides is characterized by a scaly, red rash that develops on the skin, particularly on areas that are not usually exposed to the sun. The rash may last for months or years without causing any symptoms. Over time, a thin, reddened, eczema-like rash may develop, followed by thickened, red patches of skin. Finally, tumors form which may develop into ulcers and become infected. Mycosis fungoides is difficult to cure. Treatment is usually palliative, with the intention of relieving symptoms and improving the quality of life. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mycosis fungoides	c0026948	26,768	gard	https://rarediseases.info.nih.gov/diseases/3863/mycosis-fungoides	2021-01-18T17:58:51	{"mesh": ["D009182"], "omim": ["254400"], "umls": ["C0026948"], "synonyms": ["Granuloma fungoides", "Alibert-Bazin syndrome"]}
Amish lethal microcephaly is a disorder in which infants are born with a very small head and underdeveloped brain. Infants with Amish lethal microcephaly have a sloping forehead and an extremely small head size. They may also have an unusually small lower jaw and chin (micrognathia) and an enlarged liver (hepatomegaly). Affected infants may have seizures and difficulty maintaining their body temperature. Often they become very irritable starting in the second or third month of life. A compound called alpha-ketoglutaric acid can be detected in their urine (alpha-ketoglutaric aciduria), and during episodes of viral illness they tend to develop elevated levels of acid in the blood and tissues (metabolic acidosis). Infants with this disorder typically feed adequately but do not develop skills such as purposeful movement or the ability to track faces and sounds. Affected infants live only about six months. ## Frequency Amish lethal microcephaly occurs in approximately 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population. ## Causes Mutations in the SLC25A19 gene cause Amish lethal microcephaly. The SLC25A19 gene provides instructions for producing a protein that is a member of the solute carrier (SLC) family of proteins. Proteins in the SLC family transport various compounds across the membranes surrounding the cell and its component parts. The protein produced from the SLC25A19 gene transports a molecule called thiamine pyrophosphate into the mitochondria, the energy-producing centers of cells. This compound is involved in the activity of a group of mitochondrial enzymes called the dehydrogenase complexes, one of which is the alpha-ketoglutarate dehydrogenase complex. The transport of thiamine pyrophosphate into the mitochondria is believed to be important in brain development. All known individuals with Amish lethal microcephaly have a mutation in which the protein building block (amino acid) alanine is substituted for the amino acid glycine at position 177 of the SLC25A19 protein, written as Gly177Ala or G177A. Researchers believe that this mutation interferes with the transport of thiamine pyrophosphate into the mitochondria and the activity of the alpha-ketoglutarate dehydrogenase complex, resulting in the abnormal brain development and alpha-ketoglutaric aciduria seen in Amish lethal microcephaly. ### Learn more about the gene associated with Amish lethal microcephaly * SLC25A19 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Amish lethal microcephaly	c1846648	26,769	medlineplus	https://medlineplus.gov/genetics/condition/amish-lethal-microcephaly/	2021-01-27T08:24:51	{"gard": ["8606"], "mesh": ["C538247"], "omim": ["607196"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-16 (COXPD16) is caused by homozygous mutation in the MRPL44 gene (611849) on chromosome 2. One such family has been reported. For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). Clinical Features Carroll et al. (2013) reported 2 Finnish sisters with hypertrophic cardiomyopathy and liver steatosis. One sister died of cardiac failure after a respiratory infection at age 6 months. Postmortem examination showed a pale hypertrophic heart with diffuse, mild microvesicular steatosis in cardiomyocytes. The liver showed fatty degeneration, whereas skeletal muscle was normal. The other sister was diagnosed with hypertrophic cardiomyopathy at age 8 months and treated with atenolol. She remained stable and asymptomatic throughout childhood, and attended a normal school at age 14 years. Muscle and liver biopsy showed mild microvesicular fatty degeneration, and she had elevated liver enzymes that normalized later in childhood. Ophthalmologic examination showed mild granular pigmentation in the retina. Biochemical studies showed decreased levels of mitochondrial complexes I and IV in heart and skeletal muscle of the first patient, and decreased complex IV in fibroblasts from the second patient. Complex IV activity was decreased in cardiac muscle of the first patient and in skeletal muscle of the second patient. Inheritance The transmission pattern of COXPD16 in the family reported by Carroll et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 Finnish sisters with variable expression of combined oxidative phosphorylation deficiency-16, Carroll et al. (2013) identified a homozygous mutation in the MRPL44 gene (L156R; 611849.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in several large control databases or in 436 control chromosomes. Haplotype analysis indicated distant consanguinity in the family. In vitro studies showed that the mutation caused a defect in the assembly of the mitochondrial large ribosomal subunit as well as decreased stability of 16S rRNA, leading to complex IV deficiency. Transduction of wildtype MRPL44 into patient fibroblasts corrected the COX defects and restored assembly of the large ribosomal subunit. The findings indicated that the MRPL44 mutation affected the respiratory chain in a tissue-specific manner, and suggested that MRPL44 is required for assembly and stability of the mitochondrial large ribosomal subunit. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Granular retinal pigmentation, mild (in 1 patient) CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy \- Microvesicular steatosis in cardiomyocytes \- Decreased levels and activity of mitochondrial respiratory complexes I and IV ABDOMEN Liver \- Microvesicular steatosis MUSCLE, SOFT TISSUES \- Decreased levels and activity of mitochondrial respiratory complexes I and IV LABORATORY ABNORMALITIES \- Increased serum lactate (mild) \- Abnormal liver enzymes MISCELLANEOUS \- Onset in infancy \- Variable severity \- May be fatal in infancy \- Two sisters have been reported (last curated September 2013) MOLECULAR BASIS \- Caused by mutation in the mitochondrial ribosomal protein L44 gene (MRPL44, 611849.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 16	c3809339	26,770	omim	https://www.omim.org/entry/615395	2019-09-22T15:52:26	{"doid": ["0060286"], "omim": ["615395"], "orphanet": ["352563"], "synonyms": ["COXPD16", "Combined oxidative phosphorylation defect type 16"]}
A number sign (#) is used with this entry because of evidence that squalene synthase deficiency is cause by homozygous or compound heterozygous mutations in the FDFT1 gene (184420) on chromosome 8p23. Description Squalene synthase deficiency is an autosomal recessive disorder characterized by profound developmental delay, brain abnormalities, 2/3 syndactyly of the toes, and facial dysmorphisms, as well as low total and LDL-cholesterol and abnormal urine organic acids (Coman et al., 2018). Squalene synthase deficiency has been reported in 3 patients from 2 families. Clinical Features Coman et al. (2018) reported 3 patients from 2 families with squalene synthase deficiency. The sibs from family 1 were the products of a nonconsanguineous union of European parents and had very similar features and course. They were both born at term with normal growth parameters and developed seizures in the neonatal period. Brain MRI showed hypoplasia of the corpus callosum and white matter loss. Both had profound global developmental delay at 10 and 7 years, with irritability and poor sleep initiation. Both children developed failure to thrive and required gastrostomy tube feeds. Optic nerve hypoplasia with cortical visual impairment was present, but neither had cataracts. Facial dysmorphisms included depressed nasal bridge, square nasal tip, epicanthal folds, mild micrognathia, and mild retrognathia. The 7-year-old brother had bilateral cryptorchidism, large ears, and dorsal foot fat pads. The 10-year-old sister had low-set, posteriorly rotated ears. Both had thin gracile bones, flexion deformities at the knees, and 2/3 toe syndactyly. Dry skin with photosensitivity was present, and lack of hair pigment was seen on light and electron microscopy. Total and low density lipoprotein (LDL) cholesterol were low in both, while high density lipoprotein cholesterol (HDL-C) was low for the sister, but normal for the brother. Very low density lipoprotein (VLDL) and triglycerides were normal. Plasma farnesol was more than 10 times normal in both. Gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy profiles in urine yielded a consistent and complex pattern of elevated methylsuccinic acid, mevalonate lactone, mesaconic acid, and 3-methyladipic acid. Saturated and unsaturated branched-chain dicarboxylic acids and glucuronides derived from farnesol were also observed. The boy from family 2 was also born of nonconsanguineous European parents. Findings were similar except that his brain MRI showed diffuse polymicrogyria as well as central white matter and cortical volume loss. He had hypospadias without cryptorchidism, bicuspid aortic valve, and flexion deformities of elbows rather than knees. Total cholesterol and LDL-C were low, with normal HDL-C and triglycerides. VLDL-C and farnesol were not measured. Molecular Genetics In 3 patients with squalene synthase deficiency, Coman et al. (2018) identified compound heterozygous or homozygous mutations in the FDFT1 gene by whole-exome sequencing. Two sibs were compound heterozygous for a 120-kb deletion (184420.0001) and an intronic mutation resulting in aberrant splicing (184420.0002). An unrelated child was homozygous for a 16-bp intronic deletion (184420.0003). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SQUALENE SYNTHASE DEFICIENCY	None	26,771	omim	https://www.omim.org/entry/618156	2019-09-22T15:43:20	{"omim": ["618156"], "synonyms": ["Alternative titles", "NEURODEVELOPMENTAL DISORDER WITH LOW CHOLESTEROL AND ABNORMAL URINE ORGANIC ACIDS"]}
Life-threatening allergic reaction Anaphylaxis Other namesAnaphylactoid, anaphylactic shock Angioedema of the face such that the boy cannot open his eyes. This reaction was caused by an allergen exposure. SpecialtyAllergy and immunology SymptomsItchy rash, throat swelling, shortness of breath, lightheadedness,[1] Usual onsetOver minutes to hours[1] CausesInsect bites, foods, medications[1] Diagnostic methodBased on symptoms[2] Differential diagnosisAllergic reaction, angioedema, asthma exacerbation, carcinoid syndrome[2] TreatmentEpinephrine, intravenous fluids[1] Frequency0.05–2%[3] Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.[4][5] It typically causes more than one of the following: an itchy rash, throat or tongue swelling, shortness of breath, vomiting, lightheadedness, low blood pressure.[1] These symptoms typically come on over minutes to hours.[1] Common causes include insect bites and stings, foods, and medications.[1] Other causes include latex exposure and exercise.[1] Additionally, cases may occur without an obvious reason.[1] The mechanism involves the release of mediators from certain types of white blood cells triggered by either immunologic or non-immunologic mechanisms.[6] Diagnosis is based on the presenting symptoms and signs after exposure to a potential allergen.[1] The primary treatment of anaphylaxis is epinephrine injection into a muscle, intravenous fluids, and positioning the person flat.[1][7] Additional doses of epinephrine may be required.[1] Other measures, such as antihistamines and steroids, are complementary.[1] Carrying an epinephrine autoinjector and identification regarding the condition is recommended in people with a history of anaphylaxis.[1] Worldwide, 0.05–2% of the population is estimated to experience anaphylaxis at some point in life.[3] Rates appear to be increasing.[3] It occurs most often in young people and females.[7][8] Of people who go to a hospital with anaphylaxis in the United States about 99.7% survive.[9] The term comes from the Ancient Greek: ἀνά, romanized: ana, lit. 'against', and the Ancient Greek: φύλαξις, romanized: phylaxis, lit. 'protection'.[10] ## Contents * 1 Signs and symptoms * 1.1 Skin * 1.2 Respiratory * 1.3 Cardiovascular * 1.4 Other * 2 Causes * 2.1 Food * 2.2 Medication * 2.3 Venom * 2.4 Risk factors * 3 Pathophysiology * 3.1 Immunologic * 3.2 Non-immunologic * 4 Diagnosis * 4.1 Classification * 4.2 Allergy testing * 4.3 Differential diagnosis * 4.4 Post-mortem findings * 5 Prevention * 6 Management * 6.1 Epinephrine * 6.2 Adjuncts * 6.3 Preparedness * 7 Prognosis * 8 Epidemiology * 9 History * 10 Research * 11 References * 12 External links ## Signs and symptoms[edit] Signs and symptoms of anaphylaxis Anaphylaxis typically presents many different symptoms over minutes or hours[7][11] with an average onset of 5 to 30 minutes if exposure is intravenous and 2 hours if from eating food.[12] The most common areas affected include: skin (80–90%), respiratory (70%), gastrointestinal (30–45%), heart and vasculature (10–45%), and central nervous system (10–15%)[13] with usually two or more being involved.[3] ### Skin[edit] Urticaria and flushing on the back of a person with anaphylaxis Symptoms typically include generalized hives, itchiness, flushing, or swelling (angioedema) of the afflicted tissues.[4] Those with angioedema may describe a burning sensation of the skin rather than itchiness.[12] Swelling of the tongue or throat occurs in up to about 20% of cases.[14] Other features may include a runny nose and swelling of the conjunctiva.[15] The skin may also be blue tinged because of lack of oxygen.[15] ### Respiratory[edit] Respiratory symptoms and signs that may be present include shortness of breath, wheezes, or stridor.[4] The wheezing is typically caused by spasms of the bronchial muscles[16] while stridor is related to upper airway obstruction secondary to swelling.[15] Hoarseness, pain with swallowing, or a cough may also occur.[12] ### Cardiovascular[edit] While a fast heart rate caused by low blood pressure is more common,[15] a Bezold–Jarisch reflex has been described in 10% of people, where a slow heart rate is associated with low blood pressure.[8] A drop in blood pressure or shock (either distributive or cardiogenic) may cause the feeling of lightheadedness or loss of consciousness.[16] Rarely very low blood pressure may be the only sign of anaphylaxis.[14] Coronary artery spasm may occur with subsequent myocardial infarction, dysrhythmia, or cardiac arrest.[3][13] Those with underlying coronary disease are at greater risk of cardiac effects from anaphylaxis.[16] The coronary spasm is related to the presence of histamine-releasing cells in the heart.[16] ### Other[edit] Gastrointestinal symptoms may include crampy abdominal pain, diarrhea, and vomiting.[4] There may be confusion, a loss of bladder control or pelvic pain similar to that of uterine cramps.[4][15] Dilation of blood vessels around the brain may cause headaches.[12] A feeling of anxiety or of "impending doom" has also been described.[3] ## Causes[edit] Anaphylaxis can occur in response to almost any foreign substance.[17] Common triggers include venom from insect bites or stings, foods, and medication.[8][18] Foods are the most common trigger in children and young adults while medications and insect bites and stings are more common in older adults.[3] Less common causes include: physical factors, biological agents such as semen, latex, hormonal changes, food additives such as monosodium glutamate and food colors, and topical medications.[15] Physical factors such as exercise (known as exercise-induced anaphylaxis) or temperature (either hot or cold) may also act as triggers through their direct effects on mast cells.[3][19][20] Events caused by exercise are frequently associated with cofactors such as the ingestion of certain foods[12][21] or taking an NSAID.[21] During anesthesia, neuromuscular blocking agents, antibiotics, and latex are the most common causes.[22] The cause remains unknown in 32–50% of cases, referred to as "idiopathic anaphylaxis."[23] Six vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal) are recognized as a cause for anaphylaxis, and HPV may cause anaphylaxis as well.[24] ### Food[edit] Many foods can trigger anaphylaxis; this may occur upon the first known ingestion.[8] Common triggering foods vary around the world. In Western cultures, ingestion of or exposure to peanuts, wheat, nuts, certain types of seafood like shellfish, milk, and eggs are the most prevalent causes.[3][13] Sesame is common in the Middle East, while rice and chickpeas are frequently encountered as sources of anaphylaxis in Asia.[3] Severe cases are usually caused by ingesting the allergen,[8] but some people experience a severe reaction upon contact. Children can outgrow their allergies. By age 16, 80% of children with anaphylaxis to milk or eggs and 20% who experience isolated anaphylaxis to peanuts can tolerate these foods.[17] ### Medication[edit] Any medication may potentially trigger anaphylaxis. The most common are β-lactam antibiotics (such as penicillin) followed by aspirin and NSAIDs.[13][25] Other antibiotics are implicated less frequently.[25] Anaphylactic reactions to NSAIDs are either agent specific or occur among those that are structurally similar meaning that those who are allergic to one NSAID can typically tolerate a different one or different group of NSAIDs.[26] Other relatively common causes include chemotherapy, vaccines, protamine and herbal preparations.[3] Some medications (vancomycin, morphine, x-ray contrast among others) cause anaphylaxis by directly triggering mast cell degranulation.[8] The frequency of a reaction to an agent partly depends on the frequency of its use and partly on its intrinsic properties.[27] Anaphylaxis to penicillin or cephalosporins occurs only after it binds to proteins inside the body with some agents binding more easily than others.[12] Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in fewer than one in every 50,000 courses of treatment.[12] Anaphylaxis to aspirin and NSAIDs occurs in about one in every 50,000 persons.[12] If someone has a reaction to penicillin, his or her risk of a reaction to cephalosporins is greater but still less than one in 1,000.[12] The old radiocontrast agents caused reactions in 1% of cases, while the newer lower osmolar agents cause reactions in 0.04% of cases.[27] ### Venom[edit] Venom from stinging or biting insects such as Hymenoptera (ants, bees, and wasps) or Triatominae (kissing bugs) may cause anaphylaxis in susceptible people.[7][28][29] Previous reactions, that are anything more than a local reaction around the site of the sting, are a risk factor for future anaphylaxis;[30][31] however, half of fatalities have had no previous systemic reaction.[32] ### Risk factors[edit] People with atopic diseases such as asthma, eczema, or allergic rhinitis are at high risk of anaphylaxis from food, latex, and radiocontrast agents but not from injectable medications or stings.[3][8] One study in children found that 60% had a history of previous atopic diseases, and of children who die from anaphylaxis, more than 90% have asthma.[8] Those with mastocytosis or of a higher socioeconomic status are at increased risk.[3][8] The longer the time since the last exposure to the agent in question, the lower the risk.[12] ## Pathophysiology[edit] Anaphylaxis is a severe allergic reaction of rapid onset affecting many body systems.[5][6] It is due to the release of inflammatory mediators and cytokines from mast cells and basophils, typically due to an immunologic reaction but sometimes non-immunologic mechanism.[6] Interleukin (IL)–4 and IL-13 are cytokines important in the initial generation of antibody and inflammatory cell responses to anaphylaxis. ### Immunologic[edit] In the immunologic mechanism, immunoglobulin E (IgE) binds to the antigen (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates FcεRI receptors on mast cells and basophils. This leads to the release of inflammatory mediators such as histamine. These mediators subsequently increase the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and cause heart muscle depression.[6][12] There is also a non-immunologic mechanism that does not rely on IgE, but it is not known if this occurs in humans.[6] ### Non-immunologic[edit] Non-immunologic mechanisms involve substances that directly cause the degranulation of mast cells and basophils. These include agents such as contrast medium, opioids, temperature (hot or cold), and vibration.[6][19] Sulfites may cause reactions by both immunologic and non-immunologic mechanisms.[33] ## Diagnosis[edit] Anaphylaxis is diagnosed on the basis of a person's signs and symptoms.[3] When any one of the following three occurs within minutes or hours of exposure to an allergen there is a high likelihood of anaphylaxis:[3] 1. Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure causing symptoms 2. Two or more of the following symptoms after a likely contact with an allergen: a. Involvement of the skin or mucosa b. Respiratory difficulties c. Low blood pressure d. Gastrointestinal symptoms 3. Low blood pressure after exposure to a known allergen Skin involvement may include: hives, itchiness or a swollen tongue among others. Respiratory difficulties may include: shortness of breath, stridor, or low oxygen levels among others. Low blood pressure is defined as a greater than 30% decrease from a person's usual blood pressure. In adults a systolic blood pressure of less than 90 mmHg is often used.[3] During an attack, blood tests for tryptase or histamine (released from mast cells) might be useful in diagnosing anaphylaxis due to insect stings or medications. However these tests are of limited use if the cause is food or if the person has a normal blood pressure,[3] and they are not specific for the diagnosis.[17] ### Classification[edit] There are three main classifications of anaphylaxis. * Anaphylactic shock is associated with systemic vasodilation that causes low blood pressure which is by definition 30% lower than the person's baseline or below standard values.[14] * Biphasic anaphylaxis is the recurrence of symptoms within 1–72 hours with no further exposure to the allergen.[3] Reports of incidence vary, with some studies claiming as many as 20% of cases.[34] The recurrence typically occurs within 8 hours.[8] It is managed in the same manner as anaphylaxis.[7] * Anaphylactoid reaction, non-immune anaphylaxis, or pseudoanaphylaxis, is a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation.[8][35] Non-immune anaphylaxis is the current term used by the World Allergy Organization[35] with some recommending that the old terminology[clarification needed] no longer be used.[8] ### Allergy testing[edit] Skin allergy testing being carried out on the right arm Patch test Allergy testing may help in determining the trigger. Skin allergy testing is available for certain foods and venoms.[17] Blood testing for specific IgE can be useful to confirm milk, egg, peanut, tree nut and fish allergies.[17] Skin testing is available to confirm penicillin allergies, but is not available for other medications.[17] Non-immune forms of anaphylaxis can only be determined by history or exposure to the allergen in question, and not by skin or blood testing.[35] ### Differential diagnosis[edit] It can sometimes be difficult to distinguish anaphylaxis from asthma, syncope, and panic attacks.[3] Asthma however typically does not entail itching or gastrointestinal symptoms, syncope presents with pallor rather than a rash, and a panic attack may have flushing but does not have hives.[3] Other conditions that may present similarly include: scrombroidosis and anisakiasis.[8] ### Post-mortem findings[edit] In a person who died from anaphylaxis, autopsy may show an "empty heart" attributed to reduced venous return from vasodilation and redistribution of intravascular volume from the central to the peripheral compartment.[36] Other signs are laryngeal edema, eosinophilia in lungs, heart and tissues, and evidence of myocardial hypoperfusion.[37] Laboratory findings could detect increased levels of serum tryptase, increase in total and specific IgE serum levels.[37] ## Prevention[edit] See also: Allergen immunotherapy Avoidance of the trigger of anaphylaxis is recommended. In cases where this may not be possible, desensitization may be an option. Immunotherapy with Hymenoptera venoms is effective at desensitizing 80–90% of adults and 98% of children against allergies to bees, wasps, hornets, yellowjackets, and fire ants. Oral immunotherapy may be effective at desensitizing some people to certain food including milk, eggs, nuts and peanuts; however, adverse effects are common.[3] For example, many people develop an itchy throat, cough, or lip swelling during immunotherapy.[38] Desensitization is also possible for many medications, however it is advised that most people simply avoid the agent in question. In those who react to latex it may be important to avoid cross-reactive foods such as avocados, bananas, and potatoes among others.[3] ## Management[edit] Anaphylaxis is a medical emergency that may require resuscitation measures such as airway management, supplemental oxygen, large volumes of intravenous fluids, and close monitoring.[7] Passive leg raise may also be helpful in the emergency management.[39] Administration of epinephrine is the treatment of choice with antihistamines and steroids (for example, dexamethasone) often used as adjuncts.[7] A period of in-hospital observation for between 2 and 24 hours is recommended for people once they have returned to normal due to concerns of biphasic anaphylaxis.[8][12][34][40] ### Epinephrine[edit] An old version of an EpiPen auto-injector Epinephrine (adrenaline) (1 in 1,000) is the primary treatment for anaphylaxis with no absolute contraindication to its use.[7] It is recommended that an epinephrine solution be given intramuscularly into the mid anterolateral thigh as soon as the diagnosis is suspected. The injection may be repeated every 5 to 15 minutes if there is insufficient response.[7] A second dose is needed in 16–35% of episodes with more than two doses rarely required.[7] The intramuscular route is preferred over subcutaneous administration because the latter may have delayed absorption.[7][41] Minor adverse effects from epinephrine include tremors, anxiety, headaches, and palpitations.[3] People on β-blockers may be resistant to the effects of epinephrine.[8] In this situation if epinephrine is not effective intravenous glucagon can be administered which has a mechanism of action independent of β-receptors.[8] If necessary, it can also be given intravenously using a dilute epinephrine solution. Intravenous epinephrine, however, has been associated both with dysrhythmia and myocardial infarction.[7] Epinephrine autoinjectors used for self-administration typically come in two doses, one for adults or children who weigh more than 25 kg and one for children who weigh 10 to 25 kg.[42] ### Adjuncts[edit] Antihistamines (both H1 and H2), while commonly used and assumed effective based on theoretical reasoning, are poorly supported by evidence.[43][44] A 2007 Cochrane review did not find any good-quality studies upon which to base recommendations[44] and they are not believed to have an effect on airway edema or spasm.[8] Corticosteroids are unlikely to make a difference in the current episode of anaphylaxis, but may be used in the hope of decreasing the risk of biphasic anaphylaxis. Their prophylactic effectiveness in these situations is uncertain.[34] Nebulized salbutamol may be effective for bronchospasm that does not resolve with epinephrine.[8] Methylene blue has been used in those not responsive to other measures due to its presumed effect of relaxing smooth muscle.[8] ### Preparedness[edit] People prone to anaphylaxis are advised to have an "allergy action plan." Parents are advised to inform schools of their children's allergies and what to do in case of an anaphylactic emergency. The action plan usually includes use of epinephrine autoinjectors, the recommendation to wear a medical alert bracelet, and counseling on avoidance of triggers.[45] Immunotherapy is available for certain triggers to prevent future episodes of anaphylaxis. A multi-year course of subcutaneous desensitization has been found effective against stinging insects, while oral desensitization is effective for many foods.[13] ## Prognosis[edit] In those in whom the cause is known and prompt treatment is available, the prognosis is good.[46] Even if the cause is unknown, if appropriate preventive medication is available, the prognosis is generally good.[12] If death occurs, it is usually due to either respiratory (typically asphyxia) or cardiovascular causes (shock),[6][8] with 0.7–20% of cases causing death.[12][16] There have been cases of death occurring within minutes.[3] Outcomes in those with exercise-induced anaphylaxis are typically good, with fewer and less severe episodes as people get older.[23] ## Epidemiology[edit] The number of people who get anaphylaxis is 4–100 per 100,000 persons per year,[8][47] with a lifetime risk of 0.05–2%.[48] About 30% of people get more than one attack.[47] Exercise-induced anaphylaxis affects about 1 in 2000 young people.[21] Rates appear to be increasing: with the numbers in the 1980s being approximately 20 per 100,000 per year, while in the 1990s it was 50 per 100,000 per year.[13] The increase appears to be primarily for food-induced anaphylaxis.[49] The risk is greatest in young people and females.[7][8] Anaphylaxis leads to as many as 500–1,000 deaths per year (2.7 per million) in the United States, 20 deaths per year in the United Kingdom (0.33 per million), and 15 deaths per year in Australia (0.64 per million).[8] Another estimate from the United States puts the death rate at 0.7 per million.[50] Mortality rates have decreased between the 1970s and 2000s.[51] In Australia, death from food-induced anaphylaxis occur primarily in women while deaths due to insect bites primarily occur in males.[8] Death from anaphylaxis is most commonly triggered by medications.[8] ## History[edit] The term aphylaxis was coined by French physiologist Charles Richet in 1902 and later changed to anaphylaxis due to its nicer quality of speech.[17] In his experiments, Richet injected a dog with sea anemone (Actinia) toxin in an attempt to protect it. Although the dog had previously tolerated the toxin, on re-exposure, three weeks later with the same dose, it developed fatal anaphylaxis. Thus instead of inducing tolerance (prophylaxis), when lethal responses resulted from previously tolerated doses, he coined the word a (without) phylaxis (protection). He was subsequently awarded the Nobel Prize in Physiology or Medicine for his work on anaphylaxis in 1913.[12] The phenomenon itself, however, has been described since ancient times.[35] The term comes from the Greek words ἀνά, ana, meaning "against", and φύλαξις, phylaxis, meaning "protection".[52] ## Research[edit] There are ongoing efforts to develop sublingual epinephrine to treat anaphylaxis.[8] Subcutaneous injection of the anti-IgE antibody omalizumab is being studied as a method of preventing recurrence, but it is not yet recommended.[3][53] ## References[edit] 1. ^ a b c d e f g h i j k l m n "Anaphylaxis". National Institute of Allergy and Infectious Diseases. 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S2CID 27548046. 45. ^ Martelli, A; Ghiglioni, D; Sarratud, T; Calcinai, E; Veehof, S; Terracciano, L; Fiocchi, A (August 2008). "Anaphylaxis in the emergency department: a paediatric perspective". Current Opinion in Allergy and Clinical Immunology. 8 (4): 321–9. doi:10.1097/ACI.0b013e328307a067. PMID 18596589. S2CID 205434577. 46. ^ Harris JP, Weisman MH (2007-07-26). Head and Neck Manifestations of Systemic Disease. CRC Press. pp. 325–. ISBN 978-1-4200-1756-4. 47. ^ a b Tejedor-Alonso M, A; Moro-Moro, M; Múgica-García, MV (2015). "Epidemiology of Anaphylaxis: Contributions From the Last 10 Years". Journal of Investigational Allergology & Clinical Immunology. 25 (3): 163–75, quiz follow 174–5. PMID 26182682. 48. ^ Leslie C. Grammer (2012). Patterson's Allergic Diseases (7 ed.). ISBN 9781451148633. Archived from the original on 2015-06-20. 49. ^ Koplin, JJ; Martin, PE; Allen, KJ (October 2011). "An update on epidemiology of anaphylaxis in children and adults". Current Opinion in Allergy and Clinical Immunology. 11 (5): 492–6. doi:10.1097/ACI.0b013e32834a41a1. PMID 21760501. S2CID 13164564. 50. ^ Fromer, L (December 2016). "Prevention of Anaphylaxis: The Role of the Epinephrine Auto-Injector". The American Journal of Medicine. 129 (12): 1244–1250. doi:10.1016/j.amjmed.2016.07.018. PMID 27555092. 51. ^ Demain, JG; Minaei, AA; Tracy, JM (August 2010). "Anaphylaxis and insect allergy". Current Opinion in Allergy and Clinical Immunology. 10 (4): 318–22. doi:10.1097/ACI.0b013e32833a6c72. PMID 20543675. S2CID 12112811. 52. ^ "anaphylaxis". merriam-webster.com. Archived from the original on 2010-04-10. Retrieved 2009-11-21. 53. ^ Vichyanond, P (September 2011). "Omalizumab in allergic diseases, a recent review". Asian Pacific Journal of Allergy and Immunology. 29 (3): 209–19. PMID 22053590. ## External links[edit] Classification D * ICD-10: T78.2 * ICD-9-CM: 995.0 * MeSH: D000707 * DiseasesDB: 29153 External resources * MedlinePlus: 000844 * eMedicine: med/128 Wikipedia's health care articles can be viewed offline with the Medical Wikipedia app. Look up anaphylaxis in Wiktionary, the free dictionary. Wikimedia Commons has media related to Anaphylaxis. * Anaphylaxis at Curlie * National Institute for Health and Clinical Excellence. Clinical guideline 134: Anaphylaxis: assessment to confirm an anaphylactic episode and the decision to refer after emergency treatment for a suspected anaphylactic episode. London, 2011. and Anaphylaxis pathway * "Anaphylaxis". MedlinePlus. U.S. National Library of Medicine. * v * t * e Consequences of external causes Temperature Elevated Hyperthermia Heat syncope Reduced Hypothermia Immersion foot syndromes Trench foot Tropical immersion foot Warm water immersion foot Chilblains Frostbite Aerosol burn Cold intolerance Acrocyanosis Erythrocyanosis crurum Radiation Radiation poisoning Radiation burn Chronic radiation keratosis Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy Radiation acne Radiation-induced cancer Radiation recall reaction Radiation-induced erythema multiforme Radiation-induced hypertrophic scar Radiation-induced keloid Radiation-induced morphea Air * Hypoxia/Asphyxia * Barotrauma * Aerosinusitis * Decompression sickness * High altitude * Altitude sickness * Chronic mountain sickness * Death zone * HAPE * HACE Food * Starvation Maltreatment * Physical abuse * Sexual abuse * Psychological abuse Travel * Motion sickness * Seasickness * Airsickness * Space adaptation syndrome Adverse effect * Hypersensitivity * Anaphylaxis * Angioedema * Allergy * Arthus reaction * Adverse drug reaction Other * Electrical injury * Drowning * Lightning injuries Ungrouped skin conditions resulting from physical factors * Dermatosis neglecta * Pinch mark * Pseudoverrucous papules and nodules * Sclerosing lymphangitis * Tropical anhidrotic asthenia * UV-sensitive syndrome environmental skin conditions Electrical burn frictional/traumatic/sports Black heel and palm Equestrian perniosis Jogger's nipple Pulling boat hands Runner's rump Surfer's knots Tennis toe Vibration white finger Weathering nodule of ear Wrestler's ear Coral cut Painful fat herniation Uranium dermatosis iv use Skin pop scar Skin track Slap mark Pseudoacanthosis nigricans Narcotic dermopathy * v * t * e Shock Distributive * Septic shock * Neurogenic shock * Anaphylactic shock * Toxic shock syndrome Obstructive * Abdominal compartment syndrome Low volume * Hemorrhage * Hypovolemia * Osmotic shock Other * Spinal shock * Cryptic shock * Vasodilatory shock * v * t * e Hypersensitivity and autoimmune diseases Type I/allergy/atopy (IgE) Foreign * Atopic eczema * Allergic urticaria * Allergic rhinitis (Hay fever) * Allergic asthma * Anaphylaxis * Food allergy * common allergies include: Milk * Egg * Peanut * Tree nut * Seafood * Soy * Wheat * Penicillin allergy Autoimmune * Eosinophilic esophagitis Type II/ADCC * * IgM * IgG Foreign * Hemolytic disease of the newborn Autoimmune Cytotoxic * Autoimmune hemolytic anemia * Immune thrombocytopenic purpura * Bullous pemphigoid * Pemphigus vulgaris * Rheumatic fever * Goodpasture syndrome * Guillain–Barré syndrome "Type V"/receptor * Graves' disease * Myasthenia gravis * Pernicious anemia Type III (Immune complex) Foreign * Henoch–Schönlein purpura * Hypersensitivity vasculitis * Reactive arthritis * Farmer's lung * Post-streptococcal glomerulonephritis * Serum sickness * Arthus reaction Autoimmune * Systemic lupus erythematosus * Subacute bacterial endocarditis * Rheumatoid arthritis Type IV/cell-mediated (T cells) Foreign * Allergic contact dermatitis * Mantoux test Autoimmune * Diabetes mellitus type 1 * Hashimoto's thyroiditis * Multiple sclerosis * Coeliac disease * Giant-cell arteritis * Postorgasmic illness syndrome * Reactive arthritis GVHD * Transfusion-associated graft versus host disease Unknown/ multiple Foreign * Hypersensitivity pneumonitis * Allergic bronchopulmonary aspergillosis * Transplant rejection * Latex allergy (I+IV) Autoimmune * Sjögren syndrome * Autoimmune hepatitis * Autoimmune polyendocrine syndrome * APS1 * APS2 * Autoimmune adrenalitis * Systemic autoimmune disease Authority control * NDL: 01163594 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Anaphylaxis	c0002792	26,772	wikipedia	https://en.wikipedia.org/wiki/Anaphylaxis	2021-01-18T18:33:51	{"mesh": ["D000707"], "umls": ["C0002792"], "icd-9": ["995.0"], "icd-10": ["T78.2"], "wikidata": ["Q168800"]}
