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Floating-Harbor syndrome (FHS) is named after the two hospitals that reported the first cases in the 1970s: Boston Floating Hospital and Harbor General Hospital in California. Signs and symptoms of FHS include short stature, skeletal abnormalities, delayed bone age, kidney problems, minor problems with hearing and vision, characteristic facial features, speech and language problems, and mild to moderate intellectual disabilities. Behavioral difficulties that are present in many children tend to improve with age. FHS is caused by a change (mutation) in the SRCAP gene and inheritance is autosomal dominant. The mutation can be inherited from a parent or can occur for the first time in a person with the syndrome. Communication issues and developmental disabilities may be helped with early intervention programs and special education. [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	Floating-Harbor syndrome	c0729582	27,200	gard	https://rarediseases.info.nih.gov/diseases/6455/floating-harbor-syndrome	2021-01-18T18:00:27	{"mesh": ["C537062"], "omim": ["136140"], "orphanet": ["2044"], "synonyms": ["Short stature with delayed bone age, expressive language delay, a triangular face with a prominent nose and deep-set eyes", "Pelletier-Leisti syndrome", "FHS"]}
## Description Stuttering is a disorder of the flow of speech characterized by involuntary repetitions or prolongations of sounds or syllables, and by interruptions of speech known as blocks (summary by Raza et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of stuttering, see STUT1 (184450). Clinical Features Raza et al. (2010) reported a consanguineous Pakistani family in which 5 individuals above 8 years of age had persistent stuttering for more than 6 months. Inheritance The transmission pattern of persistent stuttering in the family reported by Raza et al. (2010) was consistent with autosomal recessive inheritance. Mapping By genomewide linkage analysis followed by fine mapping in a consanguineous Pakistani family with stuttering, Raza et al. (2010) found linkage to a region on chromosome 3q13.2-q13.33 (maximum 2-point lod score of 4.23 at marker D3S1310). One individual with the associated diplotype did not stutter, suggesting incomplete penetrance. Sequencing of the coding exons of the DRD3 gene (126451) did not identify any genetic variations. [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	STUTTERING, FAMILIAL PERSISTENT, 3	c3553381	27,201	omim	https://www.omim.org/entry/614655	2019-09-22T15:54:36	{"omim": ["614655"]}
Richieri Costa-Pereira syndrome is characterized by short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies (including hypoplastic thumbs), and clubfoot. It has been described in 14 Brazilian families and in one unrelated French patient. Prominent low set ears and a highly arched palate were also observed. Transmission is autosomal 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	Richieri Costa-Pereira syndrome	c1849348	27,202	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3102	2021-01-23T17:10:40	{"gard": ["4718"], "mesh": ["C535677"], "omim": ["268305"], "umls": ["C1849348"], "icd-10": ["Q87.8"], "synonyms": ["Short stature-Pierre Robin sequence-cleft mandible-hand anomalies clubfoot syndrome", "Short stature-Pierre Robin syndrome-cleft mandible-hand anomalies clubfoot syndrome"]}
Medical sign Malar flush Differential diagnosismitral stenosis, SLE Malar flush is a plum-red discolouration of the high cheeks. It is classically associated with mitral valve stenosis due to the resulting CO2 retention and its vasodilatory effects. It can also be associated with lupus and polycythemia vera. ## Contents * 1 Definition * 2 Pathophysiology * 3 See also * 4 References ## Definition[edit] Malar flush is a plum-red discolouration of the high cheeks.[1] ## Pathophysiology[edit] Mitral valve stenosis may cause malar flush due to CO2 retention, which causes vasodilation of arterioles in the cheeks.[1] It can also be associated with other conditions, such as lupus,[2] and polycythemia vera.[3] ## See also[edit] * Malar rash ## References[edit] 1. ^ a b Topol, Eric J; Califf, Robert M (2007). Textbook of cardiovascular medicine (3rd ed.). Philadelphia: Lippincott Williams & Wilkins. p. 194. ISBN 9780781770125. Retrieved 13 January 2017. 2. ^ Dreizen, S. (January 1991). "The butterfly rash and the malar flush. What diseases do these signs reflect?". Postgraduate Medicine. 89 (1): 225–228, 233–234. doi:10.1080/00325481.1991.11700800. ISSN 0032-5481. PMID 1824645. 3. ^ Clarke, R. "Mitral Facies" (PDF). Ask Doctor Clarke. Retrieved 13 January 2017. 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	Malar flush	c3550384	27,203	wikipedia	https://en.wikipedia.org/wiki/Malar_flush	2021-01-18T18:37:32	{"umls": ["C3550384"], "wikidata": ["Q16878290"]}
Childhood brain stem glioma is a rare condition in which abnormal cells develop in the tissues of the brain stem (the part of the brain connected to the spinal cord). The condition can be benign (noncancerous) or malignant (cancerous). The severity of the condition and the associated signs and symptoms vary based on the size and location of the tumor and how quickly the tumor is growing. Common features include difficulty walking; loss of the ability to move one side of the body or face; vision or hearing problems; headaches (particularly in the morning); nausea and vomiting; unusual sleepiness; and behavioral changes. In most cases, the underlying cause of childhood brain stem glioma is unknown. Certain genetic conditions, such as neurofibromatosis type I, are associated with an increased risk of childhood brainstem glioma. Treatment varies but may include surgery, radiation therapy, chemotherapy, cerebrospinal fluid diversion, observation, and targeted therapy. [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	Childhood brain stem glioma	c0278600	27,204	gard	https://rarediseases.info.nih.gov/diseases/9306/childhood-brain-stem-glioma	2021-01-18T18:01:29	{"umls": ["C0278600"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that chilblain lupus-2 (CHBL2) is caused by heterozygous mutation in the SAMHD1 gene (606754) on chromosome 20q11. One such family has been reported. Description Chilblain lupus is a rare cutaneous form of systemic lupus erythematosus (SLE; 152700) characterized by tender, bluish-red swellings and nodules on the hands, feet, ears, and nose, with histologic changes of lupus. The phenotype is induced by cold, such that patients frequently report a worsening of lesions in the winter months (summary by Ravenscroft et al., 2011). For a general description and a discussion of genetic heterogeneity of chilblain lupus, see CHBL1 (610448). Clinical Features Ravenscroft et al. (2011) reported a mother and son with chilblain lupus. From the age of 4 years, the 46-year-old white mother experienced recurrent lesions, particularly prominent over the winter months, affecting her hands, feet, buttocks, and thighs. She also had sun sensitivity with a tendency to develop a sunburn-like reaction with minimal sun exposure. She developed angiomatous lesions on the fingers, which became persistent. Biopsy of chilblain skin demonstrated a florid lymphocytic vasculitis, with papillary dermal edema, interface dermatitis, and keratinocyte necrosis, consistent with lupus. She was managed with nifedipine over the winter months and hydroxychloroquine plus sun block in the summer. At age 3 months, her 15-year-old son developed chilblains on the feet, fingers, and ears. Later, he also experienced photosensitivity with a sunburn-like reaction to sunlight, and developed fixed angiomatous lesions on the fingers. Both patients were in otherwise good health. Inheritance The transmission pattern of chilblain lupus in the family reported by Ravenscroft et al. (2011) was consistent with autosomal dominant inheritance. Molecular Genetics In a mother and son with chilblain lupus, Ravenscroft et al. (2011) identified a heterozygous mutation in the SAMHD1 gene (I201N; 606754.0011). INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Painful bluish-red papules or nodules (fingers, toes, nose, cheek, ears) \- Cutaneous photosensitivity \- Angiomatous lesions on the fingers, persistent Skin Histology \- Lymphocytic vasculitis \- Papillary dermal edema \- Interface dermatitis \- Keratinocyte necrosis MISCELLANEOUS \- Onset in early childhood \- Phenotype is worsened by cold temperature \- One family has been reported (as of January 2012) MOLECULAR BASIS \- Caused by mutation in the SAM domain- and HD domain-containing protein 1 gene (SAMHD1, 606754.0011 ) ▲ 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	CHILBLAIN LUPUS 2	c3280721	27,205	omim	https://www.omim.org/entry/614415	2019-09-22T15:55:21	{"doid": ["0060386"], "omim": ["614415"], "orphanet": ["481662"], "synonyms": []}
Paroxysmal cold hemoglobinuria (PCH) is a very rare subtype of autoimmune hemolytic anemia (AIHA, see this term), caused by the presence of cold-reacting autoantibodies in the blood and characterized by the sudden presence of hemoglobinuria, typically after exposure to cold temperatures. ## Epidemiology PCH is thought to account for at most 2-10% of cases of AIHA, whose annual incidence is estimated to be between 1/35,000-1/80,000 in North America and Western Europe. ## Clinical description Acute cases almost exclusively affect children and are often preceded by symptoms of infection. Chronic idiopathic cases also occur but are extremely rare. Acute cases of the disease are characterized by an abrupt onset with features of severe intravascular hemolysis including high fever, chills, back and/or leg pain. Other symptoms may include nausea, headache, vomiting and diarrhea. Typically hemoglobinuria occurs, producing dark red to black urine. Hemolysis can be severe and even life-threatening and results from exposure to cold, which may even be localized (eg from drinking cold water, from washing hands in cold water). Chronic forms of PCH are characterized by recurrent episodes of hemolysis precipitated by cold exposure. ## Etiology PCH is most often acute and occurs secondary to an infection, mainly upper respiratory, and the causative agent is often not identified. Late-stage or congenital syphilis was historically linked to cases of PCH in adulthood but this is becoming less and less common. ## Diagnostic methods Diagnosis is based on evidence of anemia linked to hemolysis, the presence of hemoglobin in urine, a positive result from the Donath-Landsteiner (DL) test and evidence of anti-P specificity of the IgG autoantibodies. ## Differential diagnosis The main differential diagnosis is acute cold AIHA (see this term) induced by an infection (for example Mycoplasma pneumoniae or the Epstein Barr virus) due to the presence of IgM autoantibodies which are cold agglutinins. ## Management and treatment Most cases of PCH are self-limited so treatment is usually symptomatic, including keeping the patient warm and red blood cell transfusion if necessary. Patients with few clinical symptoms and slight anemia may not require drug therapy. Corticosteroids and splenectomy are usually ineffective and should not be considered. In cases of life-threatening PCH, plasmapheresis can temporarily dampen the hemolysis. Some patients may respond to rituximab, although responses are usually short-lived. If syphilis is present, treatment with antibiotics generally eliminates the concurrent hemolysis. [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	Paroxysmal cold hemoglobinuria	c0272129	27,206	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90035	2021-01-23T17:58:21	{"gard": ["7335"], "mesh": ["C538618"], "umls": ["C0086774", "C0272129"], "icd-10": ["D59.6"], "synonyms": ["Donath-Landsteiner hemolytic anemia", "Donath-Landsteiner syndrome", "PCH"]}
Combined vitamin K-dependent clotting factors deficiency (VKCFD) is a congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X, as well as natural anticoagulants protein C, protein S and protein Z. ## Epidemiology Prevalence is unknown but less than 30 affected families have been reported in the literature so far. ## Clinical description The spectrum of bleeding symptoms ranges from mild to severe with onset in the neonatal period in severe cases. The bleeding symptoms are often life-threatening, occur both spontaneously and in a surgical setting and usually involve the skin and mucosae. A range of nonhemostatic symptoms are often present, including developmental and skeletal anomalies (stippling of the long bones, shortness of the distal phalanges of the fingers, osteoporosis) and pseudoxanthoma elasticum-like syndrome (see this term). ## Etiology VKCFD is an autosomal recessive disorder caused by mutations in the genes encoding either gamma-glutamyl carboxylase (GGCX; 2p12) or the vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1; 16p11.2). These two proteins are necessary for gamma-carboxylation, a postsynthetic modification that allows coagulation proteins to display their proper function. The developmental and skeletal anomalies seen in VKCFD are the result of defective gamma-carboxylation of a number of nonhemostatic proteins. ## Diagnostic methods Diagnosis of VKCFD should only be considered after exclusion of acquired forms of the disease, associated with intestinal malabsorption of vitamin K in patients with inflammatory bowel diseases or celiac disease (see these terms), liver cirrhosis or accidental ingestion of warfarins and superwarfarins. After exclusion of other causes, diagnosis of VKCFD is suspected in the context of an excessive bleeding pattern compared to the extent of the decrease in individual clotting factors, and is confirmed by molecular analysis. ## Differential diagnosis Other congenital clotting defects such as isolated factor II, VII, IX (hemophilia B) and X deficiencies, combined factor VII and X deficiency (see these terms) and acquired bleeding anomalies due to the presence of autoantibodies (acquired hemophilia [see this term] and factor VII deficiency due to the presence of autoantibodies against factor VII) must also be considered as differential diagnoses. ## Antenatal diagnosis Prenatal genetic testing is not generally recommended. ## Genetic counseling Genetic counseling may be offered to affected families. ## Management and treatment Administration of vitamin K during the third trimester of pregnancy may be useful in women suspected of carrying a child with VKCFD. Vitamin K administration (oral or intravenously) is the mainstay of therapy in symptomatic VKCFD. Plasma supplementation and prothrombin complex concentrates are needed during surgery or severe bleeding episodes. In addition, combination therapy with both recombinant activated FVII (eptacog alfa) and vitamin K supplementation may constitute an alternative treatment option for surgical procedures and severe manifestations. ## Prognosis The overall prognosis is good and, with the availability of several effective therapeutic options, VKCFD has only a small impact on the quality of life of affected patients. [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	Hereditary combined deficiency of vitamin K-dependent clotting factors	c1848534	27,207	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98434	2021-01-23T18:02:37	{"mesh": ["C564741"], "omim": ["277450", "607473"], "umls": ["C1848534"], "icd-10": ["D68.2"], "synonyms": ["Hereditary combined deficiency of factors II, VII, IX and X"]}
Chromosome 11q deletion is a chromosome abnormality that occurs when there is a missing (deleted) copy of genetic material on the long arm (q) of chromosome 11. 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 11q 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 11q deletions. You can contact GARD if you have questions about a specific deletion on chromosome 11. 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 11q deletion	c2931804	27,208	gard	https://rarediseases.info.nih.gov/diseases/1735/chromosome-11q-deletion	2021-01-18T18:01:26	{"mesh": ["C538296"], "umls": ["C2931804"], "synonyms": ["Deletion 11q", "Monosomy 11q", "11q deletion", "11q monosomy", "Partial monosomy 11q"]}
## Summary ### Clinical characteristics. Systemic primary carnitine deficiency (CDSP) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. It encompasses a broad clinical spectrum including the following: * Metabolic decompensation in infancy typically presenting between age three months and two years with episodes of hypoketotic hypoglycemia, poor feeding, irritability, lethargy, hepatomegaly, elevated liver transaminases, and hyperammonemia triggered by fasting or common illnesses such as upper respiratory tract infection or gastroenteritis * Childhood myopathy involving heart and skeletal muscle with onset between age two and four years * Pregnancy-related decreased stamina or exacerbation of cardiac arrhythmia * Fatigability in adulthood * Absence of symptoms The latter two categories often include mothers diagnosed with CDSP after newborn screening has identified low carnitine levels in their infants. ### Diagnosis/testing. Plasma carnitine levels are extremely reduced in CDSP. The diagnosis is established by identification of biallelic pathogenic variants in SLC22A5 or demonstration of reduced fibroblast carnitine transport. ### Management. Treatment of manifestations: Metabolic decompensation and skeletal and cardiac muscle function improve with 100-400 mg/kg/day oral levocarnitine (L-carnitine) if it is started before irreversible organ damage occurs. Hypoglycemic episodes are treated with intravenous dextrose infusion; cardiomyopathy requires management by specialists in cardiology. Prevention of primary manifestations: Maintain appropriate plasma carnitine concentrations with oral L-carnitine supplementation; prevent hypoglycemia with frequent feeding and avoiding fasting. Hospitalization for intravenous glucose administration for individuals who are required to fast for a procedure or who cannot tolerate oral intake due to illness such as gastroenteritis. Prevention of secondary complications: Oral metronidazole and/or decreasing the carnitine dose usually results in the resolution of the fishy odor due to L-carnitine supplementation. Surveillance: Echocardiogram and electrocardiogram: annually during childhood and less frequently in adulthood; monitor plasma carnitine concentration frequently until levels reach the normal range, then, measure three times a year during infancy and early childhood, twice a year in older children, and annually in adults; evaluate serum creatine kinase concentration and liver transaminases during acute illnesses. Agents/circumstances to avoid: Fasting longer than age-appropriate periods. Evaluation of relatives at risk: Measure plasma carnitine levels in sibs of an affected individual. Pregnancy management: Pregnant women with CDSP require close monitoring of plasma carnitine levels and increased carnitine supplementation as needed to maintain normal plasma carnitine levels. ### Genetic counseling. CDSP is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the SLC22A5 pathogenic variants in the family are known. ## Diagnosis ### Suggestive Findings Systemic primary carnitine deficiency (CDSP) should be suspected in the following clinical situations: * Infant with positive newborn screening * Infants with hypoketotic hypoglycemic episodes that may be associated with hepatomegaly, elevated transaminases, and hyperammonemia * Children with skeletal myopathy and/or elevated serum concentration of creatine kinase (CK) * Children with cardiomyopathy * Adults with unexplained fatigability ### Preliminary Testing Newborn screening using tandem mass spectrometry (MS/MS) detects low levels of free carnitine (C0) and can identify infants with CDSP and mothers with CDSP. Because carnitine is transferred from the placenta to the fetus during pregnancy, an infant’s carnitine levels during the neonatal period can reflect those of the mother. Thus, unaffected infants born to affected mothers can have low carnitine levels shortly after birth [Schimmenti et al 2007, El-Hattab et al 2010, Lee et al 2010]. The ACMG recommends that total and free carnitine be determined in infants who screen positive. Extremely reduced plasma free, acylated, and total (i.e., the sum of free and acylated) carnitine levels (i.e., <10% of controls) are diagnostic of this disorder [Longo et al 2006]. In addition, plasma carnitine levels should be measured in all mothers of infants found to have low free carnitine levels on newborn screening in order to determine if the mother (rather than the infant) has CDSP, or if both mother and infant have CDSP [Schimmenti et al 2007, El-Hattab et al 2010, Lee et al 2010]. Other presentations. In infants, children, and adults with other presentations plasma carnitine levels remain the mainstay of the initial laboratory diagnosis. Of note, other biochemical studies may also have been done to address a broader differential diagnosis: * Plasma acylcarnitine profile. Because of the low level of all acylcarnitine, this study may well be unsuccessful. If a profile can be generated, there is generally no specific elevation of any acylcarnitine species. * Urine organic acid analysis. Nonspecific dicarboxylic aciduria, common in the acute decompensation of many fatty acid oxidation disorders, has been reported in some affected individuals with CDSP as well. ### Establishing the Diagnosis The diagnosis of CDSP is established in a proband by identification of biallelic pathogenic variants in SLC22A5 on molecular genetic testing (see Table 1) or, if biallelic pathogenic variants cannot be identified, by use of a skin biopsy to assess carnitine transport in cultured fibroblasts. Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Single-gene testing. Sequence analysis of SLC22A5 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. * A multigene panel that includes SLC22A5 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 if serial single-gene testing (and/or use of a multigene panel that includes SLC22A5) fails to confirm a diagnosis in an individual with features of CDSP. 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 Systemic Primary Carnitine Deficiency View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method SLC22A5Sequence analysis 3~70% 4 Gene-targeted deletion/duplication analysis 56/96 6 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. 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\. In one study, SLC22A5 sequencing performed in 70 infants with low carnitine levels detected by newborn screening identified two pathogenic variants in 23 infants and one pathogenic variant in 25 infants; no pathogenic variants were detected in 22 infants [Li et al 2010]. 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\. The Human Gene Mutation Database (HGMD) (www.hgmd.cf.ac.uk) Fibroblast carnitine transport (uptake). Carnitine transport in skin fibroblasts from affected individuals is typically reduced below 10% of control rates [Longo et al 2006]. ## Clinical Characteristics ### Clinical Description The clinical manifestations of systemic primary carnitine deficiency (CDSP) can vary widely with respect to age of onset, organ involvement, and severity of symptoms. The CDSP phenotype encompasses a broad clinical spectrum including metabolic decompensation in infancy, cardiomyopathy in childhood, fatigability in adulthood, or absence of symptoms. CDSP has typically been associated with infantile metabolic presentation in about half of affected individuals and childhood myopathic presentation in the other half. However, adults with CDSP who have mild or no symptoms have been reported. Such milder phenotypes are expected to be underdiagnosed; therefore, it is difficult to determine the relative prevalence of different phenotypes associated with CDSP [Longo et al 2006, El-Hattab & Scaglia 2015]. Infantile metabolic (hepatic) presentation. Affected children can present between age three months and two years with episodes of metabolic decompensation triggered by fasting or common illnesses such as upper-respiratory tract infection or gastroenteritis. These episodes are characterized clinically by poor feeding, irritability, lethargy, and hepatomegaly. Laboratory evaluations usually reveal hypoketotic hypoglycemia (hypoglycemia with minimal or no ketones in urine), hyperammonemia, and elevated liver transaminases. If affected children are not treated with intravenous dextrose infusion during episodes of metabolic decompensation (see Management), they may develop coma and die [Longo et al 2006, El-Hattab & Scaglia 2015]. Childhood myopathic (cardiac) presentation. The average age of myopathic presentation is between age two and four years, indicating that the myopathic manifestations of CDSP may develop over a longer period of time. Myopathic manifestations include dilated cardiomyopathy, hypotonia, skeletal muscle weakness, and elevated serum creatine kinase (CK). Death from cardiac failure can occur before the diagnosis is established, indicating that this presentation can be fatal if not treated. Older children with the infantile presentation may also develop myopathic manifestations including elevated CK, cardiomyopathy, and skeletal muscle weakness [Longo et al 2006, El-Hattab & Scaglia 2015]. Adulthood presentation. Several women have been diagnosed with CDSP after newborn screening identified low carnitine levels in their infants. About half of those women complained of fatigability, whereas the other half were asymptomatic. One woman was found to have dilated cardiomyopathy and another had arrhythmias [Schimmenti et al 2007, El-Hattab et al 2010, Lee et al 2010]. An asymptomatic adult male with CDSP has also been reported [Spiekerkoetter et al 2003]. Pregnancy-related symptoms. Pregnancy is a metabolically challenging state because energy consumption significantly increases. In addition, during pregnancy plasma carnitine levels are physiologically lower than those of non-pregnant controls. Affected women can have decreased stamina or worsening of cardiac arrhythmia during pregnancy, suggesting that CDSP may manifest or exacerbate during pregnancy [Schimmenti et al 2007, El-Hattab et al 2010]. Atypical manifestations. Other manifestations reported in individuals with CDSP include the following: * Anemia [Cano et al 2008] * Proximal muscle weakness and global developmental delays [Wang et al 2001] * Respiratory distress [Erguven et al 2007] * Arrhythmias and electrocardiographic (ECG) abnormalities [Schimmenti et al 2007, Lee et al 2010], including long QT syndrome [De Biase et al 2012] Heterozygous carriers. Heterozygous carriers are asymptomatic [Amat di San Filippo et al 2008]. Prognosis. Infantile metabolic and childhood myopathic presentations of CDSP can be fatal if untreated (see Management). The long-term prognosis is favorable as long as affected individuals remain on carnitine supplements. Repeated attacks of hypoglycemia or sudden death from arrhythmia have been described in affected individuals discontinuing carnitine supplementation [Longo et al 2006]. ### Genotype-Phenotype Correlations Fibroblast carnitine transport is reduced in all affected individuals. However, it has been demonstrated that carnitine transport is higher in the fibroblasts of asymptomatic individuals than in the fibroblasts of symptomatic individuals. Nonsense and frameshift variants in SLC22A5 are typically associated with lower carnitine transport and are more prevalent in symptomatic individuals whereas missense variants and in-frame deletions may result in protein with retained residual carnitine transport activity and are more prevalent in asymptomatic individuals [Rose et al 2012]. ### Prevalence CDSP has a frequency of 1:20,000-1:70,000 in the United States [Magoulas & El-Hattab 2012], 1:40,000 in Japan [Koizumi et al 1999], and 1:120,000 in Australia [Wilcken et al 2003]. The disease is very common in the Faroe Islands, where the prevalence is 1:300 [Rasmussen et al 2014]. ## Differential Diagnosis Systemic primary carnitine deficiency (CDSP) needs to be differentiated from secondary carnitine deficiency seen in the following situations [Flanagan et al 2010]: * Inherited metabolic disorders including organic acidemias and fatty acid oxidation defects (e.g., very long chain acyl-CoA dehydrogenase [VLCAD] deficiency, medium-chain acyl-CoA dehydrogenase [MCAD] deficiency, short-chain acyl-CoA dehydrogenase [SCAD] deficiency, carnitine-acylcarnitine translocase [CACT] deficiency [OMIM 212138], long-chain hydroxyacyl-CoA dehydrogenase [LCHAD] deficiency [OMIM 609016], and carnitine palmitoyltransferase II [CPT II] deficiency) * Pharmacologic therapy (e.g., valproate, cyclosporine, pivampicillin) * Malnutrition * Hemodialysis and renal tubular dysfunction (e.g., renal Fanconi syndrome) * Prematurity. Premature neonates may have mild reduction in plasma carnitine concentrations due to a lack of carnitine placental transfer in the third trimester and decreased tissue stores. Moreover, immature renal tubular function in premature neonates could lead to increased renal carnitine elimination [Li et al 2010, Clark et al 2014]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with systemic primary carnitine deficiency (CDSP), the following evaluations are recommended: * Echocardiogram and electrocardiogram * Serum creatine kinase (CK) concentration * Liver transaminases * Pre-prandial blood glucose concentration * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations L-carnitine supplementation. The main treatment for CDSP is oral levocarnitine (L-carnitine) supplementation. Typically, a high dose (100-400 mg/kg/day, divided in 3 doses) is required. Individuals with CDSP respond well if oral L-carnitine supplementation is started before irreversible organ damage occurs. Metabolic decompensation and skeletal and cardiac muscle function improve with L-carnitine supplementations. Oral L-carnitine supplementation in infants with CDSP identified through newborn screening results in slow normalization of the plasma carnitine concentration. The carnitine dose needs to be adjusted according to the plasma carnitine concentrations, which should be measured frequently. L-carnitine supplementation has relatively few side effects: * High doses of oral L-carnitine can cause increased gastrointestinal motility, diarrhea, and intestinal discomfort. * Oral L-carnitine can be metabolized by intestinal bacteria to produce trimethylamine, which has a fishy odor. Oral metronidazole at a dose of 10 mg/kg/day for 7-10 days and/or decreasing the carnitine dose usually results in the resolution of the odor [Longo et al 2006]. Note: (1) An unaffected infant born to a mother with CDSP can have low carnitine levels detected on newborn screening; in these infants oral L-carnitine supplementation is followed by a rise in plasma carnitine concentration within days or a few weeks [Schimmenti et al 2007, El-Hattab et al 2010]. (2) Asymptomatic adults with CDSP have been reported; however, the limited literature and the lack of follow up make it unclear whether these individuals have potential health risks. Because some fatty acid oxidation defects such as medium chain acyl CoA dehydrogenase (MCAD) deficiency can remain asymptomatic until they results in sudden death or another acute presentation during stress, it is prudent to treat asymptomatic individuals with CDSP with L-carnitine supplementation to prevent the possibility of decompensation during intercurrent illness or stress [El-Hattab et al 2010]. Other * Hypoglycemic episodes are treated with intravenous dextrose infusion. * Cardiomyopathy requires management by specialists in cardiology. ### Prevention of Primary Manifestations Maintaining appropriate plasma carnitine concentrations through oral L-carnitine supplementation (see Treatment of Manifestations) and preventing hypoglycemia (with frequent feeding and avoiding fasting) typically eliminate the risk of metabolic, hepatic, cardiac, and muscular complications. Note: Hospitalization to administer intravenous glucose is recommended for individuals with CDSP who are required to fast because of medical or surgical procedures or who cannot tolerate oral intake because of an illness such as gastroenteritis. ### Prevention of Secondary Complications L-carnitine supplementation is well tolerated and has relatively few side effects: increased gastrointestinal motility, diarrhea, and a fishy odor. Oral metronidazole and/or decreasing the carnitine dose usually results in the resolution of the odor. ### Surveillance The following evaluations have been suggested [Magoulas & El-Hattab 2012]: * Echocardiogram and electrocardiogram. Perform annually during childhood and less frequently in adulthood. Individuals with cardiomyopathy require management and follow up by specialists in cardiology. * Plasma carnitine concentration. Monitor frequently until levels reach the normal range, thereafter, measure three times a year during infancy and early childhood, twice a year in older children, and annually in adults. * Serum CK concentration and liver transaminases. Consider measuring during acute illnesses. ### Agents/Circumstances to Avoid Individuals with CDSP should avoid fasting longer than age-appropriate periods. ### Evaluation of Relatives at Risk Sibs of affected individuals should be tested by measuring plasma carnitine concentrations. If the carnitine levels are low, further evaluation for CDSP is recommended by molecular genetic testing if the SLC22A5 pathogenic variants have been identified in the family or fibroblast carnitine transport assay. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Pregnancy is a metabolically challenging state because energy consumption significantly increases. In addition, plasma carnitine levels are physiologically lower during pregnancy than those of non-pregnant controls. Affected women can have decreased stamina or worsening of cardiac arrhythmia during pregnancy, suggesting that CDSP may manifest or exacerbate during pregnancy [Schimmenti et al 2007, El-Hattab et al 2010]. Therefore, all pregnant women with CDSP, including those who are asymptomatic, require close monitoring of plasma carnitine levels and increased carnitine supplementation as needed to maintain normal plasma carnitine levels. ### 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. [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	Systemic Primary Carnitine Deficiency	c0342788	27,209	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK84551/	2021-01-18T20:53:31	{"mesh": ["C536778"], "synonyms": ["Carnitine Transport Defect", "Carnitine Uptake Defect", "CDSP"]}
An acute arboviral infection caused by an alphavirus of the Togaviridae family transmitted by an infected mosquito, that more frequently affects children and that is characterized by the presence of mild flulike symptoms (fever, chills, headache, nausea, vomiting, and anorexia) but that can progress to weakness, altered mental status, photophobia, mental confusion, seizures, somnolence, coma and/or even death. The disease can leave neurological sequelae, mainly in infants and children, such as seizures, spasticity or behavioral 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	Western equine encephalitis	c0153064	27,210	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83593	2021-01-23T19:12:25	{"gard": ["7888"], "mesh": ["D020241"], "umls": ["C0153064"], "icd-10": ["A83.1"], "synonyms": ["Western equine encephalomyelitis"]}
Diseases of mental health Dissociative disorder SpecialtyPsychiatry, psychology Dissociative disorders (DD) are conditions that involve disruptions or breakdowns of memory, awareness, identity, or perception. People with dissociative disorders use dissociation as a defense mechanism, pathologically and involuntarily. The individual suffers these dissociations to protect themselves. Some dissociative disorders are triggered by psychological trauma, but depersonalization-derealization disorder may be preceded only by stress, psychoactive substances, or no identifiable trigger at all.[1] The dissociative disorders listed in the American Psychiatric Association's DSM-5 are as follows:[2] * Dissociative identity disorder (formerly multiple personality disorder): the alternation of two or more distinct personality states with impaired recall among personality states. In extreme cases, the host personality is unaware of the other, alternating personalities; however, the alternate personalities can be aware of all the existing personalities.[3] * Dissociative amnesia (formerly psychogenic amnesia): the temporary loss of recall memory, specifically episodic memory, due to a traumatic or stressful event. It is considered the most common dissociative disorder amongst those documented. This disorder can occur abruptly or gradually and may last minutes to years depending on the severity of the trauma and the patient.[4][5] Dissociative fugue previously a separate category is now treated as a specifier for dissociative amnesia.[6] * Depersonalization-derealization disorder: periods of detachment from self or surrounding which may be experienced as "unreal" (lacking in control of or "outside" self) while retaining awareness that this is only a feeling and not a reality. * The old category of dissociative disorder not otherwise specified is now split into two: other specified dissociative disorder, and unspecified dissociative disorder. These categories are used for forms of pathological dissociation that do not fully meet the criteria of the other specified dissociative disorders; or if the correct category has not been determined; or the disorder is transient.[2] The ICD11 lists dissociative disorders as: * Dissociative neurological symptom disorder * Dissociative amnesia * Dissociative amnesia with dissociative fugue * Trance disorder * Possession trance disorder * Dissociative identity disorder * Partial dissociative identity disorder, and * Depersonalization-derealization disorder [7] ## Contents * 1 Cause and treatment * 1.1 Dissociative identity disorder * 1.2 Dissociative amnesia * 1.3 Depersonalization-derealization disorder * 2 Medications * 3 Diagnosis and prevalence * 4 Children and adolescents * 5 Current debates and the DSM-5 * 6 See also * 7 References * 8 External links ## Cause and treatment[edit] ### Dissociative identity disorder[edit] Cause: Dissociative identity disorder is caused by ongoing childhood trauma that occurs before the ages of six to nine.[8][9] People with dissociative identity disorder usually have close relatives who have also had similar experiences.[10] Treatment: Long-term psychotherapy to improve the patient's quality of life. ### Dissociative amnesia[edit] Cause: A way to cope with trauma. Treatment: Psychotherapy (e.g. talk therapy) counseling or psychosocial therapy which involves talking about your disorder and related issues with a mental health provider. Psychotherapy often involves hypnosis (help you remember and work through the trauma); creative art therapy (using creative process to help a person who cannot express his or her thoughts); cognitive therapy (talk therapy to identify unhealthy and negative beliefs/behaviors); and medications (antidepressants, anti-anxiety medications or tranquilizers). These medications help control the mental health symptoms associated with the disorders, but there are no medications that specifically treat dissociative disorders.[11] However, the medication Pentothal can sometimes help to restore the memories.[10] The length of an event of dissociative amnesia may be a few minutes or several years. If an episode is associated with a traumatic event, the amnesia may clear up when the person is removed from the traumatic situation. Dissociative fugue was a separate category but is now listed as a specifier for dissociative amnesia.[6] ### Depersonalization-derealization disorder[edit] Cause: Dissociative disorders usually develop as a way to cope with trauma. The disorders most often form in children subjected to chronic physical, sexual or emotional abuse or, less frequently, a home environment that is otherwise frightening or highly unpredictable; however, this disorder can also acutely form due to severe traumas such as war or the death of a loved one. Treatment: Same treatment as dissociative amnesia. An episode of depersonalization-derealization disorder can be as brief as a few seconds or continue for several years.[10] ## Medications[edit] There are no medications to treat dissociative disorders, however drugs to treat anxiety and depression that may accompany the disorders can be given.[12] ## Diagnosis and prevalence[edit] The lifetime prevalence of dissociative disorders varies from 10% in the general population to 46% in psychiatric inpatients.[13] Diagnosis can be made with the help of structured clinical interviews such as the Dissociative Disorders Interview Schedule (DDIS) and the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D-R), and behavioral observation of dissociative signs during the interview.[13][14] Additional information can be helpful in diagnosis, including the Dissociative Experiences Scale or other questionnaires, performance-based measures, records from doctors or academic records, and information from partners, parents, or friends.[14] A dissociative disorder cannot be ruled out in a single session and it is common for patients diagnosed with a dissociative disorder to not have a previous dissociative disorder diagnosis due to a lack of clinician training.[14] Some diagnostic tests have also been adapted or developed for use with children and adolescents such as the Adolescent Dissociative Experiences Scale,[15] Children's Version of the Response Evaluation Measure (REM-Y-71), Child Interview for Subjective Dissociative Experiences, Child Dissociative Checklist (CDC), Child Behavior Checklist (CBCL) Dissociation Subscale, and the Trauma Symptom Checklist for Children Dissociation Subscale.[16] There are problems with classification, diagnosis and therapeutic strategies of dissociative and conversion disorders which can be understood by the historic context of hysteria. Even current systems used to diagnose DD such as the DSM-IV and ICD-10 differ in the way the classification is determined.[17] In most cases mental health professionals are still hesitant to diagnose patients with Dissociative Disorder, because before they are considered to be diagnosed with Dissociative Disorder these patients have more than likely been diagnosed with major depression, anxiety disorder, and most often post-traumatic disorder.[18] An important concern in the diagnosis of dissociative disorders in forensic interviews is the possibility that the patient may be feigning symptoms in order to escape negative consequences. Young criminal offenders report much higher levels of dissociative disorders, such as amnesia. In one study it was found that 1% of young offenders reported complete amnesia for a violent crime, while 19% claimed partial amnesia.[citation needed] There have also been cases in which people with dissociative identity disorder provide conflicting testimonies in court, depending on the personality that is present.[19][better source needed] ## Children and adolescents[edit] Dissociative disorders (DD) are widely believed to have roots in adverse childhood experiences including abuse and loss, but the symptoms often go unrecognized or are misdiagnosed in children and adolescents.[16][20][21][verification needed] There are several reasons why recognizing symptoms of dissociation in children is challenging: it may be difficult for children to describe their internal experiences; caregivers may miss signals or attempt to conceal their own abusive or neglectful behaviors;[citation needed] symptoms can be subtle or fleeting;[16] disturbances of memory, mood, or concentration associated with dissociation may be misinterpreted as symptoms of other disorders.[16] In addition to developing diagnostic tests for children and adolescents (see above), a number of approaches have been developed to improve recognition and understanding of dissociation in children. Recent research has focused on clarifying the neurological basis of symptoms associated with dissociation by studying neurochemical, functional and structural brain abnormalities that can result from childhood trauma.[20] Others in the field have argued that recognizing disorganized attachment (DA) in children can help alert clinicians to the possibility of dissociative disorders.[21] Clinicians and researchers also stress the importance of using a developmental model to understand both symptoms and the future course of DDs.[16][20] In other words, symptoms of dissociation may manifest differently at different stages of child and adolescent development and individuals may be more or less susceptible to developing dissociative symptoms at different ages. Further research into the manifestation of dissociative symptoms and vulnerability throughout development is needed.[16][20] Related to this developmental approach, more research is required to establish whether a young patient's recovery will remain stable over time.[22] ## Current debates and the DSM-5[edit] A number of controversies surround DD in adults as well as children. First, there is ongoing debate surrounding the etiology of dissociative identity disorder (DID). The crux of this debate is if DID is the result of childhood trauma and disorganized attachment.[20][23] A second area of controversy surrounds the question of whether or not dissociation as a defense versus pathological dissociation are qualitatively or quantitatively different. Experiences and symptoms of dissociation can range from the more mundane to those associated with posttraumatic stress disorder (PTSD) or acute stress disorder (ASD) to dissociative disorders.[16] Mirroring this complexity, the DSM-5 workgroup considered grouping dissociative disorders with other trauma/stress disorders,[24] but instead decided to put them in the following chapter to emphasize the close relationship.[25] The DSM-5 also introduced a Dissociative subtype of PTSD.[25] A 2012 review article supports the hypothesis that current or recent trauma may affect an individual's assessment of the more distant past, changing the experience of the past and resulting in dissociative states.[26] However, experimental research in cognitive science continues to challenge claims concerning the validity of the dissociation construct, which is still based on Janetian notions of structural dissociation.[4][27] Even the claimed etiological link between trauma/abuse and dissociation has been questioned. An alternative model proposes a perspective on dissociation based on a recently established link between a labile sleep–wake cycle and memory errors, cognitive failures, problems in attentional control, and difficulties in distinguishing fantasy from reality."[28] ## See also[edit] * Complex post-traumatic stress disorder ## References[edit] 1. ^ Simeon, D; Abugel, J (2006). Feeling Unreal: Depersonalization Disorder and the Loss of the Self. New York, NY: Oxford University Press. p. 17. ISBN 0195170229. OCLC 61123091. 2. ^ a b Diagnostic and statistical manual of mental disorders : DSM-5 (5th ed.). Arlington, VA: American Psychiatric Association. 2013. pp. 291–307. ISBN 9780890425541. 3. ^ Schacter, D. L., Gilbert, D. T., & Wegner, D.M. (2011). Psychology: Second Edition, pages 572-573 New York, NY: Worth. 4. ^ a b Maldonado, R.J.; Spiegel, D. (2019). "Dissociative Disorders". In Weiss Roberts, Laura; Hales, Robert E.; Yudofsky, Stuart C. (eds.). The American Psychiatric Publishing Board Review Guide for Psychiatry (7th ed.). American Psychiatric Pub. ISBN 978-1-61537-150-1. 5. ^ First, M. B., Kay, J., Lieberman, J. A., Riba, M. B., Tasman, A., eds. Psychiatry. 4th ed. Chichester, UK: John Wiley & Sons; 2015. p1187. ISBN 978-1-118-84547-9 6. ^ a b Diagnostic and statistical manual of mental disorders : DSM-5 (5th ed.). Arlington, VA: American Psychiatric Association. 2013. p. 812. ISBN 9780890425541. 7. ^ "ICD-11 - Mortality and Morbidity Statistics". icd.who.int. 8. ^ Spigel, David; et al. "Dissociative disorders in DSM5DMS". Retrieved 3 January 2018. 9. ^ Salter, Micahel; Dorahy, Martin; Middleton, Warwick. "Dissociative identity disorder exists and is the result of childhood trauma". The Conversation. Retrieved 3 January 2018. 10. ^ a b c Miller, John L. (February 3, 2014). "Dissociative Disorders". athealth.com. Retrieved December 14, 2016. 11. ^ (Mayo, 2011, p.11) (3 Mar 2011). Mayo Clinic. 1-12. Retrieved May 5, 2015, from http://www.mayoclinic.com/health/dissociative-disorders/DS00574 12. ^ "What is dissociation and dissociative identity disorder (DID)?". What are the signs and symptoms of dissociation and dissociative disorder?. 13. ^ a b Ross; et al. (2002). "Prevalence, Reliability and Validity of Dissociative Disorders in an Inpatient Setting". Journal of Trauma and Dissociation. 3: 7–17. doi:10.1300/J229v03n01_02. S2CID 144490486. 14. ^ a b c Bailey, Tyson D.; Boyer, Stacey M.; Brand, Bethany L. (2019). "Dissociative Disorders". In Segal, Daniel L. (ed.). Diagnostic Interviewing (5th ed.). Springer. ISBN 978-1-4939-9127-3. 15. ^ "Guidelines for the Evaluation and Treatment of Dissociative Symptoms in Children and Adolescents: International Society for the Study of Dissociation" (PDF). Journal of Trauma & Dissociation. 5 (3): 119–150. 2004-10-04. doi:10.1300/J229v05n03_09. ISSN 1529-9732. S2CID 220430260. 16. ^ a b c d e f g Steiner, H.; Carrion, V.; Plattner, B.; Koopman, C. (2002). "Dissociative symptoms in posttraumatic stress disorder: diagnosis and treatment". Child and Adolescent Psychiatric Clinics North America. 12 (2): 231–249. doi:10.1016/s1056-4993(02)00103-7. PMID 12725010. 17. ^ Splitzer, C; Freyberger, H.J. (2007). "Dissoziative Störungen (Konversionsstörungen)". Psychotherapeut. 18. ^ [Nolen-Hoeksema, S. (2014). Somatic Symptom and Dissociative Disorders. In (ab)normal Psychology (6th ed., p. 164). Penn, Plaza, New York: McGraw-Hill.] 19. ^ Haley, J. (2003). "Defendant's wife testifies about his multiple personas". Bellingham Herald: B4. 20. ^ a b c d e Diseth, T. (2005). "Dissociation in children and adolescents as reaction to trauma - an overview of conceptual issues and neurobiological factors". Nordic Journal of Psychiatry. 59 (2): 79–91. doi:10.1080/08039480510022963. PMID 16195104. S2CID 25581805. 21. ^ a b Waters, F. (July–August 2005). "Recognizing dissociation in preschool children". The International Society for the Study of Dissociation News. 23 (4): 1–4. 22. ^ Jans, Thomas; Schneck-Seif, Stefanie; Weigand, Tobias; Schneider, Wolfgang; Ellgring, Heiner; Wewetzer, Christoph; Warnke, Andreas (2008). "Long-term outcome and prognosis of dissociative disorder with onset in childhood or adolescence". Child and Adolescent Psychiatry and Mental Health. 2 (1): 19. doi:10.1186/1753-2000-2-19. PMC 2517058. PMID 18651951. 23. ^ Boysen, Guy A. (2011). "The Scientific Status of Childhood Dissociative Identity Disorder: A Review of Published Research". Psychotherapy and Psychosomatics. 80 (6): 329–34. doi:10.1159/000323403. PMID 21829044. S2CID 6083787. 24. ^ Brand, Bethany L.; Lanius, Ruth; Vermetten, Eric; Loewenstein, Richard J.; Spiegel, David (2012). "Where Are We Going? An Update on Assessment, Treatment, and Neurobiological Research in Dissociative Disorders as We Move Toward the DSM-5". Journal of Trauma & Dissociation. 13 (1): 9–31. doi:10.1080/15299732.2011.620687. PMID 22211439. S2CID 8204753. 25. ^ a b American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5®) (5th ed.). American Psychiatric Pub. pp. 528–556. ISBN 978-0-89042-557-2. 26. ^ Stern DB (January 2012). "Witnessing across time: accessing the present from the past and the past from the present". The Psychoanalytic Quarterly. 81 (1): 53–81. doi:10.1002/j.2167-4086.2012.tb00485.x. PMID 22423434. S2CID 5728941. 27. ^ Heim, Gerhard; Bühler, Karl-Ernst (2019-04-03). Craparo, Giuseppe; Ortu, Francesca; van der Hart, Onno (eds.). Pierre Janet's views on the etiology, pathogenesis, and therapy of dissociative disorders 1. Rediscovering Pierre Janet (1 ed.). Routledge. pp. 178–199. doi:10.4324/9780429201875-14. ISBN 978-0-429-20187-5. Retrieved 2020-07-24. 28. ^ Lynn, SJ; et al. (2012). "Dissociation and dissociative disorders: challenging conventional wisdom". Current Directions in Psychological Science. 21 (1): 48–53. doi:10.1177/0963721411429457. S2CID 4495728. ## External links[edit] * Dissociative disorders—Mayo Clinic * Depersonalization Disorder—Cleveland Clinic * International Society for the Study of Trauma and Dissociation Classification D * ICD-10: F44 * ICD-9-CM: 300.12-300.14 * MeSH: D004213 Authority control * LCCN: sh92004916 * NDL: 01150107 [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	Dissociative disorder	c0012746	27,211	wikipedia	https://en.wikipedia.org/wiki/Dissociative_disorder	2021-01-18T18:41:27	{"mesh": ["D004213"], "umls": ["C0012746", "C0041857"], "wikidata": ["Q2627467"]}