A number sign (#) is used with this entry because of evidence that peeling skin syndrome-2 (PSS2), an acral form of the disorder, is caused by homozygous or compound heterozygous mutation in the TGM5 gene (603805) on chromosome 15q15. Description Peeling skin syndrome (PSS) is an autosomal recessive genodermatosis characterized by the shedding of the outer epidermis. In an acral form of the disorder (PSS2), the dorsa of the hands and feet are predominantly affected, and ultrastructural analysis shows separation at the junction between the granular cells and the stratum corneum in the outer epidermis (summary by Cassidy et al., 2005). For a discussion of genetic heterogeneity of peeling skin syndrome, see PSS1 (270300). Clinical Features Cassidy et al. (2005) described 2 families, 1 Dutch and 1 Scottish, with noninflammatory acral peeling skin syndrome in which peeling was accompanied by erythema. Affected patients experienced periodic, painless, and superficial skin peeling. Although the skin peeling occurred spontaneously, manual removal of strips of skin was easy. The abnormality was exacerbated by elevated ambient temperature and humidity. Peeled areas showed some residual erythema for a few days but healed spontaneously and without scarring. Histologic and ultrastructural analyses of cases of the peeling skin syndrome demonstrated that the level of blistering is high in the epidermis, at the junction of the stratum granulosum (the last living layer) and the stratum corneum (the terminally differentiated and continuously shed, cornified squamous layers). Thus the disorder is histologically distinguishable from the various forms of epidermolysis bullosa, in which blistering occurs in the basal keratinocytes of the epidermis, within or close to the dermal-epidermal basement membrane, or in the upper papillary dermis. The Dutch family included 5 affected individuals in 2 interbred sibships. Genealogic analysis established consanguinity dating to the 1780s. Consanguinity in the Scottish family could not be determined. Shwayder et al. (1997) and Hashimoto et al. (2000) described families with acral PSS. Kharfi et al. (2009) reported 2 Tunisian brothers, aged 5 years and 3 years, with focal cutaneous exfoliation of the hands and feet. The scaling occurred spontaneously, and sheets of skin could be peeled off painlessly; the underlying erythematous areas healed without scarring in a few days. The symptoms worsened with elevated ambient temperature, humidity, and friction. Only the palmoplantar areas and dorsa of hands and feet were affected. Family history included 3 more affected individuals, but they were not available for study. Histologic examination of the border of a palmar lesion showed a thickened stratum corneum with cleavage in the clear zone; ultrastructural studies showed enlarged intercellular spaces in the stratum corneum, with stellate and electron-dense keratohyalin granules of various sizes in the granular cells. No desmosomal abnormalities were observed, and cleavage occurred in the intercellular spaces between corneocytes. Kiritsi et al. (2010) studied 6 unrelated children and 1 adult patient from Germany, 1 child from Sweden, and 1 child from Finland who were clinically diagnosed with epidermolysis bullosa simplex (see 131800). The patients had blisters and peeling of acral skin; healing occurred spontaneously, sometimes with residual erythema, burning sensation, or itching, but without scarring or atrophy. Sweating, heat, humidity, or mechanical trauma aggravated symptoms. In most cases, only the volar and dorsal surfaces of hands and feet were affected, but the 47-year-old patient also exhibited exfoliation of the elbows and knees. In the older children and the adult patient, peeling of the skin was the most prominent symptom, but blisters occurred occasionally. Two of the children reported having a mildly affected parent, and the adult patient reportedly had a child with mild features of the disease. Skin samples from some of the patients showed a discrete split in the stratum corneum, suggestive of acral PSS. Mapping By genomewide linkage analysis in a consanguineous Dutch kindred, Cassidy et al. (2005) mapped a gene for an acral form of peeling skin syndrome to chromosome 15q15.2, in the interval between markers D15S1040 and D15S1016. Molecular Genetics In all affected members of a Dutch and a Scottish kindred with acral PSS, Cassidy et al. (2005) identified homozygosity for a missense mutation in the TGM5 gene (G113C; 603805.0001) that completely abolished crosslinking activity. Another homozygous TGM5 missense variant present in affected individuals, T109M, did not significantly reduce TGM5 activity, and was considered to be a rare polymorphism. The mutation was present on the same haplotype in the 2 kindreds, indicating a probable ancestral mutation. Other families with a more widespread peeling skin phenotype similar to that described in PSS (270300) lacked TGM5 mutations. In 2 Tunisian brothers with APSS, Kharfi et al. (2009) sequenced the TGM5 gene and identified homozygosity for a missense mutation (K445N; 603805.0002) that was present in heterozygosity in their unaffected first-cousin parents. The mutation was not found in 120 North African controls. In 6 unrelated children and 1 adult patient from Germany, 1 child from Sweden, and 1 child from Finland with blistering and peeling acral skin that was initially diagnosed as epidermolysis bullosa simplex and who were negative for mutations in KRT5 (148040) and KRT14 (148066), Kiritsi et al. (2010) identified homozygous or compound heterozygous mutations in the TGM5 gene (603805.0001; 603805.0003). Kiritsi et al. (2010) concluded that APSS may resemble EBS in young individuals. The authors also noted that in 3 families, vertical transmission of disease was considered, because either parents or offspring were reported to have had skin blistering in childhood; however, clinical examination of the putative affected heterozygotes was not reported. In 6 patients from 6 unrelated families with APSS, van der Velden et al. (2012) identified homozygosity for the G113C mutation in the TGM5 gene, as well as homozygosity for the T109M polymorphism. All patients reported exfoliation or blisters of hands and feet from infancy, with symptoms aggravated by heat, humidity, or friction. Genealogic research dating to the year 1650 revealed no consanguinity between the families. Haplotype analysis of these 6 families, including 5 from the Netherlands and 1 from Germany, as well as of the 2 Dutch and Scottish families previously studied by Cassidy et al. (2005), revealed that all mutation carriers were homozygous for an approximately 0.16-Mb region that begins centromeric of and includes the TGM5 gene. Van der Velden et al. (2012) noted that in contrast to the 2 Tunisian patients reported by Kharfi et al. (2009), all 21 reported European APSS patients carried the G113C mutation linked to the T109M variant, suggesting an ancestral founder mutation in the European population. In 11 patients with APSS, Pigors et al. (2012) identified homozygosity or compound heterozygosity for mutations in the TGM5 gene (see, e.g., 603805.0001 and 603805.0004-603805.0006). In addition, the recurrent G113C mutation was detected in heterozygosity in 3 of 100 controls, suggesting that APSS may be more widespread than anticipated, with the mild phenotype remaining either undiagnosed or misdiagnosed. INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- Superficial skin peeling (limited to dorsa of hands and feet) \- Erythema, residual painless \- Spontaneous, non-scarring healing Skin Histology \- Blistering at junction of stratum granulosum and stratum corneum Nails \- Normal nails MISCELLANEOUS \- Skin peeling exacerbated by heat, friction, and humidity \- See also more severe phenotype peeling skin syndrome ( 270300 ) MOLECULAR BASIS \- Caused by mutation in the transglutaminase-5 gene (TGM5, 603805.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PEELING SKIN SYNDROME 2	c1853354	26,773	omim	https://www.omim.org/entry/609796	2019-09-22T16:05:33	{"mesh": ["C536316"], "omim": ["609796"], "orphanet": ["263534"], "synonyms": ["Alternative titles", "ACRAL PEELING SKIN SYNDROME", "PEELING SKIN SYNDROME, ACRAL TYPE"], "genereviews": ["NBK1369"]}
Ruggieri et al. (2003) reported a brother and sister, offspring of nonconsanguineous Italian parents, with scimitar anomaly (106700), multiple cardiac malformations, and craniofacial and CNS anomalies. Cardiac studies in a healthy sib, the parents, and all of the grandparents were normal. In addition to partial anomalous pulmonary venous return, cardiac malformations included atrial septal defects and muscular ventricular septal defects. Craniofacial anomalies included high and broad foreheads, hypertelorism, retrognathia, and large sutures and fontanels. CNS abnormalities consisted of poor brain myelination in both sibs and an enlarged cisterna magna in the brother. Both had normal high resolution karyotypes and normal testing with subtelomeric chromosomal probes. Both sibs died of pulmonary hypertension in infancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SCIMITAR ANOMALY, MULTIPLE CARDIAC MALFORMATIONS, AND CRANIOFACIAL AND CENTRAL NERVOUS SYSTEM ABNORMALITIES	c1842315	26,774	omim	https://www.omim.org/entry/608281	2019-09-22T16:07:58	{"mesh": ["C564262"], "omim": ["608281"], "synonyms": ["Alternative titles", "ANOMALOUS PULMONARY VENOUS RETURN, MULTIPLE CARDIAC MALFORMATIONS, AND CRANIOFACIAL AND CENTRAL NERVOUS SYSTEM ABNORMALITIES"]}
Pruritus vulvae is itchiness of the vulva, which is the counterpart of pruritus scroti, and may have many different causes.[1]:56 Patch testing may be used to diagnose the cause.[2] ## Causes[edit] This condition is a symptom of an underlying condition more often than it is a primary condition. Vulva irritation can be caused by any moisture left on the skin. This moisture may be perspiration, urine, vaginal discharge or small amounts of stool. It may be caused by vaginal infections, vulvitis, HPV (human papilloma virus) infection, anal incontinence, Bowen's disease, or dietary irritants (caffeine, potatoes, chilli, capsicum, tomatoes, and peanuts). Treatment with antibiotics can lead to a yeast infection and irritation of the vulva. Some diseases increase the possibility of yeast infections, such as diabetes mellitus. Chronic inflammation of the vulva predisposes to the development of premalignant or malignant changes. ## Diagnosis[edit] This section is empty. You can help by adding to it. (May 2018) ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 2. ^ Utaş S, Ferahbaş A, Yildiz S (2008). "Patients with vulval pruritus: patch test results". Contact Dermatitis. 58 (5): 296–8. doi:10.1111/j.1600-0536.2008.01325.x. PMID 18416761. * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji * v * t * e Female diseases of the pelvis and genitals Internal Adnexa Ovary * Endometriosis of ovary * Female infertility * Anovulation * Poor ovarian reserve * Mittelschmerz * Oophoritis * Ovarian apoplexy * Ovarian cyst * Corpus luteum cyst * Follicular cyst of ovary * Theca lutein cyst * Ovarian hyperstimulation syndrome * Ovarian torsion Fallopian tube * Female infertility * Fallopian tube obstruction * Hematosalpinx * Hydrosalpinx * Salpingitis Uterus Endometrium * Asherman's syndrome * Dysfunctional uterine bleeding * Endometrial hyperplasia * Endometrial polyp * Endometriosis * Endometritis Menstruation * Flow * Amenorrhoea * Hypomenorrhea * Oligomenorrhea * Pain * Dysmenorrhea * PMS * Timing * Menometrorrhagia * Menorrhagia * Metrorrhagia * Female infertility * Recurrent miscarriage Myometrium * Adenomyosis Parametrium * Parametritis Cervix * Cervical dysplasia * Cervical incompetence * Cervical polyp * Cervicitis * Female infertility * Cervical stenosis * Nabothian cyst General * Hematometra / Pyometra * Retroverted uterus Vagina * Hematocolpos / Hydrocolpos * Leukorrhea / Vaginal discharge * Vaginitis * Atrophic vaginitis * Bacterial vaginosis * Candidal vulvovaginitis * Hydrocolpos Sexual dysfunction * Dyspareunia * Hypoactive sexual desire disorder * Sexual arousal disorder * Vaginismus * Urogenital fistulas * Ureterovaginal * Vesicovaginal * Obstetric fistula * Rectovaginal fistula * Prolapse * Cystocele * Enterocele * Rectocele * Sigmoidocele * Urethrocele * Vaginal bleeding * Postcoital bleeding Other / general * Pelvic congestion syndrome * Pelvic inflammatory disease External Vulva * Bartholin's cyst * Kraurosis vulvae * Vestibular papillomatosis * Vulvitis * Vulvodynia Clitoral hood or clitoris * Persistent genital arousal disorder This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Pruritus vulvae	c0033778	26,775	wikipedia	https://en.wikipedia.org/wiki/Pruritus_vulvae	2021-01-18T18:56:20	{"mesh": ["D011539"], "umls": ["C0033778"], "icd-10": ["L29.2"], "wikidata": ["Q7253120"]}
Elevated alkaline phosphatase Micrograph showing changes that may be associated with an elevated alkaline phosphatase (cholestasis and feathery degeneration). Liver biopsy. H&E stain. SpecialtyPathology Elevated alkaline phosphatase occurs when levels of alkaline phosphatase (ALP) exceed the reference range. This group of enzymes has a low substrate specificity and catalyzes the hydrolysis of phosphate esters in a basic environment. The major function of alkaline phosphatase is transporting across cell membranes.[1] Alkaline phosphatases are present in many human tissues, including bone, intestine, kidney, liver, placenta and white blood cells.[2] Damage to these tissues causes the release of ALP into the bloodstream. Elevated levels can be detected through a blood test. Elevated alkaline phosphate is associated with certain medical conditions[3] or syndromes (e.g., hyperphosphatasia with mental retardation syndrome, HPMRS). It serves as a significant indication for certain medical conditions, diseases and syndromes. If the reason for alkaline phosphatase is unknown, isoenzyme studies using electrophoresis can confirm the source of the ALP. Heat stability also distinguishes bone and liver isoenzymes ("bone burns, liver lasts"). ## Contents * 1 Cause * 1.1 Liver * 1.2 Bones * 1.3 Obesity * 1.4 Kidney * 1.5 Cancer * 2 Diagnosis * 3 Other * 4 Treatments * 5 References * 6 External links ## Cause[edit] ### Liver[edit] * Liver (liver ALP): * Cholestasis, cholecystitis, cholangitis, cirrhosis, primary biliary cholangitis, fatty liver, sarcoidosis, liver tumor, liver metastases, drug intoxication * Drugs: e.g. verapamil, carbamazepine, phenytoin, erythromycin, allopurinol, ranitidine, Numerous Antibiotics ### Bones[edit] * Bone disease (bone ALP): * Paget's disease,[4] osteosarcoma, bone metastases of prostatic cancer (High / very high ALP values) * Other bone metastases * Renal osteodystrophy * Fractured bone * Skeletal involvement of other primary diseases: * Osteomalacia, rickets, vitamin D deficiency (moderate rise) * Malignant tumors (ALP originating from tumor) * Renal disease (secondary hyperparathyroidism) * Primary hyperthyroidism Other unlisted musculoskeletal conditions may also cause elevated alkaline phosphatase. ### Obesity[edit] Elevated levels of the alkaline phosphatase enzyme are reported with those who have obesity. A study reported there were higher serum levels of alkaline phosphatase in obese than in the non obese. With elevated alkaline phosphatase levels there is an increase in disproportionate intracellular fat depots and thereby releasing itself into the bloodstream. The relationship between alkaline phosphatase and obesity is still being tested.[5] ### Kidney[edit] Elevated serum levels of alkaline phosphatase has been associated with Chronic Kidney Disease (CKD). Studies have shown that elevated levels may predict mortality independent of bone metabolism factors and liver function tests in CKD. Elevated levels are also associated with diabetes, hypertension, and cardiovascular disease; it was found that elevated levels are associated with elevated serum C-reactive protein (CRP), which could reflect an inflammatory and atherogenic milieu, possibly an alternative cause for elevated serum alkaline phosphatase.[6] * Chronic kidney disease [7] ### Cancer[edit] Elevated alkaline phosphatase in patients with cancer normally spans throughout the bones or liver. Metastases that exist in the lung, breast, prostate, colon, thyroid, and further organs can penetrate in the liver or bone.[8] Yet, cancers that are already present in certain organs and tissues can produce alkaline phosphatase elevations if metastasis is not present. Isoenzymes, which are certain forms of alkaline phosphatase generated by these tumors, enlarges the total volume of alkaline phosphatase levels on experiential studies. The Regan isoenzyme[9] is one of the best studies of these isoenzymes that is linked to several human cancers. Basically, the Regan isozenzyme is an alkaline phosphatase that is located in the placenta and associated with the gonadal and urologic cancers. * Breast carcinoma * Colon cancer * Leukemia – cancer of the bone marrow * Lymphoma – cancer of the white blood cells * Pancreatic cancer * Lung cancer ## Diagnosis[edit] An alkaline phosphatase isoenzyme test can be done to check for elevated ALP levels. Tissues that contain high levels of ALP include the liver, bile ducts, and bones. Normal levels of ALP range from (44 to 147) U/L (units per liter) and significantly elevated levels may be an indication of conditions such as various types of cancer, bone disease such as Paget disease, liver disease such as hepatitis, blood disorders, or other conditions.[10] Elevated alkaline phosphatase is most commonly caused by liver disease or bone disorders. Testing for ALP primarily consists of obtaining a blood sample from a patient along with several other tests for the disorder in question that may be associated with the increase in ALP in the blood serum.[11] It is possible to distinguish between the different forms (isoenzymes) of ALP produced by different types of tissues in the body, in order to pinpoint what's causing the increase of ALP, in order to treat the patient for either liver disease or bone disorder. A more rapid way for testing ALP concentration is by using p-nitrophenyl phosphate as substrate.[12] The required volume of serum is 5 mm3. for each testing. The sample is first incubated for 30 min. at 38 °C, in a buffered solution in the presence of p-nitrophenyl phosphate. By the action of ALP, phosphate groups are removed from the substrate and para\- nitrophenol is liberated giving off a yellow color in solution which can be measured spectrophotometrically.[13] Normally, children and adolescents have higher Alkaline Phosphatase levels than adults due to an increase in bone growth. ALP is especially high during a period of growth spurt which occurs are different ages in boys and girls.[14] ## Other[edit] * Lung cancer * Prostate cancer * Chlorpropamide therapy * Infectious mononucleosis * Pancreatic carcinoma * Primary sclerosing cholangitis * Polycythemia vera * Myelofibrosis * Mastocytosis * Leukemoid reaction to infection * Women using hormonal contraception * Pregnancy * Herpes zoster (shingles) * Rickets – vitamin D deficiency * Amyloidosis * Granulation tissue * Gastrointestinal inflammation – inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or ulcers)[15] * Rheumatoid arthritis * Ankylosing Spondylitis * Transient hyperphosphatasaemia of infancy: benign, often associated with infection * Seminoma[16] * Hyperthyroidism[17] * Celiac disease [18] * Sarcoid[19] * Syphilis[20] ## Treatments[edit] The following are the most common treatments of elevated alkaline phosphatase.[21] * Treatment of the underlying condition * Once doctors identifies the cause of elevated ALP and diagnose a treatment, the levels of alkaline phosphatase fluctuates back to normal * Removal of medication – that is associated with increased levels of alkaline phosphatase * Birth control pills * Anti-inflammatory medication * Narcotic medication * Hormonal drug * Steroid * Antidepressant * Dietary changes * Include foods rich in vitamin D * Lifestyle change * Healthy diet in association with physical exercise * Exposure to sunlight which increases the production of vitamin D ## References[edit] 1. ^ Celik, Handan; Tosun, Midraci; Cetinkaya, Mehmet Bilge; Bektab, Ahmet; Malatyalýodlu, Erdal (2009-08-01). "Markedly elevated serum alkaline phosphatase level in an uncomplicated pregnancy". The Journal of Maternal-Fetal & Neonatal Medicine. 22 (8): 705–707. doi:10.1080/14767050802702323. ISSN 1476-4954. PMID 19544151. 2. ^ Kaplan, Marshall M. (1972). "Alkaline Phosphatase". New England Journal of Medicine. 286 (4): 200–202. doi:10.1056/nejm197201272860407. PMID 4550137. 3. ^ Li-Fern H, Rajasoorya C (February 1999). "The elevated serum alkaline phosphatase—the chase that led to two endocrinopathies and one possible unifying diagnosis". Eur. J. Endocrinol. 140 (2): 143–7. doi:10.1530/eje.0.1400143. PMID 10069658. 4. ^ Gennari L, Di Stefano M, Merlotti D, et al. (October 2005). "Prevalence of Paget's disease of bone in Italy". J. Bone Miner. Res. 20 (10): 1845–50. doi:10.1359/JBMR.050518. PMID 16160742.[dead link] 5. ^ Khan, Abdul Rehman; Awan, Fazli Rabbi; Najam, SyedaSadia; Islam, Mehboob; Siddique, Tehmina; Zain, Maryam (2015). "Elevated serum level of human alkaline phosphatase in obesity". Journal of Pakistan Medical Association. 65 (11): 1182–1185. Retrieved 2016-05-19. 6. ^ Damera, Sriharsha; Raphael, Kalani L.; Baird, Bradley C.; Cheung, Alfred K.; Greene, Tom; Beddhu, Srinivasan (2011-01-02). "Serum alkaline phosphatase levels associate with elevated serum C-reactive protein in chronic kidney disease". Kidney International. 79 (2): 228–233. doi:10.1038/ki.2010.356. PMC 5260661. PMID 20881941. 7. ^ Damera, Sriharsha (September 2010). "Serum alkaline phosphatase levels associate with elevated serum C-reactive protein in chronic kidney disease". International Society of Nephrology. 8. ^ Christensen, Stephen. "Elevated Alkaline Phosphatase & Cancer \|". LIVESTRONG.COM. Retrieved 2016-05-10. 9. ^ Fishman, W. H. (1980-01-01). "Immunology and biochemistry of the Regan isoenzyme". The Prostate. 1 (4): 399–410. doi:10.1002/pros.2990010403. ISSN 0270-4137. PMID 7024957. 10. ^ "ALP – blood test". MedlinePlus. Retrieved 2016-05-10. 11. ^ Majeska, Robert (April 10, 1982). "The Effect of 1,25(OH)zD3 on Alkaline Phosphatase in Osteoblastic Osteosarcoma Cell". The Journal of Biological Chemistry. 12. ^ BESSEY, O. A.; LOWKY, O. H.; BROCK, M. J. (1946-01-01). "A method for the rapid determination of alkaline phosphatase with 5 mm3 of serum". Journal of Biological Chemistry. 164. ISSN 0021-9258. 13. ^ BESSEY, O. A.; LOWKY, O. H.; BROCK, M. J. (1946-01-01). "A method for the rapid determination of alkaline phosphatase with five cubic millimeters of serum". Journal of Biological Chemistry. 164. ISSN 0021-9258. 14. ^ "Transient hyperphosphatasemia of infancy and early childhood". www.uptodate.com. Retrieved 2017-05-08. 15. ^ Cappello, Maria; Randazzo, Claudia; Bravatà, Ivana; Licata, Anna; Peralta, Sergio; Craxì, Antonio; Almasio, Piero Luigi (2014). "Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey". Clinical Medicine Insights: Gastroenterology. 7: 25–31. doi:10.4137/CGast.S13125. ISSN 1179-5522. PMC 4069044. PMID 24966712. 16. ^ Lange PH, Millan JL, Stigbrand T, Vessella RL, Ruoslahti E, Fishman WH (August 1982). "Placental alkaline phosphatase as a tumor marker for seminoma". Cancer Res. 42 (8): 3244–7. PMID 7093962. 17. ^ L Tibi; A W Patrick; P Leslie; A D Toft; A F Smith (1989-07-01). "Alkaline phosphatase isoenzymes in plasma in hyperthyroidism". Clinchem.org. Retrieved 2014-07-03. 18. ^ Pruessner, Harold T, “Detecting Celiac Disease in your Patients” American Family Physician: 57 (5), March 1, 1998 pp1023-1034. 19. ^ Eur J Gastroenterol Hepatol. 2012 Jan;24(1):17–24. doi: 10.1097/MEG.0b013e32834c7b71. Liver-test abnormalities in sarcoidosis. Cremers J, Drent M, Driessen A, Nieman F, Wijnen P, Baughman R, Koek G. 20. ^ Pareek, S. S., “Liver involvement in secondary syphilis” Digestive Diseases and Sciences: 24 (1), January 1979 pp 41–43. 21. ^ "Elevated Alkaline Phosphatase – Levels, Causes and Treatment". healthh.com. Retrieved 2016-05-19. ## External links[edit] Classification D * ICD-10: R74.8 * ICD-9-CM: 790.5 * v * t * e Clinical biochemistry blood tests Electrolytes * Sodium * Potassium * Chloride * Calcium * Renal function * Creatinine * Urea * BUN-to-creatinine ratio * Plasma osmolality * Serum osmolal gap Acid-base * Anion gap * Arterial blood gas * Base excess * Bicarbonate * CO2 content * Lactate Iron tests * Ferritin * Serum iron * Transferrin saturation * Total iron-binding capacity * Transferrin * Transferrin receptor Hormones * ACTH stimulation test * Thyroid function tests * Thyroid-stimulating hormone Metabolism * Blood glucose * Hemoglobin A1c * Lipid panel * LDL * HDL * Triglycerides * Total cholesterol * Basic metabolic panel * Comprehensive metabolic panel Cardiovascular * Cardiac marker * Troponin test * CPK-MB test * Lactate dehydrogenase * Myoglobin * Glycogen phosphorylase isoenzyme BB Liver function tests * Proteins * Human serum albumin * Serum total protein * ALP * transaminases * ALT * AST * AST/ALT ratio * GGT * Bilirubin * Unconjugated * Conjugated Pancreas * Amylase * Lipase * Pancreatic lipase Small molecules Blood sugar level * Hypoglycemia * Hyperglycemia Nitrogenous * Azotemia * Hyperuricemia * Hypouricemia Proteins LFT * Elevated transaminases * Elevated ALP * Hypoproteinemia * Hypoalbuminemia Other * Elevated alpha-fetoprotein [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Elevated alkaline phosphatase	c4021240	26,776	wikipedia	https://en.wikipedia.org/wiki/Elevated_alkaline_phosphatase	2021-01-18T18:54:05	{"umls": ["C4021240"], "icd-9": ["790.5"], "icd-10": ["R74.8"], "wikidata": ["Q17011974"]}
Y chromosome microdeletion (YCM) is a family of genetic disorders caused by missing gene(s) in the Y chromosome. Many men with YCM exhibit no symptoms and lead normal lives. However, YCM is also known to be present in a significant number of men with reduced fertility.[1] Men with reduced sperm production (in up to 20% of men with reduced sperm count, some form of YCM has been detected[2]) varies from oligozoospermia, significant lack of sperm, or azoospermia, complete lack of sperm. ## Contents * 1 Cause * 2 Diagnosis * 3 Infertility * 4 See also * 5 References * 6 Further reading ## Cause[edit] The mechanism of mutation is not different for Y-chromosome microdeletion. However, the ability to repair it differs from other chromosomes. The human Y chromosome is passed directly from father to son, and is not protected against accumulating copying errors, whereas other chromosomes are error corrected by recombining genetic information from mother and father. This may leave natural selection as the primary repair mechanism for the Y chromosome. ## Diagnosis[edit] Y chromosome microdeletion is currently diagnosed by extracting DNA from leukocytes in a man's blood sample, mixing it with some of the about 300 known genetic markers for sequence-tagged sites (STS) on the Y chromosome, and then using polymerase chain reaction amplification and gel electrophoresis in order to test whether the DNA sequence corresponding to the selected markers is present in the DNA. Such procedures can test only the integrity of a tiny part of the overall 23 million base pair long Y chromosome, therefore the sensitivity of such tests depends on the choice and number of markers used. Present diagnostic techniques can only discover certain types of deletions and mutations on a chromosome and give therefore no complete picture of genetic causes of infertility. They can only demonstrate the presence of some defects, but not the absence of any possible genetic defect on the chromosome. The gold standard test for genetic mutation, namely complete DNA sequencing of a patient's Y chromosome, is still far too expensive for use in epidemiologic research or even clinical diagnostics. ## Infertility[edit] Microdeletions in the Y chromosome have been found at a much higher rate in infertile men than in fertile controls[3] and the correlation found may still go up as improved genetic testing techniques for the Y chromosome are developed. Much study has been focused upon the "azoospermia factor locus" (AZF), at Yq11.[4] A specific partial deletion of AZFc called gr/gr deletion is significantly associated with male infertility among Caucasians in Europe and the Western Pacific region.[5] Additional genes associated with spermatogenesis in men and reduced fertility upon Y chromosome deletions include RBM, DAZ, SPGY, and TSPY.[6] ## See also[edit] * Infertility * AZF1 ## References[edit] 1. ^ Carlo Foresta, et al.: Y chromosome microdeletions and alterations of spermatogenesis. Endocrine Reviews 22 (2): 226-239. 2. ^ Krausz, Csilla; Lluis Quintana-Murci; Ken McElreavey (July 2000). "Prognostic value of Y deletion analysis". Human Reproduction. 15 (7): 1431–1434. doi:10.1093/humrep/15.7.1431. PMID 10875846. 3. ^ Song NH, Wu HF, Zhang W, et al. (September 2005). "Screening for Y chromosome microdeletions in idiopathic and nonidiopathic infertile men with varicocele and cryptorchidism". Chin. Med. J. 118 (17): 1462–7. PMID 16157049. 4. ^ Poongothai J, Gopenath TS, Manonayaki S (April 2009). "Genetics of human male infertility" (PDF). Singapore Med J. 50 (4): 336–47. PMID 19421675. 5. ^ Stouffs, K.; Lissens, W.; Tournaye, H.; Haentjens, P. (2010). "What about gr/gr deletions and male infertility? Systematic review and meta-analysis". Human Reproduction Update. 17 (2): 197–209. doi:10.1093/humupd/dmq046. PMID 20959348. 6. ^ Goncalves, J; Lavinha J. (April 1998). "Y chromosome and male infertility". Acta Med Port (in Portuguese). 11 (4): 365–72. PMID 9644848. ## Further reading[edit] * GeneReviews/NCBI/NIH/UW entry on Y Chromosome Infertility * v * t * e Chromosome abnormalities Autosomal Trisomies/Tetrasomies * Down syndrome * 21 * Edwards syndrome * 18 * Patau syndrome * 13 * Trisomy 9 * Tetrasomy 9p * Warkany syndrome 2 * 8 * Cat eye syndrome/Trisomy 22 * 22 * Trisomy 16 Monosomies/deletions * (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome) * 1 * Wolf–Hirschhorn syndrome * 4 * Cri du chat syndrome/Chromosome 5q deletion syndrome * 5 * Williams syndrome * 7 * Jacobsen syndrome * 11 * Miller–Dieker syndrome/Smith–Magenis syndrome * 17 * DiGeorge syndrome * 22 * 22q11.2 distal deletion syndrome * 22 * 22q13 deletion syndrome * 22 * genomic imprinting * Angelman syndrome/Prader–Willi syndrome (15) * Distal 18q-/Proximal 18q- X/Y linked Monosomy * Turner syndrome (45,X) Trisomy/tetrasomy, other karyotypes/mosaics * Klinefelter syndrome (47,XXY) * XXYY syndrome (48,XXYY) * XXXY syndrome (48,XXXY) * 49,XXXYY * 49,XXXXY * Triple X syndrome (47,XXX) * Tetrasomy X (48,XXXX) * 49,XXXXX * Jacobs syndrome (47,XYY) * 48,XYYY * 49,XYYYY * 45,X/46,XY * 46,XX/46,XY Translocations Leukemia/lymphoma Lymphoid * Burkitt's lymphoma t(8 MYC;14 IGH) * Follicular lymphoma t(14 IGH;18 BCL2) * Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH) * Anaplastic large-cell lymphoma t(2 ALK;5 NPM1) * Acute lymphoblastic leukemia Myeloid * Philadelphia chromosome t(9 ABL; 22 BCR) * Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) * Acute promyelocytic leukemia t(15 PML,17 RARA) * Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1) Other * Ewing's sarcoma t(11 FLI1; 22 EWS) * Synovial sarcoma t(x SYT;18 SSX) * Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB) * Myxoid liposarcoma t(12 DDIT3; 16 FUS) * Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS) * Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1) Other * Fragile X syndrome * Uniparental disomy * XX male syndrome/46,XX testicular disorders of sex development * Marker chromosome * Ring chromosome * 6; 9; 14; 15; 18; 20; 21, 22 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Y chromosome microdeletion	c1507149	26,777	wikipedia	https://en.wikipedia.org/wiki/Y_chromosome_microdeletion	2021-01-18T19:10:52	{"gard": ["4230", "185"], "mesh": ["C536297"], "umls": ["C1507149"], "orphanet": ["1646"], "wikidata": ["Q8046191"]}