A number sign (#) is used with this entry because of evidence that Bethlem myopathy-2 (BTHLM2), also known as myopathic-type Ehlers-Danlos syndrome, is caused by heterozygous mutation in the COL12A1 gene (120320) on chromosome 6q. For a discussion of genetic heterogeneity of Bethlem myopathy, see BTHLM1 (158810). Clinical Features Zou et al. (2014) reported a boy with features consistent with Bethlem myopathy. Hypotonia, proximal joint contractures, and distal myopathy were noted during his first year of life. Motor development was delayed, and he started to walk shortly before his second birthday. He initially walked with stooped posture, which improved with age. Knee contractures resolved completely, and elbow contractures improved gradually. He had mild kyphosis but no scoliosis. Language development and cognition were normal. Muscle ultrasound of the thigh showed a mild diffuse increase in echogenicity without fasciculations. Nerve conduction studies were normal. Muscle biopsy showed mild variability in fiber diameter without evidence of degeneration or regeneration, consistent with a mild myopathy. The boy's nonconsanguineous parents were unaffected. Hicks et al. (2014) identified 5 members of 2 families with features of Bethlem myopathy who were found to have mutations in the COL12A1 gene. All 5 patients presented with symptoms of distal hyperlaxity, muscle weakness, skin changes, and joint contractures. The authors noted that the MRI findings in these patients differed from those in Bethlem myopathy patients with a mutation in the collagen VI genes (BTHLM1; 158810). In patients with BTHLM1, the periphery of the muscles is more affected than the central part, and in the calf, one of the first signs is often a 'rim' of fatty infiltration between the soleus and gastrocnemius muscles. In family 1 of Hicks et al. (2014), the only prominent finding on T1-weighted MR images was atrophy of the rectus femoris muscles; in their family 2, the pattern of muscle involvement correlated with disease severity, with the severely affected father showing a more pronounced pathology on MRI compared with his mildly affected sons. Inheritance The transmission pattern of Bethlem myopathy-2 in the families reported by Hicks et al. (2014) was consistent with autosomal dominant inheritance. Molecular Genetics In a boy with Bethlem myopathy in whom collagen VI was found to be normal, Zou et al. (2014) screened for mutations in the COL12A1 gene and identified a de novo heterozygous missense mutation (I2334T; 120320.0002). Patient muscle and cultured fibroblasts showed decreased extracellular immunostaining for type XII collagen. Extracellular immunostaining for type VI collagen and laminin-gamma-1 (LAMC1; 150290) was preserved. After excluding mutation in the collagen VI genes and in 12 other candidate genes related to collagen VI processing in 24 patients with a Bethlem myopathy-like phenotype, Hicks et al. (2014) identified 5 members of 2 families with heterozygous mutations in the COL12A1 gene (G2786D, 120320.0003; R1965C, 120320.0004). The mutations segregated with the phenotype in the families. Animal Model Izu et al. (2011) generated Col12a1-null mice by targeted deletion of exons 2-5. The knockout mice had fragile bones with a disorganized collagen fiber arrangement, decreased expression of bone matrix proteins, and decreased bone-forming activity associated with delayed terminal differentiation. Zou et al. (2014) showed that the knockout mice had decreased grip strength, a delay in fiber-type transition, and a deficiency in passive force generation, while the muscle seemed more resistant to eccentric contraction-induced force drop, indicating a role for a matrix-based passive force-transducing elastic element in the generation of the weakness. INHERITANCE \- Autosomal dominant HEAD & NECK Neck \- Neck weakness CHEST Ribs Sternum Clavicles & Scapulae \- Scapular winging SKELETAL \- Proximal joint contractures \- Joint laxity Spine \- Stooped posture \- Kyphosis Pelvis \- Hip dislocation (in some patients) Hands \- Distal joint hyperlaxity \- Flexion finger contractures Feet \- Distal joint hyperlaxity SKIN, NAILS, & HAIR Skin \- Atrophic scarring \- Hypertrophic scarring MUSCLE, SOFT TISSUES \- Hypotonia \- Muscle weakness, mainly proximal \- Mild myopathic changes seen on muscle biopsy \- Fibrosis \- Mild variability in fiber diameter \- Atrophy of the rectus femoris muscle NEUROLOGIC Central Nervous System \- Delayed motor development \- Delayed walking \- Inability or difficulty running LABORATORY ABNORMALITIES \- Increased serum creatine kinase \- Fibroblasts show a reduction of and disorganization in collagen XII in the extracellular matrix MISCELLANEOUS \- Onset in first decade \- Large joint contractures may resolve over time \- Muscle strength tends to improve during the teenage years MOLECULAR BASIS \- Caused by mutation in the collagen, type XII, alpha-1 gene (COL12A1, 120320.0002 ) ▲ 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	BETHLEM MYOPATHY 2	c1834674	27,212	omim	https://www.omim.org/entry/616471	2019-09-22T15:48:48	{"mesh": ["C535436"], "omim": ["616471"], "orphanet": ["610"], "synonyms": ["Alternative titles", "EHLERS-DANLOS SYNDROME, MYOPATHIC TYPE", "EDS, MYOPATHIC TYPE"]}
A number sign (#) is used with this entry because of evidence that inclusion body myopathy with Paget disease (IBMPFD3) is caused by heterozygous mutation in the HNRNPA1 gene (164017) on chromosome 12q13. One such family has been reported. Heterozygous mutations in the HNRNPA1 gene also result in amyotrophic lateral sclerosis (ALS20; 615426). For a general phenotypic description and a discussion of genetic heterogeneity of IBMPFD, see IBMPFD1 (167320). Clinical Features Kottlors et al. (2010) described a German family with 5 affected sibs with a limb girdle muscular dystrophy characterized by progressive predominantly proximal muscle weakness, mildly elevated serum creatine kinase levels, myopathic findings on muscle biopsy, and Paget disease of the bone. All affected individuals showed a pattern of muscle weakness beginning in the lower proximal extremities and later spreading to the foot dorsiflexors. Muscles of the abdominal wall and iliopsoas muscle were severely affected. Scapulae were only slightly winged, and upper extremities showed no weakness except in 1 severely affected patient. Although age of onset was between 35 and 43 years, affected members recalled having been slower and clumsier than peers as children. No patient had cognitive impairment. Histology showed myopathic changes with rimmed vacuoles and inclusion bodies on muscle biopsy. There was variability regarding Paget disease of bone; of the 3 severely affected and 2 more mildly affected members, only 2 had laboratory and radiologic evidence of Paget disease. The affected mother was deceased. The pedigree strongly suggested autosomal dominant inheritance. Kim et al. (2013) confirmed that none of the affected members in the family reported by Kottlors et al. (2010) (family 2 of Kim et al. (2013)) had motor neuron dysfunction or cognitive impairment. Family member IV9 underwent a muscle biopsy, which showed atrophic fibers, central nuclei, and rimmed vacuoles characteristic of inclusion body myopathy. Molecular Genetics In a family with IBMPFD (family 2, originally reported by Kottlors et al. (2010)) in which mutations in VCP (601023) and other myopathy-related genes had been excluded, Kim et al. (2013) detected a missense mutation in the HNRNPA1 gene (164017.0001) that substituted a valine for a highly conserved aspartate that is centered in a motif, the prion-like domain (PrLD), conserved in multiple human paralogs of the HNRNP A/B family. The mutation was predicted to enhance prion-like behavior of the motif. By sequencing coding exons of the HNRNPA1 gene, Le Ber et al. (2014) failed to identify pathogenic mutations in a cohort of 17 unrelated French patients with sporadic or familial occurrence of multiple system proteinopathy manifest as frontotemporal lobar degeneration (FTLD) and/or amyotrophic lateral sclerosis (ALS) that segregated with Paget disease of bone (PDB), and/or inclusion body myositis (IBM). No mutations were found in 60 probands with FTLD or FTLD/ALS. By sequencing the prion-like domain of the HNRNPA1 gene, Seelen et al. (2014) also failed to identify any nonsynonymous mutations in 135 patients with familial ALS, 1,084 patients with sporadic ALS, 68 patients with familial FTLD, 74 patients with sporadic FTLD, and 31 patients with sporadic IBM. All patients were from the Netherlands. The findings of both studies suggested that mutations in HNRNPA1 are a very rare cause of this spectrum of diseases. INHERITANCE \- Autosomal dominant SKELETAL \- Paget disease Spine \- Disordered and exaggerated bone remodeling \- Trabecular coarsening of the lumbar vertebral body Pelvis \- Increased osteosclerosis \- Disordered and exaggerated bone remodeling Limbs \- Increased osteosclerosis of the epiphyseal portion of the femur MUSCLE, SOFT TISSUES \- Muscle weakness (affecting lower proximal extremities, abdominal wall, and iliopsoas muscle) \- Muscle pain following exercise (in some patients) \- Multiple rimmed vacuoles seen on biopsy (in some patients) \- Inclusion bodies seen on biopsy (in some patients) \- Fiber size variation seen on biopsy (in some patients) \- Myopathic pattern seen on EMG NEUROLOGIC Central Nervous System \- Normal cognition LABORATORY ABNORMALITIES \- Elevated serum creatine kinase (up to 7 times normal limit) \- Elevated alkaline phosphatase (up to 8 times normal limit in most patients) MISCELLANEOUS \- Onset between 35-43 years of age \- Many become wheelchair bound \- One family described (last curated October 2013) MOLECULAR BASIS \- Caused by mutation in the heterogeneous nuclear ribonucleoprotein A1 gene (HNRNPA1, 164017.0001 ) ▲ 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	INCLUSION BODY MYOPATHY WITH EARLY-ONSET PAGET DISEASE WITH OR WITHOUT FRONTOTEMPORAL DEMENTIA 3	c1833662	27,213	omim	https://www.omim.org/entry/615424	2019-09-22T15:52:10	{"doid": ["0050881"], "mesh": ["C563476"], "omim": ["615424"], "orphanet": ["52430"], "synonyms": ["Alternative titles", "MULTISYSTEM PROTEINOPATHY 3"], "genereviews": ["NBK1476"]}
## Clinical Features In addition to the usual severe, recessively inherited xeroderma pigmentosum (278700-278780), the existence of a milder form behaving as a dominant was claimed by Anderson and Begg (1950) who described 11 affected persons in 5 sibships of 4 generations of a Scottish family by the name of MacPherson. The patients showed freckling and multiple skin cancers as in the recessive form but did not get into trouble as early in life and survived longer. Indeed, Anderson and Begg examined 1 affected member of the family who was 74 years of age. No affected member was said to have died of the disease. Sedano (1984) raised doubts about this family. In the Scottish family, Anderson personally examined 7 members: 'Mr. George MacPherson, sen., his wife, George, jun., Harold, Lena, Douglas, and the son of George, jun. (Ian).' All these except the wife were said to be affected; the authors even raised the question of whether the wife might be 'a mild case;' was she in fact a carrier and is this an example of pseudodominance? Actually the father of 'George, sen.,' the authors stated, 'was known to have been affected.' Anderson and Begg (1950) were attracted to the possibility that this man's wife and the wife of 'George, sen.' were both heterozygotes. Skin tumors, mostly squamous epitheliomas, had onset as early as age 14. All the affected persons were 'rufous' (red-haired). Tests for increased sensitivity to ultraviolet light were equivocal or negative. Although the disorder in this kindred was milder than ordinary xeroderma pigmentosum ('George was in a tropical climate for many years, being invalided home on two occasions on account of the disease' and 'Douglas was invalided home from North Africa in 1943'), 'Douglas was considered to be a case of xeroderma pigmentosum by all the members present when he was shown at a meeting of the North British Dermatological Society in 1946.' Imray et al. (1986) described an Australian kindred with persons in 5 generations affected by a mild form of XP. The features were marked xeroderma, generalized dark pigmentation, excessive freckling, and severe erythema in response to sunlight. Skin cancer was not common in this family; the proband had a melanoma and her mother had a basal cell carcinoma removed at age 70. Cleaver (1981) described autosomal dominant predisposition to multiple skin cancers in exposed facial skin. Fibroblasts from affected persons showed no defects in excision repair. On the other hand, in the Australian kindred, Imray et al. (1986) found, in studying lymphoblastoid cells and fibroblasts, cellular sensitivity to ultraviolet light as judged by diminished clonogenicity and increased frequency of UV-induced chromosome aberrations. After UV exposure, cells showed abnormally great depression of replicative DNA synthesis and the level of UV-induced DNA repair synthesis was lower than normal. The number of sister chromatid exchanges and 6-thioguanine-resistant mutants was not increased. Inheritance \- Autosomal dominant vs. multifactorial form \- usually autosomal recessive Misc \- Milder than recessive form Lab \- Variable cellular sensitivity to ultraviolet light Skin \- Xeroderma pigmentosum \- Freckling \- Multiple skin cancers \- Squamous epitheliomas \- Hyperpigmentation \- Severe erythema response to sunlight ▲ 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	XERODERMA PIGMENTOSUM, AUTOSOMAL DOMINANT, MILD	c0043346	27,214	omim	https://www.omim.org/entry/194400	2019-09-22T16:31:43	{"mesh": ["D014983"], "omim": ["194400"], "orphanet": ["910"]}
Infectious coryza is a serious bacterial disease of chickens which affects respiratory system and it is manifested by inflammation of the area below the eye, nasal discharge and sneezing.[1][2] The disease is found all over the world causing high economic losses. Economic loss is due to stumping off and reduction of egg production in case of laying chickens. The disease was discovered early 1930s by considering clinical signs.[1] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Transmission * 3 Diagnosis * 4 Treatment * 5 References ## Signs and symptoms[edit] Clinical appearance of the disease includes depression, a serous nasal discharge, and sporadically minor facial inflammation in mild form of the disease. In severe form, there is severe inflammation of one or both infraorbital sinuses with edema of the surrounding tissue. The swelling can cause closure of one eye or both of them. Intermandibular space and wattles of corks do swell as a course of the disease.[2][3] ## Cause[edit] The disease is caused by bacteria called Avibacterium paragallinarum, which is a gram-negative bacterium. The bacterium is microaerophilic rod-shaped and is nonmotile. Its growth requires presence of nicotinamide adenine dinucleotide. There are three serovars A, B and C of A. paragallinarum that relate by immunotype specificity.[1][2] ### Transmission[edit] The reservoirs of the disease are carrier chickens which could be healthy but harboring the disease or chronically sick chickens. The disease affects all ages of chickens. The disease can persist in the flock for 2-3 weeks and signs of the disease are seen between 1–3 days post infection. Transmission of the disease is through direct interaction, airborne droplets and drinking contaminated water. Chicken having infection and those carriers contribute highly to the disease transmission.[2][3] ## Diagnosis[edit] It is done through isolation of bacteria from chickens suspected to have history of coryza and clinical finds from infected chickens also is used in the disease diagnosis.[1][4] Polymerase chain reaction is a reliable means of diagnosis of the disease.[5][6][7][8] ## Treatment[edit] Prevention is through use of Stock coryza-free birds. In other areas culling of the whole flock is a good means of the disease control. Bacterin also is used at a dose of two to reduce brutality of the disease. Precise exposure has also has been used but it should be done with care. Vaccination of the chicks is done in areas with high disease occurrence. Treatment is done by using antibiotics such as erythromycin, dihydrostreptomycin, streptomycin, sulfonamides, tylosin, and fluoroquinolones.[2][3] ## References[edit] 1. ^ a b c d Blackall P J, Matsumoto M., Yamamoto R. Infectious coryza. In: Calnek B W, Barnes H J, Beard C W, McDougald L R, Saif Y M, editors. Diseases of poultry. 10th ed. Ames: Iowa State University Press; 1997. pp. 179–190 2. ^ a b c d e Merck Veterinary Manual, 2016 3. ^ a b c "Poultry, Poultry Health, Welfare, Diseases, Poultry News, Articles, Photos of Chickens, Poultry Photo". The Poultry Site. 4. ^ Bragg R R, Greyling J M, Verschoor J A. Isolation and identification of NAD-independent bacteria from chickens with symptoms of infectious coryza. Avian Pathol. 1997;26:595–606 5. ^ Blackall P J, Yamamoto R. Infectious coryza. In: Swayne D E, editor. A laboratory manual for the isolation and identification of avian pathogens. 4th ed. Philadelphia, Pa: American Association of Avian Pathologists; 1998. pp. 29–34 6. ^ Chen X, Chen Q, Zhang P, Feng W, Blackall P J. Evaluation of a PCR test for the detection of Haemophilus paragallinarum in China. Avian Pathol. 1998;27:296–300. 7. ^ Chen X, Miflin J K, Zhang P, Blackall P J. Development and application of DNA probes and PCR tests for Haemophilus paragallinarum. Avian Dis. 1996;40:398–407 8. ^ Chen X, Song C, Gong Y, Blackall P J. Further studies on the use of a polymerase chain reaction test for the diagnosis of infectious coryza. Avian Pathol. 1998;27:618–624. * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis * v * t * e Chicken * Rooster * Hen * Chick As poultry * Chicken as food * List of chicken dishes * Breeds * Capon * Poularde * Poussin * Pullet * Broiler Husbandry * Battery cage * Free range * Furnished cages * Yarding * Chicken tractor * Poultry farming * Broiler industry * Beak trimming * Hatchery * Chick sexing * Chick culling * Candling * Abnormal behaviour of birds in captivity * European Union Council Directive 1999/74/EC Culture * Chickens as pets * Cockatrice * Cockfighting * Kapparos * Sarimanok * Rooster Flag Diseases * Aspergillosis * Avian infectious laryngotracheitis * Avian influenza * Avian sarcoma leukosis virus * Histomoniasis (blackhead disease) * Botulism * Campylobacteriosis * Candidiasis * Coccidiosis * Colds * Dermanyssus gallinae * Egg binding * Erysipelas * Fatty liver hemorrhagic syndrome * Fowlpox * Gallid alphaherpesvirus 3 * Gapeworm * Infectious bursal disease * Infectious coryza in chickens * Marek's disease * Mycoplasmas * Newcastle disease * Omphalitis * Psittacosis * Pullorum * Scaly leg * Squamous cell carcinoma * Tibial dyschondroplasia * Toxoplasmosis [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	Infectious coryza in chickens	None	27,215	wikipedia	https://en.wikipedia.org/wiki/Infectious_coryza_in_chickens	2021-01-18T19:02:19	{"wikidata": ["Q5788570"]}
A number sign (#) is used with this entry because osteogenesis imperfecta type II (OI2) is caused by heterozygous mutation in the COL1A1 gene (120150) or the COL1A2 gene (120160). Description Osteogenesis imperfecta type II constitutes a disorder characterized by bone fragility, with many perinatal fractures, severe bowing of long bones, undermineralization, and death in the perinatal period due to respiratory insufficiency (Sillence et al., 1979; Barnes et al., 2006). Also see osteogenesis imperfecta type VII (610682), an autosomal recessive form of lethal OI caused by mutation in the CRTAP gene (605497). Clinical Features Morphologically there appear to be 2 forms of OI congenita, a thin-boned and a broad-boned type. The latter is well illustrated by the male and female sibs reported by Remigio and Grinvalsky (1970). The diagnosis is in question, however, because one had dislocated lenses, aortic coarctation, and basophilic and mucoid changes in the connective tissue of the heart valves and aorta, while the other had less pronounced changes of the same nature in the aorta. Parental consanguinity was denied. Shapiro et al. (1982) suggested that the sibs reported by Remigio and Grinvalsky (1970) may have had another variant because of conspicuous extraskeletal features. The broad-bone type is also illustrated in Figure 8-3 by McKusick (1972) and the thin-bone type in Figure 8-5. The 'broad-bone' form of osteogenesis imperfecta and type IA achondrogenesis (200600) bear similarities. In the latter condition the ribs are thin and prone to fractures but the long bones of the limbs are severely shortened and bowed. In a study in Australia, Sillence et al. (1979) encountered a seemingly recessively inherited lethal perinatal OI with radiologically crumpled femora and beaded ribs--the 'broad-bone' type. By scanning electron microscopy, Levin et al. (1982) found no abnormality of the teeth in a case of OI congenita with death from pneumonia at age 10 months. Since abnormalities have been described in reported cases, these results may reflect heterogeneity in OI congenita. Levin et al. (1982) suggested that the case best fits OI type III of Sillence et al. (1979). They agreed with Sillence et al. (1979) that the term 'congenita' has limited usefulness since it merely indicates that fractures were present at birth--a feature that may occur in type I (166200), II, or III (259420). Elejalde and Mercedes de Elejalde (1983) observed a family in which the fourth child had OIC and died a few hours after birth, and OIC was diagnosed at 17 weeks' gestation in the fifth pregnancy by ultrasonography. Diagnosis was based on low echogenic properties of all bones, abnormally shaped skull and rib cage, distally thinned ribs, and short, deformed long bones with wide metaphyses and thin diaphyses. Radiographically the disorder reported by Buyse and Bull (1978) in 3 sibs (see 259410) was indistinguishable from Sillence's group A (see HISTORY), and chondroosseous histopathology was also identical; however, low birth weight, microcephaly, and cataracts were also present. The patients may, of course, have been homozygous for 2 separate but linked mutations or for a small chromosomal aberration. Byers et al. (2006) published practice guidelines for the genetic evaluation of suspected OI. Inheritance Autosomal recessive inheritance of osteogenesis imperfecta had been proposed, but in most well-studied cases the diagnosis was found to be in error or a parent was mosaic for a heterozygous mutation in a collagen I gene. Smars et al. (1961), McKusick (1962), Awwaad and Reda (1960), and others described families with 2 or more sibs thought to have OIC but with ostensibly normal parents. Such is probably to be expected of a dominant trait with wide expressivity and does not require a recessive explanation. Hanhart (1951), however, described an inbred kindred with affected members in 5 sibships. Here germinal mosaicism is not a satisfactory explanation. In all such studies, care must be taken not to confuse hypophosphatasia (e.g., 241500) for osteogenesis imperfecta. Kaplan and Baldino (1953) described a kindred derived from an inbred, Arabic-speaking, polygamous sect called the Mozabites, living in southern Algeria. Nine cases occurred in 4 sibships among the descendants. Kaplan et al. (1958) and Laplane et al. (1959), in a follow-up of the same kindred, described 19 cases. Parental consanguinity was noted by several authors, including Freund and Lehmacher (1954) and Rohwedder (1953); the latter described a case in which the parents were brother and sister. Meyer (1955) reported 'atypical osteogenesis imperfecta' in several of the 11 offspring of a mentally defective woman by her own father. Manifestations were spontaneous fractures, generalized osteoporosis, and Wormian bones in the area of the lambdoidal sutures. Blue sclerae and deafness were not present. Young and Harper (1980) concluded that autosomal recessive inheritance is unlikely to apply to most cases of OIC, including the 'thick boned' variety. They had information on 79 cases with multiple fractures present at birth. In only 3 families was more than 1 affected child born to normal parents and only 1 of the 79 families had consanguineous parents. The empiric recurrence risk figure is probably closer to 3% than 25%. Thompson et al. (1987) thought that recessive inheritance was likely for Sillence subclassification group B of type II OI (see HISTORY) because of the frequency of parental consanguinity and multiple affected sibs. On the other hand, the evidence for dominant inheritance was strong in the case of group A (Young et al., 1987). Young et al. (1987) ascertained 30 cases of radiologically proven type II osteogenesis imperfecta of the Sillence group A subclassification. All were isolated cases, with 19 unaffected foreborn and 19 unaffected afterborn sibs. Two sets of parents, both Asian, were consanguineous. Paternal age effect was observed. Byers et al. (1988) collected family data and radiographs for 71 probands with the perinatal lethal form of OI and analyzed the collagens synthesized by dermal fibroblasts cultured from 43 of the probands, 19 parental pairs, and single parents of each of 4 additional probands. In 65 families for which there were complete data, there was recurrence of OI II in 5 families such that 6 (8.6%) of 70 sibs were affected. In 2 families with recurrence, the radiographic phenotype was milder than that for the remainder; and 1 of those families was consanguineous, suggesting autosomal recessive inheritance. In the remaining 3 families there was no evidence of consanguinity, but in one of them gonadal mosaicism in the mother was suspected because 3 affected children were born of 2 different fathers. Biochemical studies indicated that the OI II phenotype is basically heterogeneous, that most cases result from new dominant mutations in the genes encoding type I collagen, and that some recurrences can be accounted for by gonadal mosaicism in one of the parents. Daw et al. (1990) reported a remarkable family in which lethal OI of the thin-boned type occurred in 6 sibs with normal, unrelated parents. Daw et al. (1990) suggested that this was an instance of gonadal mosaicism for a dominant mutation. Bonadio et al. (1990) described an infant apparently homozygous for a point mutation in the COL1A1 gene (120150.0039), a G-to-A transition at the +5 position within the spliced donor site of intron 14. In both parents, who were normal and unrelated, Bonadio et al. (1990) found absence of the mutation in all cells studied. They found evidence for uniparental disomy for chromosome 17 (Bonadio, 1990), however. This mutation, combined with uniparental disomy, may be responsible for the functionally homozygous state of the mutation in this infant. Bonadio (1992) had not had an opportunity to study the possibility further. What one might call pseudorecessive inheritance has been observed in lethal OI congenita, which, as noted earlier, is almost always a new autosomal dominant mutation. Cohn et al. (1990) and Edwards et al. (1992) observed 2 offspring with lethal OI and demonstrated mosaicism in 1 parent. In the first case, the mutation was in the COL1A1 gene (120150.0016) and the mother had the mosaicism and was mildly affected. In the second case, the mutation was in the COL1A2 gene (120160.0019) and it was the father who was mosaic. His only manifestations of OI were shorter stature than his unaffected male relatives and mild dentinogenesis imperfecta. In an investigation of paternal age in 106 cases of nonfamilial osteogenesis imperfecta compared with matched controls, Orioli et al. (1995) found only slightly elevated mean paternal age in a South American collaboration and no increase in an Italian collaboration. This was in contrast to the findings in 78 achondroplasia (100800) patients, in which a mean paternal age was greatly increased, and in 64 cases of thanatophoric dysplasia (see 187600), in which it was less strikingly elevated. Cole and Dalgleish (1995) estimated the recurrence rate at 7%, owing to germline mosaicism in 1 parent. From molecular genetic studies of 39 cases from a series totaling 65 (40M; 25F), Tsipouras et al. (1985) concluded that most cases of OI II are the result of new dominant mutation. They observed no parental age effect. Horwitz et al. (1985) presented evidence that maternal gonadal mosaicism was responsible for 3 infants with OI II with 2 different fathers. Biochemical Features In a deceased 4-day-old infant with OIC, Trelstad et al. (1977) found that the collagen of bone had twice normal content of hydroxylysine and cartilage collagen, a 55% increase. The levels of covalently bound glucose and galactose were proportionately increased. Francis et al. (1981) found increased ratio of alpha-1(I) to alpha-2(I) and of alpha-1(III) to alpha-2(I) in both clinically normal parents of a child with severe OI. Barsh and Byers (1981) restudied the cultured cells from a multiply studied patient from the Johns Hopkins Hospital with perinatal lethal osteogenesis imperfecta. This case was the basis of the report by Penttinen et al. (1975) which provided evidence that one form of OIC has a defect in synthesis of type I collagen. The clinical findings in this case were reported by Heller et al. (1975) and the cultured fibroblasts were also studied by Delvin et al. (1979), Steinmann et al. (1979), and Turakainen et al. (1980). Barsh and Byers (1981) found that the cells produced 2 distinct pro-alpha-1 chains of type I collagen, which were synthesized at the same rate. Analysis of cyanogen bromide peptides indicated that the 2 chains differed in their primary structures. Thus, structural abnormalities of type I procollagen prevented this molecule from being secreted normally, resulting in an anomalously low ratio of type I procollagen to other extracellular matrix molecules. In 4 phenotypically identical patients, a defect in secretion of type I procollagen was demonstrated. Thus, although lethal OI congenita is probably heterogeneous, one form may be autosomal dominant new mutational in nature and have a defect in secretion of type I collagen. Byers et al. (1984) gave an update based on new biochemical information. Molecular Genetics In studies of material from the patient of Penttinen et al. (1975) and Heller et al. (1975), Williams and Prockop (1983) found deletion of about 500 bp in the gene for pro-alpha-1(I). See also Chu et al. (1983). This was probably the first characterization of a collagen gene defect. The deletion left coding sequences in register on either side. As a result, the mutant allele was expressed and half the pro-alpha-1 chains synthesized by fibroblasts were shortened by about 80 amino acids. Three-fourths of the procollagen trimers synthesized by fibroblasts contained either 1 or 2 shortened pro-alpha chains. The shortening was such that the presence of even 1 of the mutant pro-alpha-1 chains in a procollagen molecule prevented it from folding into a triple-helical configuration. Trimers containing 1 or 2 mutant pro-alpha-1 chains were rapidly degraded. Prockop (1984) called this 'protein suicide.' In further studies Chu et al. (1985) showed that the deletion eliminated 3 exons of the triple helical domain. The termini of the rearrangement were located within 2 short inverted repeats, suggesting that the self-complementary nature of these DNA elements favored formation of an intermediate that was the basis of the deletion. The patient's fibroblasts contained elevated type III collagen (120180) mRNA. The severity of the clinical presentation (with avulsion of the head and an arm during delivery) is explained. A null allele for pro-alpha-2 chains had much less deleterious effect (de Wet et al., 1983). Steinmann et al. (1982) and Steinmann et al. (1984) studied material from a male newborn with the lethal perinatal form of OI (and avulsion of an arm). The mother had the Marfan syndrome, as did several other members of the kindred including 2 sibs of the OI proband. The father was healthy and young. The infant's dermis was thinner and collagen fibrils were smaller in diameter than normal and fibroblasts showed dilated endoplasmic reticulum filled with granular material. Cultured fibroblasts synthesized 2 different species of pro-alpha-1(I) chains in about equal amounts. One chain was normal; the other contained cysteine in the triple-helical portion of the COOH-terminal cyanogen bromide peptide alpha-1(I)CB6. Collagen molecules that contained 2 copies of the mutant chain formed alpha-1(I)-dimers linked through interchain disulfide bonds. Molecules containing either 1 or 2 mutant chains were delayed in secretion and underwent excessive posttranslational modification with resulting increased lysyl hydroxylation and hydroxylysyl glycosylation. Delay in triple-helix formation seemed to be responsible for the increased modification. Neither parent had a demonstrable abnormality of collagen. The authors suspected a point mutation with substitution of cysteine for glycine. This may have been the first known example of a point mutation in a collagen gene (Steinmann, 1983). The role of the mother's Marfan syndrome is unclear; the molecular defect underlying the Marfan syndrome in this family had not been determined and it was not known whether the infant inherited the Marfan gene from the mother. The triple-helical domain of type I collagen contains no cysteine. It is made up of repeating triplets of amino acids Gly-X-Y where X and Y are any amino acid except tryptophan, tyrosine, and cysteine and most commonly proline and hydroxyproline, respectively. The fact that type III collagen contains cysteine (and tyrosine) in its triple-helical domain may indicate that its substitution for X or Y in type I collagen would not have as disruptive effects as observed here. In the lethal case thought by Steinmann et al. (1984) to represent a point mutation, Cohn et al. (1986) indeed found substitution of cysteine for glycine at position 988 of the triple-helical portion of half of the alpha-1(I) chains of type I collagen (120150.0018). The mutation disrupted the (G-X-Y)n pattern necessary for formation of the triple helix. This experiment of nature established the minimal mutation capable of producing lethal disease, and the lethality indicated the selective mechanism for stringent maintenance of collagen gene structure. A possibly high mutation rate for the OI II phenotype, which may be at least as frequent as 1 in 60,000 births, can be explained, even if most of them are dominants of the type described here. The COL1A1 gene may present a large target for lethal mutations because any change in the first 2 positions of the repeated GGN-NNN-NNN nucleotide sequence that encodes the triple-helical tripeptide Gly-X-Y is likely to be lethal if it occurs in the part of the gene encoding the carboxy-terminal half of the triple helix. Since the substitution of cysteine for glycine at position 988 of COL1A1 (120150.0018) was in the critical first position of the G-X-Y triplet, the mutation in the heterozygous state caused a lethal clinical picture. Sequence data confirmed that the mutation was a single base G-to-T change (Cohn et al., 1986). Conversely, Steinmann et al. (1986) found that the substitution of cysteine in the same domain of the alpha-1 chain in another family resulted in mild autosomal dominant OI (166200). The difference resulted from the fact that the substitution of cysteine was for X or Y rather than for G in the G-X-Y triplet. Genotype/Phenotype Correlations Bodian et al. (2009) screened DNA samples from 62 unrelated individuals with the perinatal lethal form of OI and identified COL1A1 or COL1A2 mutations in 59 samples and CRTAP or LEPRE1 (610339) mutations in 3 samples. The authors identified 61 distinct heterozygous mutations in the COL1A1 and COL1A2 genes, including 5 nonsynonymous rare variants of unknown significance. Sixty SNPs in the COL1A1 gene (including 17 novel variants) and 82 SNPs in COL1A2 (including 18 novel variants) were reported. Their findings suggested a frequency of 5% for CRTAP and LEPRE1 recessive mutations in severe/lethal OI. A computer model for predicting the outcome of glycine substitutions within the triple-helical domain of COL1A1 chains predicted lethality with 90% accuracy (26 of 29 mutations). Takagi et al. (2011) studied 4 Japanese patients, including 2 unrelated patients with what the authors called 'classic OI IIC' (see HISTORY) and 2 sibs with features of 'OI IIC' but less distortion of the tubular bones (OI dense bone variant). No consanguinity was reported in their parents. In both sibs and 1 sporadic patient, they identified heterozygous mutations in the C-propeptide region of COL1A1 (120150.0069 and 120150.0070, respectively), whereas no mutation in this region was identified in the other sporadic patient. Familial gene analysis revealed somatic mosaicism of the mutation in the clinically unaffected father of the sibs, whereas their mother and healthy older sister did not have the mutation. Histologic examination in the 2 sporadic cases showed a network of broad, interconnected cartilaginous trabeculae with thin osseous seams in the metaphyseal spongiosa. Thick, cartilaginous trabeculae (cartilaginous cores) were also found in the diaphyseal spongiosa. Chondrocyte columnization appeared somewhat irregular. These changes differed from the narrow and short metaphyseal trabeculae found in other lethal or severe cases of OI. Takagi et al. (2011) concluded that heterozygous C-propeptide mutations in the COL1A1 gene may result in OI IIC with or without twisting of the long bones and that OI IIC appears to be inherited as an autosomal dominant trait. Nomenclature The autosomal recessive form of lethal OI designated OI VII (610682) had previously been designated OI IIB (OI2B). For a short time, the autosomal dominant form of lethal OI (OI II; OI2) was designated OI IIA (OI2A). History Sillence et al. (1984) reviewed 48 cases of the perinatal lethal form of OI (OI type II) and subclassified them into 3 categories on the basis of radiologic features: group A (38 cases)--short, broad, 'crumpled' long bones, angulation of tibias and continuously beaded ribs; group B (6 cases)--short, broad, crumpled femurs, angulation of tibias but normal ribs or ribs with incomplete beading; and group C (4 cases)--long, thin, inadequately modeled long bones with multiple fractures and thin beaded ribs. Information for segregation analysis was available on 33 families. Two or more sibs were affected in 6 of the families; 3 of these 6 families were examined by the authors and found to fall into group A, 2 into group B, and 1 into group C. The parents were related in 1 family of type A and 1 family of type C. Mean paternal age was not increased. For all these reasons, Sillence et al. (1984) concluded that most cases of OI II represent an autosomal recessive disorder. There is, however, clearly an autosomal dominant form as indicated by biochemical evidence provided by the studies of Barsh and Byers (1981) that there are 2 types of collagen I alpha-1 chains synthesized by fibroblasts. Commenting on the paper of Sillence et al. (1984), Spranger (1984) stated that 'Type IIC poses no major nosologic problems' because of the radiologic distinctiveness. On radiographic grounds, Tsipouras et al. (1985) suggested that 5 types of type II OI could be distinguished. Five patients in 3 families appeared to have type 5, the least severe form. The parents of these 5 patients were consanguineous, and Tsipouras et al. (1985) suggested that the inheritance of type 5 may be autosomal recessive. Heterogeneity Aitchison et al. (1988) studied a child with type II OI of Sillence subclassification B who was the product of consanguineous Pakistani parents. A brother and sister of the proband's mother, also the product of a consanguineous mating, had died with OI in the perinatal period. The proband was heterozygous for COL1A1 and COL1A2 genotypes, suggesting that the mutation causing the disease in this child was not at either of the structural genes for type I collagen. Animal Model Stacey et al. (1988) reproduced the OI II phenotype in transgenic mice carrying a mutant alpha-1(I) collagen gene into which specific glycine substitutions had been engineered. The experiments reproduced the findings in patients in whom a single point mutation resulted in OIC: substitution of glycine by arginine at position 391 (Bateman et al., 1987) or substitution of glycine by cysteine at position 988 (Cohn et al., 1986). Constantinou et al. (1989) described a lethal variant of OI in which a G-to-T substitution converted glycine to cysteine at position 904 of the COL1A1 gene. In addition, the proband may have inherited a second mutation from her asymptomatic mother that produced an overmodified and thermally unstable species of type I procollagen. Her mother was somewhat short and had slightly blue sclerae. Lamande et al. (1989) used the method of Cotton et al. (1988) to identify single base changes in the subunits of type I collagen in 5 patients with OIC. In 4 cases, the substitution was found in the alpha-1 subunit, and in 1 it was located in the alpha-2 chain. In all 5 cases, the first glycine in the amino acid triplet was replaced: gly-973 and gly-1006 to val, gly-928 to ala, and gly-976 to arg in the alpha-1 chain and gly-865 to ser in the alpha-2 chain. These mutations emphasize the importance of the Gly-X-Y repeating amino acid triplet for normal collagen helix formation and function. The method of Cotton et al. (1988) exploits the increased chemical modification of cytosines by hydroxylamine and of thymines by osmium tetroxide, when they are not paired with their complementary base. The DNA chain is then cleaved at the modified bases with piperidine. The use of radioactively end-labeled DNA probes allows the position of the mismatched cytosines and thymines in the probe to be determined by electrophoresis of the cleavage products. Cole et al. (1992) described the occurrence of premature birth in OIC due to precocious rupture of membranes and antepartum hemorrhage. INHERITANCE \- Autosomal dominant GROWTH Height \- Short limb dwarfism Weight \- Low birth weight HEAD & NECK Eyes \- Blue sclerae Nose \- Beaked nose CARDIOVASCULAR Heart \- Congestive heart failure RESPIRATORY Lung \- Pulmonary insufficiency CHEST Ribs Sternum Clavicles & Scapulae \- Beaded ribs SKELETAL \- Numerous multiple fractures present at birth Skull \- Wormian bones \- Soft calvaria \- Absent calvarial mineralization \- Large fontanelles Spine \- Platyspondyly Pelvis \- Hips usually flexed and abducted (frog-leg position) \- Flattened acetabulae and iliac wings Limbs \- Tibial bowing \- Broad crumpled long bones \- Telescoped femur SKIN, NAILS, & HAIR Skin \- Thin skin PRENATAL MANIFESTATIONS \- Nonimmune hydrops Delivery \- Premature birth MISCELLANEOUS \- Perinatal lethal \- Survival greater than one year rare \- Gonadal and somatic mosaicism reported in parent \- Ultrasound detection in second trimester of pregnancy MOLECULAR BASIS \- Caused by mutation in the collagen I, alpha-1 polypeptide gene (COL1A1, 120150.0001 ) \- Caused by mutation in the collagen I, alpha-2 polypeptide gene (COL1A2, 120160.0007 ) ▲ 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	OSTEOGENESIS IMPERFECTA, TYPE II	c0268358	27,216	omim	https://www.omim.org/entry/166210	2019-09-22T16:37:01	{"doid": ["0110341"], "mesh": ["C536042"], "omim": ["166210"], "orphanet": ["216804", "666"], "synonyms": ["Alternative titles", "OI, TYPE II", "OSTEOGENESIS IMPERFECTA CONGENITA, PERINATAL LETHAL FORM", "OSTEOGENESIS IMPERFECTA CONGENITA", "VROLIK TYPE OF OSTEOGENESIS IMPERFECTA"], "genereviews": ["NBK1295"]}
Not to be confused with Hypopituitarism. Hyperpituitarism Pituitary gland SpecialtyEndocrinology SymptomsHirsutism[1] CausesFrom a pituitary microadenoma.[2] Diagnostic methodMRI[2] TreatmentDopamine agonists [2] Hyperpituitarism is a condition due to the primary hypersecretion of pituitary hormones;[3] it typically results from a pituitary adenoma. In children with hyperpituitarism, disruption of growth regulation is rare, either because of hormone hypersecretion or because of manifestations caused by local compression of the adenoma.[2] ## Contents * 1 Symptoms and signs * 2 Cause * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 See also * 7 References * 8 Further reading * 9 External links ## Symptoms and signs[edit] Symptoms caused by hormone excess and associated mass effects include: * Hirsutism[1] * Visual field loss or double vision[4] * Excessive sweating[4] * Decreased libido[1] * Lethargy[5] * Headache[5] * Muscle weakness[4] * Bruisability[1] ## Cause[edit] The cause of hyperpituitarism in most cases is due to pituitary adenomas. They usually come from the anterior lobe, are functional and secrete the hormone, GH and prolactin.[6] ## Mechanism[edit] Growth hormone Evidence indicates that the mechanism of hyperpituitarism can originate from genetic disruption causing pituitary tumorigenesis, most pituitary adenomas are monoclonal, which in turn indicates their origin from an event in a single cell.[2] There are three hormones that are oversecreted resulting in the pituitary adenoma: prolactin, adrenocorticotropic hormone (ACTH), and growth hormone (GH).[medical citation needed] Excess prolactin may result in a prolactinoma[7] Excess GH results in gigantism, the severity of gigantism depends on whether the epiphyseal plate is open.[8] The four most common types of hyperpituitarism are prolactinoma, corticotropinoma (Cushing's disease), somatotropinoma (gigantism), and thyrotropinoma .[9] ## Diagnosis[edit] For the diagnosis of hyperpituitarism it depends on the cell type(s) affected, clinical manifestations of hormone excess may include, gigantism or acromegaly, which can be identified by clinical and radiographic results.[10] Cushing's disease diagnosis is done with a physical examination, laboratory tests and X rays of the pituitary glands (to locate tumors)[11] For prolactinoma, diagnosis comes in the form of the measurement of serum prolactin levels and x-ray of pituitary gland.[12] ## Treatment[edit] Dopamine Treatment (for hyperpituitarism) in the case of prolactinoma consists of long-term medical management. Dopamine agonists are strong suppressors of PRL secretion and establish normal gonadal function. It also inhibits tumor cell replication (in some cases causes tumor shrinkage)[13] Treatment for gigantism begins with establishing target goals for IGF-1, transsphenoidal surgery (somatostatin receptor ligands- preoperatively) and postoperative imaging assessment.[14] For Cushing's disease there is surgery to extract the tumor; after surgery, the gland may slowly start to work again, though not always.[15] ## See also[edit] * Hypopituitarism ## References[edit] 1. ^ a b c d Hales, edited by Stuart C. Yudofsky, Robert E. (2007). The American Psychiatric Publishing textbook of neuropsychiatry and behavioral neurosciences (5th ed.). Washington, DC: American Psychiatric Pub. p. 815. ISBN 978-1-58562-239-9. Retrieved 26 August 2015.CS1 maint: extra text: authors list (link) 2. ^ a b c d e Hyperpituitarism at eMedicine 3. ^ "Hyperpituitarism". Freedictionary.com. Farlex. 2015. Retrieved 28 August 2015. 4. ^ a b c Baumle, [edited by] Lois White, Gena Duncan, Wendy (2013). Medical-surgical nursing : an integrated approach (3rd ed.). Clifton Park, NY: Delmar Cengage Learning. p. 595. ISBN 978-1-4354-8802-1. Retrieved 26 August 2015.CS1 maint: extra text: authors list (link) 5. ^ a b "Prolactinoma". MedlinePlus. NIH. Retrieved 26 August 2015. 6. ^ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon C. (2014-08-27). Robbins and Cotran Pathologic Basis of Disease, Professional Edition: Expert Consult - Online. Elsevier Health Sciences. ISBN 9780323296397. 7. ^ "Prolactinoma". NIH. NIH. 2014. Retrieved 26 August 2015. 8. ^ Gigantism and Acromegaly at eMedicine 9. ^ Aguirre, Alfredo (2014). Cellular Endocrinology in Health and Disease. Elsevier. p. 24. ISBN 978-0-12-408134-5. 10. ^ "Acromegaly". NIH. National Institute of Diabetes and Digestive, Kidney Disease. 2014. Retrieved 28 August 2015. 11. ^ "Cushing's Syndrome". www.niddk.nih.gov. Retrieved 2015-08-25. 12. ^ Laws, Edward; Ezzat, Shereen; Asa, Sylvia; Rio, Linda (2013-02-21). Pituitary Disorders: Diagnosis and Management. John Wiley & Sons. ISBN 9781118559376. 13. ^ Hyperpituitarism~treatment at eMedicine 14. ^ "National Guideline Clearinghouse \| Acromegaly: an Endocrine Society clinical practice guideline". www.guideline.gov. Archived from the original on 2015-09-07. Retrieved 2015-08-25. 15. ^ MedlinePlus Encyclopedia: Cushing disease ## Further reading[edit] * Handbook of Medical-surgical Nursing. Lippincott Williams & Wilkins. 2006-01-01. ISBN 9781582554457. * Atreja, Gaurav; Jain, Nitul; Atreja, ShikhaHanda; Sukhija, Urvashi (2012). "Oral manifestations in growth hormone disorders". Indian Journal of Endocrinology and Metabolism. 16 (3): 381–3. doi:10.4103/2230-8210.95678. PMC 3354844. PMID 22629503. * Illustrated Manual of Nursing Practice. Lippincott Williams & Wilkins. 2002-01-01. ISBN 9781582550824. ## External links[edit] Classification D * ICD-10: E22 * ICD-9-CM: 253.1 * MeSH: D006964 External resources * eMedicine: ped/1092 Scholia has a topic profile for Hyperpituitarism. * v * t * e Pituitary disease Hyperpituitarism Anterior * Acromegaly * Hyperprolactinaemia * Pituitary ACTH hypersecretion Posterior * SIADH General * Nelson's syndrome * Hypophysitis Hypopituitarism Anterior * Kallmann syndrome * Growth hormone deficiency * Hypoprolactinemia * ACTH deficiency/Secondary adrenal insufficiency * GnRH insensitivity * FSH insensitivity * LH/hCG insensitivity Posterior Neurogenic diabetes insipidus General * Empty sella syndrome * Pituitary apoplexy * Sheehan's syndrome * Lymphocytic hypophysitis * Pituitary adenoma [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	Hyperpituitarism	c0020506	27,217	wikipedia	https://en.wikipedia.org/wiki/Hyperpituitarism	2021-01-18T18:29:31	{"mesh": ["D006964"], "umls": ["C0020506"], "icd-9": ["253.1"], "icd-10": ["E22"], "wikidata": ["Q3801524"]}