Bekhterev–Mendel reflex Differential diagnosisPyramidal tract lesions The Bekhterev–Mendel reflex, also known as the Mendel reflex or Mendel–Bekhterev reflex, is a clinical sign found in patients with pyramidal tract lesions. Percussion of the dorsum of the foot causes flexion, or downward movement, of the second to the fifth toes in patients with pyramidal tract lesions, whereas percussion of the dorsum of the foot in normal patients causes extension of the toes. It is analogous to the Bekhterev–Jacobsohn reflex in the upper limb. The reflex is named after Vladimir Bekhterev and Kurt Mendel. ## References[edit] Mendel's reflex at Who Named It? This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Bekhterev–Mendel reflex	None	26,778	wikipedia	https://en.wikipedia.org/wiki/Bekhterev%E2%80%93Mendel_reflex	2021-01-18T19:09:39	{"wikidata": ["Q2204646"]}
A number sign (#) is used with this entry because immunodeficiency-33 (IMD33) is caused by mutation in the gene encoding NF-kappa-B essential modulator (NEMO, or IKBKG; 300248) on chromosome Xq28. Mutation in the NEMO gene can also cause incontinentia pigmenti (IP; 308300), an X-linked dominant disorder, and several X-linked recessive disorders, including immunodeficiency with hypohidrotic ectodermal dysplasia (300291), together with osteopetrosis and lymphedema (OLEDAID; 300301) in some patients, immunodeficiency without ectodermal dysplasia (300584), and recurrent invasive pneumococcal disease (IPD2; 300640). Description IMD33 results from X-linked recessive NEMO deficiency, which is associated with various other diseases, including immunodeficiency with hypohidrotic ectodermal dysplasia (300291), together with osteopetrosis and lymphedema (300301) in some patients, and immunodeficiency without ectodermal dysplasia (300584). In contrast with patients with these other forms of X-linked recessive NEMO deficiency, who display a broad susceptibility to infections, infections in IMD33 patients are mostly limited to mycobacterial disease, with M. avium complex being the most common cause. Furthermore, IMD33 patients lack developmental features suggestive of hypohidrotic ectodermal dysplasia. Monocytes from IMD33 patients have intrinsic defects in T cell-dependent IL12 (see 161561) production, resulting in impaired IFNG (147570) production. The prognosis of IMD33 patients is variable (review by Al-Muhsen and Casanova, 2008). Clinical Features Filipe-Santos et al. (2006) reported 4 male patients from a multiplex American kindred with disseminated mycobacterial disease. None of the patients had BCG vaccination, and the organism in each case was M. avium. All had onset of disseminated M. avium infection between ages 5 and 14 years. Treatment was only partially effective in some cases, and those that survived had recurrence of the disease as adults. Laboratory studies showed normal numbers of immune cells, normal T-cell proliferative responses, and normal immunoglobulins with proper antibody responses to vaccination. Two additional unrelated males of Italian/Serbian and German descent, respectively, had a similar disorder. The first patient had BCG vaccination at age 2 months and presented with disseminated disease at age 2 years. The other patient had recurrent infections late in childhood and presented at age 11 years with mycobacterial disease. Some of the patients had sparse or conical teeth, which was long unrecognized. Patient monocytes and monocyte-derived dendritic cells showed impaired production of IL12 and gamma-interferon upon stimulation with PHA. Inheritance The transmission pattern of IMD33 in the families reported by Filipe-Santos et al. (2006) was consistent with X-linked recessive inheritance. Molecular Genetics Filipe-Santos et al. (2006) identified 2 mutations in the NEMO gene (300248.0021 and 300248.0022) in 3 unrelated kindreds with IMD33. Both mutations occurred in the region of NEMO encoding the leucine zipper and disrupted a salt bridge. Western blot and flow cytometric analyses showed normal expression of the mutant NEMO proteins. Patient mononuclear cells responded normally to most stimuli, but IFNG (147570) and IL12 (see 161561) production in response to PHA mitogen was impaired due to defective CD40 (109535) signaling in monocytes and dendritic cells. Filipe-Santos et al. (2006) concluded that mutations in NEMO that disrupt the leucine zipper domain provide a genetic etiology to X-linked recessive susceptibility to mycobacterial disease. INHERITANCE \- X-linked recessive HEAD & NECK Teeth \- Delayed eruption of teeth (in some patients) \- Conical teeth (in some patients) IMMUNOLOGY \- Susceptibility to disseminated mycobacterial infections \- Some patients may have increased susceptibility to other infections \- Impaired production of IL-12 and gamma-interferon MISCELLANEOUS \- Onset in the first 2 decades \- Poor response to treatment \- Chronic condition MOLECULAR BASIS \- Caused by mutation in the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase of, gamma, gene (IKBKG, 300248.0021 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	IMMUNODEFICIENCY 33	c1970879	26,779	omim	https://www.omim.org/entry/300636	2019-09-22T16:19:53	{"mesh": ["C567070"], "omim": ["300636"], "orphanet": ["319612", "319605"], "synonyms": ["X-linked MSMD due to NEMO deficiency", "Alternative titles", "IMMUNODEFICIENCY 33, MYCOBACTERIOSIS, X-LINKED", "X-linked MSMD due to IKBKG deficiency", "X-linked MSMD", "X-linked mendelian susceptibility to mycobacterial diseases due to NEMO deficiency", "ATYPICAL MYCOBACTERIOSIS, FAMILIAL, X-LINKED 1"]}
Cranio-cerebello-cardiac (3C) syndrome is a rare multiple congenital anomalies syndrome characterized by craniofacial (prominent occiput and forehead, hypertelorism, ocular coloboma, cleft palate), cerebellar (Dandy-Walker malformation, cerebellar vermis hypoplasia) and cardiac (tetralogy of Fallot, atrial and ventricular septal defects) anomalies (see these terms). ## Epidemiology To date < 50 cases have been described. The syndrome appears to be panethnic. ## Clinical description 3C syndrome is a congenital disorder characterized by distinctive craniofacial features including, in decreasing frequency, low-set ears, hypertelorism, down-slanting palpebral fissures, depressed nasal bridge, prominent occiput, prominent forehead, cleft palate, micrognathia, ocular coloboma. Additional craniofacial features encompass nevus flammeus (on forehead), low posterior hairline, sparse scalp hair, eyebrows and eyelashes, open mouth with protruding tongue, and short neck. In 80% of cases, cerebellar anomalies are present and include primarily Dandy-Walker malformation or Dandy-Walker variant, cerebellar vermis hypoplasia and enlargement of cisterna magma. Affected individuals have gross motor and speech delay and intellectual disability. The cardiovascular anomalies include atrial and ventricular septal defects, patent arterial duct, tetralogy of Fallot, double outlet right ventricle, hypoplastic left heart syndrome (see these terms), aortic or pulmonary stenosis, and other valvular anomalies. Postnatal short stature is noted in most patients, and growth hormone deficiency has been reported in two patients. Additional anomalies, noted in >10% of patients, include feeding difficulties, single umbilical artery, small hands with single transverse crease, camptodactyly, equinovarus deformity, hydronephrosis, shallow scrotum, undescended testis, cryptorchidism, micropenis, hypospadias, nail hypoplasia, hearing loss, malrotation of the gut. Skeletal defects may be present with rib and vertebral anomalies (hemivertebrae). Rarely observed features include ocular (congenital glaucoma, optic nerve atrophy with eyelid ptosis, heteochromatic iris, posterior embryotoxon), renal (multicystic dysplastic kidney, horseshoe kidneys, unilateral renal agenesis) and anal (anal atresia, anteriorly placed anus malformations) anomalies. Single occurrences of renal hypoplasia, nipple hypoplasia, penile hypoplasia, unilateral adrenal aplasia, immunodeficiency have also been reported. ## Etiology The exact etiology is still unknown but mutations in KIAA0196 (8q24.13; coding for strumpellin) have been identified in a First Nations cohort and these mutations may be involved in the pathophysiology of 3C syndrome. ## Diagnostic methods The diagnostic criteria for 3C syndrome include congenital heart malformation(s) other than isolated patent arterial duct; Dandy-Walker malformation, cerebellar vermis hypoplasia, or enlarged cisterna; and cleft palate, ocular coloboma or four of the following: prominent occiput, prominent forehead, hypertelorism, micrognathia, downslanting palpebral fissures, depressed nasal bridge, low-set ears. ## Differential diagnosis Differential diagnosis includes Joubert syndrome, Ellis Van Creveld syndrome, Cornelia de Lange syndrome, distal monosomy 6p (see these terms) and Dandy Walker malformation. ## Antenatal diagnosis Prenatal diagnosis may be suspected after an ultrasound examination revealing characteristic major structural anomalies of 3C syndrome. Prenatal testing is available for families in which the disease-causing mutations have been previously identified. ## Genetic counseling Sporadic and familial cases have been reported. Transmission is autosomal recessive. Phenotypic variability exists between siblings. ## Management and treatment Management is mainly symptomatic and multidisciplinary approaches including educational programs, physical, occupational, and speech therapy may help to improve hypotonia and reduce motor developmental delay. Cardiac malformation requires specific care, often surgery. ## Prognosis Prognosis is determined by the cardiovascular malformation. Motor delay is common and associated with hypotonia secondary to cerebellar anomalies. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	3C syndrome	c0796137	26,780	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=7	2021-01-23T19:09:33	{"gard": ["5666"], "mesh": ["C535313"], "omim": ["220210", "300963"], "umls": ["C0796137"], "icd-10": ["Q87.8"], "synonyms": ["Craniocerebellocardiac dysplasia", "Ritscher-Schinzel syndrome"]}
Erythema multiforme (EM) refers to a group of hypersensitivity disorders characterized by symmetric red, patchy lesions, primarily on the arms and legs. The cause is unknown, but EM frequently occurs in association with herpes simplex virus, suggesting an immunologic process initiated by the virus. In half of the cases, the triggering agents appear to be medications, including anticonvulsants, sulfonamides, nonsteroidal anti-inflammatory drugs, and other antibiotics. In addition, some cases appear to be associated with infectious organisms such as Mycoplasma pneumoniae and many viral agents. Erythema multiforme is the mildest of three skin disorders that are often discussed in relation to each other. It is generally the mildest of the three. More severe is Stevens-Johnson syndrome. The most severe of the three is toxic epidermal necrolysis (TEN). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Erythema multiforme	c0014742	26,781	gard	https://rarediseases.info.nih.gov/diseases/6372/erythema-multiforme	2021-01-18T18:00:39	{"mesh": ["D004892"], "synonyms": ["EM", "Erythema polymorphe, erythema multiforme type", "Erythema multiforme bullosum", "Dermatostomatitis, erythema multiforme type", "Febrile mucocutaneous syndrome", "Herpes iris, erythema multiforme type"]}
Deviated septum Other namesDeviated nasal septum (DNS) An MRI image showing a congenitally deviated nasal septum SpecialtyOtorhinolaryngology Nasal septum deviation is a physical disorder of the nose, involving a displacement of the nasal septum. Some displacement is common, affecting 80% of people, mostly without their knowledge.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 4.1 Complications of septoplasty * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] Only more severe cases of a deviated septum will cause symptoms of difficulty breathing and require treatment.[1] Symptoms of a deviated septum include infections of the sinus and sleep apnea, snoring, repetitive sneezing, facial pain, nosebleeds, mouth breathing, difficulty with breathing and mild to severe loss of the ability to smell.[1][2] The nasal septum is the bone and cartilage in the nose that separates the nasal cavity into the two nostrils. The cartilage is called the quadrangular cartilage and the bones comprising the septum include the maxillary crest, vomer and the perpendicular plate of the ethmoid. Normally, the septum lies centrally, and thus the nasal passages are symmetrical.[3] A deviated septum is an abnormal condition in which the top of the cartilaginous ridge leans to the left or the right, causing obstruction of the affected nasal passage. The condition can result in poor drainage of the sinuses. People can also complain of difficulty breathing, headaches, bloody noses, or of sleeping disorders such as snoring or sleep apnea.[3] It is common for nasal septa to depart from the exact centerline; the septum is only considered deviated if the shift is substantial or causes problems.[4] Many people with a deviation are unaware they have it until some pain is produced. By itself, a deviated septum can go undetected for years and thus be without any need for correction.[4] ## Causes[edit] It is most frequently caused by impact trauma, such as by a blow to the face.[4] It can also be a congenital disorder, caused by compression of the nose during childbirth.[4] Deviated septum is associated with genetic connective tissue disorders such as Marfan syndrome, Homocystinuria and Ehlers–Danlos syndrome.[5] ## Diagnosis[edit] Nasal septum deviation is the most common cause of nasal obstruction.[6] A history of trauma to the nose is often present including trauma from the process of birth or microfractures.[6] A medical professional, such as an otorhinolaryngologist (ears, nose, and throat doctor), typically makes the diagnosis after taking a thorough history from the affected person and performing a physical examination.[6] Imaging of the nose is sometimes used to aid in making the diagnosis as well.[6] ## Treatment[edit] Medical therapy with nasal sprays including decongestants, antihistamines, or nasal corticosteroid sprays is typically tried first before considering a surgical approach to correct nasal septum deviation.[6] Medication temporarily relieves symptoms, but does not correct the underlying condition. Non-medical relief can also be obtained using nasal strips. A minor surgical procedure known as septoplasty can cure symptoms related to septal deviations. The surgery lasts roughly one hour and does not result in any cosmetic alteration or external scars. Nasal congestion, pain,[7] drainage, or swelling may occur within the first few days after the surgery.[8] Recovery from the procedure may take anywhere from 2 days to 4 weeks to heal completely.[citation needed] Septal bones never regrow. If symptoms reappear they are not related to deviations. Reappearance of symptoms may be due to mucosal metaplasia of the nose.[citation needed] Currently, the most gentle and effective treatment is laser septochondroplasty for the septal cartilage segment deformity and ultrasound septoplasty — effective for the septal cartilage and bone deformation.[citation needed] ### Complications of septoplasty[edit] * Nasal septum perforation[6] due to bilateral trauma of the mucoperichondrial flaps opposite each other. * Incomplete correction with persistent nasal symptoms[6] * External nasal deformity[6] * Septal hematoma[6] and septal abscess. * Scarring inside the nose and nose bleeding[6] * Adhesions and synechiae between septal mucosa and lateral nasal wall * Saddle nose due to over-resection of the dorsal wall of the septal cartilage * Dropped nasal tip due to resection of the caudal margin ## See also[edit] * Nasal septum perforation ## References[edit] 1. ^ a b c Robinson, Jennifer (December 11, 2016). "What Is a Deviated Septum?". WebMD. 2. ^ "Disorders of Smell & Taste". American Rhinologic Society. 17 February 2015. Archived from the original on 26 December 2017. Retrieved 19 May 2012. 3. ^ a b American Academy of Otolaryngology, Fact Sheet: Deviated Septum, retrieved 2009-02-04 4. ^ a b c d Metson, Ralph; Mardon, Steven (2005-04-05), The Harvard Medical School Guide to Healing Your Sinuses, McGraw-Hill Professional, pp. 159–161, ISBN 978-0-07-144469-9 5. ^ Child, AH (November 2017). "Non-cardiac manifestations of Marfan syndrome". Annals of Cardiothoracic Surgery (Review). 6 (6): 599–609. doi:10.21037/acs.2017.10.02. PMC 5721104. PMID 29270372. 6. ^ a b c d e f g h i j Fettman, N; Sanford, T; Sindwani, R (April 2009). "Surgical management of the deviated septum: techniques in septoplasty". Otolaryngologic Clinics of North America. 42 (2): 241–52. doi:10.1016/j.otc.2009.01.005. PMID 19328889. 7. ^ Fujiwara, Takashi; Kuriyama, Akira; Kato, Yumi; Fukuoka, Toshio; Ota, Erika (2018-08-23). Cochrane ENT Group (ed.). "Perioperative local anaesthesia for reducing pain following septal surgery". Cochrane Database of Systematic Reviews. 8: CD012047. doi:10.1002/14651858.CD012047.pub2. PMC 6513247. PMID 30136717. 8. ^ "Septoplasty: Recovery and Outlook". my.clevelandclinic.org. Cleveland Clinic. ## External links[edit] Classification D * ICD-10: J34.2 * ICD-9-CM: 470 Wikimedia Commons has media related to Nasal septum deviation. * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Nasal septum deviation	c0549397	26,782	wikipedia	https://en.wikipedia.org/wiki/Nasal_septum_deviation	2021-01-18T18:58:29	{"icd-9": ["21.88"], "icd-10": ["J34.2"], "wikidata": ["Q2271880"]}
## Description The Passovoy factor defect was originally described as an autosomal dominant bleeding disorder characterized by a prolonged activated partial thromboplastin time (APTT) (Hougie et al., 1975). However, further characterization of supposedly affected individuals has identified other causes for the prolonged APTT, thus casting doubt on the existence of the Passovoy factor defect as a distinct entity (Foster et al., 1992; Hayani et al., 1996). Clinical Features Hougie et al. (1975) described the Passovoy family in which 5 sibs and the paternal grandmother had easy bruising and a moderate bleeding diathesis. Laboratory studies showed prolonged partial thromboplastin times and normal levels of all known clotting factors. Male-to-male transmission was noted. Hougie et al. (1978) provided further analysis of the Passovoy family and presented probands from 4 additional unrelated families with a similar disorder. Bleeding episodes included menorrhagia and excessive bleeding after surgery and minor cuts. All affected individuals had prolonged partial thromboplastin times and normal levels of all known clotting factors. In all cases, admixture of normal plasma corrected the defect, suggesting that no inhibitor was present. However, mixing of plasma among the patients did not correct the defect. Hougie et al. (1975) suggested that the defect was related to the intrinsic coagulation pathway. Joist (1978) gave reasons to doubt the existence of the Passovoy factor. In a response to Joist (1978), Hougie (1978) noted that the patients in their study (Hougie et al., 1978) had at least 2 determinations of the APTT using different techniques. In addition, platelet function studies were normal, and factor VIII (F8; 300841) and factor VIII-related antigen (VWF; 613160) were normal, thus excluding von Willebrand disease (VWD; 193400). Ratnoff (1990) studied 'Passovoy plasma' and found that the titer of Hageman factor (F12; 610619) was 44% of the normal standard in his laboratory. He stated, furthermore, that an otherwise unexplained prolongation of the partial thromboplastin time such as was present in these cases, i.e., in asymptomatic individuals, is most often due to heterozygosity for Hageman trait (see 234000). Castaman et al. (1992) described a 28-year-old man who appeared to have the Passovoy defect. He presented with recurrent bleeding and hematoma after localized surgery, and had a history of gingival bleeding after a dental procedure. Laboratory studies showed consistently prolonged APTT, which was not corrected after mixing with Passovoy-deficient plasma. The addition of as little as 10% normal plasma was sufficient to correct the APTT. There was no family history of the disorder and both parents had normal clinical and laboratory findings, suggesting a recessive trait. There is only 1 commercially available Passovoy-deficient plasma pool available for diagnosis of the disorder, which is obtained from the proband described in the original report by Hougie et al. (1975). Foster et al. (1992) found multiple coagulation factor abnormalities among 3 different lots of Passovoy-deficient plasma, including low factor VIII, presence of the lupus anticoagulant and anticardiolipin Ig antibodies, and prolonged thrombin time. In particular, all 3 lots had low factor XII. Foster et al. (1992) noted that these defects could potentially contribute to a prolonged APTT. Moreover, as no specific protein had been identified as the Passovoy factor, these results called into question whether the Passovoy defect is truly an established entity. Hayani et al. (1996) studied blood isolated from 13 children with a diagnosis of Passovoy defect based on a prolonged APTT that corrected with normal plasma but not with Passovoy trait plasma. Five patients had bleeding manifestations, consistent with the diagnosis, and 8 were asymptomatic. Six patients were found to have von Willebrand disease (see 193400, 613554, and 277480), 1 had low factor XII, and 1 had lupus anticoagulant. Testing of the Passovoy trait plasma lot showed low factor VIII and presence of the lupus anticoagulant. Thus, none of the 13 patients had Passovoy defect since they either had another coagulation defect or did not have bleeding manifestations. Hayani et al. (1996) concluded that caution must be taken in diagnosing patients with Passovoy defect by mixing studies, and even questioned whether the defect actually exists. INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Epistaxis GENITOURINARY Internal Genitalia (Female) \- Menorrhagia SKIN, NAILS, & HAIR Skin \- Easy bruising HEMATOLOGY \- Bleeding tendency \- Normal levels of known coagulation factors LABORATORY ABNORMALITIES \- Prolonged partial thromboplastin time (PTT) MISCELLANEOUS \- Variable severity \- Existence as a distinct entity is not confirmed ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PASSOVOY FACTOR DEFECT	c3149707	26,783	omim	https://www.omim.org/entry/168830	2019-09-22T16:36:32	{"omim": ["168830"]}
A number sign (#) is used with this entry because hyperlysinemia type I is caused by homozygous or compound heterozygous mutation in the alpha-aminoadipic semialdehyde synthase gene (AASS; 605113) on chromosome 7q31. Description Hyperlysinemia type I is an autosomal recessive metabolic condition with variable clinical features. Some patients who present in infancy with nonspecific seizures, hypotonia, or mildly delayed psychomotor development have been found to have increased serum lysine and pipecolic acid on laboratory analysis. However, about 50% of probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant (summary by Tondo et al., 2013; Houten et al., 2013). The AASS gene encodes a bifunctional enzyme: lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase. In hyperlysinemia type I, both enzymatic functions of AASS are defective; in hyperlysinemia type II, also known as saccharopinuria (268700), some of the first enzymatic function is retained (Cox, 1985; Cox et al., 1985). Clinical Features Ghadimi et al. (1965) found hyperlysinemia in 2 unrelated mentally retarded patients, one of whom was the product of father-daughter incest. The level of lysine in the cerebrospinal fluid was also elevated. Blood levels rose abnormally with lysine loading. A block in the metabolism of lysine was postulated. The patients were aged 2 and 27 years. Impaired sexual development, lax ligaments and muscles, convulsions in early life, and perhaps mild anemia were features. Woody (1964) found elevated lysine in the blood and spinal fluid of a physically and mentally retarded girl with convulsions, muscular and ligamentous asthenia, and normocytic, normochromic anemia which responded to dietary restriction of lysine. Woody (1964) suggested that incorporation of lysine into protein was defective. An ostensibly normal cousin also had hyperlysinuria. The parents of the proband were related. Dancis et al. (1969) demonstrated reduced lysine:alpha-ketoglutarate reductase activity in skin fibroblasts from 3 affected sibs. Subluxation of the lenses developed in some of the patients (Woody, 1971; Smith et al., 1971). The hyperlysinemia in the cases studied by Dancis et al. (1969) was more marked than that in other reported cases such as that of Ghadimi et al. (1965), yet the latter cases were more severely retarded. Colombo et al. (1964) described episodic vomiting, rigidity, and coma in an infant, which was relieved by a low protein diet. During coma, ammonia was high in the blood and the amino acids lysine and arginine were also high. Defect in degradation of lysine was proposed. Lysine is a potent competitive inhibitor of arginase. As a result, urea synthesis and ammonia detoxication are interfered with. Colombo et al. (1967) demonstrated a defect in L-lysine:NAD-oxido-reductase activity in liver. This apparently is responsible for accumulation of lysine. Scriver (1987) concluded that the disorder described by Colombo et al. (1964) is the same as hyperlysinemia. Cederbaum et al. (1979) reported a 7-year-old boy with mild developmental delay, hyperactivity, and speech delay who was found to have increased serum and urinary lysine and saccharopine. Saccharopine was also present in cerebrospinal fluid. Initial studies suggested cystinuria, but further analysis indicated that the amino acid was saccharopine. Patient fibroblasts showed undetectable activities of both lysine ketoglutarate reductase and saccharopine dehydrogenase. Reexamination of the urine of previously studied cases of this double enzyme deficiency (Dancis et al., 1976) suggested that saccharopinuria of variable degree is the rule and not the exception in patients with hyperlysinemia. Dancis et al. (1983) reviewed 10 cases of familial hyperlysinemia with lysine:alpha-ketoglutarate reductase deficiency, identified through newborn screening programs or family surveys. No adverse mental or physical effects could be attributed to the hyperlysinemic mother. Treatment with low protein diet was not found to be warranted. In addition, a child with no clinical manifestations of hyperlysinemia was born to an affected mother. Further study of the patients reported by Woody (1964), inbred Louisiana Cajuns, revealed that 2 successive enzymes in the major pathway of lysine degradation are deficient, i.e., lysine ketoglutarate reductase (Dancis et al., 1969) and saccharopine dehydrogenase (Cox et al., 1975; Dancis et al., 1976), the first 2 steps in the mammalian lysine degradation pathway, suggesting the existence of a bifunctional enzyme encoded by a single locus. Tondo et al. (2013) reported 2 unrelated children with hyperlysinemia type I. Both presented in infancy with seizures and were found to have increased lysine in serum, urine, and cerebrospinal fluids. Pipecolic acid was also increased in serum and urine, whereas ornithine was decreased. The patients had mild cognitive impairment, with poor speech, hyperactivity, and poor attention span. One patient had optic nerve hypoplasia and fine motor deficits. Brain MRI showed no abnormalities, and neither patient had dysmorphic features. A lysine-restricted diet yielded mild improvement in symptoms and laboratory abnormalities, but was difficult to follow and did not reverse cognitive impairment. Houten et al. (2013) directly sequenced the AASS gene in a sample of 8 patients with hyperlysinemia who were identified retrospectively from a cohort of patient samples sent for metabolic screening due to a variety of distinct neurologic abnormalities. Biallelic mutations or deletions involving the AASS gene were identified in all samples (see, e.g., 605113.0006 and 605113.0007). Patient fibroblasts showed no detectable lysine alpha-ketoglutarate dehydrogenase or saccharopine dehydrogenase activity, and immunoblot analysis detected AASS at decreased levels in only 1 patient; the others had no detectable AASS protein. Patients had been referred for a variety of reasons, including delayed psychomotor development, failure to thrive, spastic tetraparesis or diplegia, seizures, hypotonia, and hyperactivity. Some patients had dysmorphic features. There was no definitive common phenotype among the referred patients except for increased serum lysine. Houten et al. (2013) concluded that the hyperlysinemia in these individuals resulted from mutations in the AASS gene; however, given the broad range of clinical features and the presence of consanguinity in several families, there was not strong evidence for causality. Molecular Genetics In a patient with hyperlysinemia originally reported by Dancis et al. (1976), Sacksteder et al. (2000) found homozygosity for an out-of-frame 9-bp deletion in exon 15 of the AASS gene (605113.0001). In 2 unrelated patients with type I hyperlysinemia and mild cognitive deficits, Tondo et al. (2013) identified compound heterozygous mutations in the AASS gene (605113.0002-605113.0005). All mutations affected splicing or resulted in truncated proteins, consistent with a loss of function. History Dancis (1983) suspected that ectopia lentis is not a feature of lysine:alpha-ketoglutarate reductase deficiency. The patient of Woody (1971) may have had a second recessive disorder responsible for lax ligaments and ectopia lentis. In the view of Dancis (1983), the cases of Ghadimi et al. (1965), in which lax ligaments were also described, represent a different disease in which mental retardation is prominent and hyperlysinemia relatively slight. INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Mental retardation, mild \- Cognitive impairment \- Language delay \- Motor deficits \- Seizures Behavioral Psychiatric Manifestations \- Hyperactivity \- Poor attention span LABORATORY ABNORMALITIES \- Increased serum, urinary, and CSF lysine \- Increased plasma and urinary pipecolic acid \- Decreased plasma and urinary ornithine \- Increased serum, urinary, and CSF saccharopine (in some patients) \- Lysine-ketoglutarate reductase deficiency \- Saccharopine dehydrogenase deficiency \- Aminoadipic semialdehyde synthase (AASS) deficiency MISCELLANEOUS \- Onset in infancy \- Highly variable phenotype \- May be benign condition \- About 50% of mutation carriers are asymptomatic MOLECULAR BASIS \- Caused by mutation in the alpha-aminoadipic semialdehyde synthase gene (AASS, 605113.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYPERLYSINEMIA, TYPE I	c0936256	26,784	omim	https://www.omim.org/entry/238700	2019-09-22T16:26:51	{"doid": ["9274"], "mesh": ["D020167"], "omim": ["238700"], "orphanet": ["2203"], "synonyms": ["Alternative titles", "LYSINE:ALPHA-KETOGLUTARATE REDUCTASE DEFICIENCY", "ALPHA-AMINOADIPIC SEMIALDEHYDE SYNTHASE DEFICIENCY", "LYSINE INTOLERANCE", "L-LYSINE:NAD-OXIDO-REDUCTASE DEFICIENCY"]}
For other uses, see Anthrax (disambiguation). Infection caused by Bacillus anthracis bacteria Anthrax A skin lesion caused by anthrax; the characteristic black eschar SpecialtyInfectious disease SymptomsSkin form: small blister with surrounding swelling Inhalational form: fever, chest pain, shortness of breath Intestinal form: nausea, vomiting, diarrhea, abdominal pain Injection form: fever, abscess[1] Usual onset1 day to 2 months post contact[1] CausesBacillus anthracis[2] Risk factorsWorking with animals, travelers, postal workers, military personnel[3] Diagnostic methodBased on antibodies or toxin in the blood, microbial culture[4] PreventionAnthrax vaccination, antibiotics[3][5] TreatmentAntibiotics, antitoxin[6] Prognosis20–80% die without treatment[5][7] Frequency>2,000 cases per year[8] Anthrax is an infection caused by the bacterium Bacillus anthracis.[2] It can occur in four forms: skin, lungs, intestinal, and injection.[9] Symptom onset occurs between one day to over two months after the infection is contracted.[1] The skin form presents with a small blister with surrounding swelling that often turns into a painless ulcer with a black center.[1] The inhalation form presents with fever, chest pain, and shortness of breath.[1] The intestinal form presents with diarrhea which may contain blood, abdominal pains, nausea, and vomiting.[1] The injection form presents with fever and an abscess at the site of drug injection.[1] Anthrax is spread by contact with the bacterium's spores, which often appear in infectious animal products.[10] Contact is by breathing, eating, or through an area of broken skin.[10] It does not typically spread directly between people.[10] Risk factors include people who work with animals or animal products, travelers, postal workers, and military personnel.[3] Diagnosis can be confirmed by finding antibodies or the toxin in the blood or by culture of a sample from the infected site.[4] Anthrax vaccination is recommended for people who are at high risk of infection.[3] Immunizing animals against anthrax is recommended in areas where previous infections have occurred.[10] A two-months' course of antibiotics such as ciprofloxacin, levofloxacin, and doxycycline after exposure can also prevent infection.[5] If infection occurs, treatment is with antibiotics and possibly antitoxin.[6] The type and number of antibiotics used depends on the type of infection.[5] Antitoxin is recommended for those with widespread infection.[5] A rare disease, human anthrax is most common in Africa and central and southern Asia.[11] It also occurs more regularly in Southern Europe than elsewhere on the continent, and is uncommon in Northern Europe and North America.[12] Globally, at least 2,000 cases occur a year with about two cases a year in the United States.[8][13] Skin infections represent more than 95% of cases.[7] Without treatment, the risk of death from skin anthrax is 24%.[5] For intestinal infection, the risk of death is 25 to 75%, while respiratory anthrax has a mortality of 50 to 80%, even with treatment.[5][7] Until the 20th century, anthrax infections killed hundreds of thousands of people and animals each year.[14] Anthrax has been developed as a weapon by a number of countries.[7] In plant-eating animals, infection occurs when they eat or breathe in the spores while grazing.[11] Animals may become infected by eating infected animals.[11] ## Contents * 1 Signs and symptoms * 1.1 Skin * 1.2 Injection * 1.3 Lungs * 1.4 Gastrointestinal * 2 Cause * 2.1 Bacteria * 2.2 Exposure * 2.3 Mode of infection * 3 Mechanism * 4 Diagnosis * 5 Prevention * 5.1 Vaccines * 5.2 Antibiotics * 6 Treatment * 6.1 Antibiotics * 6.2 Monoclonal antibodies * 7 Prognosis * 8 Epidemiology * 8.1 United States * 8.2 United Kingdom * 9 History * 9.1 Etymology * 9.2 Discovery * 9.3 First vaccination * 9.4 Engineered strains * 10 Society and culture * 10.1 Site cleanup * 10.2 Biological warfare * 10.2.1 Sverdlovsk incident (2 April 1979) * 10.2.2 Anthrax bioterrorism * 10.2.3 Decontaminating mail * 10.3 Popular culture * 11 Other animals * 12 References * 13 External links ## Signs and symptoms[edit] ### Skin[edit] Skin lesion from anthrax Skin anthrax lesion on the neck Cutaneous anthrax, also known as hide-porter's disease, is when anthrax occurs on the skin. It is the most common form (>90% of anthrax cases). It is also the least dangerous form (low mortality with treatment, 20% mortality without).[15] Cutaneous anthrax presents as a boil-like skin lesion that eventually forms an ulcer with a black center (eschar). The black eschar often shows up as a large, painless, necrotic ulcer (beginning as an irritating and itchy skin lesion or blister that is dark and usually concentrated as a black dot, somewhat resembling bread mold) at the site of infection. In general, cutaneous infections form within the site of spore penetration between two and five days after exposure. Unlike bruises or most other lesions, cutaneous anthrax infections normally do not cause pain. Nearby lymph nodes may become infected, reddened, swollen, and painful. A scab forms over the lesion soon, and falls off in a few weeks. Complete recovery may take longer.[16] Cutaneous anthrax is typically caused when B. anthracis spores enter through cuts on the skin. This form is found most commonly when humans handle infected animals and/or animal products. ### Injection[edit] In December 2009, an outbreak of anthrax occurred among injecting heroin users in the Glasgow and Stirling areas of Scotland, resulting in 14 deaths.[17] The source of the anthrax is believed to be dilution of the heroin with bone meal in Afghanistan.[18] It may have symptoms similar to cutaneous anthrax, but it may also have infection deep into the muscle and spread faster.[19] ### Lungs[edit] Inhalation anthrax usually develops within a week after exposure, but may take up to 2 months. During the first few days of illness, most people have fever, chills, and fatigue. These symptoms may be accompanied by cough, shortness of breath, chest pain, and nausea or vomiting, making inhalation anthrax difficult to distinguish from influenza and community-acquired pneumonia. This is often described as the prodromal period.[20] Over the next day or so, shortness of breath, cough, and chest pain become more common, and complaints not involving the chest such as nausea, vomiting, altered mental status, sweats, and headache develop in one-third or more of people. Upper respiratory tract symptoms occur in only a quarter of people, and muscle pains are rare. Altered mental status or shortness of breath generally brings people to healthcare and marks the fulminant phase of illness. It infects the lymph nodes in the chest first, rather than the lungs themselves, a condition called hemorrhagic mediastinitis, causing bloody fluid to accumulate in the chest cavity, therefore causing shortness of breath. The second (pneumonia) stage occurs when the infection spreads from the lymph nodes to the lungs. Symptoms of the second stage develop suddenly after hours or days after the first stage. Symptoms include high fever, extreme shortness of breath, shock, and rapid death within 48 hours in fatal cases.[21] ### Gastrointestinal[edit] Gastrointestinal (GI) infection is most often caused by consuming anthrax-infected meat and is characterized by diarrhea, potentially with blood, abdominal pains, acute inflammation of the intestinal tract, and loss of appetite.[22] Occasional vomiting of blood can occur. Lesions have been found in the intestines and in the mouth and throat. After the bacterium invades the gastrointestinal system, it spreads to the bloodstream and throughout the body, while continuing to make toxins. ## Cause[edit] ### Bacteria[edit] Photomicrograph of a Gram stain of the bacterium Bacillus anthracis, the cause of the anthrax disease Main article: Bacillus anthracis Bacillus anthracis is a rod-shaped, Gram-positive, facultative anaerobic bacterium about 1 by 9 μm in size.[2] It was shown to cause disease by Robert Koch in 1876 when he took a blood sample from an infected cow, isolated the bacteria, and put them into a mouse.[23] The bacterium normally rests in spore form in the soil, and can survive for decades in this state. Herbivores are often infected while grazing, especially when eating rough, irritant, or spiky vegetation; the vegetation has been hypothesized to cause wounds within the GI tract, permitting entry of the bacterial spores into the tissues, though this has not been proven. Once ingested or placed in an open wound, the bacteria begin multiplying inside the animal or human and typically kill the host within a few days or weeks. The spores germinate at the site of entry into the tissues and then spread by the circulation to the lymphatics, where the bacteria multiply. The production of two powerful exotoxins and lethal toxin by the bacteria causes death. Veterinarians can often tell a possible anthrax-induced death by its sudden occurrence, and by the dark, nonclotting blood that oozes from the body orifices. Most anthrax bacteria inside the body after death are outcompeted and destroyed by anaerobic bacteria within minutes to hours post mortem. However, anthrax vegetative bacteria that escape the body via oozing blood or through the opening of the carcass may form hardy spores. These vegetative bacteria are not contagious.[24] One spore forms per one vegetative bacterium. The triggers for spore formation are not yet known, though oxygen tension and lack of nutrients may play roles. Once formed, these spores are very hard to eradicate. The infection of herbivores (and occasionally humans) by the inhalational route normally begins with inhaled spores being transported through the air passages into the tiny air sacs (alveoli) in the lungs. The spores are then picked up by scavenger cells (macrophages) in the lungs and are transported through small vessels (lymphatics) to the lymph nodes in the central chest cavity (mediastinum). Damage caused by the anthrax spores and bacilli to the central chest cavity can cause chest pain and difficulty breathing. Once in the lymph nodes, the spores germinate into active bacilli that multiply and eventually burst the macrophages, releasing many more bacilli into the bloodstream to be transferred to the entire body. Once in the blood stream, these bacilli release three proteins named lethal factor, edema factor, and protective antigen. The three are not toxic by themselves, but their combination is incredibly lethal to humans.[25] Protective antigen combines with these other two factors to form lethal toxin and edema toxin, respectively. These toxins are the primary agents of tissue destruction, bleeding, and death of the host. If antibiotics are administered too late, even if the antibiotics eradicate the bacteria, some hosts still die of toxemia because the toxins produced by the bacilli remain in their systems at lethal dose levels. * Bacillus anthracis * Color-enhanced scanning electron micrograph shows splenic tissue from a monkey with inhalational anthrax; featured are rod-shaped bacilli (yellow) and an erythrocyte (red) * Gram-positive anthrax bacteria (purple rods) in cerebrospinal fluid: If present, a Gram-negative bacterial species would appear pink. (The other cells are white blood cells.) ### Exposure[edit] The spores of anthrax are able to survive in harsh conditions for decades or even centuries.[26] Such spores can be found on all continents, including Antarctica.[27] Disturbed grave sites of infected animals have been known to cause infection after 70 years.[28] Historically, inhalational anthrax was called woolsorters' disease because it was an occupational hazard for people who sorted wool. Today, this form of infection is extremely rare in advanced nations, as almost no infected animals remain. Occupational exposure to infected animals or their products (such as skin, wool, and meat) is the usual pathway of exposure for humans. Workers who are exposed to dead animals and animal products are at the highest risk, especially in countries where anthrax is more common. Anthrax in livestock grazing on open range where they mix with wild animals still occasionally occurs in the United States and elsewhere. Many workers who deal with wool and animal hides are routinely exposed to low levels of anthrax spores, but most exposure levels are not sufficient to develop anthrax infections. A lethal infection is reported to result from inhalation of about 10,000–20,000 spores, though this dose varies among host species.[29] Little documented evidence is available to verify the exact or average number of spores needed for infection. ### Mode of infection[edit] Inhalational anthrax, mediastinal widening Anthrax can enter the human body through the intestines (ingestion), lungs (inhalation), or skin (cutaneous) and causes distinct clinical symptoms based on its site of entry. In general, an infected human is quarantined. However, anthrax does not usually spread from an infected human to an uninfected human.[30] If the disease is fatal to the person's body, though, its mass of anthrax bacilli becomes a potential source of infection to others and special precautions should be used to prevent further contamination. Inhalational anthrax, if left untreated until obvious symptoms occur, is usually fatal.[30] Anthrax can be contracted in laboratory accidents or by handling infected animals, their wool, or their hides.[31] It has also been used in biological warfare agents and by terrorists to intentionally infect as exemplified by the 2001 anthrax attacks.[32] ## Mechanism[edit] The lethality of the anthrax disease is due to the bacterium's two principal virulence factors: the poly-D-glutamic acid capsule, which protects the bacterium from phagocytosis by host neutrophils, and the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: protective antigen (PA), edema factor (EF), and lethal factor (LF).[33] PA plus LF produces lethal toxin, and PA plus EF produces edema toxin. These toxins cause death and tissue swelling (edema), respectively. To enter the cells, the edema and lethal factors use another protein produced by B. anthracis called protective antigen, which binds to two surface receptors on the host cell. A cell protease then cleaves PA into two fragments: PA20 and PA63. PA20 dissociates into the extracellular medium, playing no further role in the toxic cycle. PA63 then oligomerizes with six other PA63 fragments forming a heptameric ring-shaped structure named a prepore. Once in this shape, the complex can competitively bind up to three EFs or LFs, forming a resistant complex.[25] Receptor-mediated endocytosis occurs next, providing the newly formed toxic complex access to the interior of the host cell. The acidified environment within the endosome triggers the heptamer to release the LF and/or EF into the cytosol.[34] It is unknown how exactly the complex results in the death of the cell. Edema factor is a calmodulin-dependent adenylate cyclase. Adenylate cyclase catalyzes the conversion of ATP into cyclic AMP (cAMP) and pyrophosphate. The complexation of adenylate cyclase with calmodulin removes calmodulin from stimulating calcium-triggered signaling, thus inhibiting the immune response.[25] To be specific, LF inactivates neutrophils (a type of phagocytic cell) by the process just described so they cannot phagocytose bacteria. Throughout history, lethal factor was presumed to cause macrophages to make TNF-alpha and interleukin 1, beta (IL1B). TNF-alpha is a cytokine whose primary role is to regulate immune cells, as well as to induce inflammation and apoptosis or programmed cell death. Interleukin 1, beta is another cytokine that also regulates inflammation and apoptosis. The overproduction of TNF-alpha and IL1B ultimately leads to septic shock and death. However, recent evidence indicates anthrax also targets endothelial cells that line serous cavities such as the pericardial cavity, pleural cavity, and peritoneal cavity, lymph vessels, and blood vessels, causing vascular leakage of fluid and cells, and ultimately hypovolemic shock and septic shock. ## Diagnosis[edit] Possible edema and necrosis in a case of injection anthrax. Various techniques may be used for the direct identification of B. anthracis in clinical material. Firstly, specimens may be Gram stained. Bacillus spp. are quite large in size (3 to 4 μm long), they may grow in long chains, and they stain Gram-positive. To confirm the organism is B. anthracis, rapid diagnostic techniques such as polymerase chain reaction-based assays and immunofluorescence microscopy may be used.[35] All Bacillus species grow well on 5% sheep blood agar and other routine culture media. Polymyxin-lysozyme-EDTA-thallous acetate can be used to isolate B. anthracis from contaminated specimens, and bicarbonate agar is used as an identification method to induce capsule formation. Bacillus spp. usually grow within 24 hours of incubation at 35 °C, in ambient air (room temperature) or in 5% CO2. If bicarbonate agar is used for identification, then the medium must be incubated in 5% CO2. B. anthracis colonies are medium-large, gray, flat, and irregular with swirling projections, often referred to as having a "medusa head" appearance, and are not hemolytic on 5% sheep blood agar. The bacteria are not motile, susceptible to penicillin, and produce a wide zone of lecithinase on egg yolk agar. Confirmatory testing to identify B. anthracis includes gamma bacteriophage testing, indirect hemagglutination, and enzyme-linked immunosorbent assay to detect antibodies.[36] The best confirmatory precipitation test for anthrax is the Ascoli test. ## Prevention[edit] Precautions are taken to avoid contact with the skin and any fluids exuded through natural body openings of a deceased body that is suspected of harboring anthrax.[37] The body should be put in strict quarantine. A blood sample is collected and sealed in a container and analyzed in an approved laboratory to ascertain if anthrax is the cause of death. The body should be sealed in an airtight body bag and incinerated to prevent transmission of anthrax spores. Microscopic visualization of the encapsulated bacilli, usually in very large numbers, in a blood smear stained with polychrome methylene blue (McFadyean stain) is fully diagnostic, though culture of the organism is still the gold standard for diagnosis. Full isolation of the body is important to prevent possible contamination of others.[37] Protective, impermeable clothing and equipment such as rubber gloves, rubber apron, and rubber boots with no perforations are used when handling the body. No skin, especially if it has any wounds or scratches, should be exposed. Disposable personal protective equipment is preferable, but if not available, decontamination can be achieved by autoclaving. Used disposable equipment is burned and/or buried after use. All contaminated bedding or clothing is isolated in double plastic bags and treated as biohazard waste.[37] Respiratory equipment capable of filtering small particles, such the US National Institute for Occupational Safety and Health\- and Mine Safety and Health Administration-approved high-efficiency respirator, is worn.[38] ### Vaccines[edit] Main article: Anthrax vaccines Vaccines against anthrax for use in livestock and humans have had a prominent place in the history of medicine. The French scientist Louis Pasteur developed the first effective vaccine in 1881.[39][40][41] Human anthrax vaccines were developed by the Soviet Union in the late 1930s and in the US and UK in the 1950s. The current FDA-approved US vaccine was formulated in the 1960s. Currently administered human anthrax vaccines include acellular (United States) and live vaccine (Russia) varieties. All currently used anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever) and serious adverse reactions occur in about 1% of recipients.[42] The American product, BioThrax, is licensed by the FDA and was formerly administered in a six-dose primary series at 0, 2, 4 weeks and 6, 12, 18 months, with annual boosters to maintain immunity. In 2008, the FDA approved omitting the week-2 dose, resulting in the currently recommended five-dose series.[43] New second-generation vaccines currently being researched include recombinant live vaccines and recombinant subunit vaccines. In the 20th century the use of a modern product (BioThrax) to protect American troops against the use of anthrax in biological warfare was controversial.[44] ### Antibiotics[edit] Preventive antibiotics are recommended in those who have been exposed.[5] Early detection of sources of anthrax infection can allow preventive measures to be taken. In response to the anthrax attacks of October 2001, the United States Postal Service (USPS) installed biodetection systems (BDSs) in their large-scale mail processing facilities. BDS response plans were formulated by the USPS in conjunction with local responders including fire, police, hospitals, and public health. Employees of these facilities have been educated about anthrax, response actions, and prophylactic medication. Because of the time delay inherent in getting final verification that anthrax has been used, prophylactic antibiotic treatment of possibly exposed personnel must be started as soon as possible. ## Treatment[edit] Play media Anthrax and antibiotics Anthrax cannot be spread from person to person, except in the rare case of skin exudates from cutaneous anthrax.[45] However, a person's clothing and body may be contaminated with anthrax spores. Effective decontamination of people can be accomplished by a thorough wash-down with antimicrobial soap and water. Waste water is treated with bleach or another antimicrobial agent.[46] Effective decontamination of articles can be accomplished by boiling them in water for 30 minutes or longer. Chlorine bleach is ineffective in destroying spores and vegetative cells on surfaces, though formaldehyde is effective. Burning clothing is very effective in destroying spores. After decontamination, there is no need to immunize, treat, or isolate contacts of persons ill with anthrax unless they were also exposed to the same source of infection. ### Antibiotics[edit] Early antibiotic treatment of anthrax is essential; delay significantly lessens chances for survival. Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as fluoroquinolones (ciprofloxacin), doxycycline, erythromycin, vancomycin, or penicillin. FDA-approved agents include ciprofloxacin, doxycycline, and penicillin.[47] In possible cases of pulmonary anthrax, early antibiotic prophylaxis treatment is crucial to prevent possible death. Many attempts have been made to develop new drugs against anthrax, but existing drugs are effective if treatment is started soon enough. ### Monoclonal antibodies[edit] In May 2009, Human Genome Sciences submitted a biologic license application (BLA, permission to market) for its new drug, raxibacumab (brand name ABthrax) intended for emergency treatment of inhaled anthrax.[48] On 14 December 2012, the US Food and Drug Administration approved raxibacumab injection to treat inhalational anthrax. Raxibacumab is a monoclonal antibody that neutralizes toxins produced by B. anthracis.[49] In March 2016, FDA approved a second anthrax treatment using a monoclonal antibody which neutralizes the toxins produced by B. anthracis. Obiltoxaximab is approved to treat inhalational anthrax in conjunction with appropriate antibacterial drugs, and for prevention when alternative therapies are not available or appropriate.[50] ## Prognosis[edit] Cutaneous anthrax is rarely fatal if treated,[51] because the infection area is limited to the skin, preventing the lethal factor, edema factor, and protective antigen from entering and destroying a vital organ. Without treatment, about 20% of cutaneous skin infection cases progress to toxemia and death. Before 2001, fatality rates for inhalation anthrax were 90%; since then, they have fallen to 45%.[20] People that progress to the fulminant phase of inhalational anthrax nearly always die, with one case study showing a death rate of 97%.[52] Anthrax meningoencephalitis is also nearly always fatal.[53] GI infections can be treated, but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences. This form of anthrax is the rarest. ## Epidemiology[edit] Globally, at least 2,000 cases occur a year.[8] ### United States[edit] The last fatal case of natural inhalational anthrax in the United States occurred in California in 1976, when a home weaver died after working with infected wool imported from Pakistan. To minimize the chance of spreading the disease, the deceased was transported to UCLA in a sealed plastic body bag within a sealed metal container for autopsy.[54] Gastrointestinal anthrax is exceedingly rare in the United States, with only two cases on record. The first case was reported in 1942, according to the Centers for Disease Control and Prevention.[55] During December 2009, the New Hampshire Department of Health and Human Services confirmed a case of gastrointestinal anthrax in an adult female. In 2007 two cases of cutaneous anthrax were reported in Danbury, Connecticut. The case involved the maker of traditional African-style drums who was working with a goat hide purchased from a dealer in New York City which had been previously cleared by Customs. While the hide was being scraped, a spider bite led to the spores entering the bloodstream. His son also became infected.[56] The CDC investigated the source of the December 2009 infection and the possibility that it was contracted from an African drum recently used by the woman taking part in a drum circle.[57] The woman apparently inhaled anthrax, in spore form, from the hide of the drum. She became critically ill, but with gastrointestinal anthrax rather than inhaled anthrax, which made her unique in American medical history. The building where the infection took place was cleaned and reopened to the public and the woman recovered. The New Hampshire state epidemiologist, Jodie Dionne-Odom, stated "It is a mystery. We really don't know why it happened."[58] ### United Kingdom[edit] In November 2008, a drum maker in the United Kingdom who worked with untreated animal skins died from anthrax.[59] In December 2009, an outbreak of anthrax occurred among heroin addicts in the Glasgow and Stirling areas of Scotland, resulting in 14 deaths.[17] The source of the anthrax is believed to be dilution of the heroin with bone meal in Afghanistan.[18] ## History[edit] See also: List of anthrax outbreaks ### Etymology[edit] The English name comes from anthrax (ἄνθραξ), the Greek word for coal,[60][61] possibly having Egyptian etymology,[62] because of the characteristic black skin lesions developed by victims with a cutaneous anthrax infection. The central, black eschar, surrounded by vivid red skin has long been recognised as typical of the disease. The first recorded use of the word "anthrax" in English is in a 1398 translation of Bartholomaeus Anglicus' work De proprietatibus rerum (On the Properties of Things, 1240).[63] Anthrax has been known by a wide variety of names, indicating its symptoms, location and groups considered most vulnerable to infection. These include Siberian plague, Cumberland disease, charbon, splenic fever, malignant edema, woolsorter's disease, and even la maladie de Bradford.[64] ### Discovery[edit] Robert Koch, a German physician and scientist, first identified the bacterium that caused the anthrax disease in 1875 in Wollstein (now part of Poland).[23][65] His pioneering work in the late 19th century was one of the first demonstrations that diseases could be caused by microbes. In a groundbreaking series of experiments, he uncovered the lifecycle and means of transmission of anthrax. His experiments not only helped create an understanding of anthrax, but also helped elucidate the role of microbes in causing illness at a time when debates still took place over spontaneous generation versus cell theory. Koch went on to study the mechanisms of other diseases and won the 1905 Nobel Prize in Physiology or Medicine for his discovery of the bacterium causing tuberculosis. Although Koch arguably made the greatest theoretical contribution to understanding anthrax, other researchers were more concerned with the practical questions of how to prevent the disease. In Britain, where anthrax affected workers in the wool, worsted, hides, and tanning industries, it was viewed with fear. John Henry Bell, a doctor born & based in Bradford, first made the link between the mysterious and deadly "woolsorter's disease" and anthrax, showing in 1878 that they were one and the same.[66] In the early 20th century, Friederich Wilhelm Eurich, the German bacteriologist who settled in Bradford with his family as a child, carried out important research for the local Anthrax Investigation Board. Eurich also made valuable contributions to a Home Office Departmental Committee of Inquiry, established in 1913 to address the continuing problem of industrial anthrax.[67] His work in this capacity, much of it collaboration with the factory inspector G. Elmhirst Duckering, led directly to the Anthrax Prevention Act (1919). ### First vaccination[edit] Further information: Anthrax vaccines Louis Pasteur inoculating sheep against anthrax Anthrax posed a major economic challenge in France and elsewhere during the 19th century. Horses, cattle, and sheep were particularly vulnerable, and national funds were set aside to investigate the production of a vaccine. Noted French scientist Louis Pasteur was charged with the production of a vaccine, following his successful work in developing methods which helped to protect the important wine and silk industries.[68] In May 1881, Pasteur – in collaboration with his assistants Jean-Joseph Henri Toussaint, Émile Roux and others – performed a public experiment at Pouilly-le-Fort to demonstrate his concept of vaccination. He prepared two groups of 25 sheep, one goat, and several cattle. The animals of one group were injected with an anthrax vaccine prepared by Pasteur twice, at an interval of 15 days; the control group was left unvaccinated. Thirty days after the first injection, both groups were injected with a culture of live anthrax bacteria. All the animals in the unvaccinated group died, while all of the animals in the vaccinated group survived.[69] After this apparent triumph, which was widely reported in the local, national, and international press, Pasteur made strenuous efforts to export the vaccine beyond France. He used his celebrity status to establish Pasteur Institutes across Europe and Asia, and his nephew, Adrien Loir, travelled to Australia in 1888 to try to introduce the vaccine to combat anthrax in New South Wales.[70] Ultimately, the vaccine was unsuccessful in the challenging climate of rural Australia, and it was soon superseded by a more robust version developed by local researchers John Gunn and John McGarvie Smith.[71] The human vaccine for anthrax became available in 1954. This was a cell-free vaccine instead of the live-cell Pasteur-style vaccine used for veterinary purposes. An improved cell-free vaccine became available in 1970.[72] ### Engineered strains[edit] This list is incomplete; you can help by adding missing items with reliable sources. * The Sterne strain of anthrax, named after the Trieste-born immunologist Max Sterne, is an attenuated strain used as a vaccine, which contains only the anthrax toxin virulence plasmid and not the polyglutamic acid capsule expressing plasmid. * Strain 836, created by the Soviet bio-weapons program in the 1980s, was later called by the Los Angeles Times "the most virulent and vicious strain of anthrax known to man".[73][74] * The virulent Ames strain, which was used in the 2001 anthrax attacks in the United States, has received the most news coverage of any anthrax outbreak. The Ames strain contains two virulence plasmids, which separately encode for a three-protein toxin, called anthrax toxin, and a polyglutamic acid capsule. * Nonetheless, the Vollum strain, developed but never used as a biological weapon during the Second World War, is much more dangerous. The Vollum (also incorrectly referred to as Vellum) strain was isolated in 1935 from a cow in Oxfordshire. This same strain was used during the Gruinard bioweapons trials. A variation of Vollum, known as "Vollum 1B", was used during the 1960s in the US and UK bioweapon programs. Vollum 1B is widely believed[75] to have been isolated from William A. Boyles, a 46-year-old scientist at the US Army Biological Warfare Laboratories at Camp (later Fort) Detrick, Maryland, who died in 1951 after being accidentally infected with the Vollum strain. * US Air Force researchers have developed a vaccine strain to produce an improved anthrax vaccine which requires a minimal number of injections to achieve and maintain long-term immunity. It is designated as the Alls/Gifford (Curlicue) strain.[76] ## Society and culture[edit] ### Site cleanup[edit] Anthrax spores can survive for very long periods of time in the environment after release. Chemical methods for cleaning anthrax-contaminated sites or materials may use oxidizing agents such as peroxides, ethylene oxide, Sandia Foam,[77] chlorine dioxide (used in the Hart Senate Office Building),[78] peracetic acid, ozone gas, hypochlorous acid, sodium persulfate, and liquid bleach products containing sodium hypochlorite. Nonoxidizing agents shown to be effective for anthrax decontamination include methyl bromide, formaldehyde, and metam sodium. These agents destroy bacterial spores. All of the aforementioned anthrax decontamination technologies have been demonstrated to be effective in laboratory tests conducted by the US EPA or others.[79] Decontamination techniques for Bacillus anthracis spores are affected by the material with which the spores are associated, environmental factors such as temperature and humidity, and microbiological factors such as the spore species, anthracis strain, and test methods used.[80] A bleach solution for treating hard surfaces has been approved by the EPA.[81] Chlorine dioxide has emerged as the preferred biocide against anthrax-contaminated sites, having been employed in the treatment of numerous government buildings over the past decade.[82] Its chief drawback is the need for in situ processes to have the reactant on demand. To speed the process, trace amounts of a nontoxic catalyst composed of iron and tetroamido macrocyclic ligands are combined with sodium carbonate and bicarbonate and converted into a spray. The spray formula is applied to an infested area and is followed by another spray containing tert-butyl hydroperoxide.[83] Using the catalyst method, a complete destruction of all anthrax spores can be achieved in under 30 minutes.[83] A standard catalyst-free spray destroys fewer than half the spores in the same amount of time. Cleanups at a Senate Office Building, several contaminated postal facilities, and other US government and private office buildings, a collaborative effort headed by the Environmental Protection Agency[84] showed decontamination to be possible, but time-consuming and costly. Clearing the Senate Office Building of anthrax spores cost $27 million, according to the Government Accountability Office. Cleaning the Brentwood postal facility in Washington cost $130 million and took 26 months. Since then, newer and less costly methods have been developed.[85] Cleanup of anthrax-contaminated areas on ranches and in the wild is much more problematic. Carcasses may be burned,[86] though often 3 days are needed to burn a large carcass and this is not feasible in areas with little wood. Carcasses may also be buried, though the burying of large animals deeply enough to prevent resurfacing of spores requires much manpower and expensive tools. Carcasses have been soaked in formaldehyde to kill spores, though this has environmental contamination issues. Block burning of vegetation in large areas enclosing an anthrax outbreak has been tried; this, while environmentally destructive, causes healthy animals to move away from an area with carcasses in search of fresh grass. Some wildlife workers have experimented with covering fresh anthrax carcasses with shadecloth and heavy objects. This prevents some scavengers from opening the carcasses, thus allowing the putrefactive bacteria within the carcass to kill the vegetative B. anthracis cells and preventing sporulation. This method also has drawbacks, as scavengers such as hyenas are capable of infiltrating almost any exclosure. The experimental site at Gruinard Island is said to have been decontaminated with a mixture of formaldehyde and seawater by the Ministry of Defence.[87] It is not clear whether similar treatments had been applied to US test sites. ### Biological warfare[edit] Main article: Anthrax weaponization Colin Powell giving a presentation to the United Nations Security Council, holding a model vial of anthrax Anthrax spores have been used as a biological warfare weapon. Its first modern incidence occurred when Nordic rebels, supplied by the German General Staff, used anthrax with unknown results against the Imperial Russian Army in Finland in 1916.[88] Anthrax was first tested as a biological warfare agent by Unit 731 of the Japanese Kwantung Army in Manchuria during the 1930s; some of this testing involved intentional infection of prisoners of war, thousands of whom died. Anthrax, designated at the time as Agent N, was also investigated by the Allies in the 1940s. A long history of practical bioweapons research exists in this area. For example, in 1942, British bioweapons trials severely contaminated Gruinard Island in Scotland with anthrax spores of the Vollum-14578 strain, making it a no-go area until it was decontaminated in 1990.[89][90] The Gruinard trials involved testing the effectiveness of a submunition of an "N-bomb" – a biological weapon containing dried anthrax spores. Additionally, five million "cattle cakes" (animal feed pellets impregnated with anthrax spores) were prepared and stored at Porton Down for "Operation Vegetarian" – antilivestock attacks against Germany to be made by the Royal Air Force.