Transthyretin (TTR)-related familial amyloidotic cardiomyopathy is a hereditary TTR-related systemic amyloidosis (ATTR) with predominant cardiac involvement resulting from myocardial infiltration of abnormal amyloid protein. ## Epidemiology Prevalence is unknown. Patients present during adulthood (usually after 30 years of age) with restrictive cardiomyopathy (with varying degrees of chronic heart failure and possible brady/tachyarrhythmias). ## Clinical description ATTR cardiomyopathy is often accompanied by sensorimotor/autonomic polyneuropathy (familial amyloid polyneuropathy; see this term) but in some cases phenotypic expression of ATTR may be exclusively cardiac. ## Etiology Over 80 pathogenetic mutations in the TTR gene (18q12.1) have been reported so far. The phenotype of ATTR varies depending on the particular TTR mutation, geographic area and the type of aggregation (endemic/non-endemic). Several specific TTR mutations are associated with predominant cardiac involvement. Among these, V122I is particularly common among African-Americans (3.5% of the population) and the L111M mutation, first reported in a Danish kindred, has been associated with exclusive cardiac involvement. ## Diagnostic methods The gold standard for diagnosis of amyloidosis is histological analysis and Congo red staining of biopsy specimens. Detection of TTR mutations allows confirmation of the diagnosis. A high level of diagnostic suspicion of cardiac amyloidosis can be generated by characteristic echocardiographic and ECG findings, and confirmed by magnetic resonance imaging with late enhancement. A family history of neurologic and/or cardiac disease may suggest TTR etiology. ## Differential diagnosis The differential diagnosis should include other infiltrative/storage myocardial diseases, including other types of cardiac amyloidosis, such as AL amyloidosis (see this term). Hypertrophic cardiomyopathy (see this term) should also be included in the differential diagnosis. ## Genetic counseling ATTR is transmitted as an autosomal dominant trait. ## Management and treatment As the abnormal protein responsible for ATTR is almost exclusively produced by the liver, the only consolidated treatment for ATTR is orthotopic liver transplantation (OLT), which provides a ``surgical gene therapy'' for patients with amyloidotic cardiomyopathy. Combined heart-liver transplantation may also be considered. ## Prognosis In patients with cardiac-related symptoms, 5-year survival is less than 50%. Major events include progressive heart failure and sudden death due to arrhythmia. [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	ATTRV122I amyloidosis	c2751492	27,218	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85451	2021-01-23T17:25:07	{"mesh": ["C567782"], "omim": ["105210"], "icd-10": ["E85.4+", "I43.1*"], "synonyms": ["ATTR cardiomyopathy", "ATTRV122I-related amyloidosis", "TTR-related amyloid cardiomyopathy", "TTR-related cardiac amyloidosis", "Transthyretin amyloid cardiopathy", "Transthyretin-related familial amyloid cardiomyopathy"]}
Corpus callosum agenesis-abnormal genitalia syndrome is a rare, genetic developmental defect during embryogenesis syndrome characterized by agenesis of the corpus callosum, mild to severe neurological manifestations (intellectual disability, developmental delay, epilepsy, dystonia), and urogenital anomalies (hypospadias, cryptorchidism, renal dysplasia, ambiguous genitalia). Additionally, skeletal anomalies (limb contractures, scoliosis), dysmorphic facial features (prominent supraorbital ridges, synophris, large eyes) and optic atrophy have been observed. [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	Corpus callosum agenesis-abnormal genitalia syndrome	c0796124	27,219	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2508	2021-01-23T18:55:55	{"gard": ["4528"], "mesh": ["C563110"], "omim": ["300004"], "icd-10": ["Q87.8"], "synonyms": ["ACC-abnormal genitalia syndrome", "Microcephaly-corpus callosum agenesis-abnormal genitalia syndrome", "Proud syndrome", "Proud-Levine-Carpenter syndrome"]}
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-26 (RP26) is caused by homozygous or compound heterozygous mutation in the CERKL gene (608381), which encodes a ceramide kinase, on chromosome 2q31. For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. Mapping Bayes et al. (1998) performed linkage analysis in a large nuclear Spanish family with 5 sibs affected by autosomal recessive retinitis pigmentosa (arRP). After excluding several genomic regions containing loci for retinal dystrophies, a genomewide search for linkage was undertaken. Positive lod scores were obtained with markers on chromosome 2q31-q33, defining an interval of about 7 cM for this novel ARRP locus, designated RP26, between D2S148 and D2S161. By homozygosity mapping, Tuson et al. (2004) refined the RP26 locus in this family to a 2.5-Mb region on chromosome 2q31.2-q32.3. Molecular Genetics Tuson et al. (2004) identified a novel gene, CERKL, in the RP26 critical linkage region and found a homozygous mutation in exon 5 (608381.0001) of this gene in all of the patients from the RP26 family reported by Bayes et al. (1998). They identified the same mutation in another unrelated Spanish pedigree with ARRP. Nishiguchi et al. (2013) performed whole-genome sequencing in 16 unrelated RP patients from diverse ethnic backgrounds and identified 2 patients of mixed European ancestry who were both compound heterozygous for nonsense and frameshift mutations in the CERKL gene (608381.0001-608381.0004). [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	RETINITIS PIGMENTOSA 26	c0035334	27,220	omim	https://www.omim.org/entry/608380	2019-09-22T16:07:55	{"doid": ["0110368"], "mesh": ["D012174"], "omim": ["608380"], "orphanet": ["791"], "genereviews": ["NBK1417"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive myosin storage myopathy (MSMB) is caused by homozygous mutation in the MYH7 gene (160760) on chromosome 14q12. An autosomal dominant form of myosin storage myopathy (MSMA; 608358) is caused by heterozygous mutation in the MYH7 gene. Clinical Features Onengut et al. (2004) reported 2 brothers with hyaline body myopathy; 1 of the brothers recalled weakness from childhood, but did not become severely symptomatic until age 28, whereas the other brother was asymptomatic until age 33 years. Both patients showed scapuloperoneal weakness and atrophy with an elevated creatine kinase (2- to 3-fold increase). The brother with earlier onset also had a long face, high-arched palate, and decreased cardiac systolic function. Muscle biopsies of both patients showed variation in fiber size with marked type I fiber predominance. Approximately 15 to 20% of the fibers had central nuclei. The most striking finding was the presence of subsarcolemmal hyalinized structures, which were present in 25 to 30% of type I fibers. The hyalinized structures lacked reactivity for periodic acid Schiff (PAS) and oxidative enzymes, and stained positive for ATPase at pH 4.3. Yuceyar et al. (2015) reported follow-up of the 2 brothers studied by Onengut et al. (2004), who were born of consanguineous Turkish parents. The older brother developed severe progressive dilated cardiomyopathy and respiratory insufficiency in his forties. Scapuloperoneal muscular atrophy and weakness was slowly progressive, and he had scapular winging. The younger brother had milder progression of the muscle weakness and mild symptoms of cardiac involvement. Tajsharghi et al. (2007) reported 3 adult sibs, born of second-cousin British parents, with myosin storage myopathy associated with hypertrophic cardiomyopathy and respiratory failure. Muscle biopsies from all 3 sibs showed findings typical for myosin storage myopathy, with hyaline bodies seen in type 1 fibers. All patients had mildly increased serum creatine kinase as well as onset of cardiac symptoms as young adults. The proband was a 44-year-old man with short stature, myopathic facies, high-arched palate, scoliosis, and proximal muscle weakness and wasting. He had leg weakness and hypercapnic respiratory failure necessitating ventilatory support. Investigation revealed hypertrophic cardiomyopathy and heart failure. His sister had progressive muscle weakness, required a wheelchair by age 45, and died of cardiac failure at age 57. His brother had mild proximal muscle weakness and wasting and died of cardiac failure at age 32. Postmortem examination of affected cardiac muscle from 1 patient showed fibrosis, loss of myocytes, and hyaline bodies in the remaining myocytes. Inheritance The transmission pattern of hyaline body myopathy in the family reported by Onengut et al. (2004) was consistent with autosomal recessive inheritance. Molecular Genetics In a 44-year-old man, born of consanguineous British parents, with autosomal recessive myosin storage myopathy, Tajsharghi et al. (2007) identified a homozygous missense mutation in the MYH7 gene (E1883K; 160760.0035). He had 2 similarly affected sibs who died of cardiac failure, but their DNA was unavailable for study. In 2 Turkish brothers, born of consanguineous parents, with autosomal recessive myosin storage myopathy, who were originally reported by Onengut et al. (2004), Yuceyar et al. (2015) identified a homozygous missense mutation in the MYH7 gene (R1820W; 160760.0047). The mutation, which was found by linkage analysis and candidate gene sequencing, segregated with the disorder in the family. Functional studies of the variant were not performed. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Myopathic facies (in some patients) Mouth \- High-arched palate (in some patients) CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy \- Dilated cardiomyopathy \- Cardiac failure \- Cardiac muscle contains hyaline bodies RESPIRATORY \- Respiratory insufficiency SKELETAL Spine \- Scoliosis (in some patients) MUSCLE, SOFT TISSUES \- Scapuloperoneal weakness \- Scapuloperoneal atrophy \- EMG shows myopathic changes \- Muscle biopsy shows type I fiber predominance \- Centralized nuclei \- Subsarcolemmal hyaline bodies in 25-30% type I fibers only \- Positive staining for ATPase activity at pH of 4.3 \- Positive staining for slow myosin heavy chain \- No staining for oxidative enzymes \- No staining for periodic acid Schiff (PAS) LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Clinical variability \- Onset ranges from childhood to young adulthood \- Slow progression \- Two unrelated families have been reported (last curated June 2015) MOLECULAR BASIS \- Caused by mutation in the myosin, heavy chain 7, cardiac muscle, beta gene (MYH7, 160760.0035 ) ▲ 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	MYOPATHY, MYOSIN STORAGE, AUTOSOMAL RECESSIVE	c1850709	27,221	omim	https://www.omim.org/entry/255160	2019-09-22T16:24:35	{"doid": ["0111268"], "mesh": ["C564970"], "omim": ["255160"], "orphanet": ["53698"], "synonyms": ["Alternative titles", "MYOPATHY, HYALINE BODY, AUTOSOMAL RECESSIVE"]}
Mabry et al. (1965) described a kindred with 9 males affected by a late-onset form of muscular dystrophy. These authors thought it to be different from the types of Duchenne, Becker and Dreifuss. They suggested that it differed from the Becker type, which it resembled most closely, by earlier onset (about puberty) and some histologic features. Misc \- Onset about puberty Neuro \- Late-onset muscular dystrophy Inheritance \- X-linked ▲ 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	MUSCULAR DYSTROPHY, MABRY TYPE	c1839670	27,222	omim	https://www.omim.org/entry/310000	2019-09-22T16:17:36	{"mesh": ["C564096"], "omim": ["310000"]}
Laryngeal papillomatosis is a form of recurrent respiratory papillomatosis where tumors (papillomas) grow in the larynx (voice box). Symptoms usually begin with hoarseness and/or a change in the voice. Some people may experience difficulty breathing (dyspnea) and/or experience other life-threatening complications if the papillomas block the airway. The tumors may vary in size and grow very quickly. They often grow back even when removed. Laryngeal papillomatosis is caused by two types of human papilloma virus (HPV), called HPV 6 and HPV 11. [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	Laryngeal papillomatosis	c0396072	27,223	gard	https://rarediseases.info.nih.gov/diseases/6864/laryngeal-papillomatosis	2021-01-18T17:59:31	{"mesh": ["C537876"], "umls": ["C0396072"], "synonyms": ["Warts in the throat", "Juvenile laryngeal papillomatosis (subtype)", "Recurrent laryngeal papillomatosis (subtype)"]}
A rare pituitary tumor originating from normally hormone-producing cells of the adenohypophysis, characterized by a sellar or extrasellar mass manifesting with clinical signs secondary to mass effect, but without evidence for hormonal hypersecretion. Typical manifestations are visual disturbances, headaches, cranial nerve dysfunction, and hypopituitarism but the mass may also be discovered incidentally. ## Epidemiology Prevalence of pituitary adenoma in the general population ranges between 1/1000 - 1,300; non-functioning pituitary adenoma (NFPA) accounts for 15-30% of these. Annual incidence is estimated at 1/100,000 worldwide. ## Clinical description NFPA is most often diagnosed in middle-aged adults (average age 50-60 years). The vast majority of NFPAs are revealed by mass effects on anatomic structures in the vicinity of the pituitary (headache, optic chiasm compression) and/or on pituitary hormonal function, leading to hypopituitarism. Pituitary stalk compression can also produce hyperprolactinemia causing amenorrhea and galactorrhea. Pituitary apoplexy may be the presenting feature of NFPA, with severe headaches of sudden onset, meningismus, a variably depressed sensorium, and visual disturbances. However, an increasing proportion of pituitary tumors are detected incidentally on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain performed for unrelated reasons. Very rarely, gonadotropin hypersecretion can stimulate the gonads: macro-orchidism has been reported in males and an ovarian hyperstimulation syndrome in premenopausal women with FSH (Follicle Stimulating Hormone)-secreting tumors. ## Etiology NFPAs are sporadic in the vast majority. The gene aryl hydrocarbon receptor interacting protein, AIP (11q13.3), has been identified as a susceptibility factor, particularly in cases of familial isolated pituitary adenomas (FIPA) or when NFPA begins in childhood or adolescence. NFPA may also be part of multiple endocrine neoplasia syndrome such as MEN1 (gene MEN1, 11q13). ## Diagnostic methods Assessment of tumor volume and extension is based on imaging studies (MRI). Potential visual problems related to compression of optic pathways are diagnosed by evaluation of visual acuity, visual fields and occasionally optic coherence tomography (OCT). Hypopituitarism is diagnosed by measurement of the various pituitary hormones and hormones from the target glands (cortisol, thyroid hormones, etc.). Dynamic tests may be necessary, particularly for assessment of corticotropic axis. Hyperprolactinemia may be found related to pituitary stalk compression and disinhibition of the dopaminergic tone that normally acts at the level of pituitary lactotrophs. Gonadotropins serum levels, particularly FSH may be increased arguing for the gonadotroph nature of the NFPA. ## Differential diagnosis In case of hyperprolactinemia, prolactin (PRL) serum levels are always below 150-200 ng/ml in patients with NFPAs. This distinguishes them from macroprolactinomas, which are associated with much higher PRL levels proportional to tumor size. Other differential diagnoses include other tumors of the sellar region (meningiomas, craniopharyngiomas, metastasis, etc.) and inflammatory process (hypophysitis, sarcoidosis, histiocytosis). ## Management and treatment Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion. Transsphenoidal surgery is often the first-line treatment. If a tumor remnant persists (a frequent situation in patients with large and often invasive adenomas), watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow. NFPA can sometimes recur even after complete resection. Postoperative irradiation is only considered in case of residual tumor growth or relapse. NFPA discovered incidentally may require a different approach, especially when they are small and/or remote from the optic pathways. If hypopituitarism persists, adequate hormone replacement is indicated. ## Prognosis A small excess mortality rate in women and in patients with a young age at diagnosis has been reported. [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	Non-functioning pituitary adenoma	c0338078	27,224	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91349	2021-01-23T17:57:21	{"umls": ["C0338078"], "icd-10": ["D35.2"], "synonyms": ["NFPA"]}
A rare autosomal dominant disorder characterized by a generalized enlargement of the gingiva occurring at birth or during childhood that is associated with generalized hypertrichosis developing at birth, during the first years of life, or at puberty and predominantly affecting the face, upper limbs, and midback. [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	Gingival fibromatosis-hypertrichosis syndrome	c1851120	27,225	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2026	2021-01-23T18:39:05	{"gard": ["2324"], "mesh": ["C565016"], "omim": ["135400"], "icd-10": ["L68.8"], "synonyms": ["CGHT", "Congenital generalized hypertrichosis terminalis", "Hirsutism-congenital gingival hyperplasia syndrome", "Hypertrichosis with or without gingival hyperplasia"]}
Majewski's polydactyly syndrome Other namesPolydactyly with neonatal chondrodystrophy type I This condition is inherited in an autosomal recessive manner Majewski's polydactyly syndrome, also known as polydactyly with neonatal chondrodystrophy type I, short rib-polydactyly syndrome type II, and shorts rib-polydactyly syndrome, is a lethal form of neonatal dwarfism characterized by osteochondrodysplasia (skeletal abnormalities in the development of bone and cartilage) with a narrow thorax, polysyndactyly, disproportionately short tibiae, thorax dysplasia, hypoplastic lungs and respiratory insufficiency. Associated anomalies include protruding abdomen, brachydactyly, peculiar faces, hypoplastic epiglottis, cardiovascular defects, renal cysts, and also genital anomalies. Death occurs before or at birth. The disease is inherited in an autosomal recessive pattern. It was characterized in 1971.[1] ## References[edit] 1. ^ Majewski, F.; Pfeiffer; Lenz; Müller; Feil; Seiler (1971). "Polysyndactyly, short limbs, and genital malformations--a new syndrome?". Zeitschrift für Kinderheilkunde. 111 (2): 118–138. doi:10.1007/BF00446428. PMID 4331366. ## External links[edit] Classification D * ICD-10: Q77.2 * OMIM: 263520 * DiseasesDB: 32793 * v * t * e Osteochondrodysplasia Osteodysplasia// osteodystrophy Diaphysis * Camurati–Engelmann disease Metaphysis * Metaphyseal dysplasia * Jansen's metaphyseal chondrodysplasia * Schmid metaphyseal chondrodysplasia Epiphysis * Spondyloepiphyseal dysplasia congenita * Multiple epiphyseal dysplasia * Otospondylomegaepiphyseal dysplasia Osteosclerosis * Raine syndrome * Osteopoikilosis * Osteopetrosis Other/ungrouped * FLNB * Boomerang dysplasia * Opsismodysplasia * Polyostotic fibrous dysplasia * McCune–Albright syndrome Chondrodysplasia/ chondrodystrophy (including dwarfism) Osteochondroma * osteochondromatosis * Hereditary multiple exostoses Chondroma/enchondroma * enchondromatosis * Ollier disease * Maffucci syndrome Growth factor receptor FGFR2: * Antley–Bixler syndrome FGFR3: * Achondroplasia * Hypochondroplasia * Thanatophoric dysplasia COL2A1 collagen disease * Achondrogenesis * type 2 * Hypochondrogenesis SLC26A2 sulfation defect * Achondrogenesis * type 1B * Autosomal recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia Chondrodysplasia punctata * Rhizomelic chondrodysplasia punctata * Conradi–Hünermann syndrome Other dwarfism * Fibrochondrogenesis * Short rib – polydactyly syndrome * Majewski's polydactyly syndrome * Léri–Weill dyschondrosteosis This article about a congenital malformation 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	Majewski's polydactyly syndrome	c0024507	27,226	wikipedia	https://en.wikipedia.org/wiki/Majewski%27s_polydactyly_syndrome	2021-01-18T18:56:07	{"gard": ["4833"], "mesh": ["D012779"], "orphanet": ["93269"], "wikidata": ["Q2753372"]}
A rare tumor of pancreas caused by mutations in the GCGR gene characterized by pancreatic alpha cell hyperplasia, pancreatic neuroendocrine tumors and markedly increased serum glucagon levels in the absence of a glucagonoma syndrome. Clinical manifestations may include abdominal pain, pancreatitis, fatigue, diarrhea, and diabetes mellitus. [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	GCGR-related hyperglucagonemia	None	27,227	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=438274	2021-01-23T18:58:39	{"gard": ["10460"], "icd-10": ["E16.3"], "synonyms": ["Mahvash disease"]}
A number sign (#) is used with this entry because this form of juvenile ALS is caused by mutations in the senataxin gene (SETX; 608465). For a phenotypic description and a discussion of genetic heterogeneity of amyotrophic lateral sclerosis (ALS), see ALS1 (105400). Description Childhood- and adolescent-onset forms of familial ALS (see ALS1, 105400) carry the designation 'juvenile ALS.' Several forms of autosomal recessive juvenile ALS have been identified; see ALS2 (205100) and ALS5 (602099). Clinical Features Chance et al. (1998) studied an 11-generation pedigree with a slowly progressive, autosomal dominant form of juvenile ALS, defined as a chronic motor neuron disease characterized by combined upper and lower motor neuron symptoms and signs with onset before age 25 years. The family was originally described by Myrianthopoulos et al. (1964) as having Charcot-Marie-Tooth disease (CMT; see 118200). They had traced ancestors to 17th-century England, and the disorder was documented in 8 generations, including 52 affected persons living in Southern Maryland and nearby states. In the study of Chance et al. (1998), diagnosis of early-onset selective upper- and lower-motor-neuron involvement was established by patient history, clinical findings, and results of electrophysiologic tests. Affected persons typically manifested symptoms in the second decade of life (mean age 17 years). They initially had difficulty walking; this was followed by weakness and wasting of small muscles of the hands and distal lower limbs. By the fourth or fifth decade, affected persons had significant proximal weakness and were frequently wheelchair-bound, and by the sixth decade, they had lost useful hand function. Bulbar muscles were not symptomatically involved. Among 49 affected and 34 at-risk individuals, pathologic hyperreflexia was found in 86% of affected individuals, and 17% had extensor plantar responses. In many affected individuals, weakness of the toe and foot extensor muscles prevented interpretation of the plantar response. Forty-four of 49 subjects tested had normal sensory examinations; 5 older individuals (mean age, 51 years) had slight elevation of the vibratory threshold in the feet. Rabin et al. (1999) reported the clinical and electrodiagnostic findings in 49 affected members and the neuropathologic findings in 2 autopsies of the Maryland family reported by Chance et al. (1998). Motor conduction studies, performed in 8 affected members, showed reduced evoked amplitudes and normal conduction parameters. Sensory conduction studies (8 individuals), quantitative sensory testing (4 individuals), and intracutaneous sensory fibers in skin biopsies (6 individuals) were normal in all patients tested. Electromyography (8 individuals) showed distal more than proximal chronic partial denervation and reinnervation. Postmortem spinal cord tissue demonstrated atrophic spinal cords with marked loss of anterior horn cells and degeneration of corticospinal tracts, as well as loss of neurons in the dorsal root ganglia and degeneration of the posterior columns. Axonal spheroids were present in the gray matter of the spinal cord, the dorsal root entry zones, and the peripheral nerves. Motor and sensory roots, as well as peripheral nerves, showed significant axonal loss. Swellings were prominent around motor neurons, probably representing changes in presynaptic terminals. De Jonghe et al. (2002) reported 3 unrelated families with a familial disorder that they diagnosed as distal hereditary motor neuropathy (dHMN). In 2 families, the age at onset was generally less than 6 years, whereas in the third family, some patients had a later onset, including 2 with adult onset. In all families, there was distal lower limb weakness and atrophy with later involvement of the upper limbs. Bulbar muscles were spared and sensory abnormalities were absent. Most patients had brisk reflexes, and 8 of 18 had extensor plantar responses. Two families had pes cavus. De Jonghe et al. (2002) explained their diagnosis of dHMN by the distal distribution of affected muscles, the absence of sensory abnormalities, and the pattern of disease progression. They also noted the phenotypic similarities to the kindred reported by Chance et al. (1998). By way of clinical characterization, Chen et al. (2004) stated that individuals affected with ALS4 usually have an onset of symptoms at age less than 25 years, a slow rate of progression, and a normal life span. Mapping Chance et al. (1998) performed a genomewide search in an 11-generation kindred with juvenile ALS and found a lod score of 18.8 at theta = 0.00 with D9S1847. Analysis of recombinant events identified D9S1831 and D9S164 as flanking markers, defining an interval of approximately 5 cM that harbors the ALS4 gene on chromosome 9q34. Thus, the gene for this disorder, designated ALS4, is genetically distinct from previously mapped familial ALS syndromes. Blair et al. (2000) refined the position of the ALS4 locus to a critical interval of less than 3 cM on 9q34. In 3 families with a clinical syndrome with similarities to both ALS4 and dHMN, De Jonghe et al. (2002) found positive linkage (lod scores greater than 3) with markers located within the ALS4 locus region on 9q34. They narrowed the locus to a 5-cM region between markers D9S64 and D9S164. Molecular Genetics To identify the molecular basis of ALS4, Chen et al. (2004) tested 19 genes within the critical region for ALS4 identified by linkage studies and detected 3 different missense mutations in the senataxin gene (SETX; 608465). Nomenclature De Jonghe et al. (2002) commented on potential nomenclature and classification confusion of the disorders designated distal HMN, distal spinal muscular atrophy, spinal CMT, and ALS that show linkage to the ALS4 locus. INHERITANCE \- Autosomal dominant SKELETAL Feet \- Pes cavus has been reported NEUROLOGIC Central Nervous System \- Difficulty walking \- Weakness of distal muscles (upper and lower limb) \- Atrophy of distal muscles \- Proximal weakness occurs later \- Lower motor neuron signs \- Upper motor neuron signs \- Hyperreflexia \- Extensor plantar responses \- Clonus may occur \- Loss of spinal cord anterior horn cells \- Corticospinal tracts with decreased myelin staining \- Pallor of dorsal columns of the spinal cord \- Diffuse axonal swelling \- No bulbar involvement Peripheral Nervous System \- Diffuse axonal swelling \- Axonal degeneration \- No sensory abnormalities MISCELLANEOUS \- Childhood or adolescent onset (usually less than 25 years) \- Slowly progressive \- Has also been called 'distal hereditary motor neuronopathy' (dHMN) and 'distal spinal muscular atrophy' (dSMA) MOLECULAR BASIS \- Caused by mutation in the senataxin gene (SETX, {608465.00006}) ▲ 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	AMYOTROPHIC LATERAL SCLEROSIS 4, JUVENILE	c1865409	27,228	omim	https://www.omim.org/entry/602433	2019-09-22T16:13:54	{"doid": ["0060196"], "mesh": ["C566550"], "omim": ["602433"], "orphanet": ["357043"], "synonyms": ["Alternative titles", "NEURONOPATHY, DISTAL HEREDITARY MOTOR, WITH PYRAMIDAL FEATURES"], "genereviews": ["NBK1450"]}
Disinhibited attachment disorder SpecialtyPsychiatry Disinhibited attachment disorder (DAD) according to the International Classification of Diseases (ICD-10), is defined as: "A particular pattern of abnormal social functioning that arises during the first five years of life and that tends to persist despite marked changes in environmental circumstances, e.g. diffuse, nonselectively focused attachment behaviour, attention-seeking and indiscriminately friendly behaviour, poorly modulated peer interactions; depending on circumstances there may also be associated emotional or behavioural disturbance." – F94.2 of the ICD-10. Disinhibited attachment disorder is a subtype of the ICD-10 category F94, "Disorders of social functioning with onset specific to childhood and adolescence". The other subtype of F94 is reactive attachment disorder of childhood (RAD – F94.1). Synonymous or similar disorders include affectionless psychopathy and institutional syndrome. Within the ICD-10 category scheme, disinhibited attachment disorder specifically excludes Asperger syndrome (F84.5), hospitalism in children (F43.2), and hyperkinetic disorders (F90.-). ## Contents * 1 Comparison with the DSM-IV * 2 Studies * 3 See also * 4 Sources * 5 External links ## Comparison with the DSM-IV[edit] The DSM-IV distinguishes two categories of RAD: an inhibited subtype and a disinhibited subtype (in the DSM it is listed as 313.89 under infant diagnoses). The ICD-10 describes the former, emotionally withdrawn subtype as RAD and the latter subtype as Disinhibited Attachment Disorder (DAD) (Zeanah et al., 2004). Generally, the DSM-IV criteria for the inhibited subtype of RAD were generated by studies done on children who were maltreated or abused. Criteria for the DSM-IV disinhibited subtype of RAD were based on research on children raised in institutions (Zeanah, 1996). This is largely based on the fact that inhibited subtype of RAD is more prevalent in maltreated children, and the disinhibited subtype of RAD is more prevalent in children raised in institutions (Zeanah, 2000). ## Studies[edit] In a study by Zeanah, (Zeanah et al., 2004) on reactive attachment disorder in maltreated toddlers, the criteria for DSM-IV disinhibited RAD (i.e. disinhibited attachment disorder) were: 1. not having a discriminated, preferred attachment figure, 2. not checking back after venturing away from the caregiver, 3. lack of reticence with unfamiliar adults, 4. a willingness to go off with relative strangers. For comparison, the criteria for DSM-IV inhibited RAD were: 1. absence of a discriminated, preferred adult, 2. lack of comfort seeking for distress, 3. failure to respond to comfort when offered, 4. lack of social and emotional reciprocity, and 5. emotion regulation difficulties. The authors found that these two disorders were not completely independent; a few children may exhibit symptoms of both types of the disorder. ## See also[edit] * Attachment disorder * Reactive attachment disorder ## Sources[edit] * Zeanah CH (1996). "Beyond insecurity: a reconceptualization of attachment disorders of infancy" (PDF). J Consult Clin Psychol. 64 (1): 42–52. doi:10.1037/0022-006X.64.1.42. PMID 8907083. Retrieved 2007-02-06. * Zeanah CH (2000). "Disturbances of attachment in young children adopted from institutions". J Dev Behav Pediatr. 21 (3): 230–36. PMID 10883884. * Zeanah CH, Scheeringa M, Boris NW, Heller SS, Smyke AT, Trapani J (August 2004). "Reactive attachment disorder in maltreated toddlers". Child Abuse Negl. 28 (8): 877–88. doi:10.1016/j.chiabu.2004.01.010. PMID 15350771. ## External links[edit] Classification D * ICD-10: F94.2 * v * t * e Emotional and behavioral disorders Emotional/behavioral * ADHD * Conduct disorder * Oppositional defiant disorder * Emotional/behavioral disorder (EBD) * Separation anxiety * Social functioning * Selective mutism * RAD * DAD * Tic disorders * Tourette syndrome * Speech disorders * Stuttering * Cluttering * Stereotypic movement disorder * Elimination disorders * Enuresis * Encopresis * v * t * e Attachment theory Theory * Affectional bond * Attachment in adults * Attachment in children * Attachment disorder * Attachment and Health * Attachment measures * Attachment theory * Dynamic-Maturational Model of Attachment and Adaptation * Fathers as attachment figures * Human bonding * Maternal deprivation * Object relations theory * Reactive attachment disorder Notable theorists * Mary Ainsworth * William E. Blatz * John Bowlby * Patricia McKinsey Crittenden * Erik Erikson * Sigmund Freud * Harry Harlow * Jerome Kagan * Melanie Klein * Konrad Lorenz * Mary Main * René Spitz * Nikolaas Tinbergen Controversy * Attachment parenting * Attachment therapy * Candace Newmaker Clinical applications * Attachment-based therapy (children) * Attachment-based psychotherapy * Dyadic developmental psychotherapy Others * History of attachment theory [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	Disinhibited attachment disorder	None	27,229	wikipedia	https://en.wikipedia.org/wiki/Disinhibited_attachment_disorder	2021-01-18T18:33:06	{"icd-10": ["F94.2"], "wikidata": ["Q3700220"]}
The Great Imitator (also The Great Masquerader) is a phrase used for medical conditions that feature nonspecific symptoms and may be confused with a number of other diseases.[1] Most great imitators are systemic in nature. Diseases sometimes referred to with this name include: * Various cancers[2] * Intravascular large B-cell lymphoma[3] * Mycosis Fungoides * Beriberi * Various rheumatic conditions, including: * Fibromyalgia[4] * Psoriatic arthritis [5] * Lupus erythematosus [6] * Systemic lupus erythematosus[7][8] * Sarcoidosis[9] * Multiple sclerosis[10] * Celiac disease[11] * Addison's disease[12] * Pulmonary embolism[13] * Various infectious diseases, including: * Syphilis[14] * Lyme disease[15] * Nocardiosis[16] * Tuberculosis[17] * Brucellosis * Infective endocarditis * Malaria[18] * Breathing-related sleep disorders (chiefly sleep apnea/hypopnea and upper-airway resistance syndrome) * Hypoglycemia as an imitator of a stroke * Amyloidosis * Pheochromocytoma * Various abdominal conditions: * Appendicitis * Pancreatitis ## References[edit] 1. ^ J.C. Segen. The Dictionary of Modern Medicine. CRC Press; 1992. ISBN 978-1-85070-321-1. p. 265. 2. ^ Kufe, Donald W. (2009). Holland-Frei cancer medicine (8th ed.). New York: McGraw-Hill Medical. pp. 1–3. ISBN 978-1-60795-014-1. 3. ^ Del Paggio, Joseph; et al. (2017). "Disturbances in blood flow and 'medicine's greatest imitator'". Internal Medicine Journal. 47 (5): 586–588. doi:10.1111/imj.13414. PMID 28503874. 4. ^ Fibromyalgia as the great imitator, retrieved December 16th, 2006 5. ^ "Psoriatic arthritis". 29 Jan 2017. 6. ^ "Right Care". 12 June 2014. 7. ^ Bell, JM; Nair, R; Solon, A; Walker, PD (2005). "SLE: The great imitator strikes again". American Journal of Kidney Diseases. 45 (1): 219–22. doi:10.1053/j.ajkd.2004.05.049. PMID 15696465. 8. ^ Rooney, J (2005). "Systemic lupus erythematosus: Unmasking a great imitator". Nursing. 35 (11): 54–60, quiz 60–61. CiteSeerX 10.1.1.1008.5428. doi:10.1097/00152193-200511000-00049. PMID 16280927. 9. ^ Tchernev, G (2006). "Cutaneous sarcoidosis: The 'great imitator': Etiopathogenesis, morphology, differential diagnosis, and clinical management". American Journal of Clinical Dermatology. 7 (6): 375–82. doi:10.2165/00128071-200607060-00006. PMID 17173472. 10. ^ Multiple Sclerosis as the great imitator Archived 2009-01-04 at the Wayback Machine, retrieved December 16th, 2006 11. ^ Woods, William (1 January 2004). "Coeliac disease: the great imitator". Med. J. Aust. 181 (7) – via eMJA. 12. ^ Williams, Penny; Evans, Sorcha; Thachil, Jecko (2010). "The Great Imitator". The American Journal of Medicine. 123 (7): e5. doi:10.1016/j.amjmed.2009.12.027. PMID 20609673. 13. ^ Sharma, GV; Sasahara, AA; McIntyre, KM (1976). "Pulmonary embolism: The great imitator". Disease-a-month. 22 (7): 4–38. doi:10.1016/s0011-5029(76)80005-3. PMID 770102. 14. ^ "STD Facts - Syphilis". 2017-12-11. 15. ^ NYT article on Lyme disease, retrieved December 16th, 2006 16. ^ Lederman, Edith R.; Crum, Nancy F. (2004). "A Case Series and Focused Review of Nocardiosis". Medicine. 83 (5): 300–13. doi:10.1097/01.md.0000141100.30871.39. PMID 15342974. 17. ^ Sivers, Maurice L. (1961). "The Second "Great Imitator" - Tuberculosis". JAMA. 176 (9): 809–810. doi:10.1001/jama.1961.63040220009017a. 18. ^ http://www.malariasite.com/clinical-features.htm[permanent dead link] This article about a disease, disorder, or medical condition 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	The great imitator	None	27,230	wikipedia	https://en.wikipedia.org/wiki/The_great_imitator	2021-01-18T18:41:02	{"wikidata": ["Q6579320"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (November 2017) 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: "Atrophia maculosa varioliformis cutis" – news · newspapers · books · scholar · JSTOR (April 2009) (Learn how and when to remove this template message) Atrophia Maculosa Varioliformis Cutis (AMVC) is a condition involving spontaneous scarring, specifically depressed scars on the face[1] which occurs over a period of months to years. It appears to only affect children and young adults, is considered to be quite rare, normally occurs on the cheeks, temple area and forehead, and is neither well understood nor presently treatable. Case reports indicate the scars deepen over time but remain relatively superficial, with the frequency of new scar appearance diminishing over time. AMVC is quite difficult to diagnose by dermatologists, for reasons including the depressed box and ice pick scars being very similar to those caused by Acne vulgaris. A confident diagnosis can be made if such scars recently appeared without present acne and without a history of acne. Otherwise, the correct diagnosis is usually not made, and even doing so provides little benefit; there is no treatment. It has been suggested in case reports that the condition, although rare, is likely underreported. ## References[edit] 1. ^ Atrophia Maculosa Varioliformis Cutis * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * 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Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [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	Atrophia maculosa varioliformis cutis	c1832465	27,231	wikipedia	https://en.wikipedia.org/wiki/Atrophia_maculosa_varioliformis_cutis	2021-01-18T18:45:18	{"mesh": ["C563349"], "umls": ["C1832465"], "wikidata": ["Q4817686"]}
Motor symptoms caused by dysfunction of the cerebellum Cerebellar ataxia SpecialtyNeurology Cerebellar ataxia is a form of ataxia originating in the cerebellum.[1] Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias. Cerebellar ataxia can occur as a result of many diseases and may present with symptoms of an inability to coordinate balance, gait, extremity and eye movements.[2] Lesions to the cerebellum can cause dyssynergia, dysmetria, dysdiadochokinesia, dysarthria and ataxia of stance and gait.[3] Deficits are observed with movements on the same side of the body as the lesion (ipsilateral).[2] Clinicians often use visual observation of people performing motor tasks in order to look for signs of ataxia.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Treatment * 3.1 Behavioral intervention * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Damage to the cerebellum causes impairment in motor skills and can cause nystagmus. Almost a third of people with isolated, late onset cerebellar ataxia go on to develop multiple system atrophy.[4] The cerebellum's role has been observed as not purely motor. It is combined with intellect, emotion and planning.[5] ## Causes[edit] Play media A male with gluten ataxia: previous situation and evolution after 3 months of gluten-free diet. There are many causes of cerebellar ataxia including, among others, gluten ataxia,[6] autoimmunity to Purkinje cells or other neural cells in the cerebellum,[7] CNS vasculitis, multiple sclerosis, infection, bleeding, infarction, tumors, direct injury, toxins (e.g., alcohol), genetic disorders and neurodegenerative diseases (such as progressive supranuclear palsy and multiple system atrophy). Gluten ataxia accounts for 40% of all sporadic idiopathic ataxias and 15% of all ataxias.[8] Primary auto-immune ataxias (PACA) lack diagnostic biomarkers.[9] Cerebellar ataxias can be classified as sporadic, autosomal recessive, X-linked, autosomal dominant and of mitochondrial origin. [10] ## Treatment[edit] "For many years, it was thought that postural and balance disorders in cerebellar ataxia were not treatable. However, the results of several recent studies suggest that rehabilitation can relieve postural disorders in patients with cerebellar ataxia...There is now moderate level evidence that rehabilitation is efficient to improve postural capacities of patients with cerebellar ataxia – particularly in patients with degenerative ataxia or multiple sclerosis. Intensive rehabilitation programs with balance and coordination exercises are necessary. Although techniques such as virtual reality, biofeedback, treadmill exercises with supported bodyweight and torso weighting appear to be of value, their specific efficacy has to be further investigated. Drugs have only been studied in degenerative ataxia, and the level of evidence is low."[11] Some effects of cerebellar ataxia may be reduced to varying degrees by means of Frenkel exercises. One main objective of the treatment is to re-establish the physiological inhibition exerted by the cerebellar cortex over cerebellar nuclei.[12] Research using Transcranial direct-current stimulation (TDCS) and Transcranial magnetic stimulation (TMS) shows promising results.[13] Additionally, mild to moderate cerebellar ataxia may be treatable with buspirone.[14] It is thought that the buspirone increases the serotonin levels in the cerebellum and so decreases ataxia. ### Behavioral intervention[edit] Behavioral intervention is successful when it involves engaging knowledge of the interests and general backgrounds of individuals with cerebellar ataxia. Communication maximizing strategies are also useful, such as exaggeration of articulatory gestures, giving full attention to their responses, repeating where necessary, and slowing down speaking rate.[15] Another intervention technique for speech is to focus on optimizing respiratory and vocal resources as well as training compensatory strategies.[16] ## See also[edit] * Autosomal recessive cerebellar ataxia * Sensory ataxia * Spinocerebellar ataxia * Vestibulocerebellar syndrome ## References[edit] 1. ^ "Cerebellar ataxia". BBC News. November 30, 2004. 2. ^ a b c Ferrarin, M.; Gironi, M.; Mendozzi, L.; Nemni, R.; Mazzoleni, P.; Rabuffetti, M. (2005). "Procedure for the quantitative evaluation of motor disturbances in cerebellar ataxic patients". Medical & Biological Engineering & Computing. 43 (3): 349–56. doi:10.1007/BF02345812. PMID 16035223. 3. ^ Diener, H.-C.; Dichgans, J. (1992). "Pathophysiology of cerebellar ataxia". Movement Disorders. 7 (2): 95–109. doi:10.1002/mds.870070202. PMID 1584245. 4. ^ Multiple System Atrophy~differential at eMedicine 5. ^ Manto, Mario; Marien, Peter (2015). "Schmahmann's syndrome - identification of the third cornerstone of clinical ataxiology". Cerebellum & Ataxias. 2 (1): 2. doi:10.1186/s40673-015-0023-1. PMC 4552302. PMID 26331045. 6. ^ Mitoma H, Adhikari K, Aeschlimann D, Chattopadhyay P, Hadjivassiliou M, Hampe CS, et al. (2016). "Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias". Cerebellum (Review). 15 (2): 213–32. doi:10.1007/s12311-015-0664-x. PMC 4591117. PMID 25823827. 7. ^ Jarius, S.; Wildemann, B. (2015). "'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia". J Neuroinflammation. 12 (1): 166. doi:10.1186/s12974-015-0356-y. PMC 4574226. PMID 26377085. 8. ^ Hadjivassiliou M, Sanders DD, Aeschlimann DP (2015). "Gluten-related disorders: gluten ataxia". Dig Dis (Review). 33 (2): 264–8. doi:10.1159/000369509. PMID 25925933. 9. ^ Hadjivassiliou, Marios; Graus, Francesc; Honnorat, Jerome; Jarius, Sven; Titulaer, Maarten; Manto, Mario; Hoggard, Nigel; Sarrigiannis, Ptolemaios; Mitoma, Hiroshi (2020-04-23). "Diagnostic Criteria for Primary Autoimmune Cerebellar Ataxia-Guidelines from an International Task Force on Immune-Mediated Cerebellar Ataxias". Cerebellum (London, England). doi:10.1007/s12311-020-01132-8. ISSN 1473-4230. PMID 32328884. 10. ^ Manto, Mario; Gruol, Donna L.; Schmahmann, Jeremy; Koibuchi, Noriyuki; Rossi, Ferdinando, eds. (2013). Handbook of the Cerebellum and Cerebellar Disorders. Springer Netherlands. ISBN 9789400713321. 11. ^ Marquer, A.; Barbieri, G.; Pérennou, D. (2014). "The assessment and treatment of postural disorders in cerebellar ataxia: A systematic review". Annals of Physical and Rehabilitation Medicine. 57 (2): 67–78. doi:10.1016/j.rehab.2014.01.002. PMID 24582474. 12. ^ Mitoma, H.; Manto, M. (2016-05-20). "The physiological basis of therapies for cerebellar ataxias". Therapeutic Advances in Neurological Disorders. 9 (5): 396–413. doi:10.1177/1756285616648940. PMC 4994778. PMID 27582895. 13. ^ Grimaldi, Giuliana; Oulad Ben Taib, Nordeyn; Manto, Mario; Bodranghien, Florian (2014). "Marked reduction of cerebellar deficits in upper limbs following transcranial cerebello-cerebral DC stimulation: tremor reduction and re-programming of the timing of antagonist commands." Front Syst Neurosci. 8 (9): 9. doi:10.3389/fnsys.2014.00009. PMC 3906576. PMID 24523678. 14. ^ Trouillas, Paul; Xie, Jing; Adeleine, Patrice (1996). "Treatment of cerebellar ataxia with buspirone: a double-blind study". The Lancet. 348 (9029): 759. doi:10.1016/S0140-6736(05)65674-7. PMID 8806320. 15. ^ Mackenzie, Catherine; Lowit, Anja (2007). "Behavioural intervention effects in dysarthria following stroke: communication effectiveness, intelligibility and dysarthria impact". International Journal of Language & Communication Disorders. 42 (2): 131–53. doi:10.1080/13682820600861776. PMID 17365091. 16. ^ Schalling, Ellika; Hartelius, Lena (2013). "Speech in spinocerebellar ataxia". Brain and Language. 127 (3): 317–22. doi:10.1016/j.bandl.2013.10.002. PMID 24182841. ## External links[edit] Classification D * ICD-10: G11.1-G11.3 * ICD-9-CM: 334.3 * MeSH: D002524 * DiseasesDB: 2218 External resources * MedlinePlus: 001397 * Lady without cerebellum * v * t * e Symptoms and signs relating to movement and gait Gait * Gait abnormality * CNS * Scissor gait * Cerebellar ataxia * Festinating gait * Marche à petit pas * Propulsive gait * Stomping gait * Spastic gait * Magnetic gait * Truncal ataxia * Muscular * Myopathic gait * Trendelenburg gait * Pigeon gait * Steppage gait * Antalgic gait Coordination * Ataxia * Cerebellar ataxia * Dysmetria * Dysdiadochokinesia * Pronator drift * Dyssynergia * Sensory ataxia * Asterixis Abnormal movement * Athetosis * Tremor * Fasciculation * Fibrillation Posturing * Abnormal posturing * Opisthotonus * Spasm * Trismus * Cramp * Tetany * Myokymia * Joint locking Paralysis * Flaccid paralysis * Spastic paraplegia * Spastic diplegia * Spastic paraplegia * Syndromes * Monoplegia * Diplegia / Paraplegia * Hemiplegia * Triplegia * Tetraplegia / Quadruplegia * General causes * Upper motor neuron lesion * Lower motor neuron lesion Weakness * Hemiparesis Other * Rachitic rosary * Hyperreflexia * Clasp-knife response * v * t * e Symptoms, signs and syndromes associated with lesions of the brain and brainstem Brainstem Medulla (CN 8, 9, 10, 12) * Lateral medullary syndrome/Wallenberg * PICA * Medial medullary syndrome/Dejerine * ASA Pons (CN 5, 6, 7, 8) * Upper dorsal pontine syndrome/Raymond-Céstan syndrome * Lateral pontine syndrome (AICA) (lateral) * Medial pontine syndrome/Millard–Gubler syndrome/Foville's syndrome (basilar) * Locked-in syndrome * Internuclear ophthalmoplegia * One and a half syndrome Midbrain (CN 3, 4) * Weber's syndrome * ventral peduncle, PCA * Benedikt syndrome * ventral tegmentum, PCA * Parinaud's syndrome * dorsal, tumor * Claude's syndrome Other * Alternating hemiplegia Cerebellum * Latearl * Dysmetria * Dysdiadochokinesia * Intention tremor) * Medial * Cerebellar ataxia Basal ganglia * Chorea * Dystonia * Parkinson's disease Cortex * ACA syndrome * MCA syndrome * PCA syndrome * Frontal lobe * Expressive aphasia * Abulia * Parietal lobe * Receptive aphasia * Hemispatial neglect * Gerstmann syndrome * Astereognosis * Occipital lobe * Bálint's syndrome * Cortical blindness * Pure alexia * Temporal lobe * Cortical deafness * Prosopagnosia Thalamus * Thalamic syndrome Other * Upper motor neuron lesion * Aphasia [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	Cerebellar ataxia	c0007758	27,232	wikipedia	https://en.wikipedia.org/wiki/Cerebellar_ataxia	2021-01-18T18:58:50	{"gard": ["12060"], "mesh": ["D002524"], "umls": ["C0007758"], "icd-9": ["334.3"], "icd-10": ["G11.1", "G11.3"], "orphanet": ["102002"], "wikidata": ["Q154709"]}
Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency is a very rare genetic skin disease characterized by severe skin laxity affecting the trunk and limbs. [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	Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency	c1835813	27,233	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91135	2021-01-23T18:43:58	{"mesh": ["C563654"], "omim": ["610842"], "umls": ["C1835813"], "icd-10": ["D68.4"], "synonyms": ["PXE-like syndrome", "Pseudoxanthoma elasticum-like syndrome"]}
Cytochrome c oxidase deficiency is a genetic condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Signs and symptoms of cytochrome c oxidase deficiency usually begin before age 2 but can appear later in mildly affected individuals. The severity of cytochrome c oxidase deficiency varies widely among affected individuals, even among those in the same family. People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other related health problems. More severely affected people have problems in multiple body systems, often including severe brain dysfunction (encephalomyopathy). Approximately one-quarter of individuals with cytochrome c oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver (hepatomegaly), which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening. Many people with cytochrome c oxidase deficiency have a specific group of features known as Leigh syndrome. The signs and symptoms of Leigh syndrome include loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome c oxidase deficiency is one of the many causes of Leigh syndrome. Many individuals with cytochrome c oxidase deficiency do not survive past childhood, although some individuals with mild signs and symptoms live into adolescence or adulthood. ## Frequency In Eastern Europe, cytochrome c oxidase deficiency is estimated to occur in 1 in 35,000 individuals. The prevalence of this condition outside this region is unknown. ## Causes Mutations in more than 20 genes have been found to cause cytochrome c oxidase deficiency. Most genes are found in DNA in the cell's nucleus (nuclear DNA). However, some genes are found in DNA in specialized cell structures called mitochondria. This type of DNA is known as mitochondrial DNA (mtDNA). Most cases of cytochrome c oxidase deficiency are caused by mutations in genes found within nuclear DNA; however, in some rare instances, mutations in genes located within mtDNA cause this condition. The genes associated with cytochrome c oxidase deficiency are involved in energy production in mitochondria through a process called oxidative phosphorylation. Mutations in these genes affect an enzyme complex called cytochrome c oxidase, which is responsible for one of the last steps in oxidative phosphorylation. Cytochrome c oxidase is made up of two large groups of enzymes (complexes) called holoenzymes, which are each composed of multiple protein parts (subunits). Many other proteins are involved in assembling these subunits into holoenzymes. In most cases, cytochrome c oxidase deficiency is caused by mutations that alter the proteins that assemble the holoenzymes. As a result, the holoenzymes are either partially assembled or not assembled at all. Without complete holoenzymes, cytochrome c oxidase cannot form. Less frequently, mutations alter the holoenzyme subunits, leading to a nonfunctional version of cytochrome c oxidase. Whether cytochrome c oxidase is not formed or not functional, this missing enzyme complex disrupts the last step of oxidative phosphorylation, causing a decrease in energy production. Researchers believe that impaired oxidative phosphorylation can lead to cell death by reducing the amount of energy available in the cell. Certain tissues that require large amounts of energy, such as the brain, muscles, and heart, seem especially sensitive to decreases in energy. Cell death in these and other sensitive tissues likely contribute to the features of cytochrome c oxidase deficiency. ### Learn more about the gene and chromosome associated with Cytochrome c oxidase deficiency * SURF1 * mitochondrial dna Additional Information from NCBI Gene: * COA3 * COA5 * COA6 * COA7 * COA8 * COX10 * COX14 * COX15 * COX20 * COX5A * COX6B1 * COX8A * FASTKD2 * LRPPRC * MT-CO1 * MT-CO2 * MT-CO3 * PET100 * PET117 * SCO1 * SCO2 * TACO1 ## Inheritance Pattern Cytochrome c oxidase deficiency can have different inheritance patterns depending on the gene involved. When this condition is caused by mutations in genes within nuclear DNA, it 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. When this condition is caused by mutations in genes within mtDNA, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their 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	Cytochrome c oxidase deficiency	c1858424	27,234	medlineplus	https://medlineplus.gov/genetics/condition/cytochrome-c-oxidase-deficiency/	2021-01-27T08:24:38	{"gard": ["48"], "mesh": ["C565784"], "omim": ["604377", "615119", "616500", "616501", "220110"], "synonyms": []}
Verloes et al. (1990) described a possibly new autosomal dominant syndrome that combined poikiloderma, alopecia, retrognathism, and cleft palate--the PARC syndrome. The family came to attention with the birth of a son who had striking alopecia with absent eyebrows and eyelashes, as well as absent lanugo of other parts of the skin except the scalp. The infant had severe microretrognathism and median posterior cleft palate without glossoptosis. The father, aged 32 years, was in good health and of normal height, but had retrognathism with overbite but no palatal defect. He was almost completely bald. Hair \- Alopecia \- Absent eyebrows and eyelashes \- Absent lanugo Inheritance \- ? Autosomal dominant Mouth \- Retrognathia \- Cleft palate \- Microretrognathia Skin \- Poikiloderma ▲ 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	PARC SYNDROME	c1838256	27,235	omim	https://www.omim.org/entry/600331	2019-09-22T16:16:16	{"mesh": ["C537174"], "omim": ["600331"], "orphanet": ["2825"], "synonyms": ["Alternative titles", "POIKILODERMA, ALOPECIA, RETROGNATHISM, AND CLEFT PALATE"]}
A rare, acquired uterine disease characterized by intrauterine adhesions associated with a history of curettage or intrauterine surgery and gynecological symptoms (secondary amenorrhea, hypomenorrhea, pelvic pain, infertility or pregnancy loss). ## Epidemiology The prevalence in the general population is unknown. In infertile populations the prevalence varies from 2.8% to 46% depending on the subpopulation. The greatest risk factor for the disease is iatrogenic trauma to the endometrium. ## Clinical description The severity of intrauterine adhesions (IUA) in Asherman's syndrome can vary between complete obliteration of the cavity to minimal, marginal adhesions. Frequently, the uterine cavity is decreased in size. The adhesions are composed of fibromuscular connective tissue bands, with or without surrounding superficial epithelium or glandular tissue. Adhesions vary markedly in their density and size and can be accompanied by areas of endometrial sclerosis. The gravid uterus appears highly predisposed to adhesions, but IUA may develop in non-gravid uterus following intrauterine trauma. Clinical manifestations include infertility, menstrual irregularities, and recurrent pregnancy losses. Amenorrhea or hypomenorrhea are the most frequent symptoms and may be accompanied by dysmenorrhea during the anticipated menstrual period; some patients continue to have normal periods. When the adhesions are exclusively located in the lower uterine tract and functioning endometrium persists, this syndrome can cause severe pelvic pain and retrograde menstruation. Recurrence of UIA post-surgery is high. ## Etiology The intrauterine adhesions result from uterine trauma including curettage, hysteroscopic myomectomy or endometrial ablation. Adhesions may also be diagnosed in women with genital tuberculosis. ## Diagnostic methods A history of uterine trauma (typically curettage) associated with menstrual abnormalities/inability to conceive are suggestive of Asherman's syndrome. Hysteroscopy provides definitive diagnosis, and can characterize the site and extent of adhesions as well as assess the endometrium. Magnetic resonance imaging (MRI) can be helpful as a supplementary diagnostic tool, especially when the adhesions involve the endocervix. IUAs are visualized as low signal intensity on T2 weighed-image inside the uterus. Transvaginal ultrasound and hysterosalpingography may be used but have lower diagnostic accuracy. ## Differential diagnosis Differential diagnosis on unenhanced ultrasound is normal intrauterine longitudinal folds, on hysterosalpingography or saline infusion ultrasonography it includes polyps and minor fibroids. ## Management and treatment For prevention of intrauterine adherences, a gentle emptying of the uterine cavity after delivery or abortion is mandatory preferably under ultrasound guidance. Intrauterine adhesions are ideally treated with hysteroscopy. Filmy adhesions may be separated by the tip of the hysteroscope. Dense adhesions are treated with hysteroscopic adhesiolysis with either mechanical, electrical or thermal energy techniques. Treatment in severe cases is difficult, and counselling should be offered regarding the lower rate of success and the higher risk of complications. Prevention of re-adhesion is important, and good results have been achieved with intrauterine devices, uterine balloon stent, Foley's catheter, and anti-adhesion barriers. In severe cases, several approaches may be required. Hormonal treatment (oestradiol, combined oestradiol/progesterone) is used to restore the normal endometrium; however, there is no consensus on timing of the administration or the type of regimen. Patients should be assessed one-two months post-operatively as complete resolution of the adhesions is not always possible with a single procedure. Ultrasound, HSG and hysteroscopy are the most common follow-up methods. ## Prognosis Whilst some women achieve pregnancy, the burden of infertility post-treatment is significant. The prognosis is worse for patients with a sclerotic, atrophic endometrium. [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	Asherman syndrome	c0156372	27,236	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137686	2021-01-23T17:16:01	{"gard": ["5853"], "mesh": ["D006175"], "umls": ["C0156372", "C0241593", "C1704274"], "icd-10": ["N85.6"]}
Reaction between an antibody and an antigen that differs from the immunogen Not to be confused with Heterosubtypic Immunity. Cross-reactivity, in a general sense, is the reactivity of an observed agent which initiates reactions outside the main reaction expected. This has implications for any kind of test or assay, including diagnostic tests in medicine, and can be a cause of false positives. In immunology, the definition of cross-reactivity refers specifically to the reaction of the immune system to antigens. There can be cross-reactivity between the immune system and the antigens of two different pathogens, or between one pathogen and proteins on non-pathogens, which in some cases can be the cause of allergies. ## Contents * 1 In medical testing * 1.1 Applications in drug development * 2 In immunology * 2.1 Allergies * 3 References * 4 External links ## In medical testing[edit] In medical tests, including rapid diagnostic tests, cross-reactivity can be either confounding or helpful, depending on the instance. An example of confounding that yields a false positive error is in a latex fixation test when agglutination occurs with another antigen rather than the antigen of interest. An example of helpful cross-reactivity is in heterophile antibody tests, which detect Epstein-Barr virus using antibodies with specificity for other antigens. Cross-reactivity is also a commonly evaluated parameter for the validation of immune and protein binding based assays such as ELISA and RIA. In this case it is normally quantified by comparing the assays response to a range of similar analytes and expressed as a percentage. In practice, calibration curves are produced using fixed concentration ranges for a selection of related compounds and the midpoints (IC50) of the calibration curves are calculated and compared. The figure then provides an estimate of the response of the assay to possible interfering compounds relative to the target analyte. ### Applications in drug development[edit] Tissue cross-reactivity assay is a standard method based on immunohistochemistry, required prior to phase I human studies for therapeutic antibodies. In drug screening, because many urine drug screens use immunoassays there is a certain amount of cross-reactivity. Certain drugs or other chemicals can give a false positive for another category of drug.[1] ## In immunology[edit] In immunology, cross-reactivity has a more narrow meaning of the reaction between an antibody and an antigen that differs from the immunogen. It is sometimes also referred to as crossimmunity or cross-protective immunity,[2] although cross-reactivity does not necessarily infer cross-protection. In some cases, the cross-reactivity can be destructive, and immune response to one pathogen can interfere with or lower the immune response to a different pathogen. An adaptive immune response is specific to the antigen that stimulated it (called the immunogen). However, many naturally occurring apparent antigens are actually a mixture of macromolecules (for example, from pathogens, toxins, proteins, or pollen) comprising several epitopes. Contact with a complex antigen such as a virus will stimulate multiple immune responses to the virus' different macromolecules as well as the individual epitopes of each macromolecule. For example, the tetanus toxin is a single protein macromolecular antigen but will stimulate many immune responses due to the tertiary structure of the protein yielding many different epitopes. The toxin that creates the immune response will have an epitope on it that stimulates the response. Denaturing the protein may 'disarm' its function but allow the immune system to have an immune response thus creating an immunity without harming the patient. Cross reactivity has implications for flu vaccination because of the large number of strains of flu, as antigens produced in response to one strain may confer protection to different strains.[3] Cross-reactivity need not be between closely related viruses, however; for example, there is cross-reactivity between influenza virus-specific CD8+ T cells and hepatitis C virus antigens.[4] ### Allergies[edit] Cross reactivity may also occur between a pathogen and a protein found on a non-pathogen (i.e. food.) There may even be cross reactivity between two non-pathogens; for example, Hevein-like protein domains are a possible cause for allergen cross-reactivity between latex and banana.[5] Cross-reactivity may be caused by identical carbohydrate structures on unrelated proteins from the same or different species. Such cross-reactive carbohydrate determinants (CCDs) are an issue in allergy diagnosis, where about a fifth of all patients displays IgE antibodies against Asn-linked oligosaccharides (N-glycans) containing core α1,3-linked fucose.[6] As CCDs apparently do not elicit allergic symptoms, a positive in vitro test based on IgE binding to CCDs must be rated as false positive. ## References[edit] 1. ^ Saitman A, Park HD, Fitzgerald RL (September 2014). "False-positive interferences of common urine drug screen immunoassays: a review". Journal of Analytical Toxicology. 38 (7): 387–96. doi:10.1093/jat/bku075. PMID 24986836. 2. ^ Porrozzi R, Teva A, Amaral VF, Santos da Costa MV, Grimaldi G (September 2004). "Cross-immunity experiments between different species or strains of Leishmania in rhesus macaques (Macaca mulatta)". The American Journal of Tropical Medicine and Hygiene. 71 (3): 297–305. doi:10.4269/ajtmh.2004.71.297. PMID 15381810. 3. ^ Mandelboim M, Bromberg M, Sherbany H, Zucker I, Yaary K, Bassal R, et al. (June 2014). "Significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift". BMC Infectious Diseases. 14: 346. doi:10.1186/1471-2334-14-346. PMC 4107950. PMID 24950742. 4. ^ Kasprowicz V, Ward SM, Turner A, Grammatikos A, Nolan BE, Lewis-Ximenez L, Sharp C, Woodruff J, Fleming VM, Sims S, Walker BD, Sewell AK, Lauer GM, Klenerman P (March 2008). "Defining the directionality and quality of influenza virus-specific CD8+ T cell cross-reactivity in individuals infected with hepatitis C virus". The Journal of Clinical Investigation. 118 (3): 1143–53. doi:10.1172/JCI33082. PMC 2214846. PMID 18246203. 5. ^ Mikkola JH, Alenius H, Kalkkinen N, Turjanmaa K, Palosuo T, Reunala T (December 1998). "Hevein-like protein domains as a possible cause for allergen cross-reactivity between latex and banana". The Journal of Allergy and Clinical Immunology. 102 (6 Pt 1): 1005–12. doi:10.1016/S0091-6749(98)70339-2. PMID 9847442. 6. ^ Altmann F (2007). "The role of protein glycosylation in allergy". International Archives of Allergy and Immunology. 142 (2): 99–115. doi:10.1159/000096114. PMID 17033195. ## External links[edit] * Cross+reactions at the US National Library of Medicine Medical Subject Headings (MeSH) * v * t * e Lymphocytic adaptive immune system and complement Lymphoid Antigens * Antigen * Superantigen * Allergen * Antigenic variation * Hapten * Epitope * Linear * Conformational * Mimotope * Antigen presentation/professional APCs: Dendritic cell * Macrophage * B cell * Immunogen Antibodies * Antibody * Monoclonal antibodies * Polyclonal antibodies * Autoantibody * Microantibody * Polyclonal B cell response * Allotype * Isotype * Idiotype * Immune complex * Paratope Immunity vs. tolerance * Action: Immunity * Autoimmunity * Alloimmunity * Allergy * Hypersensitivity * Inflammation * Cross-reactivity * Inaction: Tolerance * Central * Peripheral * Clonal anergy * Clonal deletion * Tolerance in pregnancy * Immunodeficiency * Immune privilege Immunogenetics * Affinity maturation * Somatic hypermutation * Clonal selection * V(D)J recombination * Junctional diversity * Immunoglobulin class switching * MHC/HLA Lymphocytes * Cellular * T cell * Humoral * B cell * NK cell Substances * Cytokines * Opsonin * Cytolysin [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	Cross-reactivity	None	27,237	wikipedia	https://en.wikipedia.org/wiki/Cross-reactivity	2021-01-18T18:52:57	{"mesh": ["D003429"], "wikidata": ["Q1760689"]}
A number sign (#) is used with this entry because of evidence that primary immunodeficiency-10 (IMD10) is caused by homozygous mutation in the STIM1 gene (605921) on chromosome 11p15. See IMD9 (612782) for a similar disorder due to mutation in the ORAI1 gene (610277), which acts downstream of the STIM1 gene in the same pathway. Description Immunodeficiency-10 is an autosomal recessive primary immunodeficiency characterized by onset of recurrent infections in childhood due to defective T- and NK-cell function, although the severity is variable. Affected individuals may also have hypotonia, hypohidrosis, or dental enamel hypoplasia consistent with amelogenesis imperfecta (summary by Parry et al., 2016). Clinical Features Picard et al. (2009) reported 3 sibs, born of a consanguineous family from central Europe, who had recurrent infections due to defective T-cell function. Muscle hypotonia and partial iris hypoplasia were noted in the neonatal period. Within a few months, patients developed lymphadenopathy and hepatosplenomegaly associated with autoimmune hemolytic anemia and thrombocytopenia. During the first year of life, all children developed recurrent infections. Defects in enamel dentition were also noted. One died at age 9 years from complications of a bone marrow transplant, whereas another died from the nephrotic syndrome and recurrent infections at age 18 months. The third child had a successful bone marrow transplant at age 15 months. Laboratory studies showed slightly reduced or normal lymphocyte counts, but T cells showed a severely impaired proliferative response to stimulation. Serum immunoglobulin levels were normal, but there were impaired T-cell responses to recall antigens despite immunization. Further studies showed a defect in cellular store-operated calcium entry, which is required for lymphocyte activation. Transfection of wildtype STIM1 corrected the defect in vitro. Byun et al. (2010) reported a human immunodeficiency virus (HIV)-seronegative Turkish child with STIM1 deficiency who died from disseminated Kaposi sarcoma (KS) at age 2 years. The patient was born to consanguineous parents. At age 2 years, the patient developed the first KS on her lip, followed by rapid dissemination throughout the body. She had lymphadenopathy and hepatosplenomegaly, and she died from severe pulmonary lesions 4 months later. She had no history of other severe infections or tumors, but presented with autoimmune hemolytic anemia. The counts and proportions of blood, T, B, and natural killer cells and subsets were normal, as were serum immunoglobin levels. RT-PCR analysis of Epstein-Barr virus (EBV)-transformed B cell lines from the patient showed significantly reduced STIM1 mRNA expression, and no STIM1 protein was detected by Western blot analysis. Ca(2+) influx was completely abolished in the patient's EBV-B cells, and expression of wildtype STIM1 rescued this defect. Byun et al. (2010) concluded that complete STIM1 deficiency in this patient precipitated the development of lethal classic KS upon infection with human herpesvirus (HHV)-8, the cause of all forms of KS. They noted the similarity of their patient to the patients with STIM1 deficiency reported by Picard et al. (2009). Byun et al. (2010) suggested that the muscular hypotonia, partial iris hypoplasia, and dental enamel defects in the patients reported by Picard et al. (2009) would probably not have been picked up in their patient due to the early onset and fatal outcome of KS. Fuchs et al. (2012) reported STIM1 deficiency in a 6-year-old Pakistani girl of consanguineous parents. She experienced chronic and recurrent pneumonia, diarrhea, and viremia due to infection with herpesviruses and other pathogens. Additional features included mild muscle hypotonia, anhidrosis with presence of sweat glands, enamel defect of the teeth, and nail dysplasia. Store-operated calcium entry (SOCE) was completely abolished in T cells. The patient's younger sister had a similar history and died at age 21 months. A first cord blood transplant failed in the older girl. Immunologic analysis of the surviving patient showed defects in T-cell proliferation and cytokine production in vitro, as expected, but also the generation of significant antiviral T-cell populations in vivo. The latter cells proliferated in response to viral antigens and showed normal antiviral cytotoxicity. In spite of this apparent antiviral immunity, the patient experienced chronic cytomegalovirus and EBV infections, possibly due to impaired natural killer cell function and absent natural killer T cells. The patient also experienced autoimmune cytopenia, eczema, and intermittent diarrhea, suggesting impaired immune regulation. She possessed FOXP3 (300292)-positive regulatory T (Treg) cells with an abnormal phenotype but normal function. Fuchs et al. (2012) proposed that the sum of these partial defects contribute to the overall pathogenesis of immunodeficiency and autoimmunity in STIM1 deficiency. ### Clinical Variability Wang et al. (2014) reported a 6-year-old girl, born of consanguineous Turkish parents, who presented with dental enamel abnormalities. The sizes and shapes of the dental crowns were within normal limits, but the enamel was creamy brown and showed rapid attrition that had resulted in loss of the maxillary central incisors. She also had nail dysplasia. She had a history of frequent throat infections, but no immunologic evaluation was performed, and the family was lost to follow-up. Parry et al. (2016) reported 2 patients, 11 and 18 years of age, from a large consanguineous family who presented with hypomineralized amelogenesis imperfecta and hypohidrosis associated with a homozygous missense mutation in the STIM1 gene (L74P; 605921.0012). Both had asthma; 1 had recurrent chest infections in infancy and spontaneous pneumothoraces as a teenager and was allergic to red food dye, and the other had eczema. Neither had overt features of immunodeficiency, but laboratory studies showed impaired NK cell effector function as well as defective store-operated calcium entry (SOCE) in T cells and NK cells. Only the older patient had stable CD8+ T-cell depletion. T-cell stimulation responses were normal in both patients. Parry et al. (2016) postulated that the relative preservation of T-cell function in these patients may have compensated for NK cell dysfunction, or that the patients may not have encountered a pathogen that would expose an immune system defect. Neither patient had clinical or serologic evidence of a myopathy. Mapping Immunodeficiency-10 is caused by mutation in the STIM1 gene, which Parker et al. (1996) mapped to chromosome 11p15.5. Inheritance The transmission pattern of STIM1 deficiency in the patients reported by Picard et al. (2009) and Byun et al. (2010) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sibs with immune dysfunction due to T-cell inactivation, Picard et al. (2009) identified a homozygous truncating mutation in the STIM1 gene (605921.0001). Using whole-exome sequencing, Byun et al. (2010) identified a homozygous splice site mutation at the -1 position of exon 8 in the STIM1 gene (605921.0002) in an HIV-seronegative Turkish child of consanguineous parents who died at age 2 years from disseminated Kaposi sarcoma associated with complete STIM1 deficiency. In 2 Pakistani sisters with STIM1 deficiency born to consanguineous parents, Fuchs et al. (2012) identified an arg429-to-cys (R429C; 605921.0003) mutation in the STIM1 gene. In a 6-year-old girl, born of consanguineous Turkish parents, with IMD10 manifest primarily as amelogenesis imperfecta, Wang et al. (2014) identified a homozygous missense mutation in the STIM1 gene (R426C; 605921.0011). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing; each unaffected parent was heterozygous for the mutation. Although functional studies of this variant were not performed, Wang et al. (2014) noted that a previous study (Muik et al., 2011) had demonstrated that a recombinant mutation at the same codon (R426L) prevented STIM1 from interacting with ORAI1 (610277). Wang et al. (2014) concluded that recessive loss-of-function STIM1 mutations, such as R426C, result in failure to induce calcium influx in response to ER calcium store depletion, which results in lower than normal intracellular calcium levels and impaired enamel maturation. In 2 patients from a consanguineous Pakistani family with IMD10 without overt features of immunodeficiency, Parry et al. (2016) identified a homozygous missense mutation in the STIM1 gene (L74P; 605921.0012) in the EF-hand domain. The mutation, which was found by a combination of autozygosity mapping and exome sequencing, was confirmed by Sanger sequencing, and segregated with the disorder in the family. In vitro functional expression studies in HEK293 cells showed that the mutation resulted in altered calcium dynamics that were distinct from both loss of function and constitutive activation. The patients had no clinical or serologic evidence of a myopathy, and 2 heterozygous family members did not report muscle problems, but they were not formally examined. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Iris hypoplasia, partial Teeth \- Defective enamel development \- Hypomineralized amelogenesis imperfecta SKIN, NAILS, & HAIR Skin \- Hypohidrosis Nails \- Nail dysplasia MUSCLE, SOFT TISSUES \- Muscular hypotonia \- Myopathy, nonprogressive METABOLIC FEATURES \- Intermittent fever HEMATOLOGY \- Hemolytic anemia, autoimmune \- Thrombocytopenia IMMUNOLOGY \- Recurrent bacterial infections \- Susceptibility to infection with human herpesvirus \- Lymphadenopathy \- Impaired T cell activation \- Impaired T cell proliferative response \- Normal lymphocyte counts \- Normal serum immunoglobulin levels \- Impaired seroconversion of immunoglobulins in response to vaccination \- Decreased T cell production of cytokines \- Impaired NK cell function NEOPLASIA \- Kaposi sarcoma (1 patient) MISCELLANEOUS \- Onset in childhood \- Variable severity MOLECULAR BASIS \- Caused by mutation in the stromal interaction molecule 1 gene (STIM1, 605921.0001 ) ▲ 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	IMMUNODEFICIENCY 10	c2748557	27,238	omim	https://www.omim.org/entry/612783	2019-09-22T16:00:38	{"mesh": ["C557827"], "omim": ["612783"], "orphanet": ["169090", "317430"], "synonyms": ["IMMUNE DYSFUNCTION WITH T-CELL INACTIVATION DUE TO CALCIUM ENTRY DEFECT 2", "STIM1 DEFICIENCY", "CID due to STIM1 deficiency", "Immune dysfunction due to T-cell inactivation due to calcium entry defect", "Alternative titles"]}
A rare genetic primary lymphedema characterized by lymphedema of all four limbs with age of onset ranging from birth to adulthood. Manifestations are of variable severity, and upper limb involvement may develop only later in the disease course. Recurrent episodes of cellulitis and skin infections are observed in severe cases. Varicose veins and venous incompetence have been reported in association. [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	GJC2-related late-onset primary lymphedema	None	27,239	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=568051	2021-01-23T18:38:58	{}
In cases of mucocutaneous candidiasis, Paterson et al. (1971) found that the patients' plasma inhibited the in vitro proliferative response of their own lymphocytes to various antigens. Inheritance \- Autosomal recessive Immunology \- Anergy Lab \- Inhibition of in vitro proliferative lymphocyte response to various antigens by autologous plasma Skin \- Chronic mucocutaneous candidiasis ▲ 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	LYMPHOBLASTIC TRANSFORMATION, INHIBITION OF	c1855476	27,240	omim	https://www.omim.org/entry/247430	2019-09-22T16:25:45	{"mesh": ["C565433"], "omim": ["247430"]}
A number sign (#) is used with this entry because of evidence that complement factor B deficiency (CFBD) is caused by compound heterozygous mutation in the CFB gene (138470) on chromosome 6p21. One such family has been reported. Clinical Features Slade et al. (2013) reported a 32-year-old woman, born of unrelated parents of English and Scottish heritage, who had a history of susceptibility to infection with encapsulated bacteria beginning in early childhood. She first presented at 2 years of age with pneumococcal peritonitis. Two years later, she had community-acquired pneumonia. At age 15 years, she developed Neisseria meningitis, and at age 30, she had pneumococcal pneumonia complicated by empyema and necessitating admission to the intensive care unit. Laboratory studies showed normal immunoglobulins and lymphocytes, but functional ELISA showed that the alternative complement pathway was inactive. The defect was not complemented by factor B-depleted serum, and factor B was undetectable by radial immunodiffusion. The patient was treated with vaccination and prophylactic antibiotics without recurrence. Inheritance The transmission pattern of complement factor B deficiency in the family reported by Slade et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In a woman with complement factor B deficiency, Slade et al. (2013) identified compound heterozygous truncating mutations in the CFB gene (138470.0007 and 138370.0008). The mutations were found by genome sequencing of the CFB gene and segregated with the disorder in the family. Complement studies in the parents showed normal activity of the alternative complement pathway. The findings illustrated the role of complement factor B in the protection against infection with encapsulated organisms. History Hauptmann et al. (1980) stated that 11 allotypes of Bf are known and that the principal, perhaps only, site of synthesis is the liver inasmuch as the recipient of a liver graft lost his own Bf type and acquired the donor's type. Furthermore, they observed deficiency of properdin factor B transmitted through 3 generations of a family in association with haplotype HLA-A11, B27. The deficiency had no apparent consequences in heterozygotes. [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	COMPLEMENT FACTOR B DEFICIENCY	c3809950	27,241	omim	https://www.omim.org/entry/615561	2019-09-22T15:51:36	{"omim": ["615561"]}
Infantile cerebellar-retinal degeneration is a rare, neurodegenerative disorder characterized by an early onset of truncal hypotonia, variable forms of seizures, athetosis, severe global developmental delay, intellectual disability and various ophthalmologic abnormalities, including strabismus, nystagmus, optic atrophy and retinal degeneration. [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	Infantile cerebellar-retinal degeneration	c3281192	27,242	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=313850	2021-01-23T17:54:19	{"omim": ["614559"], "icd-10": ["E88.8"]}
Scotty Cramp is a disease in Scottish Terriers causing spasms and hyperflexion and hyperextension of the legs. It is caused by a disorder in serotonin metabolism that causes a deficiency of available serotonin.[1] It is inherited as an autosomal recessive trait.[2] Scotty Cramp occurs in puppies and young dogs. Symptoms present after exercise or excitement and last a few minutes. A goose-stepping gait and arched spine are often seen, and the dog may turn somersaults as it runs. The symptoms usually resolve after ten minutes, but they may repeat several times in a day.[3] If the diagnosis is unsure, a dose of methysergide can be given. In affected dogs, this will block serotonin and increase the frequence and severity of the symptoms.[1] Diazepam or acepromazine is used to control the symptoms of Scotty Cramp. Vitamin E may also be of some benefit.[4] Because Scotty Cramp is inherited, affected dogs and their parents and siblings should not be bred. ## References[edit] 1. ^ a b Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 0-7216-6795-3. 2. ^ "Peripheral Nerve and Muscle Disorders: Small Animals". The Merck Veterinary Manual. 2006. Retrieved 2007-02-11. 3. ^ Braund, K.G. (2003). "Paroxysmal Disorders". Braund's Clinical Neurology in Small Animals: Localization, Diagnosis and Treatment. Retrieved 2007-01-28. 4. ^ Chrisman, Cheryl; Clemmons, Roger; Mariani, Christopher; Platt, Simon (2003). Neurology for the Small Animal Practitioner (1st ed.). Teton New Media. ISBN 1-893441-82-2. This veterinary medicine–related 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	Scotty Cramp	None	27,243	wikipedia	https://en.wikipedia.org/wiki/Scotty_Cramp	2021-01-18T19:07:07	{"wikidata": ["Q7438222"]}
## Cloning and Expression Partridge et al. (1998) cloned and characterized an expressed processed ZNF204 pseudogene. Mapping By somatic cell hybrid analysis and fluorescence in situ hybridization, they mapped the ZNF204 pseudogene to 6p21.3, which contains a cluster of ZNF genes. The authors presented evidence that the ZNF204 'parent gene' also maps to 6p21.3. [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	ZINC FINGER PROTEIN 204	None	27,244	omim	https://www.omim.org/entry/603282	2019-09-22T16:13:07	{"omim": ["603282"]}
Caffey disease, also called infantile cortical hyperostosis, is a bone disorder that most often occurs in babies. Excessive new bone formation (hyperostosis) is characteristic of Caffey disease. The bone abnormalities mainly affect the jawbone, shoulder blades (scapulae), collarbones (clavicles), and the shafts (diaphyses) of long bones in the arms and legs. Affected bones may double or triple in width, which can be seen by x-ray imaging. In some cases two bones that are next to each other, such as two ribs or the pairs of long bones in the forearms (radius and ulna) or lower legs (tibia and fibula) become fused together. Babies with Caffey disease also have swelling of joints and of soft tissues such as muscles, with pain and redness in the affected areas. Affected infants can also be feverish and irritable. The signs and symptoms of Caffey disease are usually apparent by the time an infant is 5 months old. In rare cases, skeletal abnormalities can be detected by ultrasound imaging during the last few weeks of development before birth. Lethal prenatal cortical hyperostosis, a more severe disorder that appears earlier in development and is often fatal before or shortly after birth, is sometimes called lethal prenatal Caffey disease; however, it is generally considered to be a separate disorder. For unknown reasons, the swelling and pain associated with Caffey disease typically go away within a few months. Through a normal process called bone remodeling, which replaces old bone tissue with new bone, the excess bone is usually reabsorbed by the body and undetectable on x-ray images by the age of 2. However, if two adjacent bones have fused, they may remain that way, possibly resulting in complications. For example, fused rib bones can lead to curvature of the spine (scoliosis) or limit expansion of the chest, resulting in breathing problems. Most people with Caffey disease have no further problems related to the disorder after early childhood. Occasionally, another episode of hyperostosis occurs years later. In addition, some adults who had Caffey disease in infancy have other abnormalities of the bones and connective tissues, which provide strength and flexibility to structures throughout the body. Affected adults may have loose joints (joint laxity), stretchy (hyperextensible) skin, or be prone to protrusion of organs through gaps in muscles (hernias). ## Frequency Caffey disease has been estimated to occur in approximately 3 per 1,000 infants worldwide. A few hundred cases have been described in the medical literature. Researchers believe this condition is probably underdiagnosed because it usually goes away by itself in early childhood. ## Causes A mutation in the COL1A1 gene causes Caffey disease. The COL1A1 gene provides instructions for making part of a large molecule called type I collagen. Collagens are a family of proteins that strengthen and support many tissues in the body, including cartilage, bone, tendon, and skin. In these tissues, type I collagen is found in the spaces around cells. The collagen molecules are cross-linked in long, thin, fibrils that are very strong and flexible. Type I collagen is the most abundant form of collagen in the human body. The COL1A1 gene mutation that causes Caffey disease replaces the protein building block (amino acid) arginine with the amino acid cysteine at protein position 836 (written as Arg836Cys or R836C). This mutation results in the production of type I collagen fibrils that are variable in size and shape, but it is unknown how these changes lead to the signs and symptoms of Caffey disease. ### Learn more about the gene associated with Caffey disease * COL1A1 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is usually sufficient to cause the disorder. About 20 percent of people who have the mutation that causes Caffey disease do not experience its signs or symptoms; this phenomenon is called incomplete penetrance. In some cases, an affected person inherits the mutation that causes Caffey disease from a 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	Caffey disease	c0020497	27,245	medlineplus	https://medlineplus.gov/genetics/condition/caffey-disease/	2021-01-27T08:25:37	{"gard": ["1051"], "mesh": ["D006958"], "omim": ["114000"], "synonyms": []}
A number sign (#) is used with this entry because Donnai-Barrow syndrome is caused by homozygous or compound heterozygous mutation in the LRP2 gene (600073) on chromosome 2q31. Description The faciooculoacousticorenal (FOAR) syndrome was first described as comprising facial anomalies, ocular anomalies, sensorineural hearing loss, and proteinuria. Facial features include prominent brow, short nose, and hypertelorism, and ocular anomalies include myopia, iris hypoplasia, and/or retinal detachment (Regenbogen and Coscas, 1985). Donnai-Barrow syndrome (DBS) was first described as a distinct disorder characterized by diaphragmatic hernia, exomphalos, absent corpus callosum, myopia, and sensorineural deafness. The classic distinguishing features between the 2 disorders were presence of proteinuria and absence of diaphragmatic hernia and corpus callosum anomalies in FOAR (Donnai and Barrow, 1993). However, early reports noted that the 2 disorders shared many phenotypic features and may be identical (e.g., Devriendt et al., 1998). Although there is variability in the expression of some features (e.g., agenesis of the corpus callosum and proteinuria), the disorders are now considered to represent the same entity (Kantarci et al., 2007). Clinical Features Murdoch and Mengel (1971), Holmes and Schepens (1972), and Ozer (1974) independently reported a brother and sister with a syndrome of ocular and facial anomalies, telecanthus, perceptive deafness, epiphyseal dysplasia of the femoral heads, and proteinuria. Myopia and both telecanthus and true hypertelorism were present. Fraser (1976) described a single case with proteinuria. Donnai and Barrow (1993) described 2 unrelated patients, a male and a female, with a syndrome of diaphragmatic hernia, exomphalos, hypertelorism, agenesis of the corpus callosum, severe sensorineural deafness, and severe myopia. One child had iris coloboma and retinal detachment. Monitoring of subsequent pregnancies in both families revealed a further affected fetus in each. In a note added in proof, Donnai and Barrow (1993) indicated that a third affected child, a female in a possibly related family, had been identified. The authors suggested autosomal recessive inheritance. Gripp et al. (1997) described a male infant, the offspring of first-cousin parents from Saudi Arabia, who had wide anterior fontanel and metopic suture with frontal bossing, hypertelorism, downslanting palpebral fissures, bilateral iris coloboma, omphalocele, and bilateral absence of the diaphragm with herniation of internal organs causing pulmonary hypoplasia and death. Autopsy also showed intestinal malrotation. The findings were considered consistent with the syndrome described by Donnai and Barrow (1993). Schowalter et al. (1997) reported an 11-year-old boy with FOAR syndrome. He had iris coloboma, iris hypoplasia, macular hypoplasia, cataract, high myopia, retinal detachment, moderate sensorineural hearing loss, and proteinuria without aminoaciduria. Facial features included prominent brow, flat nasal bridge, hypertelorism, and downslanting palpebral fissures. In contrast to the previously reported patients, he had normal intellect and was learning Braille. Devriendt et al. (1998) reported a male infant with hypertelorism, severe myopia, sensorineural deafness, diaphragmatic hernia, and proteinuria. Other features included large anterior fontanel, depressed nasal bridge, downslanting palpebral fissures, and delayed development. The proteinuria was nonselective and did not include glucose or amino acids. Although the child did not have agenesis of the corpus callosum or exomphalos, the authors concluded that FOAR and Donnai-Barrow syndrome are the same entity. Devriendt et al. (1998) postulated that the brothers reported by Ohlsson (1963) may have had the same syndrome. Avunduk et al. (2000) reported a male child, born of consanguineous parents, who had exomphalos, agenesis of the corpus callosum, right iris coloboma, high myopia, retinal anomalies, and sensorineural deafness. Facial features included prominent forehead, long nose, downslanting palpebral fissures, and hypertelorism. There was no evidence of diaphragmatic hernia or heart defects. The authors noted the striking similarities to the patients reported by Donnai and Barrow (1993). The report confirmed autosomal recessive inheritance. Chassaing et al. (2003) reported Donnai-Barrow syndrome in 2 sets of sibs and in an unrelated child, with features including diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness. Kantarci et al. (2007) reported follow-up of 1 affected girl reported by Chassaing et al. (2003). At age 6 years, she was legally blind with mild developmental delay, but was learning Braille. She had a nonacidotic proximal tubulopathy. Kantarci et al. (2007) reported a large consanguineous family from the United Arab Emirates in which 5 sibs had Donnai-Barrow syndrome. The proband had characteristic cranial features and died of complications of congenital diaphragmatic hernia. Four surviving sibs had variable clinical features, including diaphragmatic eventration with pulmonary hypoplasia, omphalocele, sensorineural deafness, agenesis of the corpus callosum, hypertelorism, high myopia, large anterior fontanel, and developmental delay. One child also had retinal dystrophy, scoliosis, rib and vertebral anomalies, and short sternum. Imaging of 1 child showed numerous brain anomalies, including partially empty sella turcica, small pons, periventricular nodular heterotopia, small optic nerves and chiasm, ocular colobomas, and malformation of the left horizontal semicircular canal and vestibule. Urine samples from affected individuals showed proteinuria with spillage of retinol-binding proteins (see RBP1, 180260) and vitamin D-binding proteins (see DBP, 139200). Inheritance Donnai-Barrow syndrome usually shows an autosomal recessive mode of inheritance. Kantarci et al. (2008) reported a 9-year-old boy with classic features of the disorder due to a homozygous truncating mutation in the LRP2 gene resulting from paternal uniparental isodisomy for chromosome 2. The unaffected mother did not carry the mutation. The boy did not have expanded features, suggesting that paternal chromosome 2 is unlikely to carry imprinted genes affecting growth or development. Kantarci et al. (2008) noted the implications for genetic counseling in this family. Mapping By linkage analysis of several families with Donnai-Barrow syndrome, Kantarci et al. (2007) identified an 18-Mb candidate region on chromosome 2q23.3-q31.1 (maximum 2-point lod score of 4.31 and multipoint lod score of 6.24 between D2S1767 and D2S142). Molecular Genetics In 4 affected sibs with Donnai-Barrow syndrome from the United Arab Emirates, Kantarci et al. (2007) identified a homozygous mutation in the LRP2 gene (600073.0001). Kantarci et al. (2007) also identified pathogenic mutations in the LRP2 gene in affected individuals reported by Donnai and Barrow (1993) (600073.0004-600073.0006) and Chassaing et al. (2003) (see, e.g., 600073.0002-600073.0003). Kantarci et al. (2007) identified mutations in the LRP2 gene (600073.0007; 600073.0008) in a Belgian child reported by Devriendt et al. (1998) as having faciooculoacousticorenal syndrome. The findings confirmed that FOAR and Donnai-Barrow syndrome are the same entity. INHERITANCE \- Autosomal recessive GROWTH Weight \- Birth weight - 50-97th percentile HEAD & NECK Head \- Large anterior fontanel \- Macrocephaly Face \- Midface hypoplasia Ears \- Deafness, sensorineural \- Low-set ears \- Posteriorly rotated ears Eyes \- Hypertelorism \- High myopia \- Loss of vision \- Iris coloboma \- Iris hypoplasia \- Cataract \- Enlarged globes \- Downslanting palpebral fissures \- Underorbital skin creases \- Retinal detachment \- Retinal dystrophy \- Prominent eyes Nose \- Short nose \- Flat nasal bridge \- Broad tip CARDIOVASCULAR Heart \- Ventricular septal defect (less common) \- Double superior vena cava (rare) RESPIRATORY Lung \- Pulmonary hypoplasia secondary to diaphragmatic hernia CHEST Diaphragm \- Diaphragmatic hernia \- Diaphragmatic eventration ABDOMEN External Features \- Omphalocele \- Umbilical hernia Gastrointestinal \- Intestinal malrotation GENITOURINARY Internal Genitalia (Female) \- Bicornuate uterus (rare) SKELETAL Skull \- Widened metopic suture SKIN, NAILS, & HAIR Skin \- Underorbital skin creases NEUROLOGIC Central Nervous System \- Partial or complete agenesis of corpus callosum \- Developmental delay LABORATORY ABNORMALITIES \- Proteinuria \- Urinary excretion of retinol-binding proteins (RBP) and vitamin D-binding proteins (DBP) MOLECULAR BASIS \- Caused by mutation in the low density lipoprotein receptor-related protein 2 gene (LRP2, 600073.0001 ) ▲ 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	DONNAI-BARROW SYNDROME	c1857277	27,246	omim	https://www.omim.org/entry/222448	2019-09-22T16:28:43	{"doid": ["0090144"], "mesh": ["C536390"], "omim": ["222448"], "orphanet": ["2143"], "synonyms": ["Alternative titles", "FACIOOCULOACOUSTICORENAL SYNDROME", "DBS/FOAR SYNDROME", "DIAPHRAGMATIC HERNIA, EXOMPHALOS, ABSENT CORPUS CALLOSUM, HYPERTELORISM, MYOPIA, SENSORINEURAL DEAFNESS, AND PROTEINURIA"], "genereviews": ["NBK1878"]}