[91] The plan was for anthrax-based biological weapons to be dropped on Germany in 1944. However, the edible cattle cakes and the bomb were not used; the cattle cakes were incinerated in late 1945. Weaponized anthrax was part of the US stockpile prior to 1972, when the United States signed the Biological Weapons Convention.[92] President Nixon ordered the dismantling of US biowarfare programs in 1969 and the destruction of all existing stockpiles of bioweapons. In 1978–79, the Rhodesian government used anthrax against cattle and humans during its campaign against rebels.[93] The Soviet Union created and stored 100 to 200 tons of anthrax spores at Kantubek on Vozrozhdeniya Island; they were abandoned in 1992 and destroyed in 2002.[citation needed] American military and British Army personnel are routinely vaccinated against anthrax prior to active service in places where biological attacks are considered a threat.[44] #### Sverdlovsk incident (2 April 1979)[edit] Main article: Sverdlovsk anthrax leak Despite signing the 1972 agreement to end bioweapon production, the government of the Soviet Union had an active bioweapons program that included the production of hundreds of tons of anthrax after this period. On 2 April 1979, some of the over one million people living in Sverdlovsk (now called Ekaterinburg, Russia), about 1,370 kilometres (850 mi) east of Moscow, were exposed to an accidental release of anthrax from a biological weapons complex located near there. At least 94 people were infected, of whom at least 68 died. One victim died four days after the release, 10 over an eight-day period at the peak of the deaths, and the last six weeks later. Extensive cleanup, vaccinations, and medical interventions managed to save about 30 of the victims.[94] Extensive cover-ups and destruction of records by the KGB continued from 1979 until Russian President Boris Yeltsin admitted this anthrax accident in 1992. Jeanne Guillemin reported in 1999 that a combined Russian and United States team investigated the accident in 1992.[94][95][96] Nearly all of the night-shift workers of a ceramics plant directly across the street from the biological facility (compound 19) became infected, and most died. Since most were men, some NATO governments suspected the Soviet Union had developed a sex-specific weapon.[97] The government blamed the outbreak on the consumption of anthrax-tainted meat, and ordered the confiscation of all uninspected meat that entered the city. They also ordered all stray dogs to be shot and people not have contact with sick animals. Also, a voluntary evacuation and anthrax vaccination program was established for people from 18 to 55.[98] To support the cover-up story, Soviet medical and legal journals published articles about an outbreak in livestock that caused GI anthrax in people having consumed infected meat, and cutaneous anthrax in people having come into contact with the animals. All medical and public health records were confiscated by the KGB.[98] In addition to the medical problems the outbreak caused, it also prompted Western countries to be more suspicious of a covert Soviet bioweapons program and to increase their surveillance of suspected sites. In 1986, the US government was allowed to investigate the incident, and concluded the exposure was from aerosol anthrax from a military weapons facility.[99] In 1992, President Yeltsin admitted he was "absolutely certain" that "rumors" about the Soviet Union violating the 1972 Bioweapons Treaty were true. The Soviet Union, like the US and UK, had agreed to submit information to the UN about their bioweapons programs, but omitted known facilities and never acknowledged their weapons program.[97] #### Anthrax bioterrorism[edit] In theory, anthrax spores can be cultivated with minimal special equipment and a first-year collegiate microbiological education.[100] To make large amounts of an aerosol form of anthrax suitable for biological warfare requires extensive practical knowledge, training, and highly advanced equipment.[101] Concentrated anthrax spores were used for bioterrorism in the 2001 anthrax attacks in the United States, delivered by mailing postal letters containing the spores.[102] The letters were sent to several news media offices and two Democratic senators: Tom Daschle of South Dakota and Patrick Leahy of Vermont. As a result, 22 were infected and five died.[25] Only a few grams of material were used in these attacks and in August 2008, the US Department of Justice announced they believed that Bruce Ivins, a senior biodefense researcher employed by the United States government, was responsible.[103] These events also spawned many anthrax hoaxes. Due to these events, the US Postal Service installed biohazard detection systems at its major distribution centers to actively scan for anthrax being transported through the mail.[104] As of 2020, no positive alerts by these systems have occurred.[105] #### Decontaminating mail[edit] In response to the postal anthrax attacks and hoaxes, the United States Postal Service sterilized some mail using gamma irradiation and treatment with a proprietary enzyme formula supplied by Sipco Industries.[106] A scientific experiment performed by a high school student, later published in the Journal of Medical Toxicology, suggested a domestic electric iron at its hottest setting (at least 400 °F (204 °C)) used for at least 5 minutes should destroy all anthrax spores in a common postal envelope.[107] ### Popular culture[edit] * In Aldous Huxley's 1932 dystopian novel Brave New World, anthrax bombs are mentioned as the primary weapon by means of which original modern society is terrorized and in large part eradicated, to be replaced by a dystopian society. * The climax of the 1947 British film The Loves of Joanna Godden involves the death of a key character by anthrax. Composer Ralph Vaughn Williams provided the affecting mood music for the scene. * The episode "Diagnosis: Danger" (1963) from the series Alfred Hitchcock Presents concerns Health Department officials working to contain an anthrax outbreak. * Anthrax attacks have featured in the storylines of various television episodes and films. A Criminal Minds episode follows the attempt to identify an attacker who released anthrax spores in a public park.[108] * In the American 2001 live-action/animated action comedy film Osmosis Jones, anthrax (referred to as 'Thrax') serves as the main antagonist; he is voiced by Laurence Fishburne. * The American thrash metal band Anthrax gets its name from the disease. ## Other animals[edit] Anthrax is especially rare in dogs and cats, as is evidenced by a single reported case in the United States in 2001.[109] Anthrax outbreaks occur in some wild animal populations with some regularity.[110] Russian researchers estimate arctic permafrost contains around 1.5 million anthrax-infected reindeer carcasses, and the spores may survive in the permafrost for 105 years.[111] A risk exists that global warming in the Arctic can thaw the permafrost, releasing anthrax spores in the carcasses. 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Retrieved 19 August 2016. ## External links[edit] Wikimedia Commons has media related to Anthrax (disease). * Anthrax at Curlie * Anthrax in humans and animals – Textbook from WHO Classification D * ICD-10: A22 * ICD-9-CM: 022 * MeSH: D000881 * DiseasesDB: 1203 * SNOMED CT: 409498004 External resources * MedlinePlus: 001325 * eMedicine: med/148 * Patient UK: Anthrax * v * t * e Biological warfare and bioterrorism Modern incidents * 1984 Rajneeshee bioterror attack * 1989 California medfly attack * 2001 anthrax attacks * Wood Green ricin plot * 2003 ricin letters * 2013 ricin letters Prevention and response * Australia Group * Caribbean Public Health Agency * Center for Health Security * Centers for Disease Control and Prevention * Chinese Center for Disease Control and Prevention * Council of Europe Convention on the Prevention of Terrorism * Defense Advanced Research Projects Agency * Defense Threat Reduction Agency * European Centre for Disease Prevention and Control * Global Health 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skin syndrome * Toxic shock syndrome * MRSA Cg- * novobiocin susceptible * S. epidermidis * novobiocin resistant * S. saprophyticus Bacillus * Bacillus anthracis * Anthrax * Bacillus cereus * Food poisoning Listeria * Listeria monocytogenes * Listeriosis Clostridia Clostridium (spore-forming) motile: * Clostridium difficile * Pseudomembranous colitis * Clostridium botulinum * Botulism * Clostridium tetani * Tetanus nonmotile: * Clostridium perfringens * Gas gangrene * Clostridial necrotizing enteritis Finegoldia (non-spore forming) * Finegoldia magna Mollicutes Mycoplasmataceae * Ureaplasma urealyticum * Ureaplasma infection * Mycoplasma genitalium * Mycoplasma pneumoniae * Mycoplasma pneumonia Anaeroplasmatales * Erysipelothrix rhusiopathiae * Erysipeloid Authority control * BNE: XX546201 * GND: 4298868-8 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Anthrax	c0003175	26,785	wikipedia	https://en.wikipedia.org/wiki/Anthrax	2021-01-18T18:49:46	{"gard": ["8157"], "mesh": ["D000881"], "umls": ["C0003175"], "wikidata": ["Q129104"]}
Leukotriene C4 synthase deficiency is an extremely rare fatal neurometabolic developmental disorder characterized clinically by muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hypotonia-failure to thrive-microcephaly syndrome	c3279662	26,786	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79507	2021-01-23T17:57:52	{"mesh": ["C565439"], "omim": ["614037"], "umls": ["C3279662"], "synonyms": ["LTC4 synthase deficiency", "Leukotriene C4 synthase deficiency"]}
Optic atrophy-intellectual disability syndrome is a rare, hereditary, syndromic intellectual disability characterized by developmental delay, intellectual disability, and significant visual impairment due to optic nerve atrophy, optic nerve hypoplasia or cerebral visual impairment. Other common clinical signs and symptoms are hypotonia, oromotor dysfunction, seizures, autism spectrum disorder, and repetitive behaviors. Dysmorphic facial features are variable and nonspecific. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Optic atrophy-intellectual disability syndrome	c3810363	26,787	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401777	2021-01-23T19:07:15	{"omim": ["615722"], "icd-10": ["H47.2"], "synonyms": ["BBSOAS", "Bosch-Boonstra-Schaaf optic atrophy syndrome"]}
## Summary ### Clinical characteristics. Autosomal dominant craniometaphyseal dysplasia (designated AD-CMD in this review) is characterized by progressive diffuse hyperostosis of cranial bones evident clinically as wide nasal bridge, paranasal bossing, widely spaced eyes with an increase in bizygomatic width, and prominent mandible. Development of dentition may be delayed and teeth may fail to erupt as a result of hyperostosis and sclerosis of alveolar bone. Progressive thickening of craniofacial bones continues throughout life, often resulting in narrowing of the cranial foramina, including the foramen magnum. If untreated, compression of cranial nerves can lead to disabling conditions such as facial palsy, blindness, or deafness (conductive and/or sensorineural hearing loss). In individuals with typical uncomplicated AD-CMD life expectancy is normal; in those with severe AD-CMD life expectancy can be reduced as a result of compression of the foramen magnum. ### Diagnosis/testing. Diagnosis is based on clinical and radiographic findings that include diffuse hyperostosis of the cranial base, cranial vault, facial bones, and mandible as well as widening and radiolucency of metaphyses in long bones. Identification of a heterozygous pathogenic variant in ANKH by molecular genetic testing can confirm the diagnosis if clinical features are inconclusive. ### Management. Treatment of manifestations: Treatment for feeding and respiratory issues per craniofacial team; surgical intervention to reduce compression of cranial nerves and the brain stem / spinal cord at the level of the foramen magnum. Severely overgrown facial bones can be contoured; however, surgical procedures can be technically difficult and bone regrowth is common. Hearing aids; vision aids and surgical treatment for optic nerve impaction; speech therapy; surgical intervention for malocclusion. Surveillance: Evaluation for feeding and respiratory issues at least annually. Neurologic evaluation for signs and symptoms of narrowing of the cranial foramina including the foramen magnum at least annually. Hearing and ophthalmologic assessment at least annually. ### Genetic counseling. By definition, AD-CMD is inherited in an autosomal dominant manner. Most individuals diagnosed with AD-CMD have an affected parent; the proportion of individuals with AD-CMD caused by a de novo pathogenic variant is thought to be very low. Each child of an individual with AD-CMD has a 50% chance of inheriting the pathogenic variant. Once the AD-CMD-causing pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis Formal diagnostic criteria for autosomal dominant craniometaphyseal dysplasia (AD-CMD) have not been established. ### Suggestive Findings AD-CMD should be suspected in individuals with the following clinical, radiographic, and laboratory features. Clinical features * Obstruction of the nasal sinuses * Characteristic facial features. Wide nasal bridge, paranasal bossing, hypertelorism with an increase in bizygomatic width, and prominent mandible (see Figure 1) * Dolichocephaly due to fronto-occipital hyperostosis #### Figure 1. Facial features of a girl age 13 years with AD-CMD Reprinted from Reichenberger et al [2001] with permission from Elsevier Radiographic features * Cranial base. Sclerosis may begin in infancy (see Figure 2). Increasing diffuse hyperostosis of the cranial base leads to narrowing of the foramen magnum. * Skull. Diffuse hyperostosis of cranial vault, facial bones, and mandible increases as the condition progresses [Lamazza et al 2009] with obstruction of the cranial foramina. * Long bones. Metaphyseal widening (described as Erlenmeyer flask- or club-shaped) with thinned cortex and decreased bony density in the metaphyses can be detected early in life. Metaphyseal changes typically develop during early childhood. The flaring is most prominent in the distal femur and tibia (see Figure 3). Diaphyseal sclerosis/hyperostosis can be present in infancy but disappears with age. Bone density of the diaphyses is normal in children and adults; cortical thickness can be increased. * Ribs and clavicles (medial portion [i.e., endochondral]) can be sclerotic in younger children but show normal bone density by age five years [Richards et al 1996]. #### Figure 2. Increased thickness of craniofacial bones in a child age three years with AD-CMD #### Figure 3. Metaphyseal widening of long bones, specifically prominent at the knee joint Laboratory features * Blood calcium and phosphate concentrations are within normal limits [Cheung et al 1997] or decreased [Sheppard et al 2003]. * Serum alkaline phosphatase activity can be elevated [Sheppard et al 2003, Wu et al 2016]. * Parathyroid hormone level is normal or can be slightly/transiently elevated [Fanconi et al 1988, Cheung et al 1997, Sheppard et al 2003, Wu et al 2016]. * Osteocalcin is decreased [Yamamoto et al 1993]. Note: Findings are based on very limited data. Variability of the described parameters can be expected. Abnormal parameters may be transient. ### Establishing the Diagnosis The diagnosis of AD-CMD is established in a proband with characteristic craniofacial hyperostosis and flaring and undertrabeculation of long bone metaphyses and/or a heterozygous pathogenic variant in ANKH identified by molecular genetic testing (see Table 1). Note: Identification of a heterozygous ANKH variant of uncertain significance does not establish or rule out the diagnosis of this disorder. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of AD-CMD is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with hyperostosis are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of AD-CMD, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of ANKH is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications. Note: To date such variants have not been identified as a cause of this disorder. * A multigene panel that includes ANKH and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the phenotype is indistinguishable from many other inherited disorders characterized by hyperostosis, comprehensive genomic testing, which does not require the clinician to determine which gene is likely involved, is most likely to establish the diagnosis. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic – and particularly when evidence supports autosomal dominant inheritance – exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. Note: To date such variants have not been identified as a cause of this disorder. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Autosomal Dominant Craniometaphyseal Dysplasia View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method ANKHSequence analysis 3~90% 4 Gene-targeted deletion/duplication analysis 5None reported 6 Unknown 7NA~10% 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Nürnberg et al [2001], Reichenberger et al [2001] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Since AD-CMD occurs through a gain-of-function/dominant negative mechanism and large intragenic deletion or duplication has not been reported, testing for intragenic deletions or duplication is unlikely to identify a disease-causing variant. 7\. Some simplex cases of CMD did not have identifiable pathogenic variants in ANKH, suggesting possible locus heterogeneity. ## Clinical Characteristics ### Clinical Description Autosomal dominant craniometaphyseal dysplasia (AD-CMD) is often detected within the first few weeks of life because of breathing or feeding problems resulting from choanal stenosis (narrowing of nasal sinus) [Haverkamp et al 1996, Cheung et al 1997, Taggart et al 2014]. Early stages of AD-CMD can be radiographically recognized as sclerosis of the cranial base. Hyperostosis of the cranial base, cranial vault, facial bones, and mandible occurs gradually. Overgrowth of the lower jaw (mandibular hyperostosis) and recessed midface (midface retrusion) are often seen [Hayashibara et al 2000]. Progressive thickening of craniofacial bones continues throughout life, often resulting in narrowing of the cranial foramina, including the foramen magnum. If untreated, compression of cranial nerves can lead to disabling conditions such as facial palsy, blindness, or deafness (conductive and/or sensorineural hearing loss) as cranial hyperostosis and sclerosis progress [Beighton et al 1979, Richards et al 1996]. Nasal obstruction and mandibular hyperostosis affect speech modulation. Associated Chiari I malformation can lead to severe headaches [Tanaka et al 2013]. Development of dentition may be delayed and teeth may fail to erupt as a result of hyperostosis and sclerosis of alveolar bone [Chen et al 2014]. Malocclusion and anterior cross-bite can be caused by jaw overgrowth [Hayashibara et al 2000]. Life expectancy. Individuals with typical uncomplicated AD-CMD have normal life expectancy. Expressivity in simplex cases (i.e., single occurrence in a family) of CMD is highly variable. ### Genotype-Phenotype Correlations No genotype-phenotype correlation has been reported. The phenotypic severity (expressivity) in AD-CMD is variable even among affected members of the same family. ### Penetrance Penetrance is 100%. Males and females are equally affected. ### Nomenclature AD-CMD was previously referred to as "craniometaphyseal dysplasia-Jackson type." ### Prevalence CMD is very rare. No epidemiology has been established. ## Differential Diagnosis ### Table 3. Genes of Interest in the Differential Diagnosis of Autosomal Dominant Craniometaphyseal Dysplasia View in own window GeneDisorderMOIClinical CharacteristicsDistinguishing Features AMER1Osteopathia striata with cranial sclerosis (OSCS) (OMIM 300373)XLLongitudinal striations of sclerotic long bones in combination w/osteosclerosis of cranial & facial bonesShort stature, delayed closure of anterior fontanelle, micrognathia, linear striations in long bones of females FLNAFrontometaphyseal dysplasia type 1 (FMD1) (see Otopalatodigital Spectrum Disorders)XLSkeletal findings are frontal bone hyperostosis & metaphyseal dysplasia (similar to those seen in Pyle disease).Urogenital defects, contractures in hands, elbows, knees, & ankles GJA1Autosomal recessive craniometaphyseal dysplasia (AR-CMD) (OMIM 218400)ARHyperostosis of cranial base & cranial vault w/metaphyseal flaring similar to AD-CMDSkeletal phenotype may be less severe than in typical AD-CMD. LRP5Autosomal dominant osteopetrosis type 1 (OMIM 607634)ADCranial sclerosis & high bone mass w/o ↑ fragilityDiffuse osteosclerosis, no metaphyseal flaring SFRP4Pyle disease (OMIM 265900)ARMetaphyseal dysplasiaLittle or no involvement of cranial bones in Pyle disease SOSTCraniodiaphyseal dysplasia (CDD) (OMIM 218300)AD * Progressive overgrowth of craniofacial bones w/deafness, facial palsy, & visual disturbance as a result of nerve entrapment * Choanal stenosis is a clinically significant complication. * Radiologically the cranial & facial bones are hyperostotic while the diaphyses of the limb bones are expanded w/thin cortices. Cranial & facial thickening are generally more severe in CDD than in CMD. Sclerosteosis (see SOST Sclerosing Bone Dysplasias)AR * Progressive skeletal overgrowth (most pronounced in the skull & mandible) & variable syndactyly * Facial distortion due to bossing of forehead & mandibular overgrowth becomes apparent in early childhood w/progression into adulthood. * Hyperostosis of the skull results in narrowing of the foramina, causing entrapment of the 7th cranial nerve (leading to facial palsy) w/other, less common nerve entrapment syndromes. * Hyperostosis of calvarium ↓ intracranial volume, ↑ risk for potentially lethal elevation of intracranial pressure. * Survival into old age is unusual but not unprecedented. Sclerosis in spine & pelvis, 2-3 finger syndactyly, nail dysplasia, no metaphyseal flaring, gigantism Van Buchem disease (see SOST Sclerosing Bone Dysplasias)AR * Progressive skeletal overgrowth * Van Buchem disease is generally milder than sclerosteosis; no syndactyly. * Life span appears to be normal. Osteosclerosis includes clavicles & ribs; hyperphosphatasemia. TGFB1Progressive diaphyseal dysplasiaADHyperostosis of skull results in narrowing of foramina, causing facial palsy & deafness.Diaphyseal hyperostosis of long bones is pronounced. AD = autosomal dominant; AD-CMD = autosomal dominant craniometaphyseal dysplasia; AR = autosomal recessive; CMD = craniometaphyseal dysplasia; MOI = mode of inheritance; XL = X-linked Braun-Tinschert type of metaphyseal dysplasia (OMIM 605946) is inherited in an autosomal dominant manner. The gene(s) in which mutation is causative are unknown [Braun et al 2001]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with autosomal dominant craniometaphyseal dysplasia (AD-CMD), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Autosomal Dominant Craniometaphyseal Dysplasia View in own window System/ConcernEvaluationComment Respiratory & feeding problems in infancyReferral for craniofacial team eval incl otolaryngologic evalIncl eval for choanal stenosis Skeletal hyperostosis * X-rays of skull, hands, knees * CT to evaluate involvement of foramina & foramen magnum Cranial nerve compressionNeurologic exam Otolaryngologic evalTo evaluate auditory system Audiologic assessmentTo evaluate for hearing loss Ophthalmologic examTo evaluate for vision loss Endocrine / Bone metabolism * Alkaline phosphatase * P1NP * CTX To evaluate bone turnover SpeechEval by speech therapistIn early childhood; progressive hearing loss, facial palsy & hyperostosis can lead to speech issues. Delayed eruption & malocclusionEval by dentistFrom the time of primary tooth eruption to identify tooth impaction or delay in tooth eruption Genetic counselingBy genetics professionals 1To inform individuals & families re nature, MOI, & implications of AD-CMD to facilitate medical & personal decision making AD-CMD = autosomal dominant craniometaphyseal dysplasia; CTX = carboxy-terminal collagen crosslinks; MOI = mode of inheritance; P1NP = procollagen type 1 N-terminal propeptide 1\. Medical geneticist, certified genetic counselor, certified advanced genetic nurse ### Treatment of Manifestations ### Table 5. Treatment of Manifestations in Individuals with Autosomal Dominant Craniometaphyseal Dysplasia View in own window Manifestation/ConcernTreatmentConsiderations/Other Feeding & respiratory issues in newborns & infantsPer craniofacial team Cranial nerve compressionSurgical interventionTo relieve severe symptoms caused by cranial nerve compression Narrowed foramen magnumSurgical interventionTo relieve headaches & risks assoc w/Chiari malformation Hyperostosis of facial bonesSevere bony overgrowth of facial bones & nasal, forehead, & cranial regions can be contoured. * Surgical procedures can be technically difficult & bone regrowth is common. * As severe complications have occurred, surgery is considered for conservative purposes to relieve severe symptoms caused by cranial nerve compression. Hearing lossHearing aidsCochlear implant may be possible. Vison loss * Surgery for optic nerve impaction * Vision aids In anticipation of progressive vision loss, children may learn Braille. Speech issuesConsider speech therapy. MalocclusionSurgical intervention for severe malocclusionDelayed tooth eruption should be considered when planning orthodontic treatment [Chen et al 2014]. ### Surveillance ### Table 6. Recommended Surveillance for Individuals with Autosomal Dominant Craniometaphyseal Dysplasia View in own window System/ConcernEvaluationFrequency Feeding & respiratory issues in newborns & infantsCraniofacial teamAnnually, or more frequently if needed Narrowing cranial foramina, incl foramen magnumNeurologic eval Hearing lossHearing assessment Vision lossOphthalmologic exam ### Evaluation of Relatives at Risk It is appropriate to evaluate relatives at risk in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures. Early diagnosis of at-risk relatives may be beneficial for management of complications from progressive hyperostosis. Evaluations can include: * Molecular genetic testing if the pathogenic variant in the family is known; * Clinical evaluation and cranial and long bone radiographs if the pathogenic variant in the family is not known. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. ### Other Calcitonin has been thought to be effective because of its inhibitory effect on bone turnover. However, previous case reports found calcitonin therapy to be ineffective in treating hyperplasia of craniofacial bones in persons with CMD [Fanconi et al 1988, Haverkamp et al 1996]. Calcitriol with a low-calcium diet to stimulate bone resorption by promoting osteoclast formation had been reported to improve facial paralysis but has no effect on metaphyseal deformity [Key et al 1988, Wu et al 2016]. Acetazolamide has been suggested for treatment of disorders with increased bone mineral density. González-Rodríguez et al [2016] reported acetazolamide use in an individual with a phenotype similar to CMD, but diagnosis of AD-CMD was not confirmed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Craniometaphyseal Dysplasia, Autosomal Dominant	c1852502	26,788	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1461/	2021-01-18T21:32:30	{"mesh": ["C565145"], "synonyms": []}
Spuhler (1950) found two alternative patterns. (1) In the transverse type, the superficial veins radiate laterally from the pectoral venous plexus toward the axillary region. (2) In the longitudinal type, the veins radiate in a fan-like pattern downward and laterally from the point where the anterior jugular vein turns beneath the sternocleidomastoid muscle. In a study in the Navajo Indians, the transverse pattern appeared to behave as a dominant. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	VEINS, PATTERN OF, ON ANTERIOR THORAX	c1860490	26,789	omim	https://www.omim.org/entry/192400	2019-09-22T16:32:01	{"omim": ["192400"]}
Axial spondyloarthritis Sacroiliac joint Axial spondyloarthritis (also often referred to as axSpA) is a chronic, autoinflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). The most known member of the axial spondyloarthritis disease family is ankylosing spondylitis. Axial spondyloarthritis is an umbrella term that was introduced in 2009 to characterize a diverse disease family that share clinical and genetic features, such as the involvement of the axial skeleton.[1] The expression was introduced in order to unify (1) less severe forms of spondylitis, (2) the early phase of ankylosing spondylitis as well as (3) ankylosing spondylitis itself into one term. ## Contents * 1 Classification * 2 Diagnosis * 3 Management * 4 History * 5 References ## Classification[edit] Axial spondyloarthritis can be divided into two classes: 1. Non-radiographic axial spondyloarthritis (nr-axSpA): This term encompasses both the early disease stage of ankylosing spondylitis, in which no radiographic changes are visible yet, as well as less severe forms of ankylosing spondylitis. 2. Radiographic axial spondyloarthritis: Synonym for ankylosing spondylitis. This class is termed radiographic axial spondyloarthritis due to the unambiguous diagnosis through radiographic changes in the sacroiliac joints and/or spine. ## Diagnosis[edit] This section is empty. You can help by adding to it. (July 2018) ## Management[edit] Traditional NSAIDs and COX-2 inhibitor NSAIDs are effective for treating axSpA.[2] The potential harms may not differ when compared to a placebo treatment in the short term.[2] Various NSAIDs are equally effective (e.g.: Cox2 NSAIDS and traditional NSAIDS).[2] Continuous NSAID use may reduce radiographic spinal progression, but this requires confirmation.[2] In 2019 the American College of Rheumatology, Spondylitis Association of America and Spondyloarthritis Research and Treatment Network published updated recommendations for the treatment of the condition[3] based un updated literature reviews. ## History[edit] In 1984, a joint effort led to the definition of specific classification criteria for ankylosing spondylitis, called the “Modified New York Criteria”.[4] One of the central New York criteria was the existence of radiographically visible changes in the sacroiliac joints and/or spine, which have formed due to bone fusion, erosion and/or formation caused by the disease.[5] Even though these criteria helped to improve uniformly define ankylosing spondylitis, such radiologic changes often only manifested several years after the first disease symptoms appeared.[5] In order to be able to study also patients with early and less typical forms, new criteria were needed that could identify the disease already at an early stage. In 2009 the Modified New York criteria were extended by a broad set of new classification criteria that aimed to classify patients based on the presence of typical spondyloarthritis disease features.[1] These included inflammatory back pain, family history for axial spondyloarthritis, response to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), past history of or current inflammation in the joints (arthritis), tendon-bone attachment of the heel (enthesitis), or eyes (uveitis), bowel (inflammatory bowel disease), skin (psoriasis) or signs of elevated inflammation (C-reactive protein and erythrocyte sedimentation rate. [1] [6] Important parts of the ASAS axSpA criteria is the biomarker HLA-B27 and magnetic resonance imaging (MRI).[1][6] The criteria can only be applied in people that have chronic back pain (at least 3 months duration) started before the age of 45 years and only in those patients that already have a diagnosis of axial SpA. Since the disease ankylosing spondylitis was still defined by the Modified New York criteria of 1984, there was the need to find a new disease term that would also include the less severe forms or early onset of ankylosing spondylitis. This expression was found in the umbrella term axial spondyloarthritis. The 2009 classification criteria are called the ASAS (Assessment of SpondyloArthritis international Society) axial spondayloarthritis criteria.[citation needed] ## References[edit] 1. ^ a b c d Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. (June 2009). "The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection". Annals of the Rheumatic Diseases. 68 (6): 777–83. doi:10.1136/ard.2009.108233. PMID 19297344. 2. ^ a b c d Kroon FP, van der Burg LR, Ramiro S, Landewé RB, Buchbinder R, Falzon L, van der Heijde D (July 2015). "Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis)". The Cochrane Database of Systematic Reviews (7): CD010952. doi:10.1002/14651858.CD010952.pub2. PMID 26186173. 3. ^ Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. (October 2019). "2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis". Arthritis & Rheumatology. 71 (10): 1599–1613. doi:10.1002/art.41042. PMC 6764882. PMID 31436036. 4. ^ van der Linden S, Valkenburg HA, Cats A (April 1984). "Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria". Arthritis and Rheumatism (Submitted manuscript). 27 (4): 361–8. doi:10.1002/art.1780270401. PMID 6231933. 5. ^ a b Taurog JD, Chhabra A, Colbert RA (June 2016). "Ankylosing Spondylitis and Axial Spondyloarthritis". The New England Journal of Medicine. 374 (26): 2563–74. doi:10.1056/NEJMra1406182. PMID 27355535. 6. ^ a b Poddubnyy D, van Tubergen A, Landewé R, Sieper J, van der Heijde D (August 2015). "Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis". Annals of the Rheumatic Diseases. 74 (8): 1483–7. doi:10.1136/annrheumdis-2014-207151. 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Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Axial spondyloarthritis	c3203547	26,790	wikipedia	https://en.wikipedia.org/wiki/Axial_spondyloarthritis	2021-01-18T18:41:07	{"umls": ["C3203547"], "wikidata": ["Q28867094"]}
A number sign (#) is used with this entry because acrocallosal syndrome (ACLS) and Joubert syndrome-12 (JBTS12), 2 similar disorders, can be caused by homozygous mutation in the KIF7 gene (611254) on chromosome 15q26. Digenic inheritance of Joubert syndrome has also been reported; see MOLECULAR GENETICS. Description The acrocallosal syndrome is an autosomal recessive mental retardation syndrome with brain abnormalities such as corpus callosum agenesis and/or Dandy-Walker malformation as well as dysmorphic features, postaxial polydactyly of the hands, and preaxial polydactyly of the feet (Schinzel and Schmid, 1980). It is considered a ciliopathy (Putoux et al., 2011). Joubert syndrome-12 is a disorder with an overlapping phenotype characterized by the hallmark finding of the molar tooth sign (MTS) on brain MRI. For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300. Hydrolethalus-2 (HLS2; 614120) is an allelic disorder with a more severe phenotype and death in utero. Clinical Features Schinzel and Schmid (1980) reported 2 unrelated patients, a 2.5-year-old girl and a 4-year-old boy, with postaxial polydactyly, hallux duplication, macrocephaly, absence of corpus callosum, and severe mental retardation. The boy had previously been reported by Schinzel (1979). The authors favored autosomal dominant mutation, although parental age was little above the mean. They suggested the designation acrocallosal syndrome. In a report of 2 more patients, an unrelated girl and boy, Nelson and Thomson (1982) stated: 'The triad of hypertelorism, polydactyly (especially of the hallux) and mental retardation strongly suggests the diagnosis which is further supported if the corpus callosum is absent.' CT scan is useful in demonstrating absence of the corpus callosum. Schinzel (1982) summarized a total of 7 cases, all sporadic. He raised the question of identity to the Greig cephalopolysyndactyly syndrome (GCPS; 175700). The digital changes are similar to those of GCPS. Legius et al. (1985) also raised the question of identity to GCPS. Hendriks et al. (1990) reported a case which suggested that increased birth weight and cerebellar hypoplasia may be features of the acrocallosal syndrome. The finding of an extra bone within the anterior fontanel in their patient suggested similarity to the Xt mouse mutant, which is homologous to GCPS in man. This was taken as additional support for the hypothesis of allelism of the GCPS and acrocallosal syndromes. Brueton et al. (1992) did linkage analysis in a family in which 2 cousins, the offspring of sisters, had acrocallosal syndrome. Using markers known to be flanking the GCPS locus on chromosome 7p, they found evidence that appeared to exclude ACLS from that region. Schinzel (1982) and Schinzel and Kaufmann (1986) observed 4 additional cases from a restricted and sparsely populated area of Switzerland, including 2 affected sisters with healthy, nonconsanguineous parents (the first familial cases) and male and female first cousins whose mothers are sisters. Thus, the disorder was considered likely recessive. Schinzel and Kaufmann (1986) pointed out that the combination of agenesis of the corpus callosum and pre- or postaxial polydactyly is also found in the Finnish 'hydrolethalus syndrome' (236680). Indeed, they raised the question of whether the latter condition might be a lethal allele of the disorder in the acrocallosal syndrome. Philip et al. (1988) described 2 unrelated 4-month-old boys, each with consanguineous parents. Both exhibited the main features of the syndrome, but neither had partial reduplication of halluces. Consequently, Philip et al. (1988) concluded that preaxial polydactyly of the feet is not a constant feature of the syndrome. Schinzel (1988) described this syndrome in male and female first cousins (referred to earlier). Both patients had a defect of the corpus callosum, macrocephaly with protruding forehead and occiput, hypertelorism, and postaxial polydactyly of the hands. The boy, in addition, had hypospadias, cryptorchidism, inguinal hernias, duplication with syndactyly of the phalanges of the big toe, and a bipartite right clavicle. The girl had an arachnoidal cyst, a calvarian defect, and digitalization of the thumbs. Motor and mental development was retarded in both patients. Yuksel et al. (1990) reported the case of a Turkish boy, born to consanguineous parents, who showed macrocephaly, prominent forehead, hypertelorism, polydactyly of the fingers and toes, severe motor and mental retardation, hypotonia, and absence of the corpus callosum. Turolla et al. (1990) described an infant with all the components of ACLS except preaxial polydactyly. Salgado et al. (1989) reported the case of an affected child whose parents were related as half first cousins. Temtamy and Meguid (1989) saw the disorder in the offspring of double first cousins. The patient of Salgado et al. (1989) and that of Moeschler et al. (1989) had hallucal duplication. The occurrence of Dandy-Walker malformation in the acrocallosal syndrome was indicated by the report of Moeschler et al. (1989). Casamassima et al. (1989) described a case in which severe congenital heart defect was present. Fryns et al. (1991) presented the cases of 2 unrelated males with minor expression of ACLS. Developmental level in both was within normal limits. Lungarotti et al. (1991) described the condition in a 2-month-old infant girl. Gelman-Kohan et al. (1991) described 3 affected sibs from a consanguineous marriage. Cataltepe and Tuncbilek (1992) stated that 21 well-documented cases had been reported. They reported a family in which the parents were first cousins. Their proband had a high birth weight (more than 90th percentile), which had been suggested by others as a feature of the disorder. Additional features included sensorineural hearing loss and diaphragm eventration. An earlier-born sib had anencephaly and postaxial polydactyly. Kedar et al. (1996) described anencephaly in a brother and sister as apparently a primary manifestation of ACLS (which they abbreviated ACS). Pfeiffer et al. (1992) reported the case of a child, of normal unrelated parents, who, in addition to typical features of this syndrome, had a mirror duplication of nearly the entire short arm of chromosome 12 (a de novo inverted tandem duplication of 12p13.3-p11.2). Since the manifestations of trisomy and tetrasomy 12p show some overlap with the acrocallosal syndrome (as in the Pallister-Killian syndrome with tetrasomy 12p), Pfeiffer et al. (1992) suggested that the mutation for acrocallosal syndrome may be situated on 12p. (For a discussion of the Pallister-Killian syndrome, see 190070; the KRAS2 gene was used in the study of this syndrome.) This is, of course, inconsistent with the idea that the acrocallosal syndrome is allelic to Greig syndrome, since the latter disorder maps to 7p13. From South Africa, Christianson et al. (1994) reported the disorder in 2 black brothers with first-cousin parents. Koenig et al. (2002) described 3 patients with ACS demonstrating a spectrum from mild to severe involvement. Two patients had only mild to moderate mental retardation at the age of 2.5 and 4 years, respectively, with surprisingly good speech development. The third patient was severely affected and died at age 7 days because of persistent apnea. All 3 patients had agenesis of the corpus callosum and large intracranial cysts, which in the third case was confirmed as a large arachnoid cyst at autopsy. Cranial cysts were also seen in 10 of 34 published cases of ACS. Thus, intracerebral cysts are a common finding in ACS and may serve in differentiating ACS from Greig cephalopolysyndactyly syndrome. Aykut et al. (2008) reported a 10-month-old female infant with findings suggestive of acrocallosal syndrome, including optic atrophy, psychomotor retardation, polydactyly, and characteristic facies with prominent forehead, hypertelorism, and high-arched palate. Brain MRI revealed cerebral atrophy, corpus callosum agenesis, dilated lateral ventricles, and unilateral right temporal lobe hypoplasia. Aykut et al. (2008) noted that temporal lobe hypoplasia had not been previously reported and may represent an additional feature in this syndrome. Putoux et al. (2011) reported 7 families and 2 sporadic individuals with ACLS. Four of the families were of Turkish origin, and the remaining patients were from Pakistan, Finland, Algeria, and Egypt. Seven of the families were consanguineous. The majority of affected individuals had macrocephaly, mental retardation, abnormal facies, and brain abnormalities, including dilated ventricles, corpus callosum agenesis or hypoplasia, and a superior vermis dysgenesis resulting in the molar tooth sign in 7 affected individuals. Seven affected individuals had postaxial polydactyly of the hands. In the feet, polydactyly was preaxial; hallux duplication was postaxial or preaxial and postaxial. Dysmorphic facial features included prominent forehead, frontal bossing, broad nasal bridge, wide nasal bridge, short philtrum, hypertelorism, low-set ears, retrognathia, and dental anomalies. Other more variable features included hypotonia, bilateral optic atrophy, and ventricular septal defect. ### Joubert Syndrome 12 Dafinger et al. (2011) reported 2 Egyptian sibs, born of consanguineous parents, with Joubert syndrome-12. The patients had mental retardation, molar tooth sign on brain MRI, and dysmorphic facial features including hypertelorism, triangular mouth, downslanting palpebral fissures, low-set ears, and prominent forehead. One patient had ataxia, agenesis of the corpus callosum, and polydactyly. Inheritance The numerous reports of consanguinity in families with ACLS indicate that it is an autosomal recessive disorder (Schinzel, 1988; Philip et al., 1988; Salgado et al., 1989 Temtamy and Meguid, 1989; Yuksel et al., 1990; Gelman-Kohan et al., 1991; Putoux et al., 2011). Molecular Genetics By genomewide linkage analysis followed by candidate gene sequencing, Putoux et al. (2011) identified 3 nonsense and 5 frameshift mutations in the KIF7 gene (see, e.g., 611254.0001-611254.0005) in ACLS patients from 6 families and in 2 individual patients. The mutations were presumably homozygous. The findings indicated that ACLS is a ciliopathy. Elson et al. (2002) identified a child with an ACLS phenotype carrying a heterozygous mutation in the GLI3 gene (165240.0013). We have classified the phenotype in this patient as severe Greig cephalopolysyndactyly syndrome because it is impossible to distinguish the disorders in a simplex case and because the molecular basis of each disorder appears to be established. Biesecker (2008) stated that patients with a phenotype consistent with GCPS and a GLI3 mutation may be diagnosed definitively as GCPS. ### Joubert Syndrome 12 Dafinger et al. (2011) identified a homozygous truncating mutation in the KIF7 gene (611254.0006) in 2 Egyptian sibs with Joubert syndrome-12. A third patient with the disorder had a heterozygous mutation (611254.0007), but a second pathogenic allele was not identified. A fourth patient with Joubert syndrome had 2 pathogenic mutations in the TMEM67 gene (609884.0013; 609884.0024), consistent with JBTS6 (610688), as well as a heterozygous mutation in the KIF7 gene (611254.0008). Knockdown of KIF7 expression in cell lines caused defects in cilia formation and induced abnormal centrosomal duplication and fragmentation of the Golgi network. These cellular phenotypes likely resulted from abnormal tubulin acetylation and decreased microtubular dynamics. The findings indicated that modified microtubule stability and growth direction caused by loss of KIF7 function may be an underlying disease mechanism contributing to Joubert syndrome. ### Digenic Inheritance In a German patient with digenic inheritance of Joubert syndrome, Lee et al. (2012) identified a heterozygous 536A-G transition in exon 7 of the CEP41 gene (610523), resulting in an arg179-to-his (R179H) substitution in a highly conserved residue consistent with JBTS15 (614464), and a heterozygous truncating mutation in the KIF7 gene (811delG; 611254.0007), consistent with JBTS12. INHERITANCE \- Autosomal recessive GROWTH Other \- Postnatal growth retardation HEAD & NECK Head \- Macrocephaly \- Large anterior fontanel \- Prominent occiput Face \- Prominent forehead \- Short philtrum \- Hypoplastic midface Ears \- Malformed ears \- Preauricular tag \- Posteriorly rotated ears \- Deep-set ears Eyes \- Strabismus \- Hypertelorism \- Epicanthal folds \- Downslanting palpebral fissures \- Optic atrophy \- Decreased retinal pigmentation \- Nystagmus \- Coloboma (1 patient) Nose \- Small nose \- Broad nasal bridge Mouth \- Triangular mouth \- Cleft lip \- Cleft palate \- Protruding lips \- High-arched palate CARDIOVASCULAR Heart \- Septal defects \- Pulmonary valve defects ABDOMEN External Features \- Umbilical hernia Gastrointestinal \- Imperforate anus \- Rectovaginal fistula GENITOURINARY External Genitalia (Male) \- Inguinal hernia \- Hypospadias \- Micropenis Internal Genitalia (Male) \- Cryptorchidism Internal Genitalia (Female) \- Rectovaginal fistula SKELETAL Hands \- Tapered fingers \- Fifth finger clinodactyly \- Brachydactyly \- Preaxial or postaxial polydactyly \- Bifid terminal phalanges of thumbs Feet \- Toe syndactyly \- Preaxial or postaxial polydactyly \- Duplicated halluces NEUROLOGIC Central Nervous System \- Severe mental retardation \- Hypoplastic or absent corpus callosum \- Seizures \- Hypotonia \- Molar tooth sign on brain MRI (subset of patients) MISCELLANEOUS \- Variable phenotype MOLECULAR BASIS \- Caused by mutation in the kinesin family member 7 gene (KIF7, 611254.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ACROCALLOSAL SYNDROME	c2931760	26,791	omim	https://www.omim.org/entry/200990	2019-09-22T16:31:37	{"doid": ["9250"], "mesh": ["C538177"], "omim": ["200990"], "orphanet": ["36"], "synonyms": ["Alternative titles", "HALLUX DUPLICATION, POSTAXIAL POLYDACTYLY, AND ABSENCE OF CORPUS CALLOSUM", "SCHINZEL ACROCALLOSAL SYNDROME"]}
"Hay fever" redirects here. For the play, see Hay Fever (play). For the 2010 film, see Hayfever (film). Human disease Allergic rhinitis Other namesHay fever, pollenosis Pollen grains from a variety of plants, enlarged 500 times and about 0.4 mm wide SpecialtyAllergy and immunology SymptomsStuffy itchy nose, sneezing, red, itchy, and watery eyes, swelling around the eyes, itchy ears[1] Usual onset20 to 40 years old[2] CausesGenetic and environmental factors[3] Risk factorsAsthma, allergic conjunctivitis, atopic dermatitis[2] Diagnostic methodBased on symptoms, skin prick test, blood tests for specific antibodies[4] Differential diagnosisCommon cold[3] PreventionExposure to animals early in life[3] MedicationNasal steroids, antihistamines such as diphenhydramine, cromolyn sodium, leukotriene receptor antagonists such as montelukast, allergen immunotherapy[5][6] Frequency~20% (Western countries)[2][7] Allergic rhinitis, also known as hay fever, is a type of inflammation in the nose which occurs when the immune system overreacts to allergens in the air.[6] Signs and symptoms include a runny or stuffy nose, sneezing, red, itchy, and watery eyes, and swelling around the eyes.[1] The fluid from the nose is usually clear.[2] Symptom onset is often within minutes following allergen exposure and can affect sleep, and the ability to work or study.[2][8] Some people may develop symptoms only during specific times of the year, often as a result of pollen exposure.[3] Many people with allergic rhinitis also have asthma, allergic conjunctivitis, or atopic dermatitis.[2] Allergic rhinitis is typically triggered by environmental allergens such as pollen, pet hair, dust, or mold.[3] Inherited genetics and environmental exposures contribute to the development of allergies.[3] Growing up on a farm and having multiple siblings decreases this risk.[2] The underlying mechanism involves IgE antibodies that attach to an allergen, and subsequently result in the release of inflammatory chemicals such as histamine from mast cells.[2] Diagnosis is typically based on a combination of symptoms and a skin prick test or blood tests for allergen-specific IgE antibodies.[4] These tests, however, can be falsely positive.[4] The symptoms of allergies resemble those of the common cold; however, they often last for more than two weeks and typically do not include a fever.[3] Exposure to animals early in life might reduce the risk of developing these specific allergies.[3] Several different types of medications reduce allergic symptoms: including nasal steroids, antihistamines, such as diphenhydramine, cromolyn sodium, and leukotriene receptor antagonists such as montelukast.[5] Oftentimes, medications do not completely control symptoms, and they may also have side effects.[2] Exposing people to larger and larger amounts of allergen, known as allergen immunotherapy (AIT), is often effective.[6] The allergen can be given as an injection under the skin or as a tablet under the tongue.[6] Treatment typically lasts three to five years, after which benefits may be prolonged.[6] Allergic rhinitis is the type of allergy that affects the greatest number of people.[9] In Western countries, between 10 and 30% of people are affected in a given year.[2][7] It is most common between the ages of twenty and forty.[2] The first accurate description is from the 10th-century physician Rhazes.[10] In 1859, Charles Blackley identified pollen as the cause.[11] In 1906, the mechanism was determined by Clemens von Pirquet.[9] The link with hay came about due to an early (and incorrect) theory that the symptoms were brought about by the smell of new hay.[12][13] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 3.1 Classification * 3.2 Local allergic rhinitis * 4 Prevention * 5 Treatment * 5.1 Antihistamines * 5.2 Steroids * 5.3 Other * 5.4 Allergen immunotherapy * 5.5 Alternative medicine * 6 Epidemiology * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] Illustration depicting inflammation associated with allergic rhinitis The characteristic symptoms of allergic rhinitis are: rhinorrhea (excess nasal secretion), itching, sneezing fits, and nasal congestion and obstruction.[14] Characteristic physical findings include conjunctival swelling and erythema, eyelid swelling with Dennie–Morgan folds, lower eyelid venous stasis (rings under the eyes known as "allergic shiners"), swollen nasal turbinates, and middle ear effusion.[15] There can also be behavioral signs; in order to relieve the irritation or flow of mucus, people may wipe or rub their nose with the palm of their hand in an upward motion: an action known as the "nasal salute" or the "allergic salute". This may result in a crease running across the nose (or above each nostril if only one side of the nose is wiped at a time), commonly referred to as the "transverse nasal crease", and can lead to permanent physical deformity if repeated enough.[16] People might also find that cross-reactivity occurs.[17] For example, people allergic to birch pollen may also find that they have an allergic reaction to the skin of apples or potatoes.[18] A clear sign of this is the occurrence of an itchy throat after eating an apple or sneezing when peeling potatoes or apples. This occurs because of similarities in the proteins of the pollen and the food.[19] There are many cross-reacting substances. Hay fever is not a true fever, meaning it does not cause a core body temperature in the fever over 37.5–38.3 °C (99.5–100.9 °F). ## Cause[edit] Allergic rhinitis triggered by the pollens of specific seasonal plants is commonly known as "hay fever", because it is most prevalent during haying season. However, it is possible to have allergic rhinitis throughout the year. The pollen that causes hay fever varies between individuals and from region to region; in general, the tiny, hardly visible pollens of wind-pollinated plants are the predominant cause. Pollens of insect-pollinated plants are too large to remain airborne and pose no risk. Examples of plants commonly responsible for hay fever include: * Trees: such as pine (Pinus), birch (Betula), alder (Alnus), cedar (Cedrus), hazel (Corylus), hornbeam (Carpinus), horse chestnut (Aesculus), willow (Salix), poplar (Populus), plane (Platanus), linden/lime (Tilia), and olive (Olea). In northern latitudes, birch is considered to be the most common allergenic tree pollen, with an estimated 15–20% of people with hay fever sensitive to birch pollen grains. A major antigen in these is a protein called Bet V I. Olive pollen is most predominant in Mediterranean regions. Hay fever in Japan is caused primarily by sugi (Cryptomeria japonica) and hinoki (Chamaecyparis obtusa) tree pollen. * "Allergy friendly" trees include: ash (female only), red maple, yellow poplar, dogwood, magnolia, double-flowered cherry, fir, spruce, and flowering plum.[20] * Grasses (Family Poaceae): especially ryegrass (Lolium sp.) and timothy (Phleum pratense). An estimated 90% of people with hay fever are allergic to grass pollen. * Weeds: ragweed (Ambrosia), plantain (Plantago), nettle/parietaria (Urticaceae), mugwort (Artemisia Vulgaris), Fat hen (Chenopodium), and sorrel/dock (Rumex) Allergic rhinitis may also be caused by allergy to Balsam of Peru, which is in various fragrances and other products.[21][22][23] Predisposing factors to allergic rhinitis include eczema (atopic dermatitis) and asthma. These three conditions can often occur together which is referred to as the atopic triad.[24] Additionally, environmental exposures such as air pollution and maternal tobacco smoking can increase an individual's chances of developing allergies.[24] ## Diagnosis[edit] Patch test Allergy testing may reveal the specific allergens to which an individual is sensitive. Skin testing is the most common method of allergy testing.[25] This may include a patch test to determine if a particular substance is causing the rhinitis, or an intradermal, scratch, or other test. Less commonly, the suspected allergen is dissolved and dropped onto the lower eyelid as a means of testing for allergies. This test should be done only by a physician, since it can be harmful if done improperly. In some individuals not able to undergo skin testing (as determined by the doctor), the RAST blood test may be helpful in determining specific allergen sensitivity. Peripheral eosinophilia can be seen in differential leukocyte count. Allergy testing is not definitive. At times, these tests can reveal positive results for certain allergens that are not actually causing symptoms, and can also not pick up allergens that do cause an individual's symptoms. The intradermal allergy test is more sensitive than the skin prick test, but is also more often positive in people that do not have symptoms to that allergen.[26] Even if a person has negative skin-prick, intradermal and blood tests for allergies, he/she may still have allergic rhinitis, from a local allergy in the nose. This is called local allergic rhinitis.[27] Specialized testing is necessary to diagnose local allergic rhinitis.[28] ### Classification[edit] Allergic rhinitis may be seasonal, perennial, or episodic.[8] Seasonal allergic rhinitis occurs in particular during pollen seasons. It does not usually develop until after 6 years of age. Perennial allergic rhinitis occurs throughout the year. This type of allergic rhinitis is commonly seen in younger children.[29] Allergic rhinitis may also be classified as Mild-Intermittent, Moderate-Severe intermittent, Mild-Persistent, and Moderate-Severe Persistent. Intermittent is when the symptoms occur <4 days per week or <4 consecutive weeks. Persistent is when symptoms occur >4 days/week and >4 consecutive weeks. The symptoms are considered mild with normal sleep, no impairment of daily activities, no impairment of work or school, and if symptoms are not troublesome. Severe symptoms result in sleep disturbance, impairment of daily activities, and impairment of school or work.[30] ### Local allergic rhinitis[edit] Local allergic rhinitis is an allergic reaction in the nose to an allergen, without systemic allergies. So skin-prick and blood tests for allergy are negative, but there are IgE antibodies produced in the nose that react to a specific allergen. Intradermal skin testing may also be negative.[28] The symptoms of local allergic rhinitis are the same as the symptoms of allergic rhinitis, including symptoms in the eyes. Just as with allergic rhinitis, people can have either seasonal or perennial local allergic rhinitis. The symptoms of local allergic rhinitis can be mild, moderate, or severe. Local allergic rhinitis is associated with conjunctivitis and asthma.[28] In one study, about 25% of people with rhinitis had local allergic rhinitis.[31] In several studies, over 40% of people having been diagnosed with nonallergic rhinitis were found to actually have local allergic rhinitis.[27] Steroid nasal sprays and oral antihistamines have been found to be effective for local allergic rhinitis.[28] As of 2014, local allergenic rhinitis had mostly been investigated in Europe; in the United States, the nasal provocation testing necessary to diagnose the condition was not widely available.[32]:617 ## Prevention[edit] Prevention often focuses on avoiding specific allergens that cause an individual's symptoms. These methods include not having pets, not having carpets or upholstered furniture in the home, and keeping the home dry.[33] Specific anti-allergy zippered covers on household items like pillows and mattresses have also proven to be effective in preventing dust mite allergies.[25] Interestingly, studies have shown that growing up on a farm and having many older brothers and sisters can decrease an individual's risk for developing allergic rhinitis.[2] Studies in young children have shown that there is higher risk of allergic rhinitis in those who have early exposure to foods or formula and/or heavy exposure to cigarette smoking within the first year of life.[34][35] ## Treatment[edit] The goal of rhinitis treatment is to prevent or reduce the symptoms caused by the inflammation of affected tissues. Measures that are effective include avoiding the allergen.[14] Intranasal corticosteroids are the preferred medical treatment for persistent symptoms, with other options if this is not effective.[14] Second line therapies include antihistamines, decongestants, cromolyn, leukotriene receptor antagonists, and nasal irrigation.[14] Antihistamines by mouth are suitable for occasional use with mild intermittent symptoms.[14] Mite-proof covers, air filters, and withholding certain foods in childhood do not have evidence supporting their effectiveness.[14] ### Antihistamines[edit] Antihistamine drugs can be taken orally and nasally to control symptoms such as sneezing, rhinorrhea, itching, and conjunctivitis. It is best to take oral antihistamine medication before exposure, especially for seasonal allergic rhinitis. In the case of nasal antihistamines like azelastine antihistamine nasal spray, relief from symptoms is experienced within 15 minutes allowing for a more immediate 'as-needed' approach to dosage. There is not enough evidence of antihistamine efficacy as an add-on therapy with nasal steroids in the management of intermittent or persistent allergic rhinitis in children, so its adverse effects and additional costs must be considered.[36] Ophthalmic antihistamines (such as azelastine in eye drop form and ketotifen) are used for conjunctivitis, while intranasal forms are used mainly for sneezing, rhinorrhea, and nasal pruritus.[37] Antihistamine drugs can have undesirable side-effects, the most notable one being drowsiness in the case of oral antihistamine tablets. First-generation antihistamine drugs such as diphenhydramine cause drowsiness, while second- and third-generation antihistamines such as cetirizine and loratadine are less likely to.[37] Pseudoephedrine is also indicated for vasomotor rhinitis. It is used only when nasal congestion is present and can be used with antihistamines. In the United States, oral decongestants containing pseudoephedrine must be purchased behind the pharmacy counter in an effort to prevent the manufacturing of methamphetamine.[37] Desloratadine/pseudoephedrine can also be used for this condition[citation needed] ### Steroids[edit] Intranasal corticosteroids are used to control symptoms associated with sneezing, rhinorrhea, itching, and nasal congestion.[24] Steroid nasal sprays are effective and safe, and may be effective without oral antihistamines. They take several days to act and so must be taken continually for several weeks, as their therapeutic effect builds up with time. In 2013, a study compared the efficacy of mometasone furoate nasal spray to betamethasone oral tablets for the treatment of people with seasonal allergic rhinitis and found that the two have virtually equivalent effects on nasal symptoms in people.[38] Systemic steroids such as prednisone tablets and intramuscular triamcinolone acetonide or glucocorticoid (such as betamethasone) injection are effective at reducing nasal inflammation,[citation needed] but their use is limited by their short duration of effect and the side-effects of prolonged steroid therapy.[39] ### Other[edit] Other measures that may be used second line include: decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies such as nasal irrigation.[14] Topical decongestants may also be helpful in reducing symptoms such as nasal congestion, but should not be used for long periods, as stopping them after protracted use can lead to a rebound nasal congestion called rhinitis medicamentosa. For nocturnal symptoms, intranasal corticosteroids can be combined with nightly oxymetazoline, an adrenergic alpha-agonist, or an antihistamine nasal spray without risk of rhinitis medicamentosa.[40] Nasal saline irrigation (a practice where salt water is poured into the nostrils), may have benefits in both adults and children in relieving the symptoms of allergic rhinitis and it is unlikely to be associated with adverse effects.[41] ### Allergen immunotherapy[edit] Allergen immunotherapy (AIT, also termed desensitization) treatment involves administering doses of allergens to accustom the body to substances that are generally harmless (pollen, house dust mites), thereby inducing specific long-term tolerance.[42] Allergen immunotherapy is the only treatment that alters the disease mechanism.[43] Immunotherapy can be administered orally (as sublingual tablets or sublingual drops), or by injections under the skin (subcutaneous). Subcutaneous immunotherapy is the most common form and has the largest body of evidence supporting its effectiveness.[44] ### Alternative medicine[edit] There are no forms of complementary or alternative medicine that are evidence-based for allergic rhinitis.[25] Therapeutic efficacy of alternative treatments such as acupuncture and homeopathy is not supported by available evidence.[45][46] While some evidence shows that acupuncture is effective for rhinitis, specifically targeting the sphenopalatine ganglion acupoint, these trials are still limited.[47] Overall, the quality of evidence for complementary-alternative medicine is not strong enough to be recommended by the American Academy of Allergy, Asthma and Immunology.[25][48] ## Epidemiology[edit] Allergic rhinitis is the type of allergy that affects the greatest number of people.[9] In Western countries, between 10 and 30 percent of people are affected in a given year.[2] It is most common between the ages of twenty and forty.[2] ## History[edit] The first accurate description is from the 10th century physician Rhazes.[10] Pollen was identified as the cause in 1859 by Charles Blackley.[11] In 1906 the mechanism was determined by Clemens von Pirquet.[9] The link with hay came about due to an early (and incorrect) theory that the symptoms were brought about by the smell of new hay.[12][13] ## References[edit] 1. ^ a b "Environmental Allergies: Symptoms". NIAID. April 22, 2015. Archived from the original on 18 June 2015. Retrieved 19 June 2015. 2. ^ a b c d e f g h i j k l m n Wheatley LM, Togias A (January 2015). "Clinical practice. Allergic rhinitis". The New England Journal of Medicine. 372 (5): 456–63. doi:10.1056/NEJMcp1412282. PMC 4324099. PMID 25629743. 3. ^ a b c d e f g h "Cause of Environmental Allergies". NIAID. April 22, 2015. Archived from the original on 17 June 2015. Retrieved 17 June 2015. 4. ^ a b c "Environmental Allergies: Diagnosis". NIAID. May 12, 2015. Archived from the original on 17 June 2015. Retrieved 19 June 2015. 5. ^ a b "Environmental Allergies: Treatments". NIAID. April 22, 2015. Archived from the original on 17 June 2015. Retrieved 17 June 2015. 6. ^ a b c d e "Immunotherapy for Environmental Allergies". NIAID. May 12, 2015. Archived from the original on 17 June 2015. Retrieved 19 June 2015. 7. ^ a b Dykewicz MS, Hamilos DL (February 2010). "Rhinitis and sinusitis". The Journal of Allergy and Clinical Immunology. 125 (2 Suppl 2): S103-15. doi:10.1016/j.jaci.2009.12.989. PMID 20176255. 8. ^ a b Covar R (2018). "Allergic Disorders". Current Diagnosis & Treatment: Pediatrics (24th ed.). NY: McGraw-Hill. ISBN 978-1-259-86290-8. 9. ^ a b c d Fireman P (2002). Pediatric otolaryngology vol 2 (4th ed.). Philadelphia, Pa.: W. B. Saunders. p. 1065. ISBN 9789997619846. 10. ^ a b Colgan R (2009). Advice to the young physician on the art of medicine. New York: Springer. p. 31. ISBN 9781441910349. Archived from the original on 2017-09-08. 11. ^ a b Justin Parkinson (1 July 2014). "John Bostock: The man who 'discovered' hay fever". BBC News Magazine. Archived from the original on 31 July 2015. Retrieved 19 June 2015. 12. ^ a b Hall M (May 19, 1838). "Dr. Marshall Hall on Diseases of the Respiratory System; III. Hay Asthma". The Lancet. 30 (768): 245. doi:10.1016/S0140-6736(02)95895-2. "With respect to what is termed the exciting cause of the disease, since the attention of the public has been turned to the subject an idea has very generally prevailed, that it is produced by the effluvium from new hay, and it has hence obtained the popular name of hay fever. [...] the effluvium from hay has no connection with the disease." 13. ^ a b History of Allergy. Karger Medical and Scientific Publishers. 2014. p. 62. ISBN 9783318021950. Archived from the original on 2016-06-10. 14. ^ a b c d e f g Sur DK, Plesa ML (December 2015). "Treatment of Allergic Rhinitis". American Family Physician. 92 (11): 985–92. PMID 26760413. Retrieved 21 April 2018. 15. ^ Valet RS, Fahrenholz JM (2009). "Allergic rhinitis: update on diagnosis". Consultant. 49: 610–3. Archived from the original on 2010-01-14. 16. ^ Pray WS (2005). Nonprescription Product Therapeutics. Lippincott Williams & Wilkins. p. 221. ISBN 978-0781734981. 17. ^ Czaja-Bulsa G, Bachórska J (December 1998). "[Food allergy in children with pollinosis in the Western sea coast region]" [Food allergy in children with pollinosis in the Western sea coast region]. Polski Merkuriusz Lekarski (in Polish). 5 (30): 338–40. PMID 10101519. 18. ^ Yamamoto T, Asakura K, Shirasaki H, Himi T, Ogasawara H, Narita S, Kataura A (October 2005). "[Relationship between pollen allergy and oral allergy syndrome]" [Relationship between Pollen Allergy and Oral Allergy Syndrome]. Nihon Jibiinkoka Gakkai Kaiho (in Japanese). 108 (10): 971–9. doi:10.3950/jibiinkoka.108.971. PMID 16285612. 19. ^ Malandain H (September 2003). "[Allergies associated with both food and pollen]" [Allergies associated with both food and pollen]. European Annals of Allergy and Clinical Immunology (in French). 35 (7): 253–6. PMID 14626714. INIST:15195402. 20. ^ "Allergy Friendly Trees". Forestry.about.com. 2014-03-05. Archived from the original on 2014-04-14. Retrieved 2014-04-25. 21. ^ Pamela Brooks (2012). The Daily Telegraph: Complete Guide to Allergies. ISBN 9781472103949. Retrieved 2014-04-27. 22. ^ Denver Medical Times: Utah Medical Journal. Nevada Medicine. 2010-01-01. Archived from the original on 2017-09-08. Retrieved 2014-04-27. 