For a phenotypic description and a discussion of genetic heterogeneity of noninsulin-dependent diabetes mellitus (NIDDM), see 125853. Clinical Features Mahtani et al. (1996) found that, among 26 families enriched for NIDDM (125853), families with the lowest insulin levels showed significant linkage to chromosome 12 near D12S1349. Lehto et al. (1997) found that NIDDM2, like MODY3 (600496), is characterized by a reduced insulin secretory response that subsequently progresses to diabetes. Mapping By screening over 4,000 individuals from a Swedish-speaking population isolate in the Botnia region of western Finland, Mahtani et al. (1996) identified 26 families (comprising 217 individuals) enriched for NIDDM and performed a genomewide scan using nonparametric linkage analysis. They found no significant evidence for linkage when the families were analyzed together, but strong evidence for linkage when families were classified according to mean insulin levels in affected individuals in oral glucose tolerance tests. Specifically, families with the lowest insulin levels showed significant linkage to chromosome 12 near D12S1349. This region contains the gene causing the rare, dominant, early-onset form of diabetes, designated MODY3. Unlike MODY3 families, the Finnish families with low insulin had an age of onset typical for NIDDM (mean = 58 years). Mahtani et al. (1996) inferred the existence of a gene NIDDM2 causing noninsulin-dependent diabetes mellitus associated with low insulin secretion and suggested that NIDDM2 and MODY3 may represent different alleles of the same gene. Lehto et al. (1997) found that NIDDM2, like MODY3, is characterized by a reduced insulin secretory response that subsequently progresses to diabetes. This, together with the common site of the gene on 12q, suggested to them that NIDDM2 with its late age of onset was due to an allelic mutation in the HNF1A gene (142410), which has been found to be mutant in MODY3. Shaw et al. (1998) reported significant linkage with the NIDDM2 region on 12q24.2 in a single pedigree in Australia in which type II diabetes segregated in an autosomal dominant pattern of inheritance. The family was negative for mutations in the HNF1A gene. To assess whether the NIDDM2 locus can be detected in the U.S. population, Bektas et al. (1999) scanned 12q for linkage to diabetes in 26 Caucasian and 6 non-Caucasian multigenerational families with early-onset autosomal dominant type II diabetes. These pedigrees were negative for mutations in the HNF1A gene, thereby excluding MODY3. The mean age at diagnosis of diabetes for affected members was 37 +/- 18 years. While no evidence for linkage was detected at the NIDDM2 locus, a linkage peak was observed 50 cM centromeric to NIDDM2 between markers D12S375 and D12S1052. In a nonparametric analysis, the combined lod score was 2.9 at D12S375, and increased to 3.8 (P = 0.007) among Caucasian families. A further increase in significance was observed in pedigrees with poor insulin response. Suggestive evidence of linkage was also detected by a parametric analysis. Bektas et al. (1999) interpreted their data as indicating that the NIDDM2 locus does not play a major role in early-onset autosomal dominant type II diabetes. They suggested that a previously undetected type II diabetes locus exists 50 cM centromeric to NIDDM2 on 12q. Lindgren et al. (2002) extended the genomewide scan of Mahtani et al. (1996) to include 32 additional families, updating the affectation status and fine-mapping regions of interest. In the analysis of all 58 families, they identified suggestive linkage to 1 region, 9p13-q21 (nonparametric linkage score, 3.9; P less than 0.0002). When chromosome 12q24 was analyzed in only the 32 additional families, a nominal P value of less than 0.04 was observed. Together with data from other published genomewide scans, these findings lent support to the hypothesis that regions on 9p13-q21 and 12q24 may harbor susceptibility genes for type II diabetes. Kato et al. (2006) performed a region-wide association analysis on 12q15-q22 using more than 500 SNPs in 1,492 unrelated Japanese individuals and identified an association between type II diabetes and a 13.6-kb haplotype block that includes the entire SOCS2 gene (605117). Five SNPs in the 5-prime region of the SOCS2 gene were significantly associated with type II diabetes. Kato et al. (2006) concluded that SOCS2 may play a role in susceptibility to type II diabetes in the Japanese. [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	DIABETES MELLITUS, NONINSULIN-DEPENDENT, 2	c1832387	27,247	omim	https://www.omim.org/entry/601407	2019-09-22T16:14:45	{"mesh": ["C563323"], "omim": ["601407"], "synonyms": ["Alternative titles", "NONINSULIN-DEPENDENT DIABETES MELLITUS 2"]}
Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals. Signs and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly). There are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause. In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood. The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma. Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3. ## Frequency PFIC is estimated to affect 1 in 50,000 to 100,000 people worldwide. PFIC type 1 is much more common in the Inuit population of Greenland and the Old Order Amish population of the United States. ## Causes Mutations in the ATP8B1, ABCB11, and ABCB4 genes can cause PFIC. ATP8B1 gene mutations cause PFIC1. The ATP8B1 gene provides instructions for making a protein that helps to maintain an appropriate balance of bile acids, a component of bile. This process, known as bile acid homeostasis, is critical for the normal secretion of bile and the proper functioning of liver cells. In its role in maintaining bile acid homeostasis, some researchers believe that the ATP8B1 protein is involved in moving certain fats across cell membranes. Mutations in the ATP8B1 gene result in the buildup of bile acids in liver cells, damaging these cells and causing liver disease. The ATP8B1 protein is found throughout the body, but it is unclear how a lack of this protein causes short stature, deafness, and other signs and symptoms of PFIC1. Mutations in the ABCB11 gene are responsible for PFIC2. The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP). This protein is found in the liver, and its main role is to move bile salts (a component of bile) out of liver cells. Mutations in the ABCB11 gene result in the buildup of bile salts in liver cells, damaging these cells and causing liver disease. ABCB4 gene mutations cause PFIC3. The ABCB4 gene provides instructions for making a protein that moves certain fats called phospholipids across cell membranes. Outside liver cells, phospholipids attach (bind) to bile acids. Large amounts of bile acids can be toxic when they are not bound to phospholipids. Mutations in the ABCB4 gene lead to a lack of phospholipids available to bind to bile acids. A buildup of free bile acids damages liver cells and leads to liver disease. Some people with PFIC do not have a mutation in the ATP8B1, ABCB11, or ABCB4 gene. In these cases, the cause of the condition is unknown. ### Learn more about the genes associated with Progressive familial intrahepatic cholestasis * ABCB11 * ABCB4 * ATP8B1 ## 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	Progressive familial intrahepatic cholestasis	c4551898	27,248	medlineplus	https://medlineplus.gov/genetics/condition/progressive-familial-intrahepatic-cholestasis/	2021-01-27T08:25:04	{"gard": ["1288", "1289"], "mesh": ["C535933"], "omim": ["211600", "601847", "602347"], "synonyms": []}
Crescent moon shape on fingernails This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Leukonychia" – news · newspapers · books · scholar · JSTOR (October 2014) Leukonychia Other namesWhite nails or Milk spots[1] SpecialtyDermatology Leukonychia (or leuconychia), is a medical term for white discolouration appearing on nails.[2] It is derived from the Greek words leuko ("white") and onyx ("nail"). The most common cause is injury to the base of the nail (the matrix) where the nail is formed. ## Contents * 1 Types * 1.1 Leukonychia totalis * 1.2 Leukonychia partialis * 1.2.1 Leukonychia striata * 1.2.2 Leukonychia punctata * 1.2.3 Longitudinal leukonychia * 2 Cause * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Types[edit] ### Leukonychia totalis[edit] Leukonychia totalis This condition consists of a whitening of the entire nail and mostly likely occurs on all nails. Whitening of one, and only one, entire nail is not recognized as a symptom of Leukonychia totalis but as a likely result of mechanical trauma. Leukonychia totalis may be a clinical sign of hypoalbuminaemia (low albumin), which can be seen in nephrotic syndrome (a form of kidney failure), liver failure, protein malabsorption and protein-losing enteropathies. A genetic condition or a side effect from taking sulphonamides (a family of antibiotics) can also cause this appearance. By 2011, only 6 cases of non-hereditary Leukonychia totalis were published.[3] ### Leukonychia partialis[edit] Leukonychia partialis This condition consists of a whitening of parts of the nail plate in the form of small white dots. There are three different variations of partial leukonychia; punctate, transverse and longitudinal leukonychia. Some of the more serious variations of leukonychia partialis may lead to leukonychia totalis.[4] #### Leukonychia striata[edit] Leukonychia striata Main article: Mees' lines Leukonychia striata, transverse leukonychia, or Mees' lines are a whitening or discoloration of the nail in bands or "stria" that run parallel the lunula (nail base). This is commonly caused by physical injury or disruption of the nail matrix. Common examples include excessive biting or tapping of the nails, trauma or injury from accidents involving doors or windows, and extensive use of manicure.[5] It may also occur in great toenails as a result of trauma from footwear. Alternatively, the condition can be caused by heavy metal poisoning, most commonly by lead.[6] Finally, it can be caused by cirrhosis of the liver or chemotherapy.[7] The tendency toward leukonychia striata is sometimes inherited in an autosomal dominant fashion. In other cases, it can be attributed to vigorous manicuring and trauma aforementioned, or to a wide variety of systemic illnesses. Serious infections known for high fevers, measles, malaria, herpes, and leprosy may also cause this condition. In many patients, there is no obvious cause, and the streaks resolve spontaneously.[8] There is a similar condition called Muehrcke's lines (apparent leukonychia) which differs from leukonychia in that the lines fade with digital compression and does not migrate with the growth of the nail.[9] #### Leukonychia punctata[edit] Also known as "true" leukonychia, this is the most common form of leukonychia, in which small white spots appear on the nails. Picking and biting of the nails are a prominent cause in young children and nail biters. Besides parakeratosis, air that is trapped between the cells may also cause this appearance.[4] It is also caused by trauma. In most cases, when white spots appear on a single or a couple of fingers or toes, the most common cause is injury to the base (matrix) of the nail. When this is the case, white spots disappear after around eight months, which is the amount of time necessary for nails to regrow completely. The pattern and number of spots may change as the nail grows.[10] #### Longitudinal leukonychia[edit] Longitudinal leukonychia is far less common and features smaller 1mm white longitudinal lines visible under the nail plate and parallel to the nail bed. It may be associated with Darier's disease.[4] ## Cause[edit] It is harmless and most commonly caused by minor injuries, such as nail biting, which occur while the nail is growing.[11] Leukonychia occurs most commonly in healthy individuals, and is unrelated to any known nutritional or physiological deficiency.[4] When caused by injury the marks will disappear as the nail grows outwards. While there are various sources that link dietary needs or vitamin deficiency with recurrent leukonychia,[12][13] this notion has been challenged by some medical researchers.[14] Other possible reasons for this problem with nail colour can be linked to: * Arsenic poisoning * Lead poisoning * Particularly large white spot. Pneumonia * Heart disease * Kidney failure * Ill health * Hypoalbuminemia * Vitamin deficiency * Ulcerative colitis * Liver cirrhosis * Psychogenic stresses * Onychophagia * Wildlife pet ownership (e.g. parrots that nip the fingers) * Occupational trauma * Zinc deficiency * Protein deficiency * Psoriasis[15] * Eczema * Iron deficiency[16] ## Diagnosis[edit] A doctor will take a thorough medical history, and may take blood tests as well as examining liver and kidney function. Intracellular (red blood cell) assays are more sensitive than tests for plasma levels.[17] ## Treatment[edit] Improvements have been reported from treating malnutrition associated with zinc deficiency and other minerals.[18][19] ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. p. 789. ISBN 0-7216-2921-0. 2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. pp. 658–59. ISBN 0-07-138076-0. 3. ^ Arsiwala, Shehnaz (2012). "Idiopathic acquired persistent true partial to total leukonychia". Indian Journal of Dermatology, Venereology, and Leprology. 78 (1): 107–8. doi:10.4103/0378-6323.90962. PMID 22199074. 4. ^ a b c d Tüzün, Yalçın; Karakuş, Özge (2009). "Leukonychia" (PDF). Journal of Turkish Academy of Leukonychia: 1–3. Archived from the original (PDF) on March 3, 2016. Retrieved April 2, 2017. 5. ^ Maino KL, Stashower ME (2004). "Traumatic Transverse Leukonychia". Skinmed. Medscape. 3 (1): 53–5. doi:10.1111/j.1540-9740.2004.02369.x. PMID 14724417. 6. ^ Baran, Robert et al. Baran and Dawber's Diseases of the Nails and Their Management. John Wiley & Sons, 2012 7. ^ Miles DW, Rubens RD (1995). "Images in clinical medicine. Transverse leukonychia". N. Engl. J. Med. 333 (2): 100. doi:10.1056/NEJM199507133330205. PMID 7777013. 8. ^ "Pictures of Nail Diseases and Problems - Leukonychia Striata". 9. ^ Huang, T.-C.; Chao, T.-Y. (14 December 2009). "Mees lines and Beau lines after chemotherapy". Canadian Medical Association Journal. 182 (3): E149. doi:10.1503/cmaj.090501. PMC 2826482. PMID 20008502. 10. ^ "My Big Fat Greek Leukonychia". 11. ^ Schocker, Laura (24 September 2013). "15 Things You Never Knew About Your Nails". HuffPost UK. 12. ^ Holland, Kimberly (29 May 2018). Cobb, Cynthia (ed.). "Why Are There White Spots on My Nails?". Healthline. "You may notice white spots or dots along your nails if you are deficient in certain minerals or vitamins." 13. ^ "White Spots On Nails: Should You Be Worried?". CureJoy. 6 March 2018. "They may also be caused by zinc or albumin deficiency, which is curable." 14. ^ Morgan, Z.; Wickett, H. (6 May 2011). "Leukonychia on finger nails as a marker of calcium and/or zinc deficiency". Journal of Human Nutrition and Dietetics. 24 (3): 294–295. doi:10.1111/j.1365-277X.2011.01175_23.x. "The results showed there was no correlation between calcium or zinc intake scores and leukonychia." 15. ^ Rendon, Adriana; Schäkel, Knut (23 March 2019). "Psoriasis Pathogenesis and Treatment". International Journal of Molecular Sciences. 20 (6): 1475. doi:10.3390/ijms20061475. PMC 6471628. PMID 30909615. 16. ^ "Leukonychia – Symptoms, Causes, Treatment, Pictures". byebyedoctor.com. Retrieved 2017-05-18. 17. ^ Kelly MP, Kight MA, Castillo S (July 1998). "Trophic implications of altered body composition observed in or near the nails of hemodialysis patients". Advances in Renal Replacement Therapy. 5 (3): 241–51. doi:10.1016/S1073-4449(98)70037-8. PMID 9686635. 18. ^ Meyer, Bhika (November 2014). "Nails as Indicators of Disease" (PDF). Science of Medicine and Art of Care – via Tibb Institute. 19. ^ Wollina U, Nenoff P, Haroske G, Haenssle HA (July 2016). "The Diagnosis and Treatment of Nail Disorders". Deutsches Ärzteblatt International. 113 (29–30): 509–18. doi:10.3238/arztebl.2016.0509. PMC 5527843. PMID 27545710. ## External links[edit] Classification D * ICD-10: L60.8, Q84.4 * ICD-9-CM: 703.8, 757.5 * DiseasesDB: 14140 Wikimedia Commons has media related to Leukonychia. * v * t * e Disorders of skin appendages Nail * thickness: Onychogryphosis * Onychauxis * color: Beau's lines * Yellow nail syndrome * Leukonychia * Azure lunula * shape: Koilonychia * Nail clubbing * behavior: Onychotillomania * Onychophagia * other: Ingrown nail * Anonychia * ungrouped: Paronychia * Acute * Chronic * Chevron nail * Congenital onychodysplasia of the index fingers * Green nails * Half and half nails * Hangnail * Hapalonychia * Hook nail * Ingrown nail * Lichen planus of the nails * Longitudinal erythronychia * Malalignment of the nail plate * Median nail dystrophy * Mees' lines * Melanonychia * Muehrcke's lines * Nail–patella syndrome * Onychoatrophy * Onycholysis * Onychomadesis * Onychomatricoma * Onychomycosis * Onychophosis * Onychoptosis defluvium * Onychorrhexis * Onychoschizia * Platonychia * Pincer nails * Plummer's nail * Psoriatic nails * Pterygium inversum unguis * Pterygium unguis * Purpura of the nail bed * Racquet nail * Red lunulae * Shell nail syndrome * Splinter hemorrhage * Spotted lunulae * Staining of the nail plate * Stippled nails * Subungual hematoma * Terry's nails * Twenty-nail dystrophy Hair Hair loss/ Baldness * noncicatricial alopecia: Alopecia * areata * totalis * universalis * Ophiasis * Androgenic alopecia (male-pattern baldness) * Hypotrichosis * Telogen effluvium * Traction alopecia * Lichen planopilaris * Trichorrhexis nodosa * Alopecia neoplastica * Anagen effluvium * Alopecia mucinosa * cicatricial alopecia: Pseudopelade of Brocq * Central centrifugal cicatricial alopecia * Pressure alopecia * Traumatic alopecia * Tumor alopecia * Hot comb alopecia * Perifolliculitis capitis abscedens et suffodiens * Graham-Little syndrome * Folliculitis decalvans * ungrouped: Triangular alopecia * Frontal fibrosing alopecia * Marie Unna hereditary hypotrichosis Hypertrichosis * Hirsutism * Acquired * localised * generalised * patterned * Congenital * generalised * localised * X-linked * Prepubertal Acneiform eruption Acne * Acne vulgaris * Acne conglobata * Acne miliaris necrotica * Tropical acne * Infantile acne/Neonatal acne * Excoriated acne * Acne fulminans * Acne medicamentosa (e.g., steroid acne) * Halogen acne * Iododerma * Bromoderma * Chloracne * Oil acne * Tar acne * Acne cosmetica * Occupational acne * Acne aestivalis * Acne keloidalis nuchae * Acne mechanica * Acne with facial edema * Pomade acne * Acne necrotica * Blackhead * Lupus miliaris disseminatus faciei Rosacea * Perioral dermatitis * Granulomatous perioral dermatitis * Phymatous rosacea * Rhinophyma * Blepharophyma * Gnathophyma * Metophyma * Otophyma * Papulopustular rosacea * Lupoid rosacea * Erythrotelangiectatic rosacea * Glandular rosacea * Gram-negative rosacea * Steroid rosacea * Ocular rosacea * Persistent edema of rosacea * Rosacea conglobata * variants * Periorificial dermatitis * Pyoderma faciale Ungrouped * Granulomatous facial dermatitis * Idiopathic facial aseptic granuloma * Periorbital dermatitis * SAPHO syndrome Follicular cysts * "Sebaceous cyst" * Epidermoid cyst * Trichilemmal cyst * Steatocystoma * simplex * multiplex * Milia Inflammation * Folliculitis * Folliculitis nares perforans * Tufted folliculitis * Pseudofolliculitis barbae * Hidradenitis * Hidradenitis suppurativa * Recurrent palmoplantar hidradenitis * Neutrophilic eccrine hidradenitis Ungrouped * Acrokeratosis paraneoplastica of Bazex * Acroosteolysis * Bubble hair deformity * Disseminate and recurrent infundibulofolliculitis * Erosive pustular dermatitis of the scalp * Erythromelanosis follicularis faciei et colli * Hair casts * Hair follicle nevus * Intermittent hair–follicle dystrophy * Keratosis pilaris atropicans * Kinking hair * Koenen's tumor * Lichen planopilaris * Lichen spinulosus * Loose anagen syndrome * Menkes kinky hair syndrome * Monilethrix * Parakeratosis pustulosa * Pili (Pili annulati * Pili bifurcati * Pili multigemini * Pili pseudoannulati * Pili torti) * Pityriasis amiantacea * Plica neuropathica * Poliosis * Rubinstein–Taybi syndrome * Setleis syndrome * Traumatic anserine folliculosis * Trichomegaly * Trichomycosis axillaris * Trichorrhexis (Trichorrhexis invaginata * Trichorrhexis nodosa) * Trichostasis spinulosa * Uncombable hair syndrome * Wooly hair nevus Sweat glands Eccrine * Miliaria * Colloid milium * Miliaria crystalline * Miliaria profunda * Miliaria pustulosa * Miliaria rubra * Occlusion miliaria * Postmiliarial hypohidrosis * Granulosis rubra nasi * Ross’ syndrome * Anhidrosis * Hyperhidrosis * Generalized * Gustatory * Palmoplantar Apocrine * Body odor * Chromhidrosis * Fox–Fordyce disease Sebaceous * Sebaceous hyperplasia * v * t * e Congenital malformations and deformations of skin appendages Nail disease * Anonychia * Leukonychia * Pachyonychia congenita/Onychauxis * Koilonychia Hair disease * hypotrichosis/abnormalities: keratin disease * Monilethrix * IBIDS syndrome * Sabinas brittle hair syndrome * Pili annulati * Pili torti * Uncombable hair syndrome * Björnstad syndrome * Giant axonal neuropathy with curly hair * hypertrichosis: Zimmermann–Laband syndrome * Medicine portal [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	Leukonychia	c0240182	27,249	wikipedia	https://en.wikipedia.org/wiki/Leukonychia	2021-01-18T19:04:12	{"icd-9": ["757.5", "703.8"], "icd-10": ["L60.8", "Q84.4"], "wikidata": ["Q2549292"]}
"Mass hysteria" redirects here. For the heavy metal band, see Mass Hysteria (band). Spread of illness symptoms through a population where there is no viral or bacterial agent responsible for contagion Mass psychogenic illness Other namesMass hysteria, epidemic hysteria, mass sociogenic illness, mass psychogenic disorder Dancing plagues of the Middle Ages are thought to have been caused by mass hysteria SpecialtyPsychiatry SymptomsHeadache, dizziness, nausea, abdominal pain, cough, fatigue, sore throat Risk factorsChildhood or adolescence, intense media coverage. Differential diagnosisActual diseases, mass delusions, somatic symptom disorder Mass psychogenic illness (MPI), also called mass sociogenic illness, mass psychogenic disorder, epidemic hysteria, or mass hysteria, is the rapid spread of illness signs and symptoms affecting members of a cohesive group, originating from a nervous system disturbance involving excitation, loss, or alteration of function, whereby physical complaints that are exhibited unconsciously have no corresponding organic aetiology.[1] ## Contents * 1 Etiology * 1.1 Common symptoms * 1.2 Prevalence and intensity * 2 Research * 3 In history * 3.1 Middle Ages * 3.2 18th to 21st centuries * 3.2.1 In factories * 3.2.2 In schools * 3.2.3 Terrorism and biological warfare * 3.2.4 Children in recent refugee families * 4 See also * 5 Notes * 6 References * 7 General references ## Etiology[edit] Mass psychogenic illness involves the spread of illness symptoms through a population where there is no viral or bacterial agent responsible for contagion.[2] MPI is distinct from other types of collective delusions by involving physical symptoms.[3] According to Balaratnasingam and Janca, "Mass hysteria is to date a poorly understood condition. Little certainty exists regarding its etiology".[4] Qualities of MPI outbreaks often include:[3] * symptoms that have no plausible organic basis; * symptoms that are transient and benign; * symptoms with rapid onset and recovery; * occurrence in a segregated group; * the presence of extraordinary anxiety; * symptoms that are spread via sight, sound or oral communication; * a spread that moves down the age scale, beginning with older or higher-status people; * a preponderance of female participants. British psychiatrist Simon Wesseley distinguishes between two forms of MPI:[1] * Mass anxiety hysteria "consists of episodes of acute anxiety, occurring mainly in schoolchildren. Prior tension is absent and the rapid spread is by visual contact."[5] * Mass motor hysteria "consists of abnormalities in motor behaviour. It occurs in any age group and prior tension is present. Initial cases can be identified and the spread is gradual. … [T]he outbreak may be prolonged."[5] While his definition is sometimes adhered to,[1][6] others such as Ali-Gombe et al. of the University of Maiduguri, Nigeria contest Wesseley's definition and describe outbreaks with qualities of both mass motor hysteria and mass anxiety hysteria.[7] The DSM-IV-TR does not have specific diagnosis for this condition but the text describing conversion disorder states that "In 'epidemic hysteria', shared symptoms develop in a circumscribed group of people following 'exposure' to a common precipitant." ### Common symptoms[edit] Timothy F. Jones of the Tennessee Department of Health compiles the following symptoms based on their commonality in outbreaks occurring in 1980–1990:[8] Symptom Percent reporting Headache 67 Dizziness or light-headedness 46 Nausea 41 Abdominal cramps or pain 39 Cough 31 Fatigue, drowsiness or weakness 31 Sore or burning throat 30 Hyperventilation or difficulty breathing 19 Watery or irritated eyes 13 Chest tightness/chest pain 12 Inability to concentrate/trouble thinking 11 Vomiting 10 Tingling, numbness or paralysis 10 Anxiety or nervousness 8 Diarrhea 7 Trouble with vision 7 Rash 4 Loss of consciousness/syncope 4 Itching 3 ### Prevalence and intensity[edit] Adolescents and children are frequently affected in cases of MPI.[8] The hypothesis that those prone to extroversion or neuroticism, or those with low IQ scores, are more likely to be affected in an outbreak of hysterical epidemic has not been consistently supported by research. Bartholomew and Wesseley state that it "seems clear that there is no particular predisposition to mass sociogenic illness and it is a behavioural reaction that anyone can show in the right circumstances."[1] Intense media coverage seems to exacerbate outbreaks.[4][6][8] The illness may also recur after the initial outbreak.[8] John Waller advises that once it is determined that the illness is psychogenic, it should not be given credence by authorities.[6] For example, in the Singapore factory case study, calling in a medicine man to perform an exorcism seemed to perpetuate the outbreak.[9] ## Research[edit] Besides the difficulties common to all research involving the social sciences, including a lack of opportunity for controlled experiments, mass sociogenic illness presents special difficulties to researchers in this field. Balaratnasingam and Janca report that the methods for "diagnosis of mass hysteria remain contentious."[4] According to Jones, the effects resulting from MPI "can be difficult to differentiate from [those of] bioterrorism, rapidly spreading infection or acute toxic exposure."[8] These troubles result from the residual diagnosis of MPI. Singer, of the Uniformed Schools of Medicine, puts the problems with such a diagnosis thus:[10] "[y]ou find a group of people getting sick, you investigate, you measure everything you can measure … and when you still can't find any physical reason, you say 'well, there's nothing else here, so let's call it a case of MPI.'" There is a lack of logic in an argument that proceeds: "There isn't anything, so it must be MPI." It precludes the notion that an organic factor could have been overlooked. Nevertheless, running an extensive number of tests extends the probability of false positives.[10] ## In history[edit] See also: List of mass hysteria cases ### Middle Ages[edit] The earliest studied cases linked with epidemic hysteria are the dancing manias of the Middle Ages, including St. John's dance and tarantism. These were supposed to be associated with spirit possession or the bite of the tarantula. Those afflicted with dancing mania would dance in large groups, sometimes for weeks at a time. The dancing was sometimes accompanied by stripping, howling, the making of obscene gestures, or even (reportedly) laughing or crying to the point of death. Dancing mania was widespread over Europe.[11] Between the 15th and 19th centuries, instances of motor hysteria were common in nunneries. The young ladies that made up these convents were typically forced there by family. Once accepted, they took vows of chastity and poverty. Their lives were highly regimented and often marked by strict disciplinary action. The nuns would exhibit a variety of behaviors, usually attributed to demonic possession. They would often use crude language and exhibit suggestive behaviors. One convent's nuns would regularly meow like cats. Priests were often called in to exorcise demons.[1] ### 18th to 21st centuries[edit] #### In factories[edit] MPI outbreaks occurred in factories following the industrial revolution in England, France, Germany, Italy and Russia[1] as well as the United States and Singapore. W. H. Phoon, Ministry of Labour in Singapore, gives a case study of six outbreaks of MPI in Singapore factories between 1973 and 1978.[9] They were characterized by (1) hysterical seizures of screaming and general violence, wherein tranquilizers were ineffective (2) trance states, where a worker would claim to be speaking under the influence of a spirit or jinn (or genie) and (3) frightened spells: some workers complained of unprecedented fear, or of being cold, numb, or dizzy. Outbreaks would subside in about a week. Often a bomoh (medicine man) would be called in to do a ritual exorcism. This technique was not effective and sometimes seemed to exacerbate the MPI outbreak. Females and Malays were affected disproportionately. Especially notable is the "June Bug" outbreak:[12] In June 1962, a peak month in factory production, 62 workers at a dressmaking factory in a textile town in the Southern United States[a] experienced symptoms including severe nausea and breaking out on the skin. Most outbreaks occurred during the first shift, where four fifths of the workers were female. Of 62 total outbreaks, 59 were women, some of whom believed they were bitten by bugs from a fabric shipment,[15] so entomologists and others were called in to discover the pathogen, but none was found. Kerchoff coordinated the interview of affected and unaffected workers at the factory and summarizes his findings: * Strain – those affected were more likely to work overtime frequently and provide the majority of the family income. Many were married with children. * Affected persons tended to deny their difficulties. Kerchoff postulates that such were "less likely to cope successfully under conditions of strain." * Results seemed consistent with a model of social contagion. Groups of affected persons tended to have strong social ties. Kerchoff also links the rapid rate of contagion with the apparent reasonableness of the bug infestation theory and the credence given to it in accompanying news stories. Stahl and Lebedun[16] describe an outbreak of mass sociogenic illness in the data center of a university town in the United States Midwest in 1974. Ten of 39 workers smelling an unconfirmed "mystery gas" were rushed to a hospital with symptoms of dizziness, fainting, nausea and vomiting. They report that most workers were young women either putting their husbands through school or supplementing the family income. Those affected were found to have high levels of job dissatisfaction. Those with strong social ties tended to have similar reactions to the supposed gas, which only one unaffected woman reported smelling. No gas was detected in subsequent tests of the data center. #### In schools[edit] Mass hysteria affected schools in Berry, Alabama and Miami Beach in 1974, with the former episode taking the form of recurring pruritus, and the latter initially triggering fears of poison gas (it was traced back to a popular student who happened to be sick with a virus).[17] Thousands were affected by the spread of a supposed illness in a province of Kosovo in March to June 1990, exclusively affecting ethnic Albanians, most of whom were young adolescents.[18] A wide variety of symptoms were manifested, including headache, dizziness, impeded respiration, weakness/adynamia, burning sensations, cramps, retrosternal/chest pain, dry mouth and nausea. After the illness had subsided, a bipartisan Federal Commission released a document, offering the explanation of psychogenic illness. Radovanovic of the Department of Community Medicine and Behavioural Sciences Faculty of Medicine in Safat, Kuwait reports: > This document did not satisfy either of the two ethnic groups. Many Albanian doctors believed that what they had witnessed was an unusual epidemic of poisoning. The majority of their Serbian colleagues also ignored any explanation in terms of psychopathology. They suggested that the incident was faked with the intention of showing Serbs in a bad light but that it failed due to poor organization. Rodovanovic expects that this reported instance of mass sociogenic illness was precipitated by the demonstrated volatile and culturally tense situation in the province.[18] The Tanganyika laughter epidemic of 1962 was an outbreak of laughing attacks rumored to have occurred in or near the village of Kanshasa on the western coast of Lake Victoria in the modern nation of Tanzania, eventually affecting 14 different schools and over 1000 people. On the morning of Thursday 7 October 1965, at a girls' school in Blackburn in England, several girls complained of dizziness.[19] Some fainted. Within a couple of hours, 85 girls from the school were rushed by ambulance to a nearby hospital after fainting. Symptoms included swooning, moaning, chattering of teeth, hyperpnea, and tetany. Moss and McEvedy published their analysis of the event about one year later. Their conclusions follow.[19] Note that their conclusion about the above-average extraversion and neuroticism of those affected is not necessarily typical of MPI:[1] * Clinical and laboratory findings were essentially negative. * Investigations by the public health authorities did not uncover any evidence of pollution of food or air. * The epidemiology of the outbreak was investigated by means of questionnaires administered to the whole school population. It was established that the outbreaks began among the 14-year-olds, but that the heaviest incidence moved to the youngest age groups. * By using the Eysenck Personality Inventory, it was established that, in all age groups, the mean E [extraversion] and N [neuroticism] scores of the affected were higher than those of the unaffected. * The younger girls proved more susceptible, but disturbance was more severe and lasted longer in the older girls. * It was considered that the epidemic was hysterical, that a previous polio epidemic had rendered the population emotionally vulnerable, and that a three-hour parade, producing 20 faints on the day before the first outbreak, had been the specific trigger. * The data collected were thought to be incompatible with organic theories and with the compromise theory of an organic nucleus. Another possible case occurred in Belgium in June 1999 when people, mainly schoolchildren, became ill after drinking Coca-Cola.[20] In the end, scientists were divided over the scale of the outbreak, whether it fully explains the many different symptoms and the scale to which sociogenic illness affected those involved.[21][22] A possible outbreak of mass psychogenic illness occurred at Le Roy Junior-Senior High School in upstate New York, US, in which multiple students began suffering symptoms similar to Tourette syndrome. Various health professionals ruled out such factors as Gardasil, drinking water contamination, illegal drugs, carbon monoxide poisoning and various other potential environmental or infectious causes, before diagnosing the students with a conversion disorder and mass psychogenic illness.[23] Starting around 2009, a spate of apparent poisonings at girls' schools across Afghanistan began to be reported; symptoms included dizziness, fainting and vomiting. The United Nations, World Health Organization and NATO's International Security Assistance Force carried out investigations of the incidents over multiple years, but never found any evidence of toxins or poisoning in the hundreds of blood, urine and water samples they tested. The conclusion of the investigators was that the girls were suffering from mass psychogenic illness.[24][25] In August 2019 the BBC reported that schoolgirls at the Ketereh national secondary school (SMK Ketereh) in Kelantan, Malaysia, started screaming, with some claiming to have seen 'a face of pure evil'. Dr Simon Wessely of King's College Hospital, London suggested it was a form of 'collective behaviour'. Robert Bartholomew, an American medical sociologist and author, said, "It is no coincidence that Kelantan, the most religiously conservative of all Malaysian states, is also the one most prone to outbreaks." This view is supported by Afiq Noor, an academic, who argues that the stricter implementation of Islamic law in school in states such as Kelantan is linked to the outbreaks. He suggested that the screaming outbreak was caused by the constricted environment. In Malaysian culture burial sites and trees are common settings for supernatural tales about the spirits of dead infants (toyol), vampiric ghosts (pontianak) and vengeful female spirits (penanggalan). Authorities responded to the Kelantan outbreak by cutting down trees around the school. Outbreaks of mass psychogenic illness have been reported in Catholic convents and monasteries across Mexico, Italy and France, in schools in Kosovo and even among cheerleaders in a rural North Carolina town.[26] Episodes of mass hysteria has been observed in schools of Nepal frequently,[27][28] even leading to closure of schools temporarily.[29] A unique phenomenon of “recurrent epidemic of mass hysteria” was reported from a school of Pyuthan district of western Nepal in 2018. After a 9-year-old school girl developed crying and shouting episodes, quickly other children of the same school were also affected resulting in 47 affected students (37 females, 10 males) in the same day. Since 2016 similar episodes of mass psychogenic illness has been occurring in the same school every year hence it was thought to be a unique case of recurrent mass hysteria.[30][31] #### Terrorism and biological warfare[edit] Bartholomew and Wessely anticipate the "concern that after a chemical, biological or nuclear attack, public health facilities may be rapidly overwhelmed by the anxious and not just the medical and psychological casualties."[1] Additionally, early symptoms of those affected by MPI are difficult to differentiate from those actually exposed to the dangerous agent.[8] The first Iraqi missile hitting Israel during the Persian Gulf War was believed to contain chemical or biological weapons. Though this was not the case, 40% of those in the vicinity of the blast reported breathing problems.[1] Right after the 2001 anthrax attacks in the first two weeks of October 2001, there were over 2300 false anthrax alarms in the United States. Some reported physical symptoms of what they believed to be anthrax.[1] Also in 2001, a man sprayed what was later found to be a window cleaner into a subway station in Maryland. Thirty-five people were treated for nausea, headaches and sore throats.[1] In 2017, some employees of the US embassy in Cuba reported symptoms (nicknamed the "Havana syndrome") attributed to "sonic attacks". The following year, some US government employees in China reported similar symptoms. Some scientists have suggested the alleged symptoms were psychogenic in nature.[32][33][34] #### Children in recent refugee families[edit] Refugee children in Sweden have been reported to fall into coma-like states on learning their families will be deported. The condition, known as resignation syndrome (Swedish: uppgivenhetssyndrom), is believed to only exist among the refugee population in the Scandinavian country, where it has been prevalent since the early part of the 21st century. Commentators state "a degree of psychological contagion" is inherent to the condition, by which young friends and relatives of the afflicted individual can also come to suffer from the condition.[35] In a 130-page report on the condition, commissioned by the government and published in 2006, a team of psychologists, political scientists and sociologists hypothesized that it was a culture-bound syndrome, a psychological illness endemic to a specific society.[36] This phenomenon has later been called into question, with children witnessing that they were forced, by their parents, to act in a certain way in order to increase chances of being granted residence permits.[37][38] As evidenced by medical records, healthcare professionals were aware of this scam, and witnessed parents who actively refused aid for their children, but remained silent. Later, Sveriges Television, Sweden's national public television broadcaster, were severely critiqued by investigative journalist Janne Josefsson for failing to uncover the truth.[39] ## See also[edit] * Psychology portal * Body-centred countertransference * Culture-bound syndrome – Combination of symptoms that are considered to be a recognizable disease only within a specific culture * Conversion disorder – Diagnostic category used in some psychiatric classification systems * Day-care sex-abuse hysteria – Moral panic and series of prosecutions in North America in the final quarter of the 20th century onwards * Folie à deux – Shared psychosis, a psychiatric syndrome in which symptoms of a delusional belief are transmitted from one individual to another (from the French for "a madness shared by two") * Herd mentality – Human tendency to adopt beliefs and behaviors favored by one's group * Hypochondriasis * Hysterical contagion * Sick building syndrome – A health concern, where people in a building suffer from symptoms of illness or become infected with chronic disease from the building in which they work or reside ## Notes[edit] 1. ^ The factory – employing 965 workers – was named the "Montana Mills", a subsidiary of a northern business that had moved into town only a few years prior.[12] It was said to be at "Strongsville", but both the factory name and place-name are the authors' pseudonyms.[13] The location has been said to be Spartanburg, South Carolina,[14] a major textile center. ## References[edit] 1. ^ a b c d e f g h i j k Bartholomew, Robert; Wessely, Simon (2002). "Protean nature of mass sociogenic illness" (PDF). The British Journal of Psychiatry. 180 (4): 300–306. doi:10.1192/bjp.180.4.300. PMID 11925351. Archived (PDF) from the original on 2019-01-30. Retrieved 2018-10-10. 2. ^ Kelly, J.R.; Iannone, R.E.; McCarty, M.K. (2014). "The function of shared affect in groups". In von Scheve, Christian; Salmella, Mikko (eds.). Collective Emotions. OUP Oxford. ISBN 978-0-19-965918-0. Archived from the original on 2020-10-29. Retrieved 2020-09-03. 3. ^ a b Weir, Erica (2005). "Mass sociogenic illness". Canadian Medical Association Journal. 172 (1): 36. doi:10.1503/cmaj.045027. PMC 543940. PMID 15632400. 4. ^ a b c Balaratnasingam, Sivasankaran; Janca, Aleksandar (March 2006). "Mass hysteria revisited" (PDF). Current Opinion in Psychiatry. 19 (2): 171–74. doi:10.1097/01.yco.0000214343.59872.7a. PMID 16612198. S2CID 10779450. Archived (PDF) from the original on 2018-10-22. Retrieved 2018-10-21. 5. ^ a b Wessely, Simon (1987). "Mass hysteria: two syndromes?". Psychological Medicine. 17 (1): 109–20. doi:10.1017/s0033291700013027. PMID 3575566. S2CID 32597423. Archived from the original on 2020-10-29. Retrieved 2019-12-07. 6. ^ a b c [1] Archived 2014-10-26 at the Wayback Machine Waller, John. "Looking Back: Dancing plagues and mass hysteria." The Psychologist 22(7) (2009): 644–47. Web. 17 Dec. 2009. 7. ^ Ali-Gombe, A. et al. "Mass hysteria: one syndrome or two?" British Journal of Psychiatry 1997; 170 387–88. Web. 17 Dec. 2009. 8. ^ a b c d e f [2] Archived 2011-06-06 at the Wayback Machine Jones, Timothy. "Mass Psychogenic Illness: Role of the Individual Physician." American Family Physician. American Family of Family Physicians: 15 Dec. 2000. Web. 28 Nov. 2009. 9. ^ a b Phoon, W. H. (1982). "Outbreaks of Mass Hysteria at Workplaces in Singapore: Some Patterns and Modes of Presentation". In J. W. Pennebaker; L. R. Murphy; M. J. Colligan (eds.). Mass Psychogenic Illness: A Social Psychological Analysis. Hillsdale, New Jersey: Lawrence Erlbaum Associates. pp. 21–31. 10. ^ a b Singer, Jerome. "Yes Virginia, There Really Is a Mass Psychogenic Illness." Mass Psychogenic Illness: A Social Psychological Analysis. Ed. Colligan et al. Hillsdale, NJ: Lawrence Erlbaum Associates, Publishers, 1982. 21–31. Print. 11. ^ Bartholomew, Robert (2001). Little Green Men, Meowing Nuns and Head-Hunting Panics. Jefferson, North Carolina: McFarland & Company, Inc. 12. ^ a b Kerchoff, Alan C. (2013). "Analyzing a Case of Mass Psychogenic Illness". In Colligan; et al. (eds.). Mass Psychogenic Illness: A Social Psychological Analysis. Routledge. pp. 5–19. ISBN 978-1-317-83864-7. Archived from the original on 2020-08-05. Retrieved 2017-10-04. 13. ^ Rowe Dynes, Russell (1994). Disasters, Collective Behavior, and Social Organization. University of Delaware Press. p. 219. ISBN 978-0-87413-498-8. Archived from the original on 2020-08-05. Retrieved 2017-10-04. "workers at the "Montana Mills" dressmaking division in "Strongsville" (both are the authors' pseudonyms)" 14. ^ Fooden, Myra (1983). The Second X and women's health. Gordian Press. p. 66. ISBN 978-0-87752-223-2. Archived from the original on 2020-08-05. Retrieved 2017-10-04 – via Google Books. "described by the sociologists Kerckhoff and Back in their book The June Bug (1968). It was reported as a case of "hysterical contagion" involving approximately sixty textile workers in Spartanburg, South Carolina." 15. ^ Miller, David L. (2013). Introduction to Collective Behavior and Collective Action (3rd ed.). Waveland Press. p. 134. ISBN 978-1-4786-1095-3. Archived from the original on 2020-04-23. Retrieved 2017-10-04. 16. ^ Stahl, Sydney; Lebedun, Morty (1974). "Mystery Gas: An Analysis of Mass Hysteria". Journal of Health and Social Behavior. 15 (1): 44–50. JSTOR 2136925. 17. ^ Roueché, Berton (14 August 1978). "Sandy". The New Yorker. Retrieved 3 December 2020. 18. ^ a b Radovanovic, Z. "On the Origin of Mass Casualty Incidents in Kosovo, Yugoslavia, in 1990." European Journal of Epidemiology 12(1) (1996):101–113. JSTOR. Web. 27 Nov. 2009. 19. ^ a b Moss, P. D. and C. P. McEvedy. "An epidemic of overbreathing among schoolgirls." British Medical Journal 2(5525) (1966):1295–1300. Web. 17 Dec. 2009. 20. ^ Nemery, Benoit; Fischler, Benjamin; Boogaerts, Marc; Lison, Dominique (1999). "Dioxins, Coca-Cola, and mass sociogenic illness in Belgium". The Lancet. 354 (9172): 77. doi:10.1016/S0140-6736(05)75348-4. PMID 10406397. S2CID 39729818. Archived from the original on 2013-10-13. Retrieved 2013-08-09. 21. ^ Van Loock, F.; Gallay, A.; Demarest, S.; et al. (1999). "Outbreak of Coca-Cola-related illness in Belgium: a true association". The Lancet. 354 (9179): 680–681. doi:10.1016/S0140-6736(05)77661-3. PMID 10466695. S2CID 205946696. Archived from the original on 2013-10-13. Retrieved 2013-08-09. 22. ^ Gallay, A. (January 2002). "Belgian Coca-Cola-related Outbreak: Intoxication, Mass Sociogenic Illness, or Both?". American Journal of Epidemiology. 155 (2): 140–47. doi:10.1093/aje/155.2.140. Archived from the original on 2013-10-25. Retrieved 2013-08-09. 23. ^ "Mass hysteria outbreak reported in N.Y. town: What does it mean?". CBS News. 19 January 2012. Archived from the original on 19 March 2013. Retrieved 16 April 2020. 24. ^ Farmer, Ben (4 July 2012). "Poisonings' at Afghan girls' schools likely mass hysteria – not Taliban, says report". Archived from the original on 5 January 2016. Retrieved 5 January 2016. 25. ^ "Are the Taliban Poisoning Afghan Schoolgirls? The Evidence". 9 July 2012. Archived from the original on 20 January 2014. Retrieved 5 January 2016. 26. ^ Chen, Heather (11 August 2019). "The mystery of screaming schoolgirls in Malaysia". BBC News. Archived from the original on 17 March 2020. Retrieved 17 August 2019. 27. ^ "Girls suffer mass hysteria in a Nepal school". The Times of India. September 8, 2003. Archived from the original on 2020-10-29. Retrieved 2020-06-10. 28. ^ "Mass hysteria hits classes in Khotang". The Himalayan Times. 2016-09-12. Archived from the original on 2020-06-10. Retrieved 2020-06-10. 29. ^ "Dhading school shut after witnessing mass hysteria symptoms". The Himalayan Times. 2016-06-26. Archived from the original on 2020-06-10. Retrieved 2020-06-10. 30. ^ "४८ विद्यार्थीमा मास हिस्टेरिया भएपछि एक महिनाका लागि विद्यालय बन्द" [School closed for a month due to mass hysteria among 48 students]. swasthyakhabar.com (in Nepali). Archived from the original on 2020-06-10. Retrieved 2020-06-10. 31. ^ Poudel, Reet; Aich, Tapas Kumar; Bhandary, Krishma; et al. (2020-05-01). "Recurrent mass hysteria in schoolchildren in Western Nepal". Indian Journal of Psychiatry. 62 (3): 316–19. doi:10.4103/psychiatry.IndianJPsychiatry_571_19. ISSN 0019-5545. PMC 7368451. PMID 32773876. 32. ^ Borger, Julian; Jaekl, Philip (2017-10-12). "Mass hysteria may explain 'sonic attacks' in Cuba, say top neurologists". The Guardian. Archived from the original on 2017-10-14. Retrieved 2017-10-14. 33. ^ Bures, Frank (February 2018). "Cuba's Sonic Attacks Show Us Just How Susceptible Our Brains Are to Mass Hysteria". Slate.com. Archived from the original on 1 April 2018. Retrieved 1 April 2018. 34. ^ Stone, Richard (February 15, 2018). "U.S. diplomats in Cuba have unusual brain syndrome, but there's no proof they were attacked, study says". Sciencemag.com. Archived from the original on 2018-11-25. 35. ^ "In Sweden, Hundreds of Refugee Children Gave Up On Life". NPR.org. Archived from the original on 2019-07-15. Retrieved 2018-04-04. 36. ^ Aviv, Rachel (27 March 2017). "The Trauma of Facing Deportation". The New Yorker. Archived from the original on 27 February 2019. Retrieved 10 February 2019 – via newyorker.com. 37. ^ Sandstig, Ola (September 23, 2019). "Ohörda rop" [Unheard cries]. magasinetfilter.se (in Swedish). Archived from the original on 2020-10-07. Retrieved November 24, 2020. 38. ^ "Sveket mot de 'apatiska' barnen är en skandal" [The betrayal of the 'apathetic' children is a scandal]. expressen.se (in Swedish). 24 September 2019. Archived from the original on 2020-05-28. Retrieved 2020-10-10. 39. ^ Josefsson, Janne (October 2, 2019). "SVT måste ta ansvar för apatiska barn-skandalen" [SVT must take responsibility for the apathetic children scandal]. expressen.se (in Swedish). Archived from the original on 2020-10-17. Retrieved 2020-10-10. ## General references[edit] * Ali-Gombe, A. et al. "Mass hysteria: one syndrome or two?" British Journal of Psychiatry 1997; 170 387–78. Web. 17 Dec. 2009. * Balaratnasingam, Sivasankaran and Aleksandar Janca. "Mass hysteria revisited." Current Opinion in Psychiatry 19(2) (2006): 171–74. Research Gate. Web. 28 Nov. 2009. * Bartholomew, Robert. Little Green Men, Meowing Nuns and Head-Hunting Panics. Jefferson, North Carolina: McFarland & Company, Inc. Publishers. 2001. Print. * Bartholomew, Robert and Simon Wessely. "Protean nature of mass sociogenic illness." The British Journal of Psychiatry 2002; 180: 300–06. Web. 28 Nov. 2009. [3] * Jones, Timothy. "Mass Psychogenic Illness: Role of the Individual Physician." American Family Physician. American Family of Family Physicians: 15 Dec. 2000. Web. 28 Nov. 2009. [4] * Kerchoff, Alan C. "Analyzing a Case of Mass Psychogenic Illness." Mass Psychogenic Illness: A Social Psychological Analysis. Ed. Colligan et al. Hillsdale, NJ: Lawrence Erlbaum Associates, Publishers, 1982. 5–19. Print. * Mass, Weir E. "Mass sociogenic illness." CMAJ 2005; 172: 36. Web. 14 Dec. 2009. [5] * Moss, P. D. and C. P. McEvedy. "An epidemic of overbreathing among schoolgirls." British Medical Journal 2(5525) (1966):1295–1300. Web. 17 Dec. 2009. * Phoon, W. H. "Outbreaks of Mass Hysteria at Workplaces in Singapore: Some Patterns and Modes of Presentation." Mass Psychogenic Illness: A Social Psychological Analysis. Ed. Colligan et al. Hillsdale, NJ: Lawrence Erlbaum Associates, Publishers, 1982. 21–31. Print. * Radovanovic, Z (1996). "On the Origin of Mass Casualty Incidents in Kosovo, Yugoslavia, in 1990". European Journal of Epidemiology. 12 (1): 101–13. doi:10.1007/bf00144437. PMID 8817187. S2CID 7676802. * Singer, Jerome. "Yes Virginia, There Really Is a Mass Psychogenic Illness." Mass Psychogenic Illness: A Social Psychological Analysis. Ed. Colligan et al. Hillsdale, NJ: Lawrence Erlbaum Associates, Publishers, 1982. 21–31. Print. * Stahl, Sydney; Lebedun, Morty (1974). "Mystery Gas: An Analysis of Mass Hysteria". Journal of Health and Social Behavior. 15 (1): 44–50. doi:10.2307/2136925. JSTOR 2136925. PMID 4464323. * Waller, John (2009). "Looking Back: Dancing plagues and mass hysteria". The Psychologist. 22 (7): 644–47. * Watson, Rory (1999-07-17). "Coca-Cola health scare may be mass sociogenic illness". British Medical Journal. 319 (7203): 146. doi:10.1136/bmj.319.7203.146a. PMC 1174603. PMID 10406745. * Weir, Erica (2005-01-04). "Mass sociogenic illness". Canadian Medical Association Journal. 172 (1): 36. doi:10.1503/cmaj.045027. PMC 543940. PMID 15632400. * Wessely, Simon (1987). "Mass hysteria: two syndromes?". Psychological Medicine. 17 (1): 109–20. doi:10.1017/s0033291700013027. PMID 3575566. S2CID 32597423. * 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 Conspiracy theories List of conspiracy theories Core topics * Antiscience * Cabals * Civil * Criminal * Deception * Espionage * Fiction * Political * Pseudoscience * Secrecy * Secret societies * Urban legend Psychology * Attitude polarization * Cognitive dissonance * Communal reinforcement * Confirmation bias * Locus of control * Mass hysteria * Paranoia * Psychological projection Assassinations and avoidable accidents * Geoffrey Chaucer (1400) * Princes in the Tower (1483) * Kaspar Hauser (1833) * Abraham Lincoln (1865) * Ludwig II of Bavaria (1886) * Franz Ferdinand (1914) * Lord Kitchener (1916) * Michael Collins (1922) * Sergey Kirov (1934) * Władysław Sikorski (1943) * Subhas Chandra Bose (1945) * Dag Hammarskjöld (1961) * Patrice Lumumba (1961) * Marilyn Monroe (1962) * John F. Kennedy (1963) * Lee Harvey Oswald (1963) * Dorothy Kilgallen (1965) * Martin Luther King Jr. (1968) * Robert F. Kennedy (1968) * Juscelino Kubitschek (1976) * Pope John Paul I (1978) * Airey Neave (1979) * Francisco de Sá Carneiro and Adelino Amaro da Costa (1980) * Olof Palme (1986) * Zia-ul-Haq (1988) * Vince Foster (1993) * Yitzhak Rabin (1995) * Diana, Princess of Wales (1997) * Nepalese royal family (2001) * Jeffrey Epstein (2019) * Chan Yin-lam (2019) False flag attacks * USS Maine (1898) * RMS Lusitania (1915) * Reichstag fire (1933) * Pearl Harbor (1941) * USS Liberty (1967) * Widerøe Flight 933 (1982) * KAL Flight 007 (1983) * Mozambican presidential jet (1986) * Pan Am Flight 103 (1988) * Oklahoma City bombing (1995) * 9/11 attacks (2001) * Advance knowledge * WTC collapse * Madrid train bombing (2004) * London bombings (2005) * Malaysia Airlines Flight 17 (2014) Various deaths and disappearances * RMS Titanic (1912) * Phar Lap (1932) * Gas chambers for Poles in Warsaw (1940s) * Mass murder of German POWs after World War II (1940s) * Adolf Hitler's death (1945) * Yemenite Children (1948–54) * Cairo Fire (1952) * Dyatlov Pass incident (1959) * Lost Cosmonauts (1950s / 1960s) * Elvis Presley's death (1977) * Jonestown (1978) * Satanic ritual abuse * MS Estonia (1994) * Kurt Cobain (1994) * Hello Garci scandal * Osama bin Laden (2011) * Lahad Datu, Malaysia standoff (2013) * Zamboanga City crisis (2013) * Malaysia Airlines Flight 370 (2014) New World Order * Black helicopters * Cultural Marxists theories * Denver International Airport * Eurabia * Georgia Guidestones * Illuminati * Judeo-Masonic plot * Jews * The Protocols of the Elders of Zion * Kalergi Plan * Freemasons * North American Union * Catholics * Jesuits * Vatican * ODESSA * Rothschild family * Skull and Bones * The Fellowship * Zionist Occupation Government By region * Conspiracy theories in the Arab world * Israeli animal theories * Conspiracy theories in Turkey UFOs * Alien abduction * Area 51 * Bermuda Triangle * Black Knight satellite * Cryptoterrestrial hypothesis * Extraterrestrial hypothesis * Interdimensional hypothesis * Dulce Base * Estimate of the Situation (1948) * Majestic 12 * Men in black * Nazi UFOs * Project Serpo * Reptilian humanoids Incidents * Tunguska (1908) * Foo Fighters (1940s) * Los Angeles (1942) * Ghost Rockets (1946) * Maury Island (1947) * Roswell (1947) * Gorman Dogfight (1948) * Mantell (1948) * McMinnville (1950) * Lubbock (1951) * Washington, D.C. (1952) * Barney and Betty Hill Abduction (1961) * Kecksburg (1965) * Westall (1966) * Jimmy Carter (1969) * Frederick Valentich (1978) * Rendlesham Forest (1980) * Cash-Landrum (1980) * Japan Air Lines (1986) * Varginha (1996) * Phoenix Lights (1997) * USS Nimitz (2004) * Chicago (2006) United States government * 1951 Pont-Saint-Esprit mass poisoning * Apollo Moon landings * Barack Obama's citizenship / religion / parentage * Belgrade Chinese embassy bombing (1999) * Black genocide * Business Plot * Clinton Body Count * CIA-Kennedy assassination link * Allegations of CIA assistance to Osama bin Laden * Dulles' Plan * FEMA concentration camps * HAARP * Jade Helm 15 (2015) * Montauk Project * October Surprise (1980) * Pizzagate (2016) * Philadelphia Experiment (1943) * Project Azorian (1974) * QAnon * Sandy Hook shooting (2012) * Seth Rich (2016) * Sovereign citizen / Redemption movement * Stop the Steal (2020) * Spygate (2016,18) * Vast right-wing conspiracy * Vietnam War POW / MIA issue * TWA Flight 800 (1996) Health * Big Pharma conspiracy theory * HIV/AIDS denialism * Discredited HIV/AIDS origins theories * OPV AIDS hypothesis * SARS (2003) * COVID-19 pandemic * Anti-vaccination * Vaccines and autism * MMR vaccine and autism * Chemtrail conspiracy theory * Water fluoridation controversy * GMO conspiracy theories * Wind turbine syndrome * Electronic harassment Energy, environment * Free energy suppression conspiracy theory * Global warming conspiracy theory Other * 2012 phenomenon * Agenda 21 (1992) * Andinia Plan * Black genocide * Cancellation of the Avro Arrow (1959) * Bible * Clockwork Orange (1970s) * Conspiracy Encyclopedia * "Death" of Paul McCartney (1969) * Judeo-Bolshevism * Judeopolonia * Homintern * Homosexual recruitment * Kalergi Plan * Knights Templar * Lilla Saltsjöbadsavtalet (1987) * Love Jihad * Mexican Reconquista * New Coke (1985) * Phantom time / New Chronology * Red mercury * Soft coup * George Soros * War against Islam * White genocide See also * Denial of mass killings (list) * Genocide denial [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	Mass psychogenic illness	None	27,250	wikipedia	https://en.wikipedia.org/wiki/Mass_psychogenic_illness	2021-01-18T19:06:09	{"wikidata": ["Q4532199"]}
Dyschondrosteosis - nephritis is characterized by the association of short stature due to mesomelic shortening of the limbs and Madelung deformity (see this term), with hereditary nephritis. ## Epidemiology It was originally described in male and female members from four generations of one large kindred. The females appeared to be more severely affected than the males, with a sex ratio (female to male) of 4:1. ## Clinical description The skeletal anomalies closely resembled those of Léri-Weill dyschondrosteosis (see this term). ## Genetic counseling The mode of transmission was reported as autosomal 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	Dyschondrosteosis-nephritis syndrome	c1851986	27,251	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1765	2021-01-23T17:41:21	{"gard": ["1994"], "mesh": ["C565080"], "omim": ["127350"], "umls": ["C1851986"], "icd-10": ["Q73.8"]}
A number sign (#) is used with this entry because familial hypertrophic cardiomyopathy-7 is caused by heterozygous mutation in the TNNI3 gene (191044) on chromosome 19q13.4. For a general phenotypic description and a discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy (CMH), see CMH1 (192600). Clinical Features Kimura et al. (1997) identified 6 probands with hypertrophic cardiomyopathy and mutations in the TNNI3 gene (CMH7). Three of these probands had ventricular hypertrophy characteristic of CMH; 3 others had apical hypertrophy (so-called Japanese-type CMH). The mutation-carrying son of one proband with apical hypertrophy had typical CMH. The 3 patients with apical hypertrophy carrying a G203S mutation (191044.0014) also exhibited Wolff-Parkinson-White ventricular preexcitation (WPW; 194200). Niimura et al. (2002) presented data from a genetic analysis of 31 individuals with late-onset hypertrophic cardiomyopathy and no other family history. They identified 2 individuals with CMH7. The mean age of symptom development was 52.5 +/- 3.6 with a mean age at diagnosis of 49.0 +/- 9.9. Arad et al. (2005) identified a proband with CMH7 with atrial fibrillation and apical cardiac hypertrophy. Five family members had undergone sudden cardiac death, and 3 additional mutation carriers in the family were found to have other CMH morphologies. In another family with the same mutation, the phenotype was primarily subaortic asymmetric hypertrophy. Molecular Genetics Kimura et al. (1997) analyzed the TNNI3 gene in 184 unrelated patients with CMH and identified 6 heterozygous mutations in 6 probands, respectively (see, e.g., 191044.0001 and 191044.0002). Although apical CMH had been associated particularly with CMH4 (115197), Kimura et al. (1997) found that 3 of 36 (8.3%) patients with apical CMH had mutations in the TNNI3 gene. In addition, all 3 individuals with the G203S mutation in the TNNI3 gene (191044.0014) exhibited Wolff-Parkinson-White ventricular preexcitation (WPW; 194200); Kimura et al. (1997) noted that although a locus for 'CMH with WPW' had been mapped to chromosome 7q3 (CMH6; 600858), their findings indicated that more than 1 form of CMH is associated with WPW syndrome. Among 31 individuals with late-onset hypertrophic cardiomyopathy and no other family history, Niimura et al. (2002) identified 2 individuals with pathogenic mutations in the TNNI3 gene. Both reported mutations (191044.0003, 191044.0004) were missense mutations in conserved residues. Arad et al. (2005) identified a heterozygous R21C mutation in the TNNI3 gene (191044.0016) in 2 families with CMH. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Ventricular hypertrophy \- Apical hypertrophy (in some patients) \- Ventricular preexcitation, Wolff-Parkinson-White (in some patients) \- Atrial fibrillation (in some patients) MISCELLANEOUS \- Genetic heterogeneity (see 192600 ) \- Sudden cardiac death in some families MOLECULAR BASIS \- Caused by mutation in the cardiac troponin I gene (TNNI3, 191044.0001 ) ▲ 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	CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 7	c1860752	27,252	omim	https://www.omim.org/entry/613690	2019-09-22T15:57:50	{"omim": ["613690"]}
Carnitine palmitoyltransferase 2 (CPT2) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). There are three main types of CPT2 deficiency: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form. The neonatal and infantile forms are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia (extremely low levels of ketones (substances produced when fat cells break down in the blood) and low blood sugar), cardiomyopathy, seizures, and early death. The myopathic form is characterized by exercise-induced muscle pain and weakness and occasional myoglobinuria (rust-colored urine indicating breakdown of muscle tissue). Mutations in the CPT2 gene cause CPT2 deficiency. It is inherited in an autosomal recessive pattern. Treatment is based on avoidance of prolonged fasting and a low-fat and high-carbohydrate 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	Carnitine palmitoyltransferase 2 deficiency	c0342790	27,253	gard	https://rarediseases.info.nih.gov/diseases/1121/carnitine-palmitoyltransferase-2-deficiency	2021-01-18T18:01:37	{"mesh": ["C535589"], "omim": ["600650"], "umls": ["C0342790"], "orphanet": ["157"], "synonyms": ["Carnitine palmitoyltransferase deficiency type 2", "CPT2", "Carnitine palmitoyltransferase II (CPT II) deficiency"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2014) Endometrial Stromal Nodule An endometrial stromal nodule is a noninfiltrative, circumscribed proliferation of endometrial stromal cells and is a benign subtype of endometrial stromal tumor. The appearance of the cells is identical to normal endometrial stromal cells. This can only be differentiated from low-grade endometrial stromal sarcoma by confirming lack of infiltration. The differential includes cellular leiomyoma. Diagnosis may be aided by immunostaining; endometrial stromal nodules are positive for CD10; leiomyomas are positive for caldesmon and desmin (and sometimes CD10). ## References[edit] 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	Endometrial stromal nodule	c0334485	27,254	wikipedia	https://en.wikipedia.org/wiki/Endometrial_stromal_nodule	2021-01-18T18:41:04	{"umls": ["C0334485"], "wikidata": ["Q16928312"]}
A rare clinical situation for which there is a European and/or American orphan designation. Characteristics include diffuse bleeding into the alveolar spaces that originate from the pulmonary microvasculature, including the alveolar capillaries, arterioles and venules. Patients present with cough, dyspnea, chest pain, fever, anemia and hemoptysis. [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	Diffuse alveolar hemorrhage	c4476767	27,255	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90060	2021-01-23T18:38:48	{"icd-10": ["J98.4"]}
A subtype of inflammatory pseudotumor of the liver characterized by a benign, well-circumscribed tumor with fibrohistiocytic infiltration (including xanthogranulomatous inflammation, multinucleated giant cells, and neutrophilic infiltration), typically localized in the peripheral hepatic parenchyma. Presentation may be of non-specific symptoms (fever, malaise, and abdominal pain) or as an incidental finding. [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	Fibrohistiocytic inflammatory pseudotumor of the liver	None	27,256	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=555434	2021-01-23T18:20:54	{"icd-10": ["K76.8"]}
Nicolau–Balus syndrome SpecialtyDermatology Nicolau–Balus syndrome is a cutaneous condition characterized by syringomas and milia.[1] ## See also[edit] * Parry–Romberg syndrome * List of cutaneous conditions * List of cutaneous neoplasms associated with systemic syndromes ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 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	Nicolau–Balus syndrome	None	27,257	wikipedia	https://en.wikipedia.org/wiki/Nicolau%E2%80%93Balus_syndrome	2021-01-18T19:09:30	{"wikidata": ["Q7029952"]}
A number sign (#) is used with this entry because of evidence that cone dystrophy-4 (COD4) and achromatopsia-5 (ACHM5) can be caused by homozygous or compound heterozygous mutation in the PDE6C gene (600827) on chromosome 10q34. For a phenotypic description and a discussion of genetic heterogeneity of achromatopsia, see ACHM2 (216900). Description Cone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (COD) and complete and incomplete achromatopsia (ACHM). Impairment or death of cone photoreceptor cells is the clinical hallmark of these disorders. COD is a progressive cone disorder in which patients may initially have normal cone function but develop progressive visual acuity loss, increasing photophobia, color vision disturbances, and diminished cone responses on ERG, usually in the first or second decade of life. The visual acuity of these patients generally worsens to legal blindness before the fourth decade of life. ACHM is a stationary congenital autosomal recessive cone disorder characterized by low visual acuity, photophobia, nystagmus, and severe color vision defects. Patients with the complete ACHM subtype have no cone function on electroretinography, whereas those with incomplete ACHM show residual cone function (summary by Thiadens et al., 2009). Clinical Features Thiadens et al. (2009) reported affected members of 4 families with early-onset cone dystrophy due to PDE6C mutations. In 1 family, 2 brothers had severe color vision defects with a reduced cone response on ERG when first examined at ages 6 and 7 years, respectively; they also had photophobia and nystagmus, with progressive decline in their visual acuity during their teens, and ERG examination at ages 51 and 47 years, respectively, revealed no cone responses whereas rod responses were normal. A sister and brother with incomplete achromatopsia, born of consanguineous parents, had nystagmus but no photophobia upon initial examination at ages 7 and 10, respectively, and initial visual acuities of 0.16 (20/100) in their best eyes declined to 0.10 (20/200) over the next decade. The brother showed significantly reduced but measurable cone responses on ERG examinations at ages 10 and 20 years, with normal rod parameters. Two sisters were clinically diagnosed with complete achromatopsia and were first examined at ages 11 and 12 years, respectively. They had severe photophobia, nystagmus, and visual acuities of 0.16 (20/100) in their best eyes, which declined to 1.10 (20/200) over the next 2 decades. ERG examinations showed no cone responses even in childhood, but normal rod responses were observed at ages 36 and 37 years, respectively. In the fourth family, Thiadens et al. (2009) reported a 4-year-old boy with complete achromatopsia. At 4 years of age, the patient had a visual acuity of 0.10 (20/200) with severe photophobia and nystagmus; ERG revealed nonrecordable cone function, with completely normal rod function. Cross-sectional retinal imaging using optical coherence tomography (OCT) in patients with PDE6C mutations revealed a more pronounced absence of cone photoreceptors in patients with achromatopsia compared to patients with early-onset cone dystrophy. ERG analysis in the sib pair with early-onset cone dystrophy, who represented the 2 oldest mutation-positive patients at ages 47 and 51 years, respectively, showed absent cone responses but no abnormal rod responses, and normal rod responses were also observed in the 3 patients with complete achromatopsia. Thiadens et al. (2009) concluded that rod involvement does not appear to be a major consequence of PDE6C mutations, although they noted that some dysfunction of rods may still occur later in life. Chang et al. (2009) studied patients with PDE6C mutations who presented with a clinical picture 'typical for' complete achromatopsia, as exemplified by 2 sisters who had photophobia and reduced visual acuity from earliest infancy and reported congenital nystagmus that persisted into adulthood. Upon examination at ages 24 and 26 years, respectively, both were myopic and had complete lack of color discrimination and a central scotoma. ERG recordings showed extinguished responses under photopic and 30-Hz flicker stimulation, whereas scotopic ERG responses were essentially normal. Funduscopy revealed atrophy of the retinal pigment epithelium in the macula; Chang et al. (2009) noted that this is an atypical feature in patients with achromatopsia, but has been seen in patients with progressive cone dystrophy. Inheritance Cone dystrophy-4 and achromatopsia-5 are autosomal recessive disorders (Thiadens et al., 2009). Molecular Genetics In 116 patients with autosomal recessive early-onset cone photoreceptor disorders, including 85 with autosomal recessive cone dystrophy (arCD), 20 with early-onset arCD, and 11 with achromatopsia, in all of whom involvement of known genes for ACHM and arCD had been excluded, Thiadens et al. (2009) performed high-resolution SNP analysis and identified large homozygous regions spanning the PDE6C gene (600827) on chromosome 10 in 1 sib pair with early-onset arCD and 1 sib pair with incomplete ACHM. Sequence analysis of the PDE6C gene detected homozygous missense mutations in both sib pairs (600827.0001 and 600827.0002, respectively). Additional sequence analysis of PDE6C in 104 patients with arCD and 10 with ACHM identified compound heterozygous PDE6C mutations in 3 patients with complete ACHM from 2 families (600827.0003-600827.0006, respectively). In 4 families with achromatopsia in at least 2 affected sibs, who were negative for mutation in known achromatopsia genes, Chang et al. (2009) performed segregation analysis using satellite markers flanking the PDE6C gene and found a pattern compatible with linkage in 2 families; screening the PDE6C gene in those 2 families revealed compound heterozygosity for 4 different mutations in affected individuals (600827.0007-600827.0010, respectively). Screening of 24 additional simplex achromatopsia patients identified 2 patients who were compound heterozygous and homozygous, respectively, for mutations in PDE6C (600827.0011-600827.0013). In a cohort of 176 patients diagnosed with achromatopsia, who were negative for mutation in the CNGA3 (600053), CNGB3 (605080), and GNAT2 (139340) genes, Weisschuh et al. (2018) screened for mutations in the PDE6C gene and identified 18 potentially pathogenic homozygous and compound heterozygous variants in 15 probands, including 1 patient compound heterozygous for the previously reported R29W mutation (600827.0001) and another missense mutation (I279T; 600827.0014). Animal Model Chang et al. (2009) demonstrated that the spontaneous mouse mutant cpfl1, in which there is lack of cone function and rapid degeneration of cone photoreceptors, represents a homologous mouse model for PDE6C (600827)-associated achromatopsia. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Colorblindness, severe to complete \- Photophobia \- Decreased visual acuity \- Nystagmus \- Absent cone responses on electroretinography (ERG) \- Normal rod function on ERG MOLECULAR BASIS \- Caused by mutation in the phosphodiesterase-6C, cGMP-specific, cone, alpha prime gene (PDE6C, 600827.0001 ) ▲ 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	CONE DYSTROPHY 4	c0271092	27,258	omim	https://www.omim.org/entry/613093	2019-09-22T15:59:41	{"doid": ["0050795"], "omim": ["613093"], "orphanet": ["1871", "49382"], "genereviews": ["NBK1418"]}
Amelogenesis imperfecta is a disorder of tooth development. This condition causes teeth to be unusually small, discolored, pitted or grooved, and prone to rapid wear and breakage. Other dental abnormalities are also possible. These defects, which vary among affected individuals, can affect both primary (baby) teeth and permanent (adult) teeth. Researchers have described at least 14 forms of amelogenesis imperfecta. These types are distinguished by their specific dental abnormalities and by their pattern of inheritance. Additionally, amelogenesis imperfecta can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body. ## Frequency The exact incidence of amelogenesis imperfecta is uncertain. Estimates vary widely, from 1 in 700 people in northern Sweden to 1 in 14,000 people in the United States. ## Causes Mutations in the AMELX, ENAM, MMP20, and FAM83H genes can cause amelogenesis imperfecta. The AMELX, ENAM, and MMP20 genes provide instructions for making proteins that are essential for normal tooth development. Most of these proteins are involved in the formation of enamel, which is the hard, calcium-rich material that forms the protective outer layer of each tooth. Although the function of the protein produced from the FAM83H gene is unknown, it is also believed to be involved in the formation of enamel. Mutations in any of these genes result in altered protein structure or prevent the production of any protein. As a result, tooth enamel is abnormally thin or soft and may have a yellow or brown color. Teeth with defective enamel are weak and easily damaged. Mutations in the genes described above account for only about half of all cases of the condition, with FAM83H gene mutations causing the majority of these cases. In the remaining cases, the genetic cause has not been identified. Researchers are working to find mutations in other genes that are involved in this disorder. ### Learn more about the genes associated with Amelogenesis imperfecta * AMELX * ENAM * FAM83H * LAMB3 * MMP20 Additional Information from NCBI Gene: * ITGB6 * KLK4 * ODAPH * SLC24A4 * WDR72 ## Inheritance Pattern Amelogenesis imperfecta can have different inheritance patterns depending on the gene that is altered. Many cases are caused by mutations in the FAM83H gene and are inherited in an autosomal dominant pattern. This type of inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Some cases caused by mutations in the ENAM gene also have an autosomal dominant inheritance pattern. Amelogenesis imperfecta can also be inherited in an autosomal recessive pattern; this form of the disorder can result from mutations in the ENAM or MMP20 gene. Autosomal recessive inheritance means two copies of the gene in each cell are altered. 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. About 5 percent of amelogenesis imperfecta cases are caused by mutations in the AMELX gene and are inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In most cases, males with X-linked amelogenesis imperfecta experience more severe dental abnormalities than females with this form of this condition. Other cases of amelogenesis imperfecta result from new gene mutations 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	Amelogenesis imperfecta	c2675858	27,259	medlineplus	https://medlineplus.gov/genetics/condition/amelogenesis-imperfecta/	2021-01-27T08:24:38	{"gard": ["5791"], "mesh": ["C567279"], "omim": ["612529", "104500", "204650", "301200", "130900"], "synonyms": []}
Representative karyotype from a well differentiated transitional cell carcinoma of the bladder. The chromosome indicated by "mar" represents unidentified marker, "r" represents ring chromosome. Arrowheads indicate breakpoints. Also evident are monosomy 9, 18, and X and trisomy 7. A ring chromosome is an aberrant chromosome whose ends have fused together to form a ring. Ring chromosomes were first discovered by Lilian Vaughan Morgan in 1926.[1] A ring chromosome is denoted by the symbol r in human genetics and R in Drosophila genetics. Ring chromosomes may form in cells following genetic damage by mutagens like radiation, but they may also arise spontaneously during development. ## Contents * 1 Formation * 2 Associated syndromes * 3 See also * 4 References * 5 External links ## Formation[edit] Formation of a ring chromosome. In order for a chromosome to form a ring, both ends of the chromosome are usually missing, enabling the broken ends to fuse together. In rare cases, the telomeres at the ends of a chromosome fuse without any loss of genetic material, which results in a normal phenotype.[2] Complex rearrangements, including segmental microdeletions and microduplications, have been seen in numerous ring chromosomes, providing important clues regarding the mechanisms of their formation.[3] Small supernumary rings can also form, resulting in a partial trisomy.[4] Ring chromosomes are unstable during cell division and can form interlocking or fused rings.[4] ## Associated syndromes[edit] Human genetic disorders can be caused by ring chromosome formation. Although ring chromosomes are very rare, they have been found in all human chromosomes. Symptoms seen in patients carrying ring chromosomes are more likely to be caused by the deletion of genes in the telomeric regions of affected chromosomes, rather than by the formation of a ring structure itself.[5] Almost all ring chromosome syndromes feature marked growth delay.[4] Ring chromosomes can be inherited or sporadic. Mosaicism is common and affects the severity of the condition.[5] Location of fusion also affects severity due to loss of differing amounts of genetic material from the ends of chromosomes. Disorders arising from the formation of a ring chromosome include: Chromosome Typical features Ring chromosome 1 Mental retardation, microcephaly, facial abnormalities [6] Ring chromosome 2 Small stature [7][8] Ring chromosome 3 [9] Ring chromosome 4 Craniofacial abnormalities [10] Ring chromosome 5 [11] Ring chromosome 6 Microcephaly, facial abnormalities, hand abnormalities [12] Ring chromosome 7 Craniofacial abnormalities, speech deficits [13] Ring chromosome 8 Craniofacial abnormalities, hydronephrosis, hand abnormalities [14] Ring chromosome 9 Delayed growth, abnormal facial features, low muscle tone [15] Ring chromosome 10 Mental retardation, delayed growth, facial dysmorphia, reproductive abnormalities [16] Ring chromosome 11 [17] Ring chromosome 12 Delayed growth, abnormal facial features, microcephaly [18][19] Ring chromosome 13 Microcephaly, delayed growth, reproductive abnormalities [20] Ring chromosome 14 Epilepsy, mental retardation [21] Ring chromosome 15 Growth delay, mental retardation, microcephaly, speech delay [22] Ring chromosome 16 Mental retardation, microcephaly, growth delay, facial abnormalities [23][24] Ring chromosome 17 [25] Ring chromosome 18 Mental retardation, growth delay, facial abnormalities [26] Ring chromosome 19 [27] Ring chromosome 20 Epilepsy, mental retardation, abnormal facial features, growth delay [28] Ring chromosome 21 Short stature, microcephaly, reproductive abnormalities [29] Ring chromosome 22 Mental retardation, hypotonia, autistic-like behavior [30] Ring chromosome X Turner syndrome Ring chromosome Y [31] ## See also[edit] * Chromosome abnormalities ## References[edit] 1. ^ Morgan, LV (Mar 1926). "Correlation between Shape and Behavior of a Chromosome". Proceedings of the National Academy of Sciences of the United States of America. 12 (3): 180–1. doi:10.1073/pnas.12.3.180. PMC 1084483. PMID 16576974. 2. ^ Mitotic and meiotic behaviour of a naturally transmitted ring Y chromosome: reproductive risk evaluation Núria Arnedo, Carme Nogués, Mercè Bosch and Cristina Templado 3. ^ Shchelochkov O et al., Mosaicism for r(X) and der(X)del(X)(p11.23)dup(X)(p11.21p11.22) Provides Insight into the Possible Mechanism of Rearrangement, Molecular Cytogenetics 2008, 1:16 4. ^ a b c Yip, Moh-Ying (2015). "Autosomal ring chromosomes in human genetic disorders". Translational Pediatrics. pp. 164–174. doi:10.3978/j.issn.2224-4336.2015.03.04. PMC 4729093. Missing or empty `\|url=` (help) 5. ^ a b Nelson Textbook of Pediatrics, Chapter 81, 604-627 https://www.clinicalkey.com/#!/content/book/3-s2.0-B9781455775668000818?scrollTo=%23hl0003126 6. ^ "Ring chromosome 1 - Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. 7. ^ "Orphanet: Ring chromosome 2 syndrome". www.orpha.net. 8. ^ "Ring 2" (PDF). 9. ^ "Orphanet: Ring chromosome 3 syndrome". www.orpha.net. 10. ^ "Orphanet: Ring chromosome 4 syndrome". www.orpha.net. 11. ^ "Orphanet: Ring chromosome 5 syndrome". www.orpha.net. 12. ^ "Orphanet: Ring chromosome 6 syndrome". www.orpha.net. 13. ^ "Orphanet: Ring chromosome 7 syndrome". www.orpha.net. 14. ^ "Ring chromosome 8 - Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. 15. ^ "Ring 9" (PDF). 16. ^ "Orphanet: Ring chromosome 10 syndrome". www.orpha.net. 17. ^ "Ring chromosome 11 - Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. 18. ^ "Orphanet: Ring chromosome 12 syndrome". www.orpha.net. 19. ^ "Ring chromosome 12 \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-12-04. 20. ^ "Ring chromosome 13 \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-12-04. 21. ^ "Orphanet: Ring chromosome 13 syndrome". www.orpha.net. 22. ^ "Ring 15" (PDF). 23. ^ "Orphanet: Ring chromosome 16 syndrome". www.orpha.net. 24. ^ "Ring chromosome 16 \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-12-04. 25. ^ "Orphanet: Ring chromosome 17 syndrome". www.orpha.net. 26. ^ "Orphanet: Ring chromosome 18 syndrome". www.orpha.net. 27. ^ "Orphanet: Ring chromosome 19 syndrome". www.orpha.net. 28. ^ "Ring chromosome 20 \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-12-04. 29. ^ "Orphanet: Ring chromosome 21 syndrome". www.orpha.net. 30. ^ "Orphanet: Ring chromosome 22 syndrome". www.orpha.net. 31. ^ "Orphanet: Ring chromosome Y syndrome". www.orpha.net. ## External links[edit] * Atlas of Genetics and Cytogenetics in Oncology and Haematology, explains HOW the ring formation causes abnormalities. * 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	Ring chromosome	None	27,260	wikipedia	https://en.wikipedia.org/wiki/Ring_chromosome	2021-01-18T18:51:19	{"mesh": ["D012303"], "orphanet": ["363203"], "synonyms": [], "wikidata": ["Q474261"]}
A rare developmental defect with connective tissue involvement characterized by multiple joint dislocations, flattened facial appearance, abnormal palmar creases, laryngotracheomalacia, and pulmonary hypoplasia. Additional signs may include a bifid tongue, micrognathia, non-immune hydrops fetalis, and brain dysplasia. The disease is lethal shortly after birth due to respiratory insufficiency. [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	Lethal Larsen-like syndrome	c1855535	27,261	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2371	2021-01-23T18:02:42	{"gard": ["3181"], "mesh": ["C537872"], "omim": ["245650"], "umls": ["C1855535"], "icd-10": ["Q74.8"]}
Inflammation of an intestinal crypt Micrograph showing cryptitis in a case of Crohn's disease. H&E stain. In histology, cryptitis refers to inflammation of an intestinal crypt. Cryptitis is a non-specific histopathologic finding that is seen in several conditions, e.g. inflammatory bowel disease,[1] diverticular disease,[2] radiation colitis,[3] infectious colitis. ## Additional images[edit] * Cryptitis. H&E stain. * Focal cryptitis and a granuloma. H&E stain. * Focal cryptitis and a granuloma. H&E stain. ## References[edit] Wikimedia Commons has media related to Cryptitis. 1. ^ Al-Hussaini, AA.; Machida, HM.; Butzner, JD. (Jul 2003). "Crohn's disease and cheilitis". Can J Gastroenterol. 17 (7): 445–7. doi:10.1155/2003/368754. PMID 12915919. 2. ^ West, AB.; Losada, M. (2004). "The pathology of diverticulosis coli". J Clin Gastroenterol. 38 (5 Suppl 1): S11–6. doi:10.1097/01.mcg.0000124005.07433.69. PMID 15115923. S2CID 42614608. 3. ^ Hovdenak, N.; Fajardo, LF.; Hauer-Jensen, M. (Nov 2000). "Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy". Int J Radiat Oncol Biol Phys. 48 (4): 1111–7. doi:10.1016/s0360-3016(00)00744-6. PMID 11072170. [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	Cryptitis	c1394254	27,262	wikipedia	https://en.wikipedia.org/wiki/Cryptitis	2021-01-18T19:08:21	{"umls": ["C1394254"], "wikidata": ["Q1790372"]}
Fetal-maternal haemorrhage SpecialtyObstetrics Fetal-maternal haemorrhage is the loss of fetal blood cells into the maternal circulation. It takes place in normal pregnancies as well as when there are obstetric or trauma related complications to pregnancy. Normally the maternal circulation and the fetal circulation are kept from direct contact with each other, with gas and nutrient exchange taking place across a membrane in the placenta made of two layers, the syncytiotrophoblast and the cytotrophoblast. Fetal-maternal haemorrhage occurs when this membrane ceases to function as a barrier and fetal cells may come in contact with and enter the maternal vessels in the decidua/endometrium. ## Contents * 1 Description * 1.1 Normal pregnancy * 1.2 Abnormal pregnancy * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Description[edit] ### Normal pregnancy[edit] It is estimated that less than 1 mL of fetal blood is lost to the maternal circulation during normal labour in around 96% of normal deliveries.[1][2] The loss of this small amount of blood may however be a sensitising event and stimulate antibody production to the foetal red blood cells, an example of which is Rhesus disease of the newborn. ### Abnormal pregnancy[edit] Causes of increased foetal-maternal haemorrhage are seen as a result of trauma, placental abruption or may be spontaneous with no cause found. Up to 30 mL of foetal-maternal transfusion may take place with no significant signs or symptoms seen in either mother or foetus.[3] Loss in excess of this may result in significant morbidity and mortality to the fetus. Foetal-maternal haemorrhage is one cause of intrauterine death (IUD). ## Diagnosis[edit] Kleihauer test, showing foetal red blood cells in rose-pink color, while adult red blood cells are only seen as "ghosts". The Kleihauer–Betke test is a blood test used to measure the amount of foetal hemoglobin transferred from a foetus to its mother's bloodstream.[4] It takes advantage of the differential resistance of foetal hemoglobin to acid. A standard blood smear is prepared from the mother's blood, and exposed to an acid bath. This removes adult hemoglobin, but not foetal hemoglobin, from the red blood cells. Subsequent staining, using Shepard's method,[5] makes fetal cells (containing foetal hemoglobin) appear rose-pink in color, while adult red blood cells are only seen as "ghosts". 2000 cells are counted under the microscope and a percentage of foetal to maternal cells is calculated. Foetal-maternal haemorrhage can also be diagnosed by flow cytometry, using anti-foetal hemoglobin antibodies (anti-HbF).[6] ## Treatment[edit] If ongoing and rapid haemorrhage is occurring then immediate delivery of the foetus may be indicated if the fetus is sufficiently developed.[7] If the haemorrhage has already occurred and now stopped, an inutero transfusion of red cells to the foetus may be recommended.[8] ## References[edit] 1. ^ Sebring ES, Polesky HF. Fetomaternal Hemorrhage: Incidence, risk factors, time of occurrence, and clinical effects" Transfusion 1990; 30:344-357. 2. ^ Medearis AL, Hensleigh Pa, Parks DR, Herzenberh LA. Detection of foetal erythrocytes in maternal blood post partum with the fluorescence-activated cell sorter. American Journal of Obstetrics and Gynaecology 1984; 48:290-295. 3. ^ Polesky HF Sebring ES. Evaluation of methods of detection and quantitation of fetal cells and their effects on Rh Ig usage. American Journal of Clinical Pathology 198 1; 76(suppl):525-529. 4. ^ Katiyar R, Kriplani A, Agarwal N, Bhatla N, Kabra M (2007). "Detection of fetomaternal hemorrhage following chorionic villus sampling by Kleihauer–Betke test and rise in maternal serum alpha feto protein". Prenat. Diagn. 27 (2): 139–42. doi:10.1002/pd.1632. PMID 17191260. 5. ^ Alcoholic haematoxylin, acidified ferric chloride, Shepard's counterstain. Shepard's Fixative/Diluent 6. ^ Kim, Yeowon A.; Makar, Robert S. (2012). "Detection of fetomaternal hemorrhage". American Journal of Hematology. 87 (4): 417–423. doi:10.1002/ajh.22255. ISSN 0361-8609. PMID 22231030. 7. ^ Massive fetomaternal hemorrhage and oxytocin contraction test: case report and review Arch Gynecol Obstet. 2004 Jan;269 (2):149-51 14648183 (P, S, G, E, B) 8. ^ Massive fetomaternal hemorrhage and oxytocin contraction test: case report and review Arch Gynecol Obstet. 2004 Jan; 269 (2):149-51 14648183 (P, S, G, E, B) ## External links[edit] Classification D * ICD-10: P50.4 * ICD-9-CM: 656.0, 772.0 * MeSH: D005331 * v * t * e Pathology of pregnancy, childbirth and the puerperium Pregnancy Pregnancy with abortive outcome * Abortion * Ectopic pregnancy * Abdominal * Cervical * Interstitial * Ovarian * Heterotopic * Embryo loss * Fetal resorption * Molar pregnancy * Miscarriage * Stillbirth Oedema, proteinuria and hypertensive disorders * Gestational hypertension * Pre-eclampsia * HELLP syndrome * Eclampsia Other, predominantly related to pregnancy Digestive system * Acute fatty liver of pregnancy * Gestational diabetes * Hepatitis E * Hyperemesis gravidarum * Intrahepatic cholestasis of pregnancy Integumentary system / dermatoses of pregnancy * Gestational pemphigoid * Impetigo herpetiformis * Intrahepatic cholestasis of pregnancy * Linea nigra * Prurigo gestationis * Pruritic folliculitis of pregnancy * Pruritic urticarial papules and plaques of pregnancy (PUPPP) * Striae gravidarum Nervous system * Chorea gravidarum Blood * Gestational thrombocytopenia * Pregnancy-induced hypercoagulability Maternal care related to the fetus and amniotic cavity * amniotic fluid * Oligohydramnios * Polyhydramnios * Braxton Hicks contractions * chorion / amnion * Amniotic band syndrome * Chorioamnionitis * Chorionic hematoma * Monoamniotic twins * Premature rupture of membranes * Obstetrical bleeding * Antepartum * placenta * Circumvallate placenta * Monochorionic twins * Placenta accreta * Placenta praevia * Placental abruption * Twin-to-twin transfusion syndrome Labor * Amniotic fluid embolism * Cephalopelvic disproportion * Dystocia * Shoulder dystocia * Fetal distress * Locked twins * Nuchal cord * Obstetrical bleeding * Postpartum * Pain management during childbirth * placenta * Placenta accreta * Preterm birth * Postmature birth * Umbilical cord prolapse * Uterine inversion * Uterine rupture * Vasa praevia Puerperal * Breastfeeding difficulties * Low milk supply * Cracked nipples * Breast engorgement * Childbirth-related posttraumatic stress disorder * Diastasis symphysis pubis * Postpartum bleeding * Peripartum cardiomyopathy * Postpartum depression * Postpartum psychosis * Postpartum thyroiditis * Puerperal fever * Puerperal mastitis Other * Concomitant conditions * Diabetes mellitus * Systemic lupus erythematosus * Thyroid disorders * Maternal death * Sexual activity during pregnancy * Category * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal [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-maternal haemorrhage	c0015959	27,263	wikipedia	https://en.wikipedia.org/wiki/Fetal-maternal_haemorrhage	2021-01-18T18:55:48	{"mesh": ["D005331"], "icd-9": ["656.0", "772.0"], "icd-10": ["P50.4"], "wikidata": ["Q3724764"]}
A number sign (#) is used with this entry because of evidence that infantile hypertrophic cardiomyopathy can be caused by mutation in the overlapping MTATP6 (516060) and MTATP8 (516070) genes. Molecular Genetics In 4 unrelated infants who presented with isolated hypertrophic cardiomyopathy and congestive heart failure and who later developed severe feeding difficulties and failure to thrive, Ware et al. (2009) identified an 8528T-C transition, resulting in concurrent changes in the overlapping MTATP6 and MTATP8 genes, M1T (516060.0010) and W55R (516070.0003), respectively. Ware et al. (2009) stated that this was the first description of a mitochondrial mutation affecting both complex V genes. [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	CARDIOMYOPATHY, INFANTILE HYPERTROPHIC	c2748884	27,264	omim	https://www.omim.org/entry/500006	2019-09-22T16:16:55	{"omim": ["500006"]}
A number sign (#) is used with this entry because this form of torsion dystonia (DYT6) is caused by a heterozygous mutation in the THAP1 gene (609520) on chromosome 8p11. Description Dystonia-6 is an autosomal dominant movement disorder characterized by early involvement of craniofacial muscles with secondary generalization often involving the arms, and laryngeal dystonia that causes speech difficulties (review by Djarmati et al., 2009). Blanchard et al. (2011) provided a review of dystonia-6 and the THAP1 gene. Clinical Features Almasy et al. (1997) performed clinical and genetic analyses of idiopathic torsion dystonia (ITD) in 2 Mennonite families that were not obviously related. Of 220 family members, a total of 15 definitely affected individuals were identified. Some affected persons had a phenotype indistinguishable from that seen in patients with DYT1 (128100) due to mutation in the TOR1A gene (605204) on chromosome 9q34. However, the average age of onset in these patients was later (18.9 vs 13.6 years) and the distribution of affected body parts different from those with the DYT1 mutation. In patients with the DYT1 mutation, symptoms start in a limb and spread to other limbs and the axial musculature, with laryngeal muscles rarely affected. In contrast, about half of the patients from the Mennonite families presented with cranial or cervical involvement and those who presented with limb symptoms later developed cranial or cervical symptoms. In 2 cases, the symptoms remained localized. Muller et al. (1998) designated the type of dystonia observed in these 2 families as adult-onset ITD of mixed type, or dystonia-6 (DYT6). Saunders-Pullman et al. (2007) reported follow-up of the families reported by Almasy et al. (1997) and identified a third affected Amish-Mennonite family. The mean age at onset was 16 years (range, 5 to 38), with more than half of patients developing symptoms before age 16 years. Dystonia was most likely to start in an arm, although many had first symptoms involving cranial muscles, such as the larynx, tongue, and facial muscles, or the neck. The leg was rarely affected first. Almost all patients had some degree of progression to other body regions, but final distribution varied widely and included focal dystonia, segmental dystonia, and generalized or multifocal dystonia. More than half of patients had severely affected speech. Penetrance was decreased (approximately 60%). Fuchs et al. (2009) reported a family of partial German ancestry in which 4 individuals had autosomal dominant dystonia. Age at onset ranged from 9 to 14 years. Three affected individuals had generalized dystonia affecting the face, and jaw, tongue, neck, arms, legs, and trunk, whereas the fourth individual had segmental dystonia only affecting the lower face and jaw. Bressman et al. (2009) reported 19 individuals from 9 unrelated North American families, mainly of mixed European origin, with DYT6 confirmed by genetic analysis. Most had childhood or adolescent onset of dystonia in the arm or simultaneous onset in the arm, leg, neck, or tongue. Three had onset in adulthood. Dystonia tended to become generalized, with 12 of 19 reporting multifocal distribution, particularly with cranial muscle and speech involvement. Women were more often affected than men. Inheritance was consistent with autosomal dominant with reduced penetrance. Clot et al. (2011) identified heterozygous mutations in the THAP1 gene in 5 index patients (4.5%) of 113 subjects with primary dystonia from France, European countries, and North Africa. Two index cases had family members with the mutation; in one family, one of these relatives was affected and the other was asymptomatic. The median age at onset in mutation carriers was 12.5 years (range 9 to 20), and the most frequent site of dystonia at onset was the neck (4/6). During the course of the disease, 5 patients developed cranial muscle and upper limb involvement, and 4 had impaired speech. Four patients developed generalized dystonia after a median disease duration of 20 years, but 1 patient's dystonia remained segmental and another's remained focal. Two patients had myoclonic jerks that were superimposed on dystonia. The mutation frequency rose to 12% in patients in whom dystonia began in the neck or cranial muscles. ### Neuroradiologic Studies Using PET scans, Carbon et al. (2004) found that manifesting gene carriers of DYT1 and DYT6 had bilateral hypermetabolism in the presupplementary motor area and parietal association cortices compared to their respective nonmanifesting gene carriers. DYT1 carriers as a whole showed increased metabolism in the inferior cerebellum and putamen, with decreases in the anterior cingulate. In contrast, DYT6 carriers as a whole showed hypometabolism in the putamen and hypermetabolism in the temporal cortex. Carbon et al. (2004) concluded that dystonia in general is a disease of 'movement preparation' driven by a disruption of sensorimotor integration but that unique metabolic abnormalities, particularly in subcortical structures, suggested genotype-specific differences. Using PET scans and radiolabeled raclopride, Carbon et al. (2009) found significant reductions in caudate and putamen DRD2 (126450) availability in 21 individuals with DYT1, including 12 nonmanifesting and 9 manifesting carriers, and 12 individuals with DYT6, including 4 nonmanifesting and 8 manifesting carriers, compared to 13 controls. There was no significant difference between manifesting and nonmanifesting mutation carriers within either group, but those with DYT6 mutations had greater reductions than those with DYT1 mutations. Voxel-based analysis using stringent thresholds showed that the lateral putamen and right ventrolateral thalamus were most affected, with DYT6 carriers again more affected than DYT1 carriers. In addition, DYT6 carriers showed significantly greater reduction in the posterior putamen than DYT1 carriers. Carbon et al. (2009) emphasized that there was no difference between manifesting and nonmanifesting mutation carriers, suggesting that alterations in dopamine neurotransmission are susceptibility factors for the development of clinical symptoms, but that there likely needs to be an additional insult for manifestation. Mapping By linkage analysis in the Mennonite families, Almasy et al. (1997) mapped the DYT6 gene to 8p21-q22 with a maximum lod score of 3.69 at theta = 0.0 for marker D8S1797 in family 'M' and 2.11 in family 'C,' giving a combined lod score of 5.80 at D8S1797. Inferred haplotypes across the candidate region were identical in affected members of the 2 families, suggesting a founder effect and common mutation. Saunders-Pullman et al. (2007) found additional affected members in the DYT6 families reported by Almasy et al. (1997) and reported another Amish family with the disorder. Linkage analysis refined the locus to a 23-cM candidate region between markers D8S2323 and D8S2317 surrounding the centromere of chromosome 8. Genealogic sources indicated 5 common ancestral pairs between 2 of the families, 4 of whom were also shared by the third family, suggesting a founder effect. The most recent common ancestral pair that was unique to all families was an Amish couple, of whom the husband was born in 1791. Molecular analysis excluded mutations in 7 candidate genes within the region. Heterogeneity Saunders-Pullman et al. (2007) identified 2 Amish-Mennonite families with primary torsion dystonia that did not map to the DYT6 locus on chromosome 8p. The phenotype differed from those with DYT6 by later age at onset (46.9 years versus 16 years in DYT6), and by a greater incidence of focal dystonia beginning in the cervical muscles. The findings suggested that there is another locus for autosomal dominant dystonia in this population. Molecular Genetics In affected members of 3 Amish families with DYT6 (Almasy et al., 1997; Saunders-Pullman et al., 2007), Fuchs et al. (2009) identified a heterozygous truncating mutation in the THAP1 gene (609520.0001). An additional Amish family with the disorder also carried the same mutation. Fuchs et al. (2009) identified another heterozygous mutation in the THAP1 gene (609520.0002) in affected members of a German family with DYT6. In 9 (25%) of 36 unrelated families with primary dystonia, Bressman et al. (2009) identified 9 different heterozygous mutations in the THAP1 gene (see, e.g., 609520.0003 and 609520.0004), including 1 family of mixed European ancestry that had the Amish founder mutation (609520.0001). Most of the mutations were in the DNA-binding domain, and 1 was predicted to disrupt the nuclear-localization signal. There were no genotype/phenotype correlations. Djarmati et al. (2009) identified 2 different heterozygous mutations in the THAP1 gene (609520.0005 and 609520.0006) in 2 (1%) of 160 German patients with dystonia. Both mutation carriers had laryngeal dystonia beginning in childhood that progressed to generalized dystonia. One of the patients had 2 family members with very subtle findings of dystonia. Xiao et al. (2010) identified 9 different sequence variants in the THAP1 gene in 16 (1.4%) of 1,114 individuals with various forms of dystonia. Six of the variants were predicted to result in missense mutations (see, e.g., G9C; 609520.0007). Functional studies were not performed. Houlden et al. (2010) identified 9 different novel mutations in the THAP1 gene in 9 (2.5%) of 362 British patients with dystonia. One individual had a homozygous missense mutation and no family history of dystonia, but functional studies of the mutation were not performed. Lohmann et al. (2012) identified 6 different heterozygous pathogenic mutations in the THAP1 gene in 6 (1.1%) of 567 patients with dystonia. Five of the mutations (see, e.g., 609520.0008 and 609520.0009) were located in the DNA-binding domain and shown to cause decreased THAP1 activity (20-80% of controls) using a luciferase assay. In a review, Blanchard et al. (2011) noted that 53 different THAP1 mutations had been identified in 56 families with DYT6; there were no apparent genotype/phenotype correlations. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Cranial dystonia Face \- Facial dystonia \- Jaw dystonia Mouth \- Tongue dystonia Neck \- Torticollis RESPIRATORY Larynx \- Laryngeal dystonia SKELETAL Limbs \- Dystonia, upper and lower limbs NEUROLOGIC Central Nervous System \- Torsion dystonia \- Dystonia, trunk and limbs (upper and lower) \- Writer's cramp \- Dysarthria \- Dysphonia \- Myoclonus (less common) MISCELLANEOUS \- Variable distribution, may be focal, segmental, multifocal, or generalized \- Average age at onset 19 years (range 5 to 38) \- Often presents with cranial or cervical involvement \- Reduced penetrance (about 60%) MOLECULAR BASIS \- Caused by mutation in the THAP domain-containing protein 1 gene (THAP1, 609520.0001 ) ▲ 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	DYSTONIA 6, TORSION	c1414216	27,265	omim	https://www.omim.org/entry/602629	2019-09-22T16:13:34	{"doid": ["0090039"], "mesh": ["C538003"], "omim": ["602629"], "orphanet": ["98806"], "synonyms": ["Alternative titles", "TORSION DYSTONIA, ADULT-ONSET, MIXED TYPE"]}
A partial autosomal monosomy characterized clinically by lethal pulmonary disease that presents as severe respiratory distress and refractory pulmonary hypertension within a few hours after birth and typically results in death from respiratory failure within the first months of life. Characteristic histological features of lung tissue include paucity of alveolar wall capillaries, alveolar wall thickening, muscular hypertrophy of the pulmonary arteries, and malposition of the small pulmonary veins. Various additional congenital malformations may be associated, mostly gastrointestinal (intestinal malrotation and atresias, anular pancreas), genitourinary (dilatation of urinary tracts, duplicated uterus) and cardiovascular anomalies (hypoplastic left heart and other congenital heart defects). [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	16q24.1 microdeletion syndrome	None	27,266	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=352629	2021-01-23T19:10:17	{"icd-10": ["Q93.5"], "synonyms": ["Del(16)(q24.1)", "Monosomy 16q24.1"]}
Familial bicuspid aortic valve is a rare, genetic, aortic malformation defined as a presence of abnormal two-leaflet aortic valve in at least 2 first-degree relatives. It is frequently asymptomatic or may be associated with progressive aortic valve disease (aortic regurgitation and/or aortic stenosis, typically due to valve calcification) and a concomitant aortopathy (i.e. aortic dilation, aortic aneurysm and/or dissection). [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	Familial bicuspid aortic valve	c0149630	27,267	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=402075	2021-01-23T18:59:46	{"mesh": ["C562388"], "omim": ["109730", "614823"], "icd-10": ["Q23.1"], "synonyms": ["Familial BAV"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-103 (DFNB103) is caused by homozygous mutation in the CLIC5 gene (607293) on chromosome 6p21. One such family has been reported. Clinical Features Seco et al. (2015) reported 2 sibs, born of consanguineous Turkish parents, with early-onset nonsyndromic sensorineural deafness. The hearing impairment was probably not congenital, as both children had evidence of normal hearing at ages 7 to 9 months and 3 months, respectively. The hearing loss initially affected mid and high frequencies, but progressed to a severe/profound hearing loss affecting all frequencies. The audiogram was downsloping. Both individuals also showed vestibular areflexia during the rotary test at ages 16 and 11 years. One affected sib showed some evidence of mild renal dysfunction, which Seco et al. (2015) noted should be followed to determine if it is indeed an unrelated nephropathy or if it is linked with the mutation. (Seco et al. (2015) designated the disorder in this family autosomal recessive deafness-102, but this designation had already been given to another form of deafness; see 615974). Inheritance The transmission pattern of nonsyndromic sensorineural deafness in the family reported by Seco et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sibs, born of consanguineous Turkish parents, with early-onset autosomal recessive deafness-103, Seco et al. (2015) identified a homozygous truncating mutation in the CLIC5 gene (C32X; 607923.0001). The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. Screening for mutations in the CLIC5 gene in over 200 mostly Dutch or Spanish probands with hearing impairment did not identify any other mutations. Seco et al. (2015) noted that the phenotype was similar to that observed in the 'Jitterbug' mouse mutant, which results from a recessive null Clic5 allele (see ANIMAL MODEL). Animal Model The 'Jitterbug' (jbg/jbg) mutant mouse is an autosomal recessive phenotype characterized by overt head-bobbing and circling behavior with an inability to swim, indicating vestibular dysfunction. Mutant mice also show hearing loss that progresses to complete deafness. Gagnon et al. (2006) found that 12-month-old jbg/jbg mice had severe degeneration of the organ of Corti and a reduced density of spiral ganglion cells compared to controls. Vestibular hair cells showed progressive degeneration, first affecting the outer hair cells and later affecting the inner hair cells. Jbg/jbg mutant mice also showed emphysema-like lung pathology with a progressive enlargement of alveolar spaces. Linkage analysis and candidate gene analysis identified a homozygous intragenic deletion in the Clic5 gene resulting in a truncated protein as responsible for the phenotype. Studies of wildtype mouse embryos showed Clic5 expression in the basal region of the hair bundle of the inner ear. During cochlear development, Clic5 was closely associated with microvilli on the apical surfaces of interdental cells and columnar epithelial cells of Kolliker's organ and with stereocilia of inner and outer hair cells. The pattern of expression matched that of radixin (RDX; 179410), suggesting that CLIC5 associates with radixin in hair cell stereocilia and may help form or stabilize connections between the plasma membrane and the cytoskeletal filamentous actin core. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural \- Downsloping audiogram \- Vestibular areflexia \- Vestibular dysfunction MISCELLANEOUS \- Onset in infancy (first year of life) \- Loss initially affects mid and high frequencies \- Progression to profound hearing loss affecting all frequencies \- One consanguineous Turkish family has been reported (last curated November 2014) MOLECULAR BASIS \- Caused by mutation in the chloride intracellular channel-5 gene (CLIC5, 607293.0001 ) ▲ 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 RECESSIVE 103	c4015050	27,268	omim	https://www.omim.org/entry/616042	2019-09-22T15:50:03	{"doid": ["0110464"], "omim": ["616042"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
A number sign (#) is used with this entry because Koolen-De Vries syndrome can be caused either by heterozygous mutation in the KANSL1 gene (612452) on chromosome 17q21.31 or by a larger deletion of several genes on chromosome 17q21.31. See also chromosome 17q21.31 duplication syndrome (613533). Description Koolen-De Vries syndrome is characterized by moderate to severe intellectual disability, hypotonia, friendly demeanor, and highly distinctive facial features, including tall, broad forehead, long face, upslanting palpebral fissures, epicanthal folds, tubular nose with bulbous nasal tip, and large ears. More variable features include cardiac or genitourinary anomalies and seizures (summary by Koolen et al., 2012). Clinical Features Using array-based comparative genomic hybridization (array CGH) in a study of 1,200 mentally retarded individuals, Koolen et al. (2006) identified 3 individuals with interstitial, overlapping 17q21.31 microdeletions and a clearly recognizable clinical phenotype of mental retardation, hypotonia, and characteristic face. All 3 individuals showed severe hypotonia from birth onwards, leading to severely delayed motor development. None of the individuals could stand and/or walk before the age of 3 years. Facial features included long hypotonic face with ptosis, blepharophimosis, large and low-set ears, tubular pear-shaped nose with bulbous nasal tip, long columella with hypoplastic alae nasi, and a broad chin. In addition, they all had long fingers, nasal speech, and an amiable and friendly disposition. The deletions encompassed the MAPT (157140) and CRHR1 (122561) genes and were associated with a common inversion polymorphism. All 3 deletions were confirmed by fluorescence in situ hybridization and shown to have arisen de novo. Koolen et al. (2008) described the clinical and molecular features of 22 patients with 17q21.31 deletion syndrome, including 11 previously reported patients and 11 newly ascertained patients. Common features included developmental delay with mild to moderate mental retardation, characteristic facies with long face, high forehead, large, prominent ears, upward-slanting palpebral fissures, epicanthal folds, bulbous nasal tip, pear-shaped nose, and long, slender features. Other features included cardiac septal defects, seizures, and cryptorchidism. Most patients had a friendly demeanor. Tan et al. (2009) reported 11 patients with the 17q21.31 deletion syndrome. The facial appearance was characterized by a long face with tall or broad forehead, upslanting palpebral fissures, anteverted ears with thickened or overfolded helices, tubular or pear-shaped nose with bulbous tip, and frequently open mouth. The facial features became more distinctive in early childhood compared to infancy. All patients had hypotonia, global delay, and expressive language delay, and most had a friendly disposition. Congenital cardiac defects included pulmonary stenosis in 3 (27.3%), septal defects in 2 (18.2%), and bicuspid aortic valve in 2 (18.2%), and 1 patient had a dilated aortic root. Other features included urologic anomalies, such as cryptorchidism, hypospadias, vesicoureteric reflux, duplex kidney, renal scarring, and hydronephrosis, and CNS anomalies, such as seizures, corpus callosum defects, and ventriculomegaly. Joint hypermobility and/or hip dislocation/dysplasia were commonly seen, as were ectodermal anomalies of the hair, skin, and teeth. Previously unreported features included persistent fetal fingertip pads, recurrent elbow dislocation, conductive hearing loss, dental abnormalities, and hypertension due to renal scarring. In a study of copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) compared to CNVs in 8,329 unaffected adult controls, Cooper et al. (2011) identified the 17q21.31 deletion in 23 individuals and atypical deletions in 3 individuals. Detailed clinical information on 2 individuals with the atypical deletion showed typical phenotypic features of the syndrome. Zollino et al. (2012) reported 2 unrelated girls with Koolen-De Vries syndrome due to de novo heterozygous truncating mutations in the KANSL1 gene (612452.0001 and 612452.0002). Both had failure to thrive in infancy, hypotonia, and delayed psychomotor development. Characteristic facial features included broad forehead, upslanting palpebral fissures, epicanthal folds, 'pear'-shaped nose with bulbous nasal tip, long philtrum, large ears, broad chin, abnormal hair texture, and sparse eyebrows. Both also had joint hyperextensibility. Neither had seizures, heart defects, or urinary anomalies. Both had a happy disposition. Koolen et al. (2012) reported 2 unrelated patients with Koolen-De Vries syndrome due to de novo heterozygous truncating mutations in the KANSL1 gene (612452.0003 and 612452.0004). Both patients had delayed psychomotor development, intellectual disability, hypotonia, friendly personality, and characteristic facial features, including broad forehead, long face, upslanting palpebral fissures, epicanthal folds, and tubular nose with bulbous nasal tip. Both also had joint laxity, slender lower limbs, pes planus, sacral dimple, and abnormal hair color or texture. One patient had additional features, including cleft lip/palate, ventricular septal defect, cryptorchidism, hypermetropia, strabismus, and scoliosis. Koolen et al. (2016) compared the clinical features of 45 patients with KDVS, including 33 with a 17q21.31 deletion and 12 with a KANSL1 mutation. Three of the patients had previously been reported. There were no differences of clinical importance between the 2 groups, indicating that haploinsufficiency for KANKL1 is sufficient to cause the core phenotype. However, 44% of those in the deletion group had large ears, compared to none in the mutation group. The patients had strikingly similar dysmorphic features, including long face, upslanting and narrow palpebral fissures, ptosis, epicanthal folds, tubular- or pear-shaped nose with bulbous nasal tip, and everted lower lip. Many had poor overall growth or short stature. Most had hypotonia, particularly in the neonatal period, and all showed delayed development with intellectual disability, ranging from borderline/mild to severe, and speech delay. Expressive language was more severely affected than receptive language, and 4 patients (11%) were nonverbal. About half of patients had seizures that were usually well-controlled, and although the majority (89%) had an amiable affect, about half had neuropsychologic disorders, including hyperactivity, anxiety, autistic features, impulsivity, and depression. Structural brain abnormalities occurred in 53% of patients and mainly consisted of corpus callosum hypoplasia/aplasia, enlarged ventricles, hydrocephalus, and/or heterotopias. Musculoskeletal anomalies were present in 77% of patients, and included tracheo/laryngomalacia, pectus excavatum or carinatum, scoliosis/kyphosis, hip dislocation/dysplasia, joint hypermobility, and positional deformities of the feet. Other common abnormalities included congenital heart defects (39%), urogenital anomalies (45%), and ectodermal abnormalities (67%). Myers et al. (2017) reviewed the seizure phenotypes of 31 patients with KDVS who had seizures, noting that seizures occur in about 50% of patients with the disorder. The mean age at seizure onset was 3.5 years (range, 4 months to 24 years). Most patients presented with focal impaired awareness and staring spells in infancy, often associated with autonomic signs, such as pallor, vomiting, and oxygen desaturation. Twenty-one patients had prolonged seizures, including status epilepticus. Nine (41%) of 22 patients had refractory seizures, but seizures could be variably controlled in the long term in other patients. EEG studies were available for 26 patients, most of which showed focal or multiform epileptiform discharges; 2 patients had spike-wave discharges with 3-4 Hz frequency. Variable structural brain abnormalities were found in all patients, and mainly included corpus callosum dysgenesis, abnormal hippocampi, and dilated ventricles. Less common MRI findings included periventricular nodular heterotopia, focal cortical dysplasia, abnormal sulcation, and abnormalities of the brainstem and cerebellum. All individuals had delayed development and intellectual disability, but the degree of cognitive impairment varied, with 6 patients mildly affected, 8 patients moderately affected, and 17 more severely affected. Mapping Koolen et al. (2006) found that the deletions in 17q21.31 in 3 mentally retarded individuals were all located within a genomic region that harbors a common 900-kb inversion polymorphism that was previously described by Stefansson et al. (2005) (see 157140). For this region, 2 major and highly divergent haplotypes, designated H1 and H2, had been found. The H2 lineage, representing the 900-kb inversion polymorphism, is found at a frequency of 20% in Europeans. For all 3 individuals, 1 of the parents carried the H2 haplotype. Parent-of-origin analysis showed that the deletion occurred on the H2 haplotype in 2 individuals, but was inconclusive in the third. The H2 haplotype differs from the H1 by a directly oriented low-copy repeat (LCR) that immediately flanked the breakpoints in all 3 individuals. This suggested that these deletions resulted from nonallelic homologous recombination, mediated by this H2-specific LCR. Shaw-Smith et al. (2006) likewise described 3 individuals with a heterozygous 17q21.3 deletion detected by array CGH. In each case the parent-of-origin of the deleted chromosome 17 carried at least 1 H2 chromosome. Approximately 5% of the human genome is composed of segmental duplications that are more than 1 kb long and show more than 90% sequence identity, the majority of which have an interspersed, rather than tandem, distribution (Bailey et al., 2002; Cheung et al., 2001). These duplication blocks act as substrates for nonallelic homologous recombination, leading to the deletion, duplication, or inversion of the intervening sequence (Stankiewicz and Lupski, 2002). Based on the duplication architecture of the genome, Sharp et al. (2006) investigated 130 regions that they hypothesized as candidates for previously undescribed genomic disorders. They tested 290 individuals with mental retardation by BAC array CGH and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in 4 individuals. By using oligonucleotide arrays, they refined the breakpoints of this microdeletion, defining a 478-kb critical region containing 6 genes that were deleted in all 4 individuals; they noted that 2 of these, CRHR1 and MAPT, are highly expressed in brain and have been implicated in neurodegenerative and behavioral phenotypes and are therefore excellent candidates for dosage-sensitive genes underlying this microdeletion syndrome. Using high resolution oligonucleotide arrays to analyze 22 patients with 17q21.31 deletion syndrome, Koolen et al. (2008) narrowed the critical region to a 424-kb genomic segment encompassing at least 6 genes, including MAPT. Five deletion carriers had a greater than 500 bp rearrangement at the proximal breakpoint within an L2 LINE motif, suggesting a hotspot for nonallelic homologous recombination. In addition, every case examined showed that the parent originating the deletion carried the H2 haplotype, indicating that this inversion is a necessary factor for deletion to occur. Cooper et al. (2011) compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. They identified the 17q21.31 deletion in 23 individuals and atypical deletions in 3 individuals. The smallest deletion refined the phenotype-associated critical region (Chr17:41,356,798-41,631,306, NCBI36) to encompass only 5 RefSeq genes. Molecular Genetics Among 11 patients with 17q21.31 deletion syndrome, Tan et al. (2009) found that the deletions ranged from 0.44 to 0.68 Mb in size, and included the CRHR1 (122561), MAPT (157140), IMP5 (608284),and STH (607067) genes, and part of the KIAA1267 gene (KANSL1; 612452). By exome sequencing of a girl with classic features of chromosome 17q21.31 deletion syndrome who did not have a deletion on FISH or array CGH analysis, Zollino et al. (2012) identified a de novo heterozygous truncating mutation in the KANSL1 gene (612452.0001). Direct sequencing of this gene in another unrelated girl with features of the disorder in whom no deletion could be detected identified a second truncating mutation (612452.0002). The findings indicated that point mutation in the KANSL1 gene is sufficient for full manifestations of chromosome 17q21.31 deletion syndrome, and indicated that it is a monogenic disorder caused by haploinsufficiency of KANSL1. By Sanger sequencing of the KANSL1 gene in 16 individuals with features of 17q21.31 deletion syndrome who did not have copy number variations in the MAPT or KANSL1 genes, Koolen et al. (2012) identified different de novo heterozygous truncating mutations in the KANSL1 gene (612452.0003 and 612452.0004) in 2 unrelated patients. Whole-transcriptome sequencing of 3 individuals with the classic 17q21.31 deletion showed that expression levels of KANSL1 were reduced by half. Whole-transcriptome sequencing of 1 of the patients with a point mutation showed differential expression of similar genes as those in patients with deletions; these genes are believed to be involved in neuronal/synaptic processes. The findings showed that haploinsufficiency of KANSL1 is sufficient to cause the classic 17q21.31 microdeletion syndrome phenotype, and provided evidence that the histone acetyltransferase complex may have a role in human cognitive function and developmental processes. Itsara et al. (2012) used a combination of somatic cell hybrids, array comparative genomic hybridization, and the specificity of next-generation sequencing to determine breakpoints that occur within segmental duplications at the 17q21.31 locus in 3 deletion-bearing individuals. For 2 cases, Itsara et al. (2012) observed breakpoints consistent with nonallelic homologous recombination involving only H2 chromosomal haplotypes, as expected. Molecular resolution revealed that the breakpoints occurred at different locations within a 145-kb segment of greater than 99% identity and disrupted KANSL1. In the remaining case, they found that unequal crossover occurred interchromosomally between the H1 and H2 haplotypes and that this event was mediated by a homologous sequence that was once again missing from the human reference. Interestingly, the breakpoints mapped preferentially to gaps in the current reference genome assembly, which were resolved in this study. Kaminsky et al. (2011) presented the largest copy number variant case-control study to that time, comprising 15,749 International Standards for Cytogenomic Arrays cases and 10,118 published controls, focusing on recurrent deletions and duplications involving 14 copy number variant regions. Compared with controls, 14 deletions and 7 duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic. The 17q21.31 deletion was identified in 22 cases and no controls for a p value of 2.49 x 10(-5) and a frequency of 1 in 716 cases. Koolen et al. (2016) reported 45 patients with KDVS confirmed by genetic analysis, including 33 with a 17q21.21 microdeletion encompassing the KANSL1 gene and 12 with a de novo heterozygous mutation in KANSL1 (see, e.g., 612452.0004-612452.0006), all of which were predicted to result in haploinsufficiency. Functional studies of the variants were not performed. Koolen et al. (2016) noted that genetic testing of the 17q21.31 locus can be challenging because of the structural complexity of the genomic region. Population Genetics Koolen et al. (2008) estimated the prevalence of the syndrome to be 1 in 16,000 and suggested that it is currently underdiagnosed. Evolution The analysis of Zody et al. (2008) of the evolutionary history of the European-enriched 17q21.31 MAPT inversion polymorphism favored the H2 configuration and sequence haplotype as the likely great ape and human ancestral state, with inversion recurrences during primate evolution. The authors further showed that the H2 architecture has evolved more extensive sequence homology, perhaps explaining its tendency to undergo microdeletion associated with mental retardation in European populations. Steinberg et al. (2012) investigated the genetic diversity of the 17q21.31 inversion polymorphism in 2,700 individuals, with an emphasis on African populations. Steinberg et al. (2012) characterized 8 structural haplotypes due to complex rearrangements that varied in size from 1.08 to 1.49 Mb and provided evidence for a 30-kb H1-H2 double recombination event. They showed that recurrent partial duplications of the KANSL1 gene (612452) have occurred on both the H1 and H2 haplotypes and have risen to high frequency in European populations. The authors identified a likely ancestral H2 haplotype (H2-prime) lacking these duplications that is enriched among African hunter-gatherer groups yet essentially absent from West African populations. Whereas H1 and H2 segmental duplications arose independently and before human migration out of Africa, they have reached high frequencies recently in Europeans, either because of extraordinary genetic drift or selective sweeps. Boettger et al. (2012) developed a population genetics approach to analyze complex genome structures and identified 9 segregating structural forms of 17q21.31. Both the H1 and H2 forms of the 17q21.31 inversion polymorphism contain independently derived, partial duplications of the KANSL1 gene; these duplications, which produce novel KANSL1 transcripts, have both recently risen to high allele frequencies (26% and 19%) in Europeans. An older H2 form lacking such a duplication is present at low frequency in European and central African hunter-gatherer populations. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (35%) Weight \- Low birth weight (27%) Other \- Intrauterine growth retardation \- Failure to thrive HEAD & NECK Face \- Long face (74%) \- High, broad forehead (68%) \- Broad chin (42%) Ears \- Large, prominent ears (59%) \- Anteverted ears \- Overfolded helices Eyes \- Hypermetropia (36%) \- Pale irides (45%) \- Strabismus (45%) \- Upward-slanted palpebral fissures (68%) \- Blepharophimosis (36%) \- Ptosis (50%) \- Epicanthal folds (68%) Nose \- Tubular nose (82%) \- Pear-shaped nose (82%) \- Bulbous nasal tip (95%) \- High nasal bridge Mouth \- High, narrow palate (50%) \- Cleft lip \- Cleft palate \- Everted lower lip \- Open mouth Teeth \- Small widely spaced teeth CARDIOVASCULAR Heart \- Heart defects (40%) \- Atrial septal defect \- Ventricular septal defect \- Pulmonary valve stenosis \- Bicuspid aortic valve \- Aortic dilatation (reported in 1 patient) RESPIRATORY Larynx \- Tracheo/laryngomalacia CHEST Ribs Sternum Clavicles & Scapulae \- Pectus abnormalities (23%) \- Widely spaced nipples ABDOMEN Gastrointestinal \- Poor feeding GENITOURINARY \- Kidney/urologic anomalies (45%) Internal Genitalia (Male) \- Cryptorchidism Kidneys \- Hydronephrosis \- Duplex renal system Bladder \- Vesicoureteric reflux SKELETAL \- Hypermobile joints Spine \- Scoliosis/kyphosis (36%) Pelvis \- Hip dislocation (27%) Limbs \- Slender lower limbs (41%) Hands \- Narrow hands (28%) \- Long, slender fingers (61%) \- Hypoplasia of the hand muscles (29%) Feet \- Positional foot deformity (27%) SKIN, NAILS, & HAIR Skin \- Ectodermal abnormalities (67%) \- Dry skin \- Eczema \- Pigmentary abnormalities \- Sacral dimple Hair \- Abnormal hair pigmentation (55%) \- Abnormal hair texture (55%) MUSCLE, SOFT TISSUES \- Hypotonia \- Hypoplasia of the hand muscles (29%) NEUROLOGIC Central Nervous System \- Developmental delay (100%) \- Mental retardation, mild to severe \- Poor speech development \- Hypotonia (96%) \- Seizures (50%) \- Structural brain abnormalities, variable (in some patients) \- Ventriculomegaly (38%) \- Hypoplastic corpus callosum \- Abnormal hippocampi \- Heterotopia Behavioral Psychiatric Manifestations \- Friendly behavior (89%) Autistic features \- Hyperactivity \- Anxiety \- Impulsivity VOICE \- Nasal speech (50%) MISCELLANEOUS \- All cases are de novo \- Estimated prevalence of 1 in 16,000 \- Contiguous gene deletion of 17q21.3 involves a region which harbors a 900kb inversion polymorphism MOLECULAR BASIS \- Caused by mutation in the KAT8 regulatory NSL complex subunit 1 gene (KANSL1, 612452.0001 ) \- Contiguous gene syndrome caused by microdeletion (600-800kb) of chromosome 17q21.31 encompassing genes CRHR1 ( 122561 ), MAPT ( 157140 ), STH ( 607067 ), IMP5 ( 608284 ), and KANSL1 ( 612452 ) ▲ 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	KOOLEN-DE VRIES SYNDROME	c1864871	27,269	omim	https://www.omim.org/entry/610443	2019-09-22T16:04:30	{"doid": ["0050880"], "mesh": ["C566476"], "omim": ["610443"], "orphanet": ["96169", "363958"], "synonyms": ["Alternative titles", "CHROMOSOME 17q21.31 DELETION SYNDROME", "MICRODELETION 17q21.31 SYNDROME"], "genereviews": ["NBK24676"]}
A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by an onset in late adolescence or early adulthood of slowly progressive, proximal weakness and atrophy of shoulder and pelvic girdle muscles. Cardiac and respiratory muscles are not involved. Hypertrophy of the calf muscles and highly elevated serum creatine kinase levels are frequently observed. [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	Dysferlin-related limb-girdle muscular dystrophy R2	c1850889	27,270	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268	2021-01-23T17:53:41	{"gard": ["8574"], "mesh": ["C535899"], "omim": ["253601"], "umls": ["C1850889"], "icd-10": ["G71.0"], "synonyms": ["Autosomal recessive limb-girdle muscular dystrophy type 2B", "Dysferlin-related LGMD R2", "LGMD due to dysferlin deficiency", "LGMD type 2B", "LGMD2B", "Limb-girdle muscular dystrophy due to dysferlin deficiency", "Limb-girdle muscular dystrophy type 2B"]}
Congenital generalized hypertrichosis, Ambras type is an extremely rare type of hypertrichosis lanuginosa congenita, a congenital skin disease, that is characterized by the presence of vellus-type hair on the entire body, especially on the face, ears and shoulders, with the exception of palms, soles, and mucous membranes. Facial and dental anomalies can also be observed, such as triangular, coarse face, bulbous nasal tip, long palpebral fissures, delayed tooth eruption and absence of teeth. [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 generalized hypertrichosis, Ambras type	c1840362	27,271	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1023	2021-01-23T17:43:22	{"gard": ["8206"], "mesh": ["C536605"], "omim": ["145701"], "umls": ["C1840362"], "icd-10": ["Q84.2"], "synonyms": ["Ambras syndrome"]}
Ferro-cerebro-cutaneous syndrome is a rare, genetic, metabolic liver disease characterized by progressive neurodegeneration, cutaneous abnormalities, including varying degrees of ichthyosis or seborrheic dermatitis, and systemic iron overload. Patients manifest with infantile-onset seizures, encephalopathy, abnormal eye movements, axial hypotonia with peripheral hypertonia, brisk reflexes, cortical blindness and deafness, myoclonus and hepato/splenomegaly, as well as oral manifestations, including microdontia, wiedely spaced and pointed teeth with delayed eruption, and gingival overgrowth. [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	Ferro-cerebro-cutaneous syndrome	None	27,272	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397922	2021-01-23T18:32:01	{"icd-10": ["G23.0"], "synonyms": ["Cerebro-cutaneous syndrome with iron overload"]}
Spinal muscular atrophy with lower extremity predominance (SMA-LED) is characterized by muscle weakness and wasting (atrophy) in the lower limbs, most severely affecting the thigh muscles (quadriceps). (In SMA-LED, the "D" stands for dominant, which refers to the inheritance pattern of this condition.) The loss of nerve cells that control muscle movement (motor neurons) leads to atrophy of the muscles in the lower limbs. Affected individuals often have a waddling or unsteady walk and walk on the balls of their feet. They may have difficulty rising from a seated position and climbing stairs. Some people with SMA-LED also have weakness in upper limb muscles. Joint deformities (contractures) in the hips, knees, feet, and ankles can occur in SMA-LED, and in severe cases are present from birth and can impair walking. Some individuals with this disorder have rigidity of joints (arthrogryposis) in their shoulders, elbows, and hands. In most people with SMA-LED, the muscle problems are apparent in infancy or early childhood; however, about one-quarter of affected individuals do not develop muscle weakness until adulthood. The muscle weakness and related health problems typically do not worsen over time. ## Frequency SMA-LED is thought to be a rare condition; its prevalence is unknown. ## Causes SMA-LED is caused by mutations in the DYNC1H1 gene or BICD2 gene. When this condition is caused by mutations in the DYNC1H1 gene, it is often known as SMA-LED type 1 or SMA-LED1, and when it is caused by mutations in the BICD2 gene, the condition is often known as SMA-LED type 2 or SMA-LED2. The DYNC1H1 gene provides instructions for making a protein that is part of a group (complex) of proteins called dynein. This complex is part of a network that moves (transports) proteins and other materials within cells. The protein produced from the BICD2 gene attaches (binds) to the dynein complex, turning it on (activating it) and helping it bind to other cellular materials for transport. The BICD2 protein and the dynein complex help neighboring neurons communicate by transporting sac-like structures called synaptic vesicles that contain chemical messengers. The BICD2 protein also helps maintain the structure of a cell component called the Golgi apparatus, in which newly produced proteins are modified so they can carry out their functions. DYNC1H1 and BICD2 gene mutations that cause SMA-LED disrupt the function of the dynein complex. As a result, transport of proteins, synaptic vesicles, and other materials within cells is reduced. Decreased synaptic vesicle transport in motor neurons, leading to impaired growth of neurons, is thought to contribute to the muscle weakness and atrophy experienced by people with SMA-LED. It is unclear why this condition primarily affects the lower limbs. Additionally, BICD2 gene mutations impair the BICD2 protein's ability to maintain the structure of the Golgi apparatus within cells. As a result, the Golgi apparatus breaks down into small fragments and the altered BICD2 protein becomes trapped within these fragments. Loss of these cell components likely further contributes to the signs and symptoms of SMA-LED. ### Learn more about the genes associated with Spinal muscular atrophy with lower extremity predominance * BICD2 * DYNC1H1 ## 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 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	Spinal muscular atrophy with lower extremity predominance	c1834690	27,273	medlineplus	https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy-with-lower-extremity-predominance/	2021-01-27T08:25:05	{"gard": ["13222"], "mesh": ["C563560"], "omim": ["158600", "615290"], "synonyms": []}
"MPS I" redirects here. For zhuyin or bopomofo, a Chinese phonetic system, also known as Mandarin phonetic symbols I, see Bopomofo. Mucopolysaccharidosis type I Other namesMPS ! Structure of dermatan sulfate, one of the molecules that accumulates in the lysosomes of MPS I patients CausesDeficiency of the alpha-L iduronidase enzyme Differential diagnosisHunter syndrome; other mucopolysaccharidoses TreatmentEnzyme replacement therapy with iduronidase; surgery PrognosisDeath usually occurs before 12 years (Hurler syndrome/severe form); lifespan may be normal (Scheie syndrome/attenuated form) Frequency1:100,000 (Hurler syndrome/severe); 1:115,000 (Hurler-Scheie syndrome/intermediate); 1:500,000 (Scheie syndrome/attenuated)[1] Mucopolysaccharidosis type I is a spectrum of diseases in the mucopolysaccharidosis family. It results in the buildup of glycosaminoglycans (or GAGs, or mucopolysaccharides) due to a deficiency of alpha-L iduronidase, an enzyme responsible for the degradation of GAGs in lysosomes. Without this enzyme, a buildup of dermatan sulfate and heparan sulfate occurs in the body. MPS I may present with a wide spectrum of symptoms, depending on how much functional enzyme is produced. In severe forms, symptoms appear during childhood, and early death can occur due to organ damage. In mild cases, the patient may live into adulthood. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 3.1 Classification * 4 Management * 5 References ## Signs and symptoms[edit] MPS I affects multiple organ systems. Children with Hurler syndrome (severe MPS I) may appear normal at birth and develop symptoms over the first years of life. Developmental delay may become apparent by age 1-2 years, with a maximum functional age of 2-4 years. Progressive deterioration follows. One of the first abnormalities that may be detected is coarsening of the facial features; these symptoms can begin at 3-6 months of age. Skeletal abnormalities occur by about age 6 months, but may not be clinically obvious until 10-14 months. Patients may experience debilitating spine and hip deformities, carpal tunnel syndrome, and joint stiffness. Patients may be normal height in infancy, but stop growing by the age of 2 years. They may not reach a height of greater than 4 feet. Other early symptoms may include inguinal and umbilical hernias. Clouding of the cornea and retinal degeneration may lead to blindness. The liver and spleen may be enlarged due to the deposition of GAGs. Aortic valve disease may occur. Upper and lower respiratory-tract infections can be frequent. Most children develop limited language capabilities. Death usually occurs by age 10.[2][3] In less severe cases, (Scheie syndrome, or attenuated MPS I), the presentation can vary considerably. Although symptoms generally begin to appear after age 5, the diagnosis is usually made after age 10. Intelligence may be normal, or mild learning disabilities may be present. As with the severe forms, visual problems may lead to blindness. Skeletal deformities and aortic valve disease may occur. These patients may live into adulthood.[1] ## Genetics[edit] MPS I has an autosomal recessive pattern of inheritance. MPS I is inherited in an autosomal recessive manner. This means that patients with MPS I carry two defective copies of the IDUA gene on chromosome 4, with one defective copy being inherited from each parent. Persons born with one normal copy and one defective copy of the IDUA are called carriers. They produce less α-L-iduronidase than an individual with two normal copies of the gene. The reduced production of the enzyme in carriers, however, remains sufficient for normal function; the person should not show any symptoms of the disease. ## Diagnosis[edit] ### Classification[edit] MPS I is divided into three subtypes based on severity of symptoms. All three types result from an absence of, or insufficient levels of, the enzyme α-L-iduronidase. MPS I H, or Hurler syndrome, is the most severe of the MPS I subtypes. The other two types are MPS I S (Scheie syndrome) and MPS I H-S (Hurler-Scheie syndrome).[citation needed] Because of the substantial overlap between Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome, some sources consider these terms to be outdated. Instead, MPS I may be divided into "severe", "intermediate", and "attenuated" forms.[4][1] ## Management[edit] This section is empty. You can help by adding to it. (July 2018) ## References[edit] 1. ^ a b c "Mucopolysaccharidoses Fact Sheet". National Institute of Neurological Disorders and Stroke. 15 Nov 2017. Retrieved 11 May 2018. 2. ^ Banikazemi, Maryam (12 Oct 2014). "Hurler syndrome, Hurler-Scheie Syndrome, and Scheie Syndrome (Mucopolysaccharidosis Type I)". Medscape. Retrieved 10 May 2018. 3. ^ Moore, David; Connock, Martin J.; Wraith, Ed; Lavery, Christine (2008-01-01). "The prevalence of and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK". Orphanet Journal of Rare Diseases. 3: 24. doi:10.1186/1750-1172-3-24. ISSN 1750-1172. PMC 2553763. PMID 18796143. 4. ^ "Mucopolysaccharidosis type I". Genetics Home Reference. Retrieved 10 May 2018. * v * t * e Lysosomal storage diseases: Inborn errors of carbohydrate metabolism (Mucopolysaccharidoses) Catabolism * MPS I * Hurler Syndrome, Hurler-Scheie Syndrome, Scheie Syndrome * MPS II: Hunter Syndrome * MPS III: Sanfilippo Syndrome * MPS IV: Morquio Syndrome * MPS VI: Maroteaux-Lamy Syndrome * MPS VII: Sly Syndrome * MPS IX: Hyaluronidase 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	Mucopolysaccharidosis type I	c0023786	27,274	wikipedia	https://en.wikipedia.org/wiki/Mucopolysaccharidosis_type_I	2021-01-18T18:29:36	{"mesh": ["D008059"], "wikidata": ["Q55165792"]}
A rare, benign, superficial fibromatosis disease characterized by single or multiple, uni- or bilateral, fixed, slow-growing, round, firm nodules typically located on the medial portion of the plantar aponeurosis, with no calcification. Patients are often asymptomatic or may present with foot pain, difficulty to walk or stand and, rarely, toe contractures. Histopathology reveals dense fibrocellular tissue with parallel and nodular arrays of fibrocytes and fibrillar collagen with a distinctive cork-screw morphology and no atypia. [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	Ledderhose disease	c0158360	27,275	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199251	2021-01-23T18:09:01	{"gard": ["6873"], "mesh": ["C537000", "D000071380"], "umls": ["C0158360"], "icd-10": ["M72.2"], "synonyms": ["Plantar fibromatosis"]}
Melanomas found under the dock of the tail An equine melanoma is a tumor that results from the abnormal growth of melanocytes in horses. Unlike in humans, melanomas in horses are not thought to be caused by exposure to ultraviolet light.[1] Melanomas are the third most common type of skin cancer in horses, with sarcoids being the first most prevalent and squamous-cell carcinoma being second.[2] Melanomas are typically rounded black nodules that vary in size and are usually be found underneath the dock of the tail, in the anal, perianal and genital regions, on the perineum, lips, eyelids, and sometimes near the throatlatch.[3] These tumors can be either benign, meaning not cancerous, or malignant, meaning cancerous;[4] while the benign tumors typically need little treatment to no treatment, the malignant tumors can cause serious problems and can potentially be life-threatening.[5] Different methods are used to determine if the tumor is malignant and whether it has spread to other organs. Methods used to determine malignancy include fine needle aspirate, biopsy, or complete removal.[4] To determine if the tumor has metastasized, a rectal examination or an ultrasound can be performed; the most frequent location for metastasis include the lymph nodes, spleen, liver, the abdominal wall, the lungs, and blood vessels.[6] If the tumor becomes large enough, it can cause weight loss or colic. It may also affect the horse's ability to turn their head from side to side and eat and drink comfortably if the tumor is on the throat latch area, or cause faecal impaction if tumor is on the anal region.[3] If melanomas become large and ulcerate, they may become infected.[5] ## Contents * 1 Melanoma in gray horses * 1.1 Frequency * 2 Types of melanoma * 2.1 Melanocytic nevus * 2.2 Dermal melanoma * 2.3 Dermal melanomatosis * 2.4 Anaplastic melanoma * 3 Treatment * 3.1 Surgical removal * 3.2 Intralesional cisplatin * 3.3 Cimetidine * 3.4 Melanoma vaccine * 4 References ## Melanoma in gray horses[edit] Melanomas found on the lip See also: Gray (horse) Gray horses have a higher susceptibility to melanoma than any other coat color, with up to 80% of gray horses developing some kind of melanoma in their lifetime.[4] Some sources state that up to 66% of those melanomas will become malignant.[3] The gray coat color comes from a gene that is responsible for the gradual depigmentation of the horse's coat; horses with this gene are born darker and over time, they lose their coat pigmentation. The gray gene is the strongest coat color modifier, and will act on any base color.[5] The gray coat color is the result of an autosomal dominant trait that is caused by a 4.6-kb duplication in the 6th intron of the gene syntaxin-17 (STX17).[7] The region of this mutation contains four genes: NR4A3 (nuclear receptor subfamily 4, group A, member 3), STX17, TXNDC4 (thioredoxin domain–containing-4¢) and INVS (inversin).[7] To determine what makes gray horses more susceptible to melanomas, researchers have used different techniques such as the Northern Blot technique[8] and Real-Time PCR.[9] From these studies, it was concluded that the STX17 gene and the NR4A3 gene are both being over-expressed in gray horses, which is responsible for the increased incidences of melanoma in horses with the gray gene.[7] ### Frequency[edit] One study of gray Quarter horses found that 17.7% had melanomas. The average age of the horses was 9.2 years, and melanomas were much more common in older horses than in younger. When split by age, prevalence was 52% in horse over 15 years old compared to 10% in horses under. This is lower than in other breeds and the authors postulate it may have been because only a few of the horses were homozygous for gray, that the chestnut allele of extension may be protective against melanomas caused by gray, or that the breed's genetic background may lower the risk.[10] In Lipizzaners, 50% of gray horses had melanotic tumors. Divided by age, 56% of horses under 16 years and 94% of horses older were affected.[11] ## Types of melanoma[edit] Not all melanoma tumors are the same; there are four different types of melanomas that can be found in horses. ### Melanocytic nevus[edit] This type of tumor is found in younger horses, around 5 years of age, and are usually benign. They can develop on horses of any color as small single masses, less than 2.5 cm (0.98 in), anywhere on the body.[12] ### Dermal melanoma[edit] These tumors are usually benign, but can become malignant over time. They vary in size, and can be found as singles or multiples. They are most commonly found in mature grey horses (less than 15 years old), typically under the tail, around the anus, and on the external genitalia.[12] ### Dermal melanomatosis[edit] These tumors are frequently malignant and have a high tendency to spread to other organs. They are most commonly found in gray horses over the age of 15 as a large coalescing mass under the tail, around the anus, on the external genitalia, or the parotid salivary gland.[12] ### Anaplastic melanoma[edit] These tumors are malignant and frequently spread to other organs. These are rare tumors, typically found in older (more than 20 years of age) non-gray horses.[12] ## Treatment[edit] There are several treatment options when a horse is found to have a melanoma tumor. ### Surgical removal[edit] The surgical removal of a melanoma tumor is performed when the tumors are small; this prevents the tumors from spreading to the surrounding areas.[13] ### Intralesional cisplatin[edit] Cisplatin is a chemotherapy drug that is injected into the tumor itself; this drug is commonly used along with surgical removal. That being said, this drug has been shown to resolve tumors with or without surgical removal for at least 2 years.[14] ### Cimetidine[edit] Cimetidine works by slowing tumor growth; it is a histamine blocker that maintains the body's immune response which aids in the killing of tumor cells. Cimetidine has not been proven to efficiently resolve tumors completely.[15] ### Melanoma vaccine[edit] A vaccine that is similar to the effective canine melanoma vaccine has been created for equine melanoma, [16] and is being studied at the College of Veterinary Medicine at the University of Florida [4] ## References[edit] 1. ^ "NADIS - National Animal Disease Information Service -". www.nadis.org.uk. Retrieved 2016-11-26. 2. ^ Valentine (2006). "Survey of equine cutaneous neoplasia in the Pacific Northwest". J Vet Diagn Invest. 18. 3. ^ a b c Moore, J. S; Shaw, E; Buechner‐Maxwell, V; Scarratt, W. K; Crisman, M; Furr, M; Robertson, J (2013). "Melanoma in horses: Current perspectives". Equine Veterinary Education. 25: 144–151. doi:10.1111/j.2042-3292.2011.00368.x. 4. ^ a b c d Tannler, B (2013). "Equine Melanoma" (PDF). Equine Health Update. 15: 1–2. 5. ^ a b c "Gray Coat Color/ Melanoma". www.horsetesting.com. Retrieved 2016-11-26. 6. ^ MacGillivray, Katherine Cole; Sweeney, Raymond W.; Piero, Fabio Del (July 2002). "Metastatic melanoma in horses". Journal of Veterinary Internal Medicine. 16 (4): 452–456. doi:10.1111/j.1939-1676.2002.tb01264.x. PMID 12141308. 7. ^ a b c Pielberg, G.; Golovko, A.; Sundström, E.; Curik, I.; Lennartsson, J.; Seltenhammer, M.; Druml, T.; Binns, M.; Fitzsimmons, C.; Lindgren, G.; Sandberg, K.; Baumung, R.; Vetterlein, M.; Strömberg, S.; Grabherr, M.; Wade, C.; Lindblad-Toh, K.; Pontén, F.; Heldin, C.; Sölkner, J.; Andersson, L. (2008). "A Cis-acting Regulatory Mutation Causes Premature Hair Graying and Susceptibility to Melanoma in the Horse". Nature Genetics. 40 (8): 1004. doi:10.1038/ng.185. PMID 18641652. 8. ^ "Northern Blotting". www.lifetechnologies.com. Retrieved 2016-11-26. 9. ^ Wang, X., Seed, B. (2003). A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Research, 31(24), e154; 1-8 10. ^ Teixeira; Rendahl; Anderson; Mickelson; Sigler; Buchanan (2013). "Coat color genotypes and risk and severity of melanoma in gray quarter horses". Journal of Veterinary Internal Medicine. doi:10.1111/jvim.12133. PMID 23875712. 11. ^ . doi:10.1034/j.1600-0749.2000.130108.x. Cite journal requires `\|journal=` (help); Missing or empty `\|title=` (help) 12. ^ a b c d Valentine, Beth A. (September 1995). "Equine melanocytic tumors: a retrospective study of 53 horses (1988 to 1991)". Journal of Veterinary Internal Medicine. 9 (5): 291–297. doi:10.1111/j.1939-1676.1995.tb01087.x. PMID 8531173. 13. ^ Rowe, E.L.; Sullins, K.E. (2004). "Excision as treatment of dermal melanomatosis in horses: 11 cases (1994-2000)". Journal of the American Veterinary Medical Association. 225 (1): 94–96. doi:10.2460/javma.2004.225.94. 14. ^ Hewes, C.A.; Sullins, K.E. (2006). "Use of cisplatin-containing biodegradable beads for treatment of cutaneous neoplasia in Equidae: 59 cases (2000-2004)". Journal of the American Veterinary Medical Association. 229 (10): 1617–1622. doi:10.2460/javma.229.10.1617. 15. ^ Goetz, T. E.; Ogilvie, G. K.; Keegan, K. G.; Johnson, P. J. (1990). "Cimetidine for treatment of melanomas in three horses". J Am Vet Med Assoc. 196 (3): 449–52. 16. ^ Bergman, P.J.; Camps-Palau, M.A.; Mcknight, J.A.; Leibman, N.F.; Craft, D.M.; Leung, C.; Liao, J.; Riviere, I.; Sadelain, M.; Hohenhaus, A.E.; Gregor, P.; Houghton, A.N.; Perales, M.A.; Wolchok, J.D. (2006). "Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center". Vaccine. 24 (21): 4582–4585. doi:10.1016/j.vaccine.2005.08.027. [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	Equine melanoma	None	27,276	wikipedia	https://en.wikipedia.org/wiki/Equine_melanoma	2021-01-18T19:10:11	{"wikidata": ["Q28456356"]}
Hereditary keratitis is characterised by opacification and vascularisation of the cornea, often associated with macula hypoplasia. ## Epidemiology The prevalence is unknown. ## Clinical description The presence of macular hypoplasia and iris anomalies in some familial cases suggest that in these cases the disease may be a form of aniridia. ## Etiology The syndrome is transmitted in an autosomal dominant manner and is associated with mutations in the PAX6 gene. [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 dominant keratitis	c1835698	27,277	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2334	2021-01-23T17:57:35	{"gard": ["3089"], "mesh": ["C537022"], "omim": ["148190"], "umls": ["C1835698"], "icd-10": ["H16.8"], "synonyms": ["Hereditary keratitis"]}
Thoracic aortic aneurysm Other namesAneurysm - thoracic aortic[1] SpecialtyCardiology A thoracic aortic aneurysm is an aortic aneurysm that presents primarily in the thorax. A thoracic aortic aneurysm is the "ballooning" of the upper aspect of the aorta, above the diaphragm. Untreated or unrecognized they can be fatal due to dissection or "popping" of the aneurysm leading to nearly instant death. Thoracic aneurysms are less common than an abdominal aortic aneurysm.[2] However, a syphilitic aneurysm is more likely to be a thoracic aortic aneurysm than an abdominal aortic aneurysm. This condition is commonly treated via a specialized multidisciplinary approach with both vascular surgeons and cardiac surgeons. ## Contents * 1 Presentation * 1.1 Complications * 2 Causes * 2.1 Age * 3 Risk factors * 4 Diagnosis * 5 Screening * 6 Treatment * 7 Epidemiology * 8 References * 9 External links ## Presentation[edit] Thoracic aortic aneurysm with arrow marking the lateral border of the aorta. ### Complications[edit] A contrast enhanced CT demonstrating a large thoracic aneurysm of about 7 cm which has ruptured. The principal causes of death due to thoracic aneurysmal disease are dissection and rupture. Once rupture occurs, the mortality rate is 50–80%. Most deaths in patients with Marfan syndrome are the result of aortic disease. ## Causes[edit] There are a number of causes, [3] Aneurysms in patients younger than 40 usually involve the ascending aorta due to a weakening of the aortic wall associated with connective tissue disorders like the Marfan and Ehler-Danlos syndromes or congenital bicuspid aortic valve. Younger patients may develop aortic aneurysms of the thoracoabdominal aorta after an aortic dissection. It can also be caused by blunt injury. Atherosclerosis is the principal cause of descending aortic aneurysms, while aneurysms of the aortic arch may be due to dissection, atherosclerosis or inflammation. ### Age[edit] The diagnosis of thoracic aortic aneurysm usually involves patients in their 60s and 70s. ## Risk factors[edit] Hypertension and cigarette smoking are the most important risk factors, though the importance of genetic factors has been increasingly recognized. Approximately 10 percent of patients may have other family members who have aortic aneurysms. It is also important to note that individuals with a history of aneurysms in other parts of the body have a higher chance of developing a thoracic aortic aneurysm.[4] ## Diagnosis[edit] Aorta segments, with thoracic aorta in area marked in green. Thoracic aortic aneurysm is defined as a cross-sectional diameter exceeding the following cutoff: * 4.5 cm in the United States[5] * 4.0 cm in South Korea[6] A diameter of 3.5 cm is generally considered dilated.[5] However, average values vary with age and size of the reference population, as well as different segments of the aorta. Upper limits of the standard reference range of the thoracic aorta in a United States population:[7] Small and young Large and elderly Ascending aorta 3.3 cm 4.3 cm Descending aorta 2.3 cm 3.2 cm ## Screening[edit] Play media Ruptured thoracic aortic aneurysm as seen on ultrasound[8] Guidelines were issued in March 2010 for early detection of thoracic aortic disease, by the American College of Cardiology, the American Heart Association, and other groups. Among the recommendations: * First-degree relatives of people with thoracic aortic aneurysm or dissection should have aortic imaging to identify asymptomatic disease. * People with symptoms suggestive of thoracic aortic dissection should be routinely evaluated "to establish a pretest risk of disease that can then be used to guide diagnostic decisions." * People diagnosed with Marfan syndrome should immediately have an echocardiogram to measure the aorta, and followed up 6 months later to check for aortic enlargement.[9] ## Treatment[edit] A stent graft placed in the thoracic aorta to treat a thoracic aortic aneurysm. The size cut off for aortic aneurysm is crucial to its treatment. A thoracic aorta greater than 4.5 cm is generally defined as aneurysmal, while a size greater than 6 cm is the distinction for treatment, which can be either endovascular or surgical, with the former reserved for pathology at the descending aorta.[10] Indication for surgery may depend upon the size of the aneurysm. Aneurysms in the ascending aorta may require surgery at a smaller size than aneurysms in the descending aorta.[11] Treatment may be via open or via endovascular means. ## Epidemiology[edit] Each year in the United States, some 45,000 people die from diseases of the aorta and its branches. Acute aortic dissection, a life-threatening event due to a tear in the aortic wall, affects 5 to 10 patients per million population each year, most often men between the ages of 50 and 70; of those that occur in women younger than 40, nearly half arise during pregnancy. The majority of these deaths occur as a result of complications of thoracic aneurysmal disease ## References[edit] 1. ^ "Thoracic aortic aneurysm: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 29 May 2019. 2. ^ Thoracic Aortic Aneurysm at eMedicine 3. ^ Aneurysms: Aneurysms and Aortic Dissection at Merck Manual of Diagnosis and Therapy Home Edition 4. ^ Thoracic Aortic Disease - Northwestern Memorial Hospital. Thoracic Aortic Aneurysm Archived 2012-05-02 at the Wayback Machine 5. ^ a b Bret P Nelson (2015-10-01). "Thoracic Aneurysm". Medscape. Retrieved 2017-04-16. 6. ^ Cho, In-Jeong; Jang, Sung-Yeol; Chang, Hyuk-Jae; Shin, Sanghoon; Shim, Chi Young; Hong, Geu-Ru; Chung, Namsik (2014). "Aortic Aneurysm Screening in a High-Risk Population: A Non-Contrast Computed Tomography Study in Korean Males with Hypertension". Korean Circulation Journal. 44 (3): 162–169. doi:10.4070/kcj.2014.44.3.162. ISSN 1738-5520. PMC 4037638. PMID 24876857. 7. ^ Wolak, Arik; Gransar, Heidi; Thomson, Louise E.J.; Friedman, John D.; Hachamovitch, Rory; Gutstein, Ariel; Shaw, Leslee J.; Polk, Donna; Wong, Nathan D.; Saouaf, Rola; Hayes, Sean W.; Rozanski, Alan; Slomka, Piotr J.; Germano, Guido; Berman, Daniel S. (2008). "Aortic Size Assessment by Noncontrast Cardiac Computed Tomography: Normal Limits by Age, Gender, and Body Surface Area". JACC: Cardiovascular Imaging. 1 (2): 200–209. doi:10.1016/j.jcmg.2007.11.005. ISSN 1936-878X. PMID 19356429. 8. ^ "UOTW #64 - Ultrasound of the Week". Ultrasound of the Week. 25 November 2015. Retrieved 27 May 2017. 9. ^ Hiratzka LF, Bakris GL, Beckman JA, et al. (April 2010). "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine". J. Am. Coll. Cardiol. 55 (14): e27–e129. doi:10.1016/j.jacc.2010.02.015. PMID 20359588. Archived from the original on 2010-10-23. 10. ^ Makaroun MS, Dillavou ED, Kee ST, et al. (January 2005). "Endovascular treatment of thoracic aortic aneurysms: results of the phase II multicenter trial of the GORE TAG thoracic endoprosthesis". J. Vasc. Surg. 41 (1): 1–9. doi:10.1016/j.jvs.2004.10.046. PMID 15696036. 11. ^ "Treatment Considerations related to Thoracic Aortic Aneurysm". Retrieved 2010-10-23. ## External links[edit] Classification D * ICD-10: I71.1, I71.2 * ICD-9-CM: 441.1, 441.2 * MeSH: D017545 External resources * MedlinePlus: 001119 * eMedicine: article/761627 article/424904 article/418480 * 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 [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	Thoracic aortic aneurysm	c0162872	27,278	wikipedia	https://en.wikipedia.org/wiki/Thoracic_aortic_aneurysm	2021-01-18T19:02:17	{"mesh": ["D017545"], "umls": ["C0162872"], "icd-9": ["441.1"], "icd-10": ["I71.2"], "orphanet": ["91387"], "wikidata": ["Q3616648"]}
Papular purpuric gloves and socks syndrome SpecialtyDermatology Papular purpuric gloves and socks syndrome is a cutaneous condition characterized by pruritus, edema, and erythema of the hands and feet, occurring primarily in teenagers and young adults.[1]:401 An association with parvovirus B19 has been described.[2] It was discovered by a duo of medical students; Kishorkumar Osman and Sulaiman Saloojee, during a ward round. ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 2. ^ Fölster-Holst R, Kreth HW (May 2009). "Viral exanthems in childhood--infectious (direct) exanthems. Part 2: Other viral exanthems". J Dtsch Dermatol Ges. 7 (5): 414–9. doi:10.1111/j.1610-0387.2008.06869.x. PMID 18808380. This infection-related 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	Papular purpuric gloves and socks syndrome	c1274339	27,279	wikipedia	https://en.wikipedia.org/wiki/Papular_purpuric_gloves_and_socks_syndrome	2021-01-18T18:34:51	{"umls": ["C1274339"], "wikidata": ["Q16948321"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Hepatization of lungs" – news · newspapers · books · scholar · JSTOR (July 2019) Hepatization is conversion into a substance resembling the liver; a state of the lungs when gorged with effuse matter, so that they are no longer pervious to the air. Red hepatization is when there are red blood cells, neutrophils, and fibrin in the pulmonary alveolus/ alveoli; it precedes gray hepatization, where the red cells have been broken down leaving a fibrinosuppurative exudate. The main cause is lobar pneumonia. Transformation from Red hepatization to gray hepatization is an example for acute inflammation turning into a chronic inflammation. ## References[edit] ## Further reading[edit] * Lectures on the diseases of the lungs and heart by Thomas Davies * Medical Times 1841 * London Medical Gazette, December 8, 1843 Wikimedia Commons has media related to Category:Hepatization of lungs. 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	Hepatization of lungs	None	27,280	wikipedia	https://en.wikipedia.org/wiki/Hepatization_of_lungs	2021-01-18T19:01:43	{"wikidata": ["Q1607632"]}
A rare congenital anomaly of the kidney and urinary tract (CAKUT) in which one or both kidneys (unilateral or bilateral MCDK respectively) are large, distended by multiple cysts, and non-functional. Unilateral MCDK is typically asymptomatic if the other kidney is fully functional but may occasionally present with abdominal obstructive signs when the cysts become too large. Bilateral MCDK is considered a lethal entity and neonates present with features of the Potter sequence, severe pulmonary hypoplasia and severe renal failure, and generally die shortly after birth. [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	Multicystic dysplastic kidney	c3714581	27,281	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1851	2021-01-23T17:56:55	{"mesh": ["D021782"], "umls": ["C0345335", "C3714581"], "icd-10": ["Q61.4"], "synonyms": ["MCDK", "Multicystic renal dysplasia"]}
A rare, slowly progressive neurological disorder involving central nervous system demyelination, leading to autonomic dysfunction, ataxia and mild cognitive impairment. ## Epidemiology More than 20 families in different ethnic groups have been reported to date. Exact prevalence and incidence data are however lacking. ## Clinical description Unlike most forms of leukodystrophy which appear in childhood, ADLD occurs in the 4th to 6th decade of life. ADLD may clinically resemble multiple sclerosis in the initial phase. In most patients, the initial manifestation of the disease is autonomic dysfunction resulting in micturition urgency, bladder retention, constipation, postural hypotension and erectile dysfunction in affected males. Decreased sweating is reported in some cases. Some patients develop autonomic dysfunction later in the disease course. The other features are cerebellar dysfunction (gait ataxia, nystagmus, dysmetria, loss of fine motor control, and action tremors), pyramidal signs (spasticity, weakness of both upper and lower extremities, hyperreflexia), and cognitive impairment possibly with personality changes. These manifestations may not develop for years following initial presentation. Neuroradiological characteristics include extensive symmetrical white matter changes, corpus callosum atrophy, and brain stem and spinal cord atrophy. The disease follows a slow progressive course with an eventual loss of walking ability and slightly shortened lifespan. ## Etiology ADLD is caused by chromosomal rearrangements with duplications of the LMNB1 gene (5q23.2) or a ''position effect'' due to a genomic deletion upstream of the gene causing its upregulation. Overexpression of LMNB1 causes myelin disruption in the central nervous system for which the precise underlying pathogenic mechanisms have not been elucidated. Alteration of splicing patterns suggests that ADLD is a spliceopathy. ## Genetic counseling Genetic counseling should be provided to affected families indicating the autosomal dominant pattern of inheritance. [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	Adult-onset autosomal dominant leukodystrophy	c1868512	27,282	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99027	2021-01-23T18:21:18	{"gard": ["10587"], "mesh": ["C566813"], "omim": ["169500"], "umls": ["C1868512", "C3164344"], "icd-10": ["E75.2"], "synonyms": ["ADLD", "Adult-onset autosomal dominant demyelinating leukodystrophy"]}
A number sign (#) is used with this entry because of evidence that Pierpont syndrome (PRPTS) is caused by heterozygous mutation in the TBL1XR1 gene (608628) on chromosome 3q26. Description Pierpont syndrome is a multiple congenital anomaly syndrome associated with learning disability. Key features include distinctive facial characteristics, especially when smiling, plantar fat pads, and other limb anomalies (summary by Burkitt Wright et al., 2011). Clinical Features Pierpont et al. (1998) suggested that 2 unrelated boys had a previously undescribed disorder characterized by global developmental delay and a phenotype of microcephaly, midface hypoplasia, enlarged fleshy ears, depressed nasal bridge, anteverted nostrils, central palatal ridge, and high forehead. Bilateral congenital fat pads were present anteromedial to the heels. Fetal finger and toe pads were also present, and palmar and plantar grooves were deeper than normal with 'pillowing' of the areas between the grooves. Congenital fatty heel pads, which have been described as an isolated clinical finding (Livingstone and Burd, 1995), are rare. Oudesluijs et al. (2005) reported a 2.5-year-old boy with axial hypotonia in the first few months of life, prolonged feeding problems, moderate developmental delay, no speech development, deep palmar and plantar grooves, and fat pads at the anteromedial aspect of the heels. Examination at 7 months of age revealed a distinct facial phenotype, with high forehead, high anterior hairline, mild midface hypoplasia, markedly narrow and upwardly slanting palpebral fissures, broad nasal ridge and tip, broad philtrum, bowed upper lip with 'pouting' and hypotonic lower lip, full cheeks, and flat occiput. His neck was short, internipple distance was large, and areolas were small. His penis was small with slightly underdeveloped scrotum. There was excessive skin over the hands and feet, causing them to have a puffy appearance, and on the palms and soles there was pillowing of the areas between the grooves. At 2.5 years of age, the patient had no speech development and could not crawl; he could roll over and sit independently, however, and he moved around by shuffling on his back. Facial features were essentially unchanged, although there was now evidence of widely spaced teeth, with a broad right upper incisor and an irregular edge to all incisors. Oudesluijs et al. (2005) stated that this patient had a phenotype 'almost identical' to that of the 2 boys reported by Pierpont et al. (1998), and proposed the designation 'Pierpont syndrome' for the condition. Burkitt Wright et al. (2011) provided follow-up on the 3 previously described patients with Pierpont syndrome and reported 7 additional patients with a similar phenotype, including 1 girl and a pair of monozygotic twin boys. The new patients were ascertained by the presence of fat pads anteromedial to their heels, fetal digital pads, learning disability, and characteristic facial dysmorphism. Burkitt Wright et al. (2011) noted that the narrow palpebral fissures took on a distinctive crescent moon shape when smiling due to the fullness of the cheeks in these patients. Heinen et al. (2016) reported 2 patients with Pierpont syndrome. Both had severely delayed psychomotor development with lack of speech and significant hypotonia in infancy. They had poor overall growth and unusual facial features, including high anterior hairline, narrow palpebral fissures, microcornea, flat cheek bones, broad nasal ridge and tip, smooth philtrum, thin upper vermilion, large ears, and widely spaced teeth. Other features included scoliosis, short fingers and toes, and marked finger and toe pads as well as subcalcaneal fat pads. One patient had hearing loss. Kahlert et al. (2017) reported a male child with typical features of Pierpont syndrome, including developmental delay, distinctive facial dysmorphic features, dystrophy, and abnormal fat distribution in the feet. In addition, the child had microphthalmia, pendular nystagmus, cryptorchidism, dermal sinus, and peripheral joint laxity. Lemattre et al. (2018) reported 2 unrelated patients with Pierpont syndrome. Both had typical facial features, growth restriction, and severely impaired intellectual development. One patient had a Chiari malformation, and the other had a gyration disorder with myelination delay. The characteristic palmar and plantar grooves seen in other patients with PRPTS were less prominent in these patients. Inheritance Pierpont syndrome is an autosomal dominant disorder (Heinen et al., 2016). Oudesluijs et al. (2005) stated that the advanced paternal age in the cases described by Pierpont et al. (1998) was suggestive of an autosomal dominant spontaneous mutation; however, the fact that all 3 reported patients were boys was also in keeping with X-linked recessive inheritance. Burkitt Wright et al. (2011) noted that their identification of a female patient with Pierpont syndrome made X-linked recessive inheritance less likely. Molecular Genetics In 6 unrelated patients with Pierpont syndrome, including the 2 unrelated patients originally reported by Pierpont et al. (1998) and the patient reported by Oudesluijs et al. (2005), Heinen et al. (2016) identified the same de novo heterozygous missense mutation in the TBL1XR1 gene (Y446C; 608628.0005). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The mutant protein assembled correctly into its complex, but further functional studies were not performed. In a male child with Pierpont syndrome, Kahlert et al. (2017) identified heterozygosity for the same missense mutation (Y466C) in the TBL1XR1 gene that was identified by Heinen et al. (2016). By whole-exome sequencing in 2 unrelated patients with Pierpont syndrome, Lemattre et al. (2018) identified novel de novo heterozygous missense mutations in the TBL1XR1 gene. One mutation (Y446H; 608628.0006) occurred at the same amino acid as the recurrent mutation previously identified in patients with Pierpont syndrome (Y446C); the other mutation (C325Y; 608628.0007) occurred in the same area of the protein, at the inner surface of the WD40 ring. Cytogenetics In a 2.5-year-old boy with Pierpont syndrome, Oudesluijs et al. (2005) performed whole-genome microarray CGH but did not identify any abnormalities. In 7 patients with Pierpont syndrome, Burkitt Wright et al. (2011) performed routine karyotyping but did not find any abnormalities. Genomewide copy number analysis by SNP array in the 2 boys originally reported by Pierpont et al. (1998), the boy previously studied by Oudesluijs et al. (2005), and 3 additional patients with Pierpont syndrome revealed a 3.17-Mb deletion at chromosome 10q21.3 in 1 of 2 monozygotic twin boys. FISH analysis revealed that the deletion occurred on the maternal allele and was present in his affected twin brother. INHERITANCE \- Autosomal dominant GROWTH Height \- Less than tenth centile Weight \- Less than fiftieth centile Other \- Failure to thrive (in some patients) HEAD & NECK Head \- Brachycephaly \- Microcephaly Face \- Broad face \- High forehead \- High anterior hairline \- Midface hypoplasia \- Full cheeks \- Broad, flat philtrum Ears \- Fleshy ears \- Posteriorly rotated ears Eyes \- Short and narrow palpebral fissures \- Hypertelorism or telecanthus \- Deep-set eyes \- Strabismus (in some patients) \- Microphthalmia (in 1 patient) \- Pendular nystagmus (in 1 patient) Nose \- Short, broad nose Mouth \- Long upper lip with thin vermilion border \- Everted lower lip \- Central palatal ridge (in some patients) Teeth \- Widely spaced teeth Neck \- Short neck CHEST Breasts \- Widely spaced nipples \- Hypoplastic areolae ABDOMEN Gastrointestinal \- Feeding difficulties (in some patients) GENITOURINARY External Genitalia (Male) \- Small penis (in some patients) SKELETAL Spine \- Scoliosis, progressive (in some patients) Limbs \- Fat pads anterior to calcanei Hands \- Deep creases on palms, with pillowing in between \- Fetal finger pads \- Short, broad hands Feet \- Deep grooves on soles, with pillowing in between \- Fetal toe pads \- Short, broad feet SKIN, NAILS, & HAIR Skin \- Dermal sinus (in 1 patient) Hair \- High anterior hairline NEUROLOGIC Central Nervous System \- Global developmental delay \- Speech delay \- Seizures (in some patients) Peripheral Nervous System \- Hypotonia, truncal \- Hypertonia (in some patients) MISCELLANEOUS \- Fat pads become less prominent with time \- Mutations occur de novo MOLECULAR BASIS \- Caused by mutation in the transducin-beta-like 1 receptor 1 gene (TBL1XR1, 608628.0005 ) ▲ 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	PIERPONT SYNDROME	c1865644	27,283	omim	https://www.omim.org/entry/602342	2019-09-22T16:13:51	{"mesh": ["C566559"], "omim": ["602342"], "orphanet": ["487825"], "synonyms": ["PLANTAR LIPOMATOSIS, UNUSUAL FACIES, AND DEVELOPMENTAL DELAY", "Alternative titles", "Plantar lipomatosis-unusual facies-developmental delay syndrome", "Plantar lipomatosis-facial dysmorphism-developmental delay syndrome"]}
A number sign (#) is used with this entry because of evidence that oculoectodermal syndrome (OES) is caused by somatic mosaicism for mutations in the KRAS gene (190070) on chromosome 12p12. Description Oculoectodermal syndrome (OES) is characterized by the association of epibulbar dermoids and aplasia cutis congenita. Affected individuals exhibit congenital scalp lesions which are atrophic, nonscarring, hairless regions that are often multiple and asymmetric in distribution, and may have associated hamartomas. Ectodermal changes include linear hyperpigmentation that may follow the lines of Blaschko and, rarely, epidermal nevus-like lesions. Epibulbar dermoids may be uni- or bilateral. Additional ocular anomalies such as skin tags of the upper eyelid and rarely optic nerve or retinal changes or microphthalmia can be present. Phenotypic expression is highly variable, and various other abnormalities have occasionally been reported, including growth failure, lymphedema, and cardiovascular defects, as well as neurodevelopmental symptoms such as developmental delay, epilepsy, learning difficulties, and behavioral abnormalities. Benign tumor-like lesions such as nonossifying fibromas of the long bones and giant cell granulomas of the jaws have repeatedly been observed and appear to be age-dependent, becoming a common manifestation in individuals aged 5 years or older (summary by Boppudi et al., 2016). Clinical Features Toriello et al. (1993) reported 2 unrelated boys with aplasia cutis congenita, epibulbar dermoids, and cutaneous hyperpigmentation. Additional features of 1 of these patients (patient 2) included giant cell granulomas and nonossifying fibromas (Toriello et al., 1999). Peacock et al. (2015) reported that patient 2's nonossifying fibromas spontaneously resolved following skeletal maturity. At age 25, he was healthy and had normal cognitive function. Gardner and Viljoen (1994) described 2 unrelated South African girls with aplasia cutis congenita, epibulbar dermoids, and strabismus. Evers et al. (1994) described a similar case in a female child who also had macrocephaly. Lees et al. (2000) reported 2 unrelated patients with the combination of aplasia cutis congenita and epibulbar dermoids. In addition, 1 patient had bladder exstrophy with epispadias. Martin et al. (2007) reported the eleventh published case of oculoectodermal syndrome in a 6-year-old Chinese girl who had aplasia cutis, left epibulbar dermoid and left eyelid coloboma, macrocephaly, minor dysmorphism, and mild facial asymmetry. CT scan of the head revealed an arachnoid cyst, which the authors stated was the third to be described in the 6 patients with oculoectodermal syndrome who had undergone cranial imaging. Martin et al. (2007) suggested that arachnoid cyst may be a phenotypic feature of the syndrome. Federici et al. (2004) reported a patient with oculoectodermal syndrome who developed giant cell granulomas of the jaw. They reviewed the findings in 10 reported patients and suggested that the development of giant cell granulomas in childhood is part of what they referred to as a new tumor predisposition syndrome. Ardinger et al. (2007) reported 2 new cases and reviewed 13 previously reported cases of oculoectodermal syndrome. Their patient 1 had a scalp lesion histologically interpreted as a smooth muscle hamartoma (with some features suggestive of nevus psiloliparus). When they evaluated the 15 cases by the diagnostic criteria of Hunter (2006), 8 had a definite and 7 had a probable diagnosis of encephalocraniocutaneous lipomatosis (ECCL; see 176920). Ardinger et al. (2007) proposed that OES may be a mild variant of ECCL, differing primarily by lack of intracranial anomalies on brain imaging. Horev et al. (2011) described 2 patients with alopecia of the scalp and epibulbar dermoids, including 1 of the patients reported by Lees et al. (2000), both of whom also had coarctation of the descending aorta, cerebral arterioocclusive vasculopathy, and moyamoya-type collaterals presenting as seizures, recurrent transient ischemic attacks, and cerebrovascular accidents during early childhood. Horev et al. (2011) suggested that vascular findings are an integral part of the unifying diagnosis of OES and that disturbance in vasculogenesis contributes to the pathogenesis. Epibulbar dermoids occur with Goldenhar syndrome (164210) and with Proteus syndrome (176920). Aplasia cutis congenita occurs as an isolated defect (107600) or in association with gastrointestinal atresia in Carmi syndrome (226730), with limb defects in Adams-Oliver syndrome (100300), and with other associated abnormalities (see 302803, 100300, and 207731). Chacon-Camacho et al. (2019) reported 2 Mexican children with OES and somatic mosaicism for mutations in the KRAS gene (see MOLECULAR GENETICS). Additional clinical findings in these patients included facial asymmetry, left body hemihypertrophy, atrial septal defect, patent ductus arteriosus, and supernumerary nipple in the 4-year-old girl (patient 1), and microcornea, nystagmus, short neck, and hypertrophic cardiomyopathy in the 12-year-old boy (patient 2). Inheritance Toriello et al. (1993) concluded that a new dominant mutation is possible in this disorder, but autosomal recessive inheritance could not be excluded. Molecular Genetics In an 8-year-old girl (patient 1) and an unrelated 25-year-old man (patient 2) with oculoectodermal syndrome, Peacock et al. (2015) identified somatic missense mutations in the KRAS gene (190070.0003 and 190070.0024, respectively). The man was one of the original boys with OES (patient 2) described by Toriello et al. (1993). Allele frequencies fell below 40% in all tissues examined in both patients, suggesting that OES is a mosaic RAS-related disorder ('RASopathy'). In 3 unrelated children with OES, including a 6-year-old boy who was originally described by Aslan et al. (2014), Boppudi et al. (2016) identified somatic missense mutations in the KRAS gene, A146T (190070.0027) and A146V (190070.0028), that were mosaic in lesional tissue and absent from leukocyte DNA. Proportions of mutant alleles ranged from less than 10% to 40% in lesional tissue samples. In a 4-year-old Mexican girl (patient 1) and an unrelated 12-year-old Mexican boy (patient 2) with OES, Chacon-Camacho et al. (2019) identified somatic mosaicism for the previously reported KRAS variants, A146T and A146V, respectively. The mutant allele frequency was approximately 30% in lesional tissues, and the variants were not detected in DNA isolated from blood leukocytes or buccal cells. INHERITANCE \- Somatic mutation GROWTH Other \- Growth failure \- Left body hemihypertrophy HEAD & NECK Head \- Macrocephaly (in some patients) Face \- Frontal parietal bossing (in some patients) \- Facial asymmetry \- Giant cell granuloma of the jaw Eyes \- Epicanthal folds \- Epibulbar dermoids \- Astigmatism (in some patients) \- Cloudy cornea (in some patients) \- Strabismus (in some patients) \- Eyelid coloboma \- Dermolipoma \- Proptosis \- Anisometropia \- Astigmatism \- Nystagmus \- Microcornea \- Optic nerve excavation Nose \- Broad nasal bridge (in some patients) \- Flat nasal bridge (in some patients): Neck \- Short neck CARDIOVASCULAR Heart \- Coarctation of the aorta \- Atrial septal defect \- Patent ductus arteriosus \- Hypertrophic cardiomyopathy Vascular \- Moyamoya disease \- Transient ischemic attacks CHEST Breasts \- Supernumerary nipple GENITOURINARY Bladder \- Bladder exstrophy \- Rhabdosarcoma, embryonal SKELETAL Skull \- Giant cell granuloma of jaw Limbs \- Lower limb asymmetry \- Nonossifying fibromas of long bones SKIN, NAILS, & HAIR Skin \- Aplasia cutis congenita \- Cutaneous hyperpigmentation (in some patients) \- Epidermal nevus MUSCLE, SOFT TISSUES \- Lymphedema NEUROLOGIC Central Nervous System \- Developmental delay (in some patients) \- Arachnoid cyst (in some patients) \- Epilepsy \- Moderate learning difficulties Behavioral Psychiatric Manifestations \- Hyperactive behavior, mild MISCELLANEOUS \- Variable phenotype MOLECULAR BASIS \- Caused by somatic mutation in the KRAS protooncogene, GTPase gene (KRAS, 190070.0024 ) ▲ 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	OCULOECTODERMAL SYNDROME	c1838329	27,284	omim	https://www.omim.org/entry/600268	2019-09-22T16:16:27	{"mesh": ["C563969"], "omim": ["600268"], "orphanet": ["3339"], "synonyms": ["Alternative titles", "APLASIA CUTIS CONGENITA WITH EPIBULBAR DERMOIDS"]}
Glycerol kinase deficiency Other namesGKD Glycerol kinase deficiency (GKD) is an X-linked recessive enzyme defect that is heterozygous in nature. Three clinically distinct forms of this deficiency have been proposed, namely infantile, juvenile, and adult. National Institutes of Health and its Office of Rare Diseases Research branch classifies GKD as a rare disease, known to affect fewer than 200,000 individuals in the United States. The responsible gene lies in a region containing genes in which deletions can cause Duchenne muscular dystrophy and adrenal hypoplasia congenita. Combinations of these three genetic defects including GKD are addressed medically as Complex GKD.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Effect on glycolysis * 4 Diagnosis * 4.1 Classification * 5 Treatment * 6 References ## Signs and symptoms[edit] Glycerol Kinase Deficiency causes the condition known as hyperglycerolemia,[2] an accumulation of glycerol in the blood and urine. This excess of glycerol in bodily fluids can lead to many more potentially dangerous symptoms. Common symptoms include vomiting and lethargy.[3] These tend to be the only symptoms, if any, present in adult GKD which has been found to present with fewer symptoms than infant or juvenile GKD.[4] When GKD is accompanied by Duchenne muscular dystrophy and Adrenal Hypoplasia Congenita, also caused by mutations on the Xp21 chromosome,[5] the symptoms can become much more severe. Symptoms visible at or shortly after birth include: * cryptorchidism * strabismus * seizures[3] Some other symptoms that become more noticeable with time would be: * metabolic acidosis * hypoglycemia * adrenal cortex insufficiency[6] * learning disabilities * osteoporosis * myopathy Many of the physically visible symptoms, such as cryptorchidism, strabismus, learning disabilities,[5] and myopathy, tend to have an added psychological effect on the subject due to the fact that they can set him or her apart from those without GKD. Cryptorchidism, the failure of one or both of the testes to descend to the scrotum, has been known to lead to sexual identity confusion amongst young boys because it is such a major physiological anomaly.[7] Strabismus is the misalignment of one's eyes. Typically, one is focused but the other is “lazy” and is directed inward or out ward (up and down is less common but does occur). ## Causes[edit] Glycerol kinase deficiency has two main causes. * The first cause is isolated enzyme deficiency. The enzyme glycerol kinase is encoded by the X-chromosome in humans.[8] It acts as a catalyst in the phosphorylation of glycerol to glycerol-3-phosphate which plays a key role in formation of triacylglycerol (TAG) and fat storage. There is no genotype–phenotype correlation in isolated GKD and it can be either symptomatic or asymptomatic.[9] Symptomatic means that GKD shows symptoms when it persists in the body and asymptomatic means that the no symptoms appear in the body. In this deficiency the genotype is not associated with the phenotype. The presence of certain mutations in genes has no relation with the phenotype i.e. any resulting physical traits or abnormality.[10] Location of the Glycerol Kinase gene on the X chromosome * The second cause is a deletion or mutation of a single gene. GKD is described by Mendelian inheritance and is an X-linked recessive trait due to which it occurs mainly in males and occasionally in females.[11] GKD results when the glycerol kinase gene present on the locus Xp21 of the X chromosome is either deleted or mutated. Females have two X chromosomes and males have one X and one Y chromosome. The expression of recessive genes on the X chromosome is different in males and females. This is due to the fact that genes present on the Y chromosome do not pair up with genes on the X chromosome in males. In females the disorder is expressed only when there are two copies of the affected gene present on each X chromosome but since the glycerol kinase gene is present only on one X chromosome the disorder is not expressed in women. Women have a second good copy that can compensate for the defect on the first copy. On the other hand, males only need a single copy of the recessive gene for the disorder to be expressed. They do not have a second copy that can protect against any defect on the first copy.[12] ## Effect on glycolysis[edit] The metabolic pathway of glycolysis releases energy by converting glucose to pyruvate by via a series of intermediate metabolites. Each chemical modification (red box) is performed by a different enzyme. In order to understand how this condition affects a person you must first have a basic understanding of the process called glycolysis. This fundamental metabolic pathway is found in all known organisms. The process provides energy for our cells to carry out their daily functions. The overall reaction involves a cell taking in the sugar glucose and converting it into the energy rich molecule pyruvate. Inside the overall reaction there lie many steps that need to be followed in order for the original glucose molecule to be transformed into pyruvate. The glucose first gathers a phosphate group from an ATP molecule in order to become glucose-6-phosphate. It is then changed into fructose 6-phosphate, with the assistance of phosphoglucose isomerase, which is then changed into fructose 1,6-biphosphate when the fructose molecule receives a phosphate group from another ATP. The next step in the chain is crucial for cells in order to make more energy than they expend through the process of glycolysis; this step is when the fructose 1,6-bisphosphate molecule breaks down into two molecules of dihydroxyacetone phosphate (DHAP), so from this point on whenever ATP is being generated from ADP there are really two ATP molecules generated because there are two molecules undergoing the same reaction.[13] One molecule that takes advantage of this second part of the metabolic process is the fatty molecule glycerol. This is unfortunately prevented if someone is experiencing Glycerol Kinase Deficiency. When a human's body needs to use stored fat for energy it will release glycerol and other fatty acids into the bloodstream. However, these glycerol molecules must contribute to the process of glycolysis before they can provide energy to the body, as they do not hold the necessary energy within themselves. So before glycerol can enter the pathway of glycolysis it must be converted into an intermediate molecule, which in this case is dihydroxyacetone phosphate (DHAP). This is where glycerol kinase comes into the picture. The enzyme is used in the first step in turning glycerol into dihydroxyacetone phosphate (DHAP). It catalyzes the transfer of a phosphate group from an ATP to a glycerol molecule forming glycerol (3) phosphate. Then glycerol 3-phosphate, with the assistance of glycerol 3-phosphate dehydrogenase, can be dehydrogenated into DHAP. This molecule can then enter the metabolic pathway of glycolysis and provide more energy for the cell.[14] Looking at the entire glycolysis pathway this conversion would yield an extra ATP for each glycerol molecule that eventually made its way into a DHAP molecule, which demonstrates the benefit of releasing glycerol into the bloodstream. However, when suffering from a glycerol kinase deficiency many of the glycerol molecules released into the bloodstream end up not being converted to dihydroxyacetone phosphate (DHAP), because the host does not have enough of the enzyme to catalyze all of the reactions waiting to occur. These extra molecules of glycerol are left floating around in the cell and can cause serious damage if left untreated. ## Diagnosis[edit] ### Classification[edit] GKD can be divided into three distinct forms: infantile, juvenile, and adult. Out of all of these the infantile form is the most clinically relevant because it leads to developmental delay and adrenal insufficiency.[11] * The infantile form is referred to as complex GKD because the defect in the gene for the glycerol kinase enzyme is interconnected with defects in one or both of its affected genes that are responsible for Duchenne muscular dystrophy and adrenal hypoplasia congenita.[1] The cause of this form is deletion of the Xp21 gene on the X chromosome. Patients have increased levels of serum creatine phosphokinase, which leads to myopathic changes in muscle biopsies resembling Duchenne muscular dystrophy. * The juvenile form does not show myopathy and patients have normal adrenal function. The main cause leading to this form of GKD is isolated enzyme deficiency. * The adult form is also caused by an isolated enzyme deficiency. Patients having this form of the disorder are clinically normal.[11] ## Treatment[edit] Treatments for Glycerol Kinase Deficiency are targeted to treat the symptoms because there are no permanent treatments for this disease. The main way to treat these symptoms is by using corticosteroids, glucose infusion, or mineralocorticoids. Corticosteroids are steroid hormones that are naturally produced in the adrenal glands. These hormones regulate stress responses, carbohydrate metabolism, blood electrolyte levels, as well as other uses. The mineralocorticoids, such as aldosterone control many electrolyte levels and allow the kidneys to retain sodium. Glucose infusion is coupled with insulin infusion to monitor blood glucose levels and keep them stable.[15] Due to the multitude of varying symptoms of this disease, there is no specific treatment that will cure this disease altogether. The symptoms can be treated with many different treatments and combinations of medicines to try to find the correct combination to offset the specific symptoms. Everyone with Glycerol Kinase Deficiency has varying degrees of symptoms and thereby requires different medicines to be used in combination to treat the symptoms; however, this disease is not curable and the symptoms can only be managed, not treated fully.[16] ## References[edit] 1. ^ a b Office of Rare Diseases, National Institutes of Health (25 January 2005). "Annual Report on the Rare Diseases and Conditions Research Activities of the National Institutes of Health 1997" (pdf). Retrieved 21 December 2012. 2. ^ Sjarif, D. R.; Hellerud, C.; Van Amstel, J. K. P. V.; Kleijer, W. J.; Sperl, W.; Lacombe, D.; Sass, J. R. O.; Beemer, F. A.; Duran, M.; Poll-The, B. T. (2004). "Glycerol kinase deficiency: Residual activity explained by reduced transcription and enzyme conformation". European Journal of Human Genetics. 12 (6): 424–432. doi:10.1038/sj.ejhg.5201172. PMID 15026783. 3. ^ a b Wishart, David (6 March 2010). "Glycerol Kinase Deficiency". Small Molecule Pathway Database. Archived from the original on 2 July 2012. Retrieved 21 December 2012. 4. ^ "Hyperglycerolemia". Online Mendelian Inheritance in Man. National Center for Biotechnology Information. 29 June 2010. Retrieved 21 December 2012. 5. ^ a b "Chromosome Xp21 Deletion Syndrome". Online Mendelian Inheritance in Man. National Center for Biotechnology Information. 8 December 2010. Retrieved 21 December 2012. 6. ^ Seltzer, W. K.; Firminger, H.; Klein, J.; Pike, A.; Fennessey, P.; McCabe, E. R. B. (1985). "Adrenal dysfunction in glycerol kinase deficiency". Biochemical Medicine. 33 (2): 189–199. doi:10.1016/0006-2944(85)90027-4. PMID 2988520. 7. ^ Galifer, R. B.; Kalfa, N.; Guibal, M. P. (2004). "What a hidden testicle can hide?...or the clinical traps of cryptorchidism". Archives de Pédiatrie. 11 (4): 350–359. doi:10.1016/j.arcped.2003.11.015. PMID 15139321. 8. ^ Mahbubul Huq, A. H. M.; Lovell, R. S.; Ou, C. -N.; Beaudet, A. L.; Craigen, W. J. (1997). "X-Linked Glycerol Kinase Deficiency in the Mouse Leads to Growth Retardation, Altered Fat Metabolism, Autonomous Glucocorticoid Secretion and Neonatal Death". Human Molecular Genetics. 6 (11): 1803–1809. doi:10.1093/hmg/6.11.1803. PMID 9302256. 9. ^ Rahib, L.; MacLennan, N. K.; Horvath, S.; Liao, J. C.; Dipple, K. M. (2007). "Glycerol kinase deficiency alters expression of genes involved in lipid metabolism, carbohydrate metabolism, and insulin signaling". European Journal of Human Genetics. 15 (6): 646–657. doi:10.1038/sj.ejhg.5201801. PMID 17406644. 10. ^ National Library of Medicine (17 December 2012). "Genotype-Phenotype Correlation". Genetics Home Reference. Retrieved 21 December 2012. 11. ^ a b c Francke, U.; Harper, J. F.; Darras, B. T.; Cowan, J. M.; McCabe, E. R.; Kohlschütter, A.; Seltzer, W. K.; Saito, F.; Goto, J.; Harpey, J. P.; Wise, J. E. (1987). "Congenital adrenal hypoplasia, myopathy, and glycerol kinase deficiency: Molecular genetic evidence for deletions". American Journal of Human Genetics. 40 (3): 212–227. PMC 1684111. PMID 2883886. 12. ^ Richards, Julia E.; Hawley, R. Scott (2010). The Human Genome: A User's Guide. Academic Press. ISBN 978-0-12-333445-9. 13. ^ Benson, Darik (14 August 2012). "Glycolysis". UC Davis ChemWiki. Retrieved 21 December 2012., . "." . University California Davis, 2 Nov. 2010. Web. <> 14. ^ Medh, Jheem D. (August 2006). "Glycolysis" (PDF). Retrieved 21 December 2012. 15. ^ Blau, Nenad; Hoffmann, Georg F.; Leonard, James; Clarke, Joe T.R. (2005). Physician's Guide to the Treatment and Follow-Up of Metabolic Diseases. Springer. ISBN 978-3540229544. 16. ^ "Glycerol Kinase Deficiency". MIC - Metabolic & Genetic Information Centre. 17 October 2010. Retrieved 21 December 2012. [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	Glycerol kinase deficiency	c0574108	27,285	wikipedia	https://en.wikipedia.org/wiki/Glycerol_kinase_deficiency	2021-01-18T18:30:26	{"umls": ["C0574108"], "orphanet": ["308993", "408"], "wikidata": ["Q5572555"]}
Coats disease (CD) is an idiopathic disorder characterized by retinal telangiectasia with deposition of intraretinal or subretinal exudates, potentially leading to retinal detachment and unilateral blindness. CD is classically an isolated and unilateral condition affecting otherwise healthy young children. ## Epidemiology Annual incidence is <1/1,000,000 in the UK, approximately 80% of cases occur in males. ## Clinical description CD onset predominantly occurs in male children between 6 and 8 years old. Early stages of the disease are generally asymptomatic and evolution is variable. As children with unilateral vision loss usually do not complain of symptoms, the diagnosis is often based on an abnormal appearance of the pupillary