23. ^ George Clinton Andrews; Anthony Nicholas Domonkos (1998-07-01). Diseases of the Skin: For Practitioners and Students. Archived from the original on 2017-09-08. Retrieved 2014-04-27. 24. ^ a b c Cahill K (2018). "Urticaria, Angioedema, and Allergic Rhinitis." 'Harrison's Principles of Internal Medicine (20th ed.). NY: McGraw-Hill. pp. Chapter 345. ISBN 978-1-259-64403-0. 25. ^ a b c d "American Academy of Allergy Asthma and Immunology". 26. ^ "Allergy Tests". Archived from the original on 2012-01-14. 27. ^ a b Rondón C, Canto G, Blanca M (February 2010). "Local allergic rhinitis: a new entity, characterization and further studies". Current Opinion in Allergy and Clinical Immunology. 10 (1): 1–7. doi:10.1097/ACI.0b013e328334f5fb. PMID 20010094. S2CID 3472235. 28. ^ a b c d Rondón C, Fernandez J, Canto G, Blanca M (2010). "Local allergic rhinitis: concept, clinical manifestations, and diagnostic approach". Journal of Investigational Allergology & Clinical Immunology. 20 (5): 364–71, quiz 2 p following 371. PMID 20945601. 29. ^ "Rush University Medical Center". Archived from the original on 2015-02-19. Retrieved 2008-03-05. 30. ^ Bousquet J, Reid J, van Weel C, Baena Cagnani C, Canonica GW, Demoly P, et al. (August 2008). "Allergic rhinitis management pocket reference 2008". Allergy. 63 (8): 990–6. doi:10.1111/j.1398-9995.2008.01642.x. PMID 18691301. S2CID 11933433. 31. ^ Rondón C, Campo P, Galindo L, Blanca-López N, Cassinello MS, Rodriguez-Bada JL, et al. (October 2012). "Prevalence and clinical relevance of local allergic rhinitis". Allergy. 67 (10): 1282–8. doi:10.1111/all.12002. PMID 22913574. S2CID 22470654. 32. ^ Flint PW, Haughey BH, Robbins KT, Thomas JR, Niparko JK, Lund VJ, Lesperance MM (2014-11-28). Cummings Otolaryngology - Head and Neck Surgery E-Book. Elsevier Health Sciences. ISBN 9780323278201. 33. ^ "Prevention". nhs.uk. 3 October 2018. Retrieved 17 February 2019. 34. ^ Akhouri S, House SA. Allergic Rhinitis. [Updated 2020 Nov 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538186/ 35. ^ Skoner DP (July 2001). "Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis". The Journal of Allergy and Clinical Immunology. 108 (1 Suppl): S2-8. doi:10.1067/mai.2001.115569. PMID 11449200. 36. ^ Nasser M, Fedorowicz Z, Aljufairi H, McKerrow W (July 2010). "Antihistamines used in addition to topical nasal steroids for intermittent and persistent allergic rhinitis in children". The Cochrane Database of Systematic Reviews (7): CD006989. doi:10.1002/14651858.CD006989.pub2. PMC 7388927. PMID 20614452. 37. ^ a b c May JR, Smith PH (2008). "Allergic Rhinitis". In DiPiro JT, Talbert RL, Yee GC, Matzke G, Wells B, Posey LM (eds.). Pharmacotherapy: A Pathophysiologic Approach (7th ed.). New York: McGraw-Hill. pp. 1565–75. ISBN 978-0071478991. 38. ^ Karaki M, Akiyama K, Mori N (June 2013). "Efficacy of intranasal steroid spray (mometasone furoate) on treatment of patients with seasonal allergic rhinitis: comparison with oral corticosteroids". Auris, Nasus, Larynx. 40 (3): 277–81. doi:10.1016/j.anl.2012.09.004. PMID 23127728. 39. ^ Ohlander BO, Hansson RE, Karlsson KE (1980). "A comparison of three injectable corticosteroids for the treatment of patients with seasonal hay fever". The Journal of International Medical Research. 8 (1): 63–9. doi:10.1177/030006058000800111. PMID 7358206. S2CID 24169670. 40. ^ Baroody FM, Brown D, Gavanescu L, DeTineo M, Naclerio RM (April 2011). "Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis". The Journal of Allergy and Clinical Immunology. 127 (4): 927–34. doi:10.1016/j.jaci.2011.01.037. PMID 21377716. 41. ^ Head K, Snidvongs K, Glew S, Scadding G, Schilder AG, Philpott C, Hopkins C (June 2018). "Saline irrigation for allergic rhinitis". The Cochrane Database of Systematic Reviews. 6: CD012597. doi:10.1002/14651858.CD012597.pub2. PMC 6513421. PMID 29932206. 42. ^ Van Overtvelt L, Batard T, Fadel R, Moingeon P (December 2006). "Mécanismes immunologiques de l'immunothérapie sublinguale spécifique des allergènes". Revue Française d'Allergologie et d'Immunologie Clinique. 46 (8): 713–720. doi:10.1016/j.allerg.2006.10.006. 43. ^ Creticos P. "Subcutaneous immunotherapy for allergic disease: Indications and efficacy". UpToDate. 44. ^ Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S (January 2007). "Allergen injection immunotherapy for seasonal allergic rhinitis". The Cochrane Database of Systematic Reviews (1): CD001936. doi:10.1002/14651858.CD001936.pub2. PMC 7017974. PMID 17253469. 45. ^ Passalacqua G, Bousquet PJ, Carlsen KH, Kemp J, Lockey RF, Niggemann B, et al. (May 2006). "ARIA update: I--Systematic review of complementary and alternative medicine for rhinitis and asthma". The Journal of Allergy and Clinical Immunology. 117 (5): 1054–62. doi:10.1016/j.jaci.2005.12.1308. PMID 16675332. 46. ^ Terr AI (2004). "Unproven and controversial forms of immunotherapy". Clinical Allergy and Immunology. 18: 703–10. PMID 15042943. 47. ^ Fu Q, Zhang L, Liu Y, Li X, Yang Y, Dai M, Zhang Q (12 March 2019). "Effectiveness of Acupuncturing at the Sphenopalatine Ganglion Acupoint Alone for Treatment of Allergic Rhinitis: A Systematic Review and Meta-Analysis". Evidence-Based Complementary and Alternative Medicine. 2019: 6478102. doi:10.1155/2019/6478102. PMC 6434301. PMID 30992709. 48. ^ Witt CM, Brinkhaus B (October 2010). "Efficacy, effectiveness and cost-effectiveness of acupuncture for allergic rhinitis - An overview about previous and ongoing studies". Autonomic Neuroscience. 157 (1–2): 42–5. doi:10.1016/j.autneu.2010.06.006. PMID 20609633. S2CID 31349218. ## External links[edit] * Allergic rhinitis at Curlie * v * t * e Allergic conditions Respiratory system * Allergic rhinitis (hay fever) * Asthma * Hypersensitivity pneumonitis * Eosinophilic pneumonia * Eosinophilic granulomatosis with polyangiitis * Allergic bronchopulmonary aspergillosis * Farmer's lung * Laboratory animal allergy Skin * Angioedema * Urticaria * Atopic dermatitis * Allergic contact dermatitis * Hypersensitivity vasculitis Blood and immune system * Serum sickness Circulatory system * Anaphylaxis Digestive system * Coeliac disease * Eosinophilic gastroenteritis * Eosinophilic esophagitis * Food allergy * Egg allergy * Milk intolerance Nervous system * Eosinophilic meningitis Genitourinary system * Acute interstitial nephritis Other conditions * Drug allergy * Allergic conjunctivitis * Latex allergy * v * t * e Hypersensitivity and autoimmune diseases Type I/allergy/atopy (IgE) Foreign * Atopic eczema * Allergic urticaria * Allergic rhinitis (Hay fever) * Allergic asthma * Anaphylaxis * Food allergy * common allergies include: Milk * Egg * Peanut * Tree nut * Seafood * Soy * Wheat * Penicillin allergy Autoimmune * Eosinophilic esophagitis Type II/ADCC * * IgM * IgG Foreign * Hemolytic disease of the newborn Autoimmune Cytotoxic * Autoimmune hemolytic anemia * Immune thrombocytopenic purpura * Bullous pemphigoid * Pemphigus vulgaris * Rheumatic fever * Goodpasture syndrome * Guillain–Barré syndrome "Type V"/receptor * Graves' disease * Myasthenia gravis * Pernicious anemia Type III (Immune complex) Foreign * Henoch–Schönlein purpura * Hypersensitivity vasculitis * Reactive arthritis * Farmer's lung * Post-streptococcal glomerulonephritis * Serum sickness * Arthus reaction Autoimmune * Systemic lupus erythematosus * Subacute bacterial endocarditis * Rheumatoid arthritis Type IV/cell-mediated (T cells) Foreign * Allergic contact dermatitis * Mantoux test Autoimmune * Diabetes mellitus type 1 * Hashimoto's thyroiditis * Multiple sclerosis * Coeliac disease * Giant-cell arteritis * Postorgasmic illness syndrome * Reactive arthritis GVHD * Transfusion-associated graft versus host disease Unknown/ multiple Foreign * Hypersensitivity pneumonitis * Allergic bronchopulmonary aspergillosis * Transplant rejection * Latex allergy (I+IV) Autoimmune * Sjögren syndrome * Autoimmune hepatitis * Autoimmune polyendocrine syndrome * APS1 * APS2 * Autoimmune adrenalitis * Systemic autoimmune disease * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis * v * t * e Decongestants and other nasal preparations (R01) Topical Sympathomimetics, plain * Cyclopentamine * Ephedrine * Epinephrine * Fenoxazoline * Levomethamphetamine * Metizoline * Naphazoline * Oxymetazoline * Phenylephrine * Propylhexedrine * Tetryzoline * Tramazoline * Tuaminoheptane * Tymazoline * Xylometazoline Antiallergic agents, excluding corticosteroids * Spaglumic acid * histamine antagonists (Levocabastine * Antazoline * Thonzylamine) * mast cell stabilizer (some are also antihistamines) (Cromoglicic acid * Nedocromil * Azelastine * Olopatadine * Lodoxamide) Corticosteroids * Beclometasone dipropionate * Betamethasone# * Budesonide * Ciclesonide * Dexamethasone * Flunisolide * Fluticasone (Fluticasone furoate, Fluticasone propionate) * Mometasone furoate * Prednisolone# * Tixocortol * Triamcinolone * Triamcinolone acetonide Other nasal preparations * Cafaminol * Calcium hexamine thiocyanate * Eucalyptus oil * Framycetin * Hexamidine * Hyaluronan * Ipratropium bromide * Mupirocin * Retinol * Ritiometan * Saline water Combination products * Olopatadine/mometasone Systemic use: Sympathomimetics * Phenylephrine * Phenylpropanolamine * Pseudoephedrine (+loratadine) * #WHO-EM * ‡Withdrawn from market * Clinical trials: * †Phase III * §Never to phase III Classification D * ICD-10: J30 * ICD-9-CM: 477 * OMIM: 607154 * MeSH: D012221 * DiseasesDB: 31140 External resources * MedlinePlus: 000813 * eMedicine: ent/194 med/104, ped/2560 * Patient UK: Allergic rhinitis * Medicine portal Authority control * GND: 4024774-0 * NDL: 00807766 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Allergic rhinitis	c2607914	26,792	wikipedia	https://en.wikipedia.org/wiki/Allergic_rhinitis	2021-01-18T18:43:56	{"mesh": ["D065631"], "umls": ["C2607914", "C0847614", "C0002103"], "icd-10": ["J30"], "wikidata": ["Q272436"]}
A number sign (#) is used with this entry because thrombocythemia-3 (THCYT3) is caused by heterozygous germline or somatic mutation in the JAK2 gene (147796) on chromosome 9p24. Description Thrombocythemia-3 is an autosomal dominant hematologic disorder characterized by increased platelet production resulting in increased numbers of circulating platelets. Thrombocythemia can be associated with thrombotic episodes, such as cerebrovascular events or myocardial infarction (summary by Mead et al., 2012). For a discussion of genetic heterogeneity of thrombocythemia, see THCYT1 (187950). Clinical Features Mead et al. (2012) reported a 3-generation family with autosomal dominant inheritance of thrombocythemia. The proband presented at age 53 years with an ischemic cerebrovascular event associated with long-standing thrombocytosis (700 x 10(9) to 970 x 10(9)). There were 5 additional family members with thrombocytosis, including 1 with a myocardial infarction at age 46 and another with a myocardial infarction at age 65 and an ischemic cerebrovascular event at age 72. Bone marrow biopsy showed megakaryocyte hyperplasia without fibrosis. In addition, none of the patients had splenomegaly or evidence of leukemic transformation. Inheritance The transmission pattern of thrombocythemia in the family reported by Mead et al. (2012) was consistent with autosomal dominant inheritance. Molecular Genetics ### Germline Mutation in the JAK2 Gene In affected members of a family with thrombocythemia, Mead et al. (2012) identified a germline heterozygous gain-of-function mutation in the JAK2 gene (V617I; 147796.0004). Examination of peripheral blood cells showed normal baseline STAT3 (102582) activity and lack of cytokine-independent colony formation. However, after stimulation with granulocyte colony-stimulating factor (GCSF; 138970), V617I-containing CD33+ myeloid and CD34+ stem cells showed a marked increase in STAT3 levels, particularly in response to low levels of GCSF, suggesting that the mutation causes limited constitutive activation with a reduced threshold for cytokine-induced activation. ### Somatic Mutation in the JAK2 Gene Baxter et al. (2005) and Kralovics et al. (2005) found that 57% (29 of 51) and 23% (21 of 93) of patients with essential thrombocytopenia, respectively, carried a somatic mutation in the JAK2 gene (V617F; 147796.0001). In a 45-year-old man with no cardiovascular risk factors who presented in cardiogenic shock and was found to have coronary occlusion, myocardial infarction, and multiple myocardial microthrombi, Lata et al. (2010) identified at least 1 mutated V617F JAK2 allele on a peripheral blood smear. The patient, who had a platelet count of 529,000 per cubic millimeter, died in irreversible asystole after multiple percutaneous transluminal coronary angioplasties, stenting, and intracoronary fibrinolysis. Considering this to represent a fulminant initial presentation of occult essential thrombocythemia, Lata et al. (2010) stated that screening for the JAK2 mutation would likely be of value in selected patients with otherwise unexplained coronary ischemic events and mild thrombocytosis. INHERITANCE \- Autosomal dominant \- Somatic mutation CARDIOVASCULAR Heart \- Myocardial infarction, increased risk of HEMATOLOGY \- Thrombocythemia \- Increased megakaryocytes in bone marrow MISCELLANEOUS \- Germline or somatic mutations may cause the disorder \- Increased risk of myeloproliferative disorders in those with somatic mutations MOLECULAR BASIS \- Caused by mutation in the janus kinase 2 gene (JAK2, 147796.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	THROMBOCYTHEMIA 3	c0040028	26,793	omim	https://www.omim.org/entry/614521	2019-09-22T15:54:54	{"doid": ["2224"], "mesh": ["D013920"], "omim": ["614521"], "orphanet": ["71493", "3318"], "synonyms": ["Alternative titles", "THROMBOCYTOSIS 3", "Hereditary thrombocythemia", "Familial thrombocythemia"]}
Sézary disease Other namesSézary's disease, Sézary('s) syndrome The bright red rash of Sezary syndrome Pronunciation * /ˌseɪˌzɑːˈriː/ SpecialtyOncology, dermatology Sézary disease, or Sézary syndrome[1] is a type of cutaneous T-cell lymphoma that was first described by Albert Sézary.[2] The affected T-cells known as Sézary's cells, and also as Lutzner cells, have pathological quantities of mucopolysaccharides. Sézary disease is sometimes considered a late stage of mycosis fungoides with lymphadenopathy.[3][4] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 3.1 Radiation therapy * 3.2 Chemotherapy * 4 Epidemiology * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] Sézary cell: pleomorphic abnormal T cell with the characteristic cerebriform nuclei (Peripheral blood - MGG stain). Sézary disease and mycosis fungoides are cutaneous T-cell lymphomas having a primary manifestation in the skin.[5] The disease's origin is a peripheral CD4+ T-lymphocyte,[3] although rarer CD8+/CD4- cases have been observed.[3] Epidermotropism (lymphocytes residing in the epidermis)[6] by neoplastic CD4+ lymphocytes with the formation of Pautrier's microabscesses is the hallmark sign of the disease. Although the condition can affect people of all ages, it is commonly diagnosed in adults over age 60.[7][3] The dominant signs and symptoms of the disease are: 1. Generalized erythroderma– redness of the skin[3] 2. Lymphadenopathy – swollen, enlarged lymph nodes[3] 3. Atypical T-cells – malignant lymphocytes known as "Sézary cells" seen in the peripheral blood with typical cerebriform nuclei (brain-shaped, convoluted nuclei)[8][3] 4. Hepatosplenomegaly– enlarged liver and spleen[9] 5. Palmoplantar keratoderma – thickening of the palms of the hands, and soles of the feet[10][11] ## Diagnosis[edit] Sézary syndrome in a 61-year-old man presenting in 1972 with unrelenting itchiness of six months’ duration. On the right is his peripheral blood film stained with Periodic Acid-Schiff (PAS) showing a neoplastic T cell (Sézary cell). Those who have Sézary disease often present with skin lesions that do not heal with normal medication.[12] A blood test generally reveals any change in the levels of lymphocytes in the blood, which is often associated with a cutaneous T-cell lymphoma.[12] Finally, a biopsy of a skin lesion can be performed to rule out any other causes.[12] The immunohistochemical features are very similar to those presented in mycosis fungoides except for the following differences:[13] 1. More monotonous cellular infiltrates (large, clustered atypical pagetoid cells) in Sézary syndrome 2. Sometimes absent epidermotropism 3. Increased lymph node involvement with infiltrates of Sézary syndrome. ## Treatment[edit] Treatment typically includes some combination of photodynamic therapy, radiation therapy, chemotherapy, and biologic therapy.[14] Treatments are often used in combination with phototherapy and chemotherapy, though pure chemotherapy is rarely used today.[3] No single treatment type has revealed clear-cut benefits in comparison to others, treatment for all cases remains problematic.[15] ### Radiation therapy[edit] A number of types of radiation therapy may be used including total skin electron therapy.[16] While this therapy does not generally result in systemic toxic effects it can produce side effects involving the skin.[16] It is only available at a few institutions.[16] ### Chemotherapy[edit] Romidepsin, vorinostat and a few others are a second-line drug for cutaneous T-cell lymphoma.[17] Mogamulizumab has been approved in Japan[citation needed] and the United States.[18] ## Epidemiology[edit] In the Western population, there are around 3 cases of Sézary syndrome per 1,000,000 people.[3] Sézary disease is more common in males with a ratio of 2:1,[3] and the mean age of diagnosis is between 55 and 60 years of age.[3][9] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Reference, Genetics Home. "Sézary syndrome". Genetics Home Reference. 2. ^ Sézary's cell at Who Named It? 3. ^ a b c d e f g h i j k Cuneo, A; Castoldi, GL (2005). "Mycosis fungoidses/Sezary's syndrome". Atlas Genet Cytogenet Oncol Haematol. 9 (3): 242–243. Retrieved 2008-02-15. 4. ^ Thangavelu M, Finn WG, Yelavarthi KK, Roenigk Jr HH, Samuelson E, Peterson L, Kuzel TM, Rosen ST (May 1997). "Recurring Structural Chromosome Abnormalities in Peripheral Blood Lymphocytes of Patients With Mycosis Fungoides/Sézary Syndrome". Blood. 89 (9): 3371–7. doi:10.1182/blood.V89.9.3371. PMID 9129044. 5. ^ Cerroni, Lorenzo; Kevin Gatter; Helmut Kerl (2005). An illustrated guide to Skin Lymphomas. Malden, Massachusetts: Blackwell Publishing. p. 39. ISBN 978-1-4051-1376-2. 6. ^ Mutasim, Diya F. (2015). "What Is Dermatitis with Epidermotropism?". Practical Skin Pathology. Springer International Publishing. pp. 37–39. doi:10.1007/978-3-319-14729-1_8. ISBN 978-3-319-14728-4. 7. ^ "Sezary syndrome". genetic and rare diseases information center. Retrieved 17 April 2018. 8. ^ Park, HS; McIntosh, L; Braschi-Amirfarzan, M; Shinagare, AB; Krajewski, KM (January 2017). "T-Cell Non-Hodgkin Lymphomas: Spectrum of Disease and the Role of Imaging in the Management of Common Subtypes". Korean Journal of Radiology. 18 (1): 71–83. doi:10.3348/kjr.2017.18.1.71. PMC 5240486. PMID 28096719. 9. ^ a b Lorincz, A. I. "Sezary syndrome". Retrieved 2008-02-15. 10. ^ Fragkos, Konstantinos C. (2017). "Plantar keratoderma of Sézary syndrome". Clinical Case Reports. 5 (10): 1726–1727. doi:10.1002/ccr3.1168. ISSN 2050-0904. PMC 5628207. PMID 29026585. 11. ^ Martin, Stephanie J.; Duvic, Madeleine (2012-10-01). "Prevalence and treatment of palmoplantar keratoderma and tinea pedis in patients with Sézary syndrome". International Journal of Dermatology. 51 (10): 1195–1198. doi:10.1111/j.1365-4632.2011.05204.x. ISSN 1365-4632. PMID 22994666. 12. ^ a b c "Diagnosis". Retrieved 2008-02-15. 13. ^ Beigi, Pooya Khan Mohammad (2017). "Diagnosis and Management". Clinician's Guide to Mycosis Fungoides. Bulletin of the New York Academy of Medicine. 35. Springer International Publishing. pp. 13–18. doi:10.1007/978-3-319-47907-1_4. ISBN 9783319479064. PMC 1806090. PMID 13618707. 14. ^ "Mycosis Fungoides (Including Sézary Syndrome) Treatment". National Cancer Institute. 7 September 2017. Retrieved 1 December 2017. 15. ^ Cerroni, Lorenzo; Kevin Gatter; Helmut Kerl (2005). An illustrated guide to Skin Lymphomas. Malden, Massachusetts: Blackwell Publishing. p. 41. ISBN 978-1-4051-1376-2. 16. ^ a b c "Mycosis Fungoides (Including Sézary Syndrome) Treatment". National Cancer Institute. 12 July 2017. Retrieved 1 December 2017. 17. ^ Jawed, SI; Myskowski, PL; Horwitz, S; Moskowitz, A; Querfeld, C (February 2014). "Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions". Journal of the American Academy of Dermatology. 70 (2): 223.e1–17, quiz 240–2. doi:10.1016/j.jaad.2013.08.033. PMID 24438970. 18. ^ "FDA approves mogamulizumab-kpkc for mycosis fungoides or Sézary syndrome". U.S. Food and Drug Administration. 2018-08-08. Retrieved 2020-08-04. ## External links[edit] Classification D * ICD-10: C84.1 * ICD-9-CM: 202.2 * ICD-O: M9701/3 * MeSH: D012751 * DiseasesDB: 8595 External resources * eMedicine: med/1541 derm/566 med/3486 * Illustration of Sezary cells * Sezary Syndrome lymphoma information * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Sézary disease	c0036920	26,794	wikipedia	https://en.wikipedia.org/wiki/S%C3%A9zary_disease	2021-01-18T18:53:05	{"gard": ["7629"], "mesh": ["D012751"], "umls": ["C0036920"], "orphanet": ["3162"], "wikidata": ["Q2165399"]}
Autosomal recessive spastic paraplegia type 25 (SPG25) is a rare, complex type of hereditary spastic paraplegia characterized by adult-onset spastic paraplegia associated with spinal pain that radiates to the upper or lower limbs and is related to disk herniation (with minor spondylosis), as well as mild sensorimotor neuropathy. The SPG25 phenotype has been mapped to a locus on chromosome 6q23-q24.1. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autosomal recessive spastic paraplegia type 25	c2936860	26,795	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101005	2021-01-23T17:02:00	{"gard": ["9582"], "mesh": ["C536861"], "omim": ["608220"], "umls": ["C2936860"], "icd-10": ["G11.4"], "synonyms": ["Autosomal recessive spastic paraplegia-disc herniation syndrome", "SPG25"]}
Erdheim-Chester disease is a rare type of slow-growing blood cancer called a histiocytic neoplasm, which results in overproduction of cells called histiocytes. Histiocytes normally function to destroy foreign substances and protect the body from infection. In Erdheim-Chester disease, the excess production of histiocytes (histiocytosis) leads to inflammation that can damage organs and tissues throughout the body, causing them to become thickened, dense, and scarred (fibrotic); this tissue damage may lead to organ failure. People with Erdheim-Chester disease often have bone pain, especially in the lower legs and upper arms, due to an abnormal increase in bone density (osteosclerosis). Damage to the pituitary gland (a structure at the base of the brain that produces several hormones, including a hormone that controls the amount of water released in the urine) may result in hormonal problems such as a condition called diabetes insipidus that leads to excessive urination. Abnormally high pressure of the cerebrospinal fluid within the skull (intracranial hypertension) caused by accumulation of histiocytes in the brain may result in headaches, seizures, cognitive impairment, or problems with movement or sensation. People with this condition can also have shortness of breath, heart or kidney disease, protruding eyes (exophthalmos), skin growths, or inability to conceive a child (infertility). Affected individuals may also experience fever, night sweats, fatigue, weakness, and weight loss. The signs and symptoms of Erdheim-Chester disease usually appear between the ages of 40 and 60, although the disorder can occur at any age. The severity of the condition varies widely; some affected individuals have few or no associated health problems, while others have severe complications that can be life-threatening. ## Frequency Erdheim-Chester disease is a rare disorder; its exact prevalence is unknown. More than 500 affected individuals worldwide have been described in the medical literature. For unknown reasons, men are slightly more likely to develop the disease, accounting for about 60 percent of cases. ## Causes More than half of people with Erdheim-Chester disease have a specific mutation in the BRAF gene. Mutations in other genes are also thought to be involved in this disorder. The BRAF gene provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell's nucleus. This protein is part of a signaling pathway known as the RAS/MAPK pathway, which controls several important cell functions. Specifically, the RAS/MAPK pathway regulates the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis). The BRAF gene mutation that causes Erdheim-Chester disease is somatic, which means that it occurs during a person's lifetime and is present only in certain cells. The mutation occurs in histiocytes or in immature precursor cells that will develop into histiocytes. This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell growth and division. The unregulated overproduction of histiocytes results in their accumulation in the body's tissues and organs, leading to the signs and symptoms of Erdheim-Chester disease. ### Learn more about the gene associated with Erdheim-Chester disease * BRAF ## Inheritance Pattern This condition is not inherited. It arises from a somatic mutation in histiocytes or their precursor cells during an individual's lifetime. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Erdheim-Chester disease	c0878675	26,796	medlineplus	https://medlineplus.gov/genetics/condition/erdheim-chester-disease/	2021-01-27T08:25:46	{"gard": ["6369"], "mesh": ["D031249"], "synonyms": []}
A number sign (#) is used with this entry because nephronophthisis-12 (NPHP12) is caused by homozygous or compound heterozygous mutation in the TTC21B gene (612014) on chromosome 2q24. Heterozygous mutation in the TTC21B gene has been found in patients with Joubert syndrome-11 (JBTS11), a related cilopathy. For a general phenotypic description and a discussion of genetic heterogeneity of NPHP, see 256100. For a general phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300. Molecular Genetics In affected members of 2 unrelated consanguineous families with nephronophthisis-12, Davis et al. (2011) identified a homozygous mutation in the TTC21B gene (P209L; 612014.0001). One family was of Portuguese and the other of Egyptian descent. In vitro and in vivo functional expression studies in mammalian cells and zebrafish indicated that the mutant protein was a hypomorphic allele. In 2 additional families with early-onset NPHP with extrarenal manifestations, the P209L allele was found in compound heterozygosity with another pathogenic TTC21B allele: C552X (612014.0002) and a splice site mutation (612014.0003), respectively. Both of the latter mutations were shown by expression studies to be functionally null alleles. Haplotype analysis indicated a founder effect for the P209L allele. In addition, heterozygous functionally pathogenic alleles were found in about 5% of the total cohort, including 3 unrelated patients with Joubert syndrome-11 (JBTS11) suggesting that TTC21B might be a common contributor to the total mutational load in ciliopathies. No clinical details on the patients were provided. INHERITANCE \- Autosomal dominant \- Autosomal recessive MISCELLANEOUS \- Three patients classified as having Joubert syndrome had heterozygous mutations in TTC21B, no detailed clinical information was provided \- Four families classified as having nephronophthisis had either homozygous or compound heterozygous TTC21B mutations, no detailed clinical information was provided MOLECULAR BASIS \- Caused by mutation in the tetratricopeptide repeat domain 21B gene (TTC21B, 612014.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	NEPHRONOPHTHISIS 12	c0687120	26,797	omim	https://www.omim.org/entry/613820	2019-09-22T15:57:31	{"doid": ["0111119"], "omim": ["613820"], "orphanet": ["655"], "genereviews": ["NBK368475", "NBK1325"]}
Pain management in children Pain scale used in children SpecialtyPediatrics, anesthesia, palliative medicine Pain management in children is the assessment and treatment of pain in infants and children.[1] ## Contents * 1 Types * 1.1 Acute * 1.2 Neuropathic * 1.3 Cancer pain * 1.4 Chronic * 2 Diagnosis * 2.1 Younger infants * 2.2 Older infants * 2.3 Toddlers * 2.4 School-age children * 2.5 Adolescent * 2.6 Quantitative pain assessment * 2.7 Pain scales * 3 Causes * 3.1 During treatment * 3.2 After treatment * 4 Management * 4.1 Atraumatic measures * 4.2 Non-pharmacological * 4.3 Medication * 4.4 Chronic pain treatment * 4.5 Acute pain treatment * 4.5.1 Postoperative pain * 4.5.2 Dental pain * 4.6 Cancer pain * 4.6.1 Non-steroidal anti-inflammatory drugs (NSAIDs) * 4.6.2 Opioids * 5 Society and culture * 6 See also * 7 References * 8 Bibliography * 9 External links ## Types[edit] ### Acute[edit] Usually, acute pain has an obvious cause and is expected to last for a few days or weeks. It is usually managed with medication and non-pharmacological treatment to provide comfort.[2] Acute pain is an indication for needed assessment, treatment and prevention. While a child is experiencing pain, physiological consequences can jeopardize healing and recovery. Unrelieved pain can cause alkalosis and hypoxemia that result from rapid, shallow breathing. This shallow breathing can lead to the accumulation of fluid in the lungs, taking away the ability to cough. Pain can cause an increase in blood pressure and heart rate, putting stress on the heart. Pain also increases the release of anti-inflammatory steroids that reduce the ability to fight infection, increase the metabolic rate and affect healing. Another harmful outcome of acute pain is an increase in sympathetic effects such as the inability to urinate. Pain can also slow the gastrointestinal system. Inadequate pain management in children can lead to psycho-social consequences, including lack of interest in food, apathy, sleep problems, anxiety, avoidance of discussions about health, fear, hopelessness and powerlessness. Other consequences include extended hospital stays, high re-admission rates and longer recovery.[3] Examples of harmful consequences of unrelieved pain include:[4] * Infants who have had more than average heel pricks can have poor cognitive and motor function; * Associations of needles with distress may make later medical treatments more difficult; * Children who have experienced invasive procedures often develop post-traumatic stress; * Boys circumcised without anesthesia were found to have greater distress than uncircumcised boys;[5] * Severe pain as a child is associated with higher reports of pain in adults.[6] ### Neuropathic[edit] Neuropathic pain is associated with nerve injuries or abnormal sensitivities to touch or contact. Though neuropathic pain is relatively uncommon in children compared to adults, greater awareness of these conditions is on the rise.[7] Some causes may include past surgeries and amputations,[8] "autoimmune and degenerative neuropathies",[7] and injury to the spinal cord.[7] Symptoms may include a tingling, shooting, prickling or burning sensation. The pain can be intermittent or continual and is often exacerbates in the evenings.[8][9] Neuropathic pain can be peripheral or central. Peripheral neuropathic pain refers to disturbance in the function of peripheral nerves while central neuropathic pain refers to nerves in the central nervous system. Though not FDA-approved to address pain in children, anticonvulsants such as gabapentin and pregabalin have been used in severe neuropathic impairment (SNI).[9] Other options are serotonin-norepinephrine reuptake inhibitors (SNRIs). Despite limited studies in children (limited to those with depression), SNRIs such as Venlafaxine have been shown to be effective.[9] ### Cancer pain[edit] Cancer pain in children may be caused by the cancer itself or the side effects of treatment. Tumors can cause pain in two different ways, either by the physical pressure it places on organs or by occluding normal bodily functions. Treatment such as surgery and injections can also lead to significant pain for the patient.[10] If untreated, the pain can suppress the immune, interfere with sleep, and increase the chance of depression. Many different health care professionals will manage the child's pain and are referred to as the patient's palliative care team, these include oncologists, anesthesiologists, neurologists, surgeons, psychiatrists, and pharmacists. Hospitals may also hire individuals who specialize in music or art therapy, these therapies include acupuncture, biofeedback, massage therapy, and hypnosis.[11] Treatment of the cancer pain is tailored to the child based on age, treatment, and side effects. The goal is to achieve sufficient background control of pain and minimize any acute exacerbation of severe pain. Oftentimes medications such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or opiates are used to manage the pain. Additionally, non-pharmacological can also be used to manage the child's pain, this includes distracting the child, massages, acupuncture, heat/cold therapy, exercise, and quality sleep.[11][12] ### Chronic[edit] Chronic pain in children is unresolved pain that affects activities of daily living and may result in a significant amount of missed school days. Chronic pain is present for long periods of time and is characterized as mild to severe.[medical citation needed] Chronic pain has also been described as the pain experienced when the child reports a headache, abdominal pain, back pain, generalized pain or combination of these.[medical citation needed] Chronic pain can develop from disease or injury and can occur simultaneously with acute pain. Children who experience chronic pain can have psychological effects. Caring for a child in pain may cause distress to the caregiver, may cause costs due to healthcare or lost wages from time off work, and may stop caregivers from leaving the house. ## Diagnosis[edit] Further information: Pain assessment Example pain assessment chart Assessment of pain in children depends on the cooperation and developmental stage of the child. Some children cannot assist in their assessment because they have not matured enough cognitively, emotionally, or physically.[13] The following sections list signs of distress and possible pain in children by age group: ### Younger infants[edit] Further information: Infant crying * Inability to distinguish the stimulus from the pain * Ability to exhibit a reflexive response to pain * Expressions of pain * Tightly closed eyes[medical citation needed] * Open mouth resembling a square rather than an oval or circle * Eyebrows lowered and tightly drawn together * Rigid body * Thrashing * Loud crying[13] * Increase in heart rate, even while sleeping ### Older infants[edit] * Deliberate withdrawal from pain and possible guarding * Loud crying * Painful facial expressions[13] ### Toddlers[edit] Toddlers show signs of distress and possible pain by: * Expressing pain verbally * Thrashing extremities * Crying loudly * Screaming * Being uncooperative * Palpating (examining with the hands) a source of pain * Anticipating a pain-inducing procedure or event * Requesting to be comforted * Clinging to a significant person, possibly one perceived as protective[13] ### School-age children[edit] School-age children show signs of distress and possible pain by: * Anticipating the pain but less intensively, (understands concepts of time, i.e., imminent vs future pain) * Stalling, trying to talk out of the situation where pain is anticipated * Having muscular rigidity[13] ### Adolescent[edit] Adolescents show signs of distress and possible pain: * With muscle tension, but with control * With verbal expressions and descriptions[13] ### Quantitative pain assessment[edit] Although pain is subjective and can occur in a continuous spectrum of intensities, there are assessment tools that compare pain levels over time. This kind of assessment incorporates pain scales and requires a high enough developmental level for the child to respond to questions.[13] A verbal response is not always necessary to quantify pain. ### Pain scales[edit] A pain scale measures a patient's pain intensity and other features. Pain scales can be based on observational (behavioral) or physiological data, as well as self-report. Self-report is considered primary and should be obtained if possible. Pain measurements help determine the severity, type, and duration of pain. They are also used in diagnosis, to determine a treatment plan, and to evaluate the effectiveness of treatment. Pain scales are available for neonates, infants, children, adolescents, adults, seniors, and persons with impaired communication. Pain assessments are often regarded as "the 5th vital sign".[14] Examples of pain scales Self-report Observational Physiological Infant — Premature Infant Pain Profile; Neonatal/Infant Pain Scale — Child Wong-Baker Faces Pain Rating Scale – Revised;[15] Coloured Analogue Scale[16] FLACC (Face Legs Arms Cry Consolability Scale); CHEOPS (Children's Hospital of Eastern Ontario Pain Scale)[17] Comfort Adolescent Visual Analog Scale (VAS); Verbal Numerical Rating Scale (VNRS); Verbal Descriptor Scale (VDS); Brief Pain Inventory — — ## Causes[edit] The causes of pain in children are similar to the causes in adults. Pain can be experienced in many ways and depends on the following factors in each child: * Prior painful episodes or treatments * Age and developmental stage * Disease or type of trauma * Personality * Culture * Socioeconomic status * Presence of family members and family dynamics.[13] ### During treatment[edit] A physical therapist uses play as part of a child's treatment plan Clinicians responsible for a child monitor the child frequently in tertiary care centers (hospitals). Pharmacological and non-pharmacological treatments are used to manage the pain. Parents or caregivers are also requested to provide their own pain assessments. At the beginning of pharmacological treatment, clinicians monitor the child for adverse reactions to the medications. The levels of some medications are monitored to ensure that the child is not over-medicated and does not receive toxic levels of any drug. The levels also indicate whether there would be enough drug in the blood to be effective in managing the pain. Medications are metabolized differently between children of the same age. Factors that influence the levels of medications controlling pain include the height, weight, and body surface of the child, as well as any other illnesses.[13] Some medications may have a paradoxical effect in children, which is an effect that is the opposite of the expected effect. Clinicians monitor for this and any other reactions to medication.[18][19] ### After treatment[edit] Post-procedural treatment in children is primarily prescription opioids. Morphine is effective and relatively safe, and is often used with moderate to severe pain.[20] Codeine and tramadol should be avoided especially in children younger than 12 years old since metabolism varies due to genetic differences between individuals.[21] However, other interventions include medications classified as non-opioid analgesics, which are useful in post surgical treatment.[22] For example, acetaminophen or ibuprofen can be used as a non-opioid analgesics. Unlike acetaminophen, ibuprofen has anti-inflammatory property which can be useful for pain in inflammatory conditions. Aspirin is not used in pediatric population due to its association with Reye's syndrome. ## Management[edit] ### Atraumatic measures[edit] Because children process information differently from adults, treatment centers for children often use atraumatic measures to reduce anxiety and stress. Examples include: * Allowing the parent or caregiver to be present for painful procedures * Using a treatment room for painful procedures to ensure that the child's room is a place where little pain can be expected * Establishing other "pain-free zones" where no medical procedures are allowed, such as a playroom * Offering choices to the child to give them some control over the procedures * Modelling procedures with dolls and toys * Using age-appropriate anatomical terms and other vocabulary.[13] ### Non-pharmacological[edit] Depending on the source of pain, there are many non-pharmacological options to be considered. Also, depending on the age of the child, different approaches may be more suitable. Non-pharmacological methods to manage discomfort during immunizations include putting sugar on a pacifier, comforting the child during and after the injection, chest-to-chest hugging, and letting the child choose the injection site.[23] Other non-pharmacological treatments that have been found to be effective include: * Carefully explaining a procedure with pictures or other visual aids * Allowing the child to ask questions of medical staff * Touring the place where the procedures will occur * Allowing small children to play with dolls or other toys with a clinician to understand the procedure * Allowing older children to watch a video that explains the procedure * Providing distraction with songs, stories, toys, color, videos, TV, or music * Using relaxation techniques such as deep breathing or massage [24] Non-pharmacological treatment for pain associated with venipuncture in children includes hypnosis and distraction. These treatments reduced self-reported pain and when combined with cognitive-behavioural therapy (CBT) the reduction of pain was even greater. Other interventions have not been found to be effective and these are suggestion, blowing out air, and distraction with parent coaching did not differ from control for pain and distress.[25] Breastfeeding during painful procedures has been found to be more effective in controlling pain than placebo or positioning. Breastmilk or 'sugar' water has a similar effect, though studies in preterm infants have yet to be done.[26] Skin-to-skin care (kangaroo care) is thought be effective for pain control during painful procedures.[27] For children and adolescents who experience chronic pain- behavioral treatment, relaxation training, cognitive behavioral therapy (CBT) and acupuncture have been proven to be effective for some patients.[28] For recurrent abdominal pain a 2017 Cochrane review found some evidence that CBT and hypnotherapy were effective in reducing pain for the short term.[29] ### Medication[edit] Further information: Analgesic adjuvant Acute pain, chronic pain, neuropathic pain and recurrent pain in children is most often managed with medication. Most of these medications are analgesics. These include acetaminophen, NSAIDs, local anesthetics, opioids, and medications for neuropathic pain. The most effective approach to pain management in children is to provide pain control around the clock instead of providing pain relief as needed. Regional anesthesia is also effective and recommended whenever possible. It is important to use caution when administering opioids to neonates and young infants. There is a higher risk for apnea and hypoventilation in this population, due to their decreased breathing response.[1] ### Chronic pain treatment[edit] Chronic pain is treated with a variety of medications and non-pharmacological interventions. The World Health Organization recommends using a two step treatment approach based on the level of pain in children. The first step explains mild pain treatment, while the second step considers moderate to severe pain. Opioids, such as morphine, is an example of a drug of choice for moderate-severe pain in children with medical illnesses.[30] Some side effects of opioid use can include cognition deficits, dependence, altered mood, and disturbances of endocrine development. Non-pharmacological treatment for children to help relieve periodic pain includes counseling and behavior modification therapy.[medical citation needed]The American Association of Pediatrics states that psychological interventions, such as relaxation and cognitive strategies, have strong evidence for pain management.[31] ### Acute pain treatment[edit] The approach to acute pain should take into account the severity of the pain. Non-opioid analgesics, such as acetaminophen and NSAIDs, can be used alone to treat mild pain.[1] For moderate to severe pain, it is optimal to use a combination of multiple agents, including opioid and non-opioid agents.[1] #### Postoperative pain[edit] A panel, including the American Pain Society and American Society of Regional Anesthesia and Pain Medicine, recommends multimodal analgesia, which they define as a combination of pharmacological agents and non-pharmacological techniques to treat postoperative pain.[32] A significant benefit of this technique is that non-opioid analgesics used in combination with opioids can decrease the amount of opioids required and reduce the risk of opioid-related side effects.[1] Medications can be delivered as needed or around-the-clock depending on the patient's needs. For children, intravenous patient-controlled analgesia (IV-PCA) can be used when parenteral administration is preferred.[32] IV-PCA allows for consistent opioid levels, which can be a better alternative to scheduled intramuscular injections.[1] In addition, studies have shown that children as young as 6 years old can use the IV-PCA correctly.[32] #### Dental pain[edit] For projected moderate to severe pain, analgesics can be used on a regular schedule for the first 36 to 48 hours after a dental procedure.[33] NSAIDs are preferred over other analgesics to treat acute mild to moderate postoperative pain, due to the inflammatory component of dental pain.[33][34] Alternating between the NSAIDs and acetaminophen in combination is another option.[33] In addition, these two agents are considered equivalent or better than opioids for managing musculoskeletal pain, which includes dental pain.[34] ### Cancer pain[edit] Cancer pain is managed differently in children. Typically, medical history, physical examinations, age and overall health of the child are evaluated. The type of cancer may influence decisions about pain management. The extent of the cancer, and the tolerance of the child to specific medications, procedures or therapies are also taken into account, as well as the preferences of the parent or caregiver.[medical citation needed] Medications used to treat cancer pain include non-steroidal anti-inflammatory drugs (NSAIDs)[35] and opioids.[36] #### Non-steroidal anti-inflammatory drugs (NSAIDs)[edit] * Used as treatment for pain and anti-inflammatory * Can be administered as oral tablet or liquid * Recommended to use lowest dose and shortest duration possible to control pain * Not approved for infants < 3 months old * General adverse effects for NSAIDs: * Renal impairment * Hepatic impairment * Gastrointestinal issues (Nausea, diarrhea, constipation, flatulence) * Dyspepsia * Rash * Dizziness * Abdominal pain * Contraindicated for: * Hypersensitivity reactions * Cardiac impairment * Reye's syndrome * Coagulation defects * Ibuprofen 5–10 mg/kg every 6–8 hours (Max dose 1200 mg/day) #### Opioids[edit] * Doses based on child's body weight * Can be administered as oral, parenteral, buccal, transdermal, nasal or rectal formulations * Recommended to start at low dose and titrate up to effect * General adverse effects for opioids: * Constipation * Hives * Nausea * Vomiting * Pruritus * Respiratory depression The frequency of prescribing for these pain medications has more than doubled from 1990 to 2010 with 20-50% of adolescents who complain of headache, back pain, or joint pain receiving a prescribed opioid.[37][38] Before an adolescent or young adult is prescribed opioids, they should be screened for risk factors for opioid drug abuse. Prescription drug monitoring programs (PDMs) are now available in 37 states and 11 states have programs in development.[39] The use of opioids can result in a number of complications in children, including respiratory depression and risk for unintended overdose and opioid misuse later in life. These risks can be reduced by the use of NSAIDs (e.g. ibuprofen) and paracetamol. Using NSAIDs and paracetamol can be opioid-sparing, leading to less opioid use in situations such as peri-operative pain management.[40] The efficacy and safety of opioids in children have not been established.[41] A 2014 Cochrane Review for nalbuphine for postoperative pain treatment in children, reported insufficient evidence of the efficacy and adverse events of nalbuphine in this population; further research is needed in this area.[42] Other side effects of opioids are constipation, fatigue, and disorientation. Children can develop opioid tolerance, where larger doses are needed to have the same effect. Tolerance occurs earlier in children than in adults, especially with prolonged use.[43] When tolerance to opioids develop, it takes a larger dose of the opioid to achieve the same analgesic effect.[44] Non-pharmacological treatments have few side effects.[medical citation needed] ## Society and culture[edit] The indications that treatment is needed are not always clear for children because of poor assessments and the tendency to undertreat pain.. Misconceptions about pain in children Incorrect Valid References Infants cannot sense pain like adults Nerve pathways exist at birth, albeit immature Newborns experience physiological changes and surges in hormones that indicate stress [45] Infants cannot feel pain because their nerve fibers are not myelinated Complete myelination is not necessary for the transmission of pain impulses to the brain [45] Young children cannot indicate where pain originates Young children may have the cognitive ability to use a body chart and explain where their pain is coming from [45] A child able to sleep must not be in pain Sleep occurs because of exhaustion [46] ## See also[edit] Pain ## References[edit] 1. ^ a b c d e f Verghese ST, Hannallah RS (July 2010). "Acute pain management in children". Journal of Pain Research. 3: 105–23. doi:10.2147/jpr.s4554. PMC 3004641. PMID 21197314. 2. ^ Twycross, p. 140. sfn error: no target: CITEREFTwycross (help) 3. ^ Twycross, p. 3. sfn error: no target: CITEREFTwycross (help) 4. ^ Twycross, p. 1. sfn error: no target: CITEREFTwycross (help) 5. ^ twycross, p. 3. sfn error: no target: CITEREFtwycross (help) 6. ^ Twycross, p. 2. sfn error: no target: CITEREFTwycross (help) 7. ^ a b c Walco GA, Dworkin RH, Krane EJ, LeBel AA, Treede RD (March 2010). "Neuropathic pain in children: Special considerations". Mayo Clinic Proceedings. 85 (3 Suppl): S33–41. doi:10.4065/mcp.2009.0647. PMC 2844006. PMID 20194147. 8. ^ a b "Neuropathic pain". Retrieved 2018-11-02. 9. ^ a b c Hauer J, Houtrow AJ (June 2017). "Pain Assessment and Treatment in Children With Significant Impairment of the Central Nervous System". Pediatrics. 139 (6): e20171002. doi:10.1542/peds.2017-1002. PMID 28562301. 10. ^ "Pain in children - Canadian Cancer Society". www.cancer.ca. Retrieved 2018-11-19. 11. ^ a b "Children with Cancer: A Guide for Parents". National Cancer Institute. 2015-09-09. Retrieved 2018-11-19. 12. ^ Friedrichsdorf, Stefan J; Postier, Andrea (2014-03-07). "Management of breakthrough pain in children with cancer". Journal of Pain Research. 7: 117–123. doi:10.2147/JPR.S58862. ISSN 1178-7090. PMC 3953108. PMID 24639603. 13. ^ a b c d e f g h i j Henry, p. 43. sfn error: no target: CITEREFHenry (help) 14. ^ "Pain: current understanding of assessment, management and treatments" (PDF). Joint Commission on Accreditation of Healthcare Organizations andnthe National Pharmaceutical Council, Inc. December 2001. Retrieved 2018-01-25. [needs update] 15. ^ Drendel AL, Kelly BT, Ali S (August 2011). "Pain assessment for children: overcoming challenges and optimizing care". Pediatric Emergency Care. 27 (8): 773–81. doi:10.1097/PEC.0b013e31822877f7. PMID 21822093. S2CID 11017123. 16. ^ Stinson JN, Kavanagh T, Yamada J, Gill N, Stevens B (November 2006). "Systematic review of the psychometric properties, interpretability and feasibility of self-report pain intensity measures for use in clinical trials in children and adolescents". Pain. 125 (1–2): 143–57. doi:10.1016/j.pain.2006.05.006. PMID 16777328. S2CID 406102. 17. ^ von Baeyer CL, Spagrud LJ (January 2007). "Systematic review of observational (behavioral) measures of pain for children and adolescents aged 3 to 18 years". Pain. 127 (1–2): 140–50. doi:10.1016/j.pain.2006.08.014. PMID 16996689. S2CID 207307157. 18. ^ Moon YE (July 2013). "Paradoxical reaction to midazolam in children". Korean Journal of Anesthesiology. 65 (1): 2–3. doi:10.4097/kjae.2013.65.1.2. PMC 3726842. PMID 23904931. 19. ^ Mancuso CE, Tanzi MG, Gabay M (September 2004). "Paradoxical reactions to benzodiazepines: literature review and treatment options". Pharmacotherapy. 24 (9): 1177–85. doi:10.1592/phco.24.13.1177.38089. PMID 15460178. S2CID 38614605. [needs update] 20. ^ Friedrichsdorf SJ, Kang TI (October 2007). "The management of pain in children with life-limiting illnesses". Pediatric Clinics of North America. 54 (5): 645–72, x. doi:10.1016/j.pcl.2007.07.007. PMID 17933616. 21. ^ Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G (August 2009). "Codeine, ultrarapid-metabolism genotype, and postoperative death". The New England Journal of Medicine. 361 (8): 827–8. doi:10.1056/nejmc0904266. PMID 19692698. 22. ^ White PF (November 2005). "The changing role of non-opioid analgesic techniques in the management of postoperative pain". Anesthesia and Analgesia. 101 (5 Suppl): S5–22. doi:10.1213/01.ANE.0000177099.28914.A7. PMID 16334489. S2CID 24348334. [needs update] 23. ^ "Managing Your Child's Pain While Getting a Shot". HealthyChildren.org. Retrieved 20 August 2017. 24. ^ Chambers, Christine (2009). "Psychological interventions for reducing pain and distress during routine childhood immunizations: A systematic review". Clinical Therapeutics. 31: S77–S103. doi:10.1016/j.clinthera.2009.07.023. PMID 19781437. 25. ^ Robertson J (July 2007). "Review: distraction, hypnosis, and combined cognitive-behavioural interventions reduce needle related pain and distress in children and adolescents". Evidence-Based Nursing. 10 (3): 75. doi:10.1136/ebn.10.3.75. PMID 17596380. S2CID 34364928. 26. ^ Shah PS, Herbozo C, Aliwalas LL, Shah VS (December 2012). "Breastfeeding or breast milk for procedural pain in neonates". The Cochrane Database of Systematic Reviews. 12: CD004950. doi:10.1002/14651858.CD004950.pub3. PMID 23235618. S2CID 32696139. 27. ^ Johnston C, Campbell-Yeo M, Disher T, Benoit B, Fernandes A, Streiner D, Inglis D, Zee R (February 2017). "Skin-to-skin care for procedural pain in neonates". The Cochrane Database of Systematic Reviews. 2: CD008435. doi:10.1002/14651858.CD008435.pub3. PMC 6464258. PMID 28205208. 28. ^ Mu, Pei-Fan (2009). "The effectiveness of non-pharmacological pain management in relieving chronic pain for children and adolescents". JBI Library of Systematic Reviews. 7 (34): 1489–1543. doi:10.11124/jbisrir-2009-215. PMID 27820170. 29. ^ Abbott, Rebecca A.; Martin, Alice E.; Newlove-Delgado, Tamsin V.; Bethel, Alison; Thompson-Coon, Joanna; Whear, Rebecca; Logan, Stuart (10 January 2017). "Psychosocial interventions for recurrent abdominal pain in childhood". The Cochrane Database of Systematic Reviews. 1: CD010971. doi:10.1002/14651858.CD010971.pub2. ISSN 1469-493X. PMC 6464036. PMID 28072460. 30. ^ World Health Organization. (2012). Pharmacological treatment of persistent pain in children with medical illnesses. Retrieved from http://apps.who.int/iris/bitstream/handle/10665/44540/9789241548120_Guidelines.pdf?sequence=1 31. ^ American Pain Society. (2012). Assessment and Management of Children with Chronic Pain [Position statement]. Retrieved from http://americanpainsociety.org/uploads/get-involved/pediatric-chronic-pain-statement.pdf 32. ^ a b c Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, Carter T, Cassidy CL, Chittenden EH, Degenhardt E, Griffith S, Manworren R, McCarberg B, Montgomery R, Murphy J, Perkal MF, Suresh S, Sluka K, Strassels S, Thirlby R, Viscusi E, Walco GA, Warner L, Weisman SJ, Wu CL (February 2016). "Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council". The Journal of Pain. 17 (2): 131–57. doi:10.1016/j.jpain.2015.12.008. PMID 26827847. 33. ^ a b c "Policy on Acute Pediatric Dental Pain Management". American Academy of Pediatric Dentistry. 2017. Retrieved 29 October 2018. 34. ^ a b Becker DE (2010). "Pain management: Part 1: Managing acute and postoperative dental pain". Anesthesia Progress. 57 (2): 67–78, quiz 79–80. doi:10.2344/0003-3006-57.2.67. PMC 2886920. PMID 20553137. 35. ^ Cooper, Tess E; Heathcote, Lauren C; Anderson, Brian; Grégoire, Marie-Claude; Ljungman, Gustaf; Eccleston, Christopher (2017-07-24). "Non-steroidal anti-inflammatory drugs (NSAIDs) for cancer-related pain in children and adolescents". Cochrane Database of Systematic Reviews. 7: CD012563. doi:10.1002/14651858.CD012563.pub2. ISSN 1465-1858. PMC 6484396. PMID 28737843. 36. ^ Wiffen, Philip J; Cooper, Tess E; Anderson, Anna-Karenia; Gray, Andrew L; Grégoire, Marie-Claude; Ljungman, Gustaf; Zernikow, Boris (2017-07-19). "Opioids for cancer-related pain in children and adolescents". Cochrane Database of Systematic Reviews. 7: CD012564. doi:10.1002/14651858.cd012564.pub2. ISSN 1465-1858. PMC 6484393. PMID 28722116. 37. ^ DeVries A, Koch T, Wall E, Getchius T, Chi W, Rosenberg A (July 2014). "Opioid use among adolescent patients treated for headache". The Journal of Adolescent Health. 55 (1): 128–33. doi:10.1016/j.jadohealth.2013.12.014. PMID 24581795. 38. ^ Mazer-Amirshahi M, Mullins PM, Rasooly IR, van den Anker J, Pines JM (April 2014). "Trends in prescription opioid use in pediatric emergency department patients". Pediatric Emergency Care. 30 (4): 230–5. doi:10.1097/pec.0000000000000102. PMID 24651218. S2CID 35304503. 39. ^ Peck KR, Ehrentraut JH, Anghelescu DL (2016-05-01). "Risk factors for opioid misuse in adolescents and young adults with focus on oncology setting". Journal of Opioid Management. 12 (3): 205–16. doi:10.5055/jom.2016.0333. PMID 27435441. 40. ^ Wong I, St John-Green C, Walker SM (June 2013). "Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children". Paediatric Anaesthesia. 23 (6): 475–95. doi:10.1111/pan.12163. PMC 4272569. PMID 23570544. 41. ^ Cooper, Tess E.; Fisher, Emma; Gray, Andrew L.; Krane, Elliot; Sethna, Navil; van Tilburg, Miranda Al; Zernikow, Boris; Wiffen, Philip J. (Jul 2017). "Opioids for chronic non-cancer pain in children and adolescents". The Cochrane Database of Systematic Reviews. 7: CD012538. doi:10.1002/14651858.CD012538.pub2. ISSN 1469-493X. PMC 6477875. PMID 28745394. 42. ^ Schnabel, Alexander; Reichl, Sylvia U.; Zahn, Peter K.; Pogatzki-Zahn, Esther (2014-07-31). "Nalbuphine for postoperative pain treatment in children". The Cochrane Database of Systematic Reviews (7): CD009583. doi:10.1002/14651858.CD009583.pub2. ISSN 1469-493X. PMID 25079857. 43. ^ Anand KJ, Willson DF, Berger J, Harrison R, Meert KL, Zimmerman J, Carcillo J, Newth CJ, Prodhan P, Dean JM, Nicholson C (May 2010). "Tolerance and withdrawal from prolonged opioid use in critically ill children". Pediatrics. 125 (5): e1208–25. doi:10.1542/peds.2009-0489. PMC 3275643. PMID 20403936. 44. ^ Cahill, Catherine M.; Walwyn, Wendy; Taylor, Anna M.W.; Pradhan, Amynah A.A.; Evans, Christopher J. (Nov 2016). "Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation". Trends in Pharmacological Sciences. 37 (11): 963–976. doi:10.1016/j.tips.2016.08.002. ISSN 0165-6147. PMC 5240843. PMID 27670390. 45. ^ a b c Twycross, p. 7. sfn error: no target: CITEREFTwycross (help) 46. ^ Twycross & page 7. sfn error: no target: CITEREFTwycrosspage_7 (help) ## Bibliography[edit] * Henry N (2016). RN nursing care of children : review module. Stilwell, KS: Assessment Technologies Institute. ISBN 9781565335714. * Roberts M (2017). Handbook of pediatric psychology. New York: The Guilford Press. ISBN 9781462529780. * Twycross A (2014). Managing pain in children : a clinical guide for nurses and healthcare professionals. Hoboken: Wiley Blackwell. ISBN 9780470670545. ## External links[edit] Classification D * ICD-10: R52 * ICD-9-CM: 338 * MeSH: D010146 * DiseasesDB: 9503 External resources * MedlinePlus: 002164 * Wong-Baker Faces Foundation * International Children's Palliative Care Network * Palliative Care * WHO guidelines on persisting pain in children [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Pain management in children	None	26,798	wikipedia	https://en.wikipedia.org/wiki/Pain_management_in_children	2021-01-18T18:54:39	{"wikidata": ["Q37062409"]}
A number sign (#) is used with this entry because of evidence that 46,XX sex reversal is caused by heterozygous mutation in the NR5A1 gene (184757) on chromosome 9q33. Clinical Features Bashamboo et al. (2016) reported 4 unrelated families with 46,XX sex reversal. The first family, of European-American ancestry, had two 46,XX children with ovotestes. The first child presented with ambiguous genitalia at birth. Gonads were palpable in the right inguinal region and in the left labioscrotal fold. The karyotype was SRY-negative. Vaginoscopy revealed a rudimentary vagina and uterine cervix. Gonadal histology showed a left dysgenetic testis and a right ovotestis. The second child had ambiguous genitalia, abdominal gonads that were both ovotestes, and a uterus. The mother had no known androgenization but had menopause at age 40. The second family, of Latino-Hispanic origin, had a boy referred at 7 months of age for small penis with palpable gonads; by 9 months, the gonads were no longer palpable. Karyotype was 46,XX, SRY-negative. By ultrasound, 2 structures were identified in the inguinal region that had the morphology and Doppler appearance of testes. AMH (600957) and inhibin B (see 147290) levels were in the normal range. There was a good testosterone response to 3-day hCG (see 118860) stimulation. Family 3, of African and African-American ancestry, had a son presenting with small testes and low testosterone at age 16. At age 30, he was found to have bilateral atrophic testes and a small penis. Karyotype was 46,XX, SRY-negative. Endocrine evaluation showed primary testicular failure, but normal adrenal function. Semen analysis showed azoospermia. Family 4, of South Asian ancestry, had a girl who presented with labial fusion and mild clitoral enlargement at age 6 years. Karyotype was 46,XY, SRY-positive. Palpable inguinal gonads were dysgenetic testes. There was no uterus. A younger brother was born with severe penoscrotal hypospadias but palpable gonads in the scrotum. Biopsy of the right testis showed dysgenetic testicular tissue. The karyotype was 46,XX, SRY-negative. The mother had no reported androgenization but had very irregular periods all her life. Baetens et al. (2017) reported 3 unrelated Northern European children with 46,XX sex reversal. The first case was the second child of healthy, nonconsanguineous parents. Mild hypertrophy of the clitoris was noted at birth, and vaginoscopy showed a cervix and right hemiuterus, a left epididymis, and male vasculature. Biopsy of the left gonad revealed testicular differentiation with germ cells present; the right gonad contained only fibrotic tissue. An hCG stimulation test showed elevated testosterone and AMH level between the male and female reference levels. A chromosome microarray showed a normal female pattern, and FISH for SRY was negative. The second case was a 22-year-old woman who presented with ambiguous genitalia at birth and a short, blind-ending vagina. At age 4, she underwent clitoroplasty and bilateral gonadectomy of abdominal ovotestes. FISH for SRY was negative. Chromosome microarray showed a female pattern and a small benign chromosome 8 duplication. The third case was a 23-year-old man with 46,XX testicular DSD. Micropenis, hypospadias, and bilateral scrotal but atrophic testes were noted at birth. Gonadal biopsies at age 2 years showed bilateral testicular differentiation without germ cells. Hypergonadotrophic hypogonadism developed, requiring testosterone supplementation at age 13. FISH for SRY was negative and array CGH was normal. Two younger brothers were unaffected. Igarashi et al. (2017) reported 2 unrelated Japanese patients with 46,XX sex reversal. The first patient presented with ambiguous genitalia and was found to have no uterus or vagina. Abdominal gonads were testis-like on the right and ovotesticular on the left. The ovotestis was both SOX9 (608160)- and FOXL2 (605597)-positive. The second patient was raised as male and presented with hypospadias and bifid scrotum. Gonads were palpable, and biopsy revealed testicular tissue and spermatic cord. There was no uterus or vagina. Gonadotropin and testosterone levels were almost comparable to those of unaffected boys. At 14 years and 10 months, the patient had descended testes of 2 ml in volume and Tanner stage 2-3 pubic hair. Swartz et al. (2017) reported a 3-year-old 46,XX child of European ancestry with clitoromegaly, rugated labia, no palpable gonads, and a small uterus. Abdominal gonads were ovotestes with dysgenetic testicular tissue lacking germ cells. Pathogenesis Baetens et al. (2017) hypothesized that in the female embryo, the arg92-to-trp mutation in NR5A1 (see MOLECULAR GENETICS) downregulates the pro-ovarian WNT4 (603490)/beta-catenin (116806) pathway, resulting in loss of stable SOX9 repression and tipping the balance toward male development. Molecular Genetics Using whole-exome, whole-genome, or direct sequencing, Bashamboo et al. (2016) showed that a specific recurrent heterozygous missense mutation, arg92 to trp (R92W; 184757.0019) in the accessory DNA-binding region of NR5A1 is associated with a variable degree of testis development in 46,XX children and adults from 4 unrelated families. Remarkably, in 1 family a sib of the proband, raised as a girl and carrying the R92W mutation, was found to have a 46,XY karyotype and partial testicular dysgenesis. Bashamboo et al. (2016) concluded that these findings highlighted how a specific variant in a developmental transcription factor can switch organ fate from the ovary to testis in mammals and represented the first missense mutation causing isolated, nonsyndromic 46,XX testicular/ovotesticular DSD in humans. Baetens et al. (2017) screened a cohort of 11 unrelated cases and 2 sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD) using whole-exome sequencing in 9 patients, targeted resequencing in 4, and haplotyping. Immunohistochemistry of sex-specific markers was performed on patients' gonads. The consequences of mutation were investigated using luciferase assays, localization studies, and RNA-seq. Baetens et al. (2017) identified a heterozygous NR5A1 mutation, c.274C-T (R92W; 184757.0019), in 3 unrelated patients. The arg92 residue is highly conserved and located in the Ftz-F1 region, which is thought to be involved in DNA-binding specificity and stability. There were no consistent changes in transcriptional activation or subcellular localization. Transcriptomics in patient-derived lymphocytes showed upregulation of MAMLD1 (300120), a direct NR5A1 target previously associated with 46,XY DSD. In gonads of affected individuals, ovarian FOXL2 (605597) and testicular SRY-independent SOX9 (608160) expression was observed. Baetens et al. (2017) proposed NR5A1, previously associated with 46,XY DSD and 46,XX primary ovarian insufficiency, as a novel gene for 46,XX (ovo)testicular DSD and hypothesized that the R92W mutation results in decreased inhibition of the male developmental pathway through downregulation of female antitestis genes, thereby tipping the balance toward testicular differentiation in 46,XX individuals. Baetens et al. (2017) concluded that their study supported a role for NR5A1 in testis differentiation in the XX gonad. In the first family reported by Baetens et al. (2017), the proband's healthy sister, father, paternal uncle and grandfather all carried the R92W mutation in NR5A1. A younger sister of the second proband carried the same mutation and displayed normal puberty. In the third family, the proband's 2 younger brothers and mother, all unaffected, carried the R92W mutation. All affected mutation carriers shared a common haplotype spanning a 1.5-Mb region. No other known variants associated with 46,XX sex reversal were identified in any of the probands. Igarashi et al. (2017) detected the R92W mutation in the NR5A1 gene in 2 unrelated Japanese patients with 46,XX sex reversal. The mutation was absent from the clinically normal mothers and from 200 unaffected Japanese individuals. In a 46,XX patient with bilateral ovotestes, Swartz et al. (2017) identified a heterozygous arg92-to-gln (R92Q; 184757.0003) mutation, inherited from the unaffected father. This mutation had previously been reported in a patient with 46,XY DSD (SRXY3; 612965) and in a 46,XX infant with normal female phenotype and adrenal insufficiency (see 612964). INHERITANCE \- Autosomal dominant GENITOURINARY External Genitalia (Male) \- Small penis (46XX) \- Retractile testes (46XX) \- Atrophic testes (46XX) External Genitalia (Female) \- Ambiguous genitalia (46XX) \- Clitoromegaly (46XX) \- Rugated labia majora (46XX) \- Labial fusion (46XY) Internal Genitalia (Male) \- Dysgenetic testes (46XY, 46XX) \- Penoscrotal hypospadias (46XX) Internal Genitalia (Female) \- Ovotestes (46XX) \- Short, blind-ending vagina (46XX) ENDOCRINE FEATURES \- Low testosterone \- Normal baseline and stimulated adrenal hormones and precursors MISCELLANEOUS \- Incomplete penetrance \- Variable features may be present MOLECULAR BASIS \- Caused by mutation in the nuclear receptor subfamily 5, group A, member 1 gene (NR5A1, 184757.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	46,XX SEX REVERSAL 4	c4479552	26,799	omim	https://www.omim.org/entry/617480	2019-09-22T15:45:45	{"omim": ["617480"], "synonyms": ["Alternative titles", "46,XX SEX REVERSAL, SRY-NEGATIVE"]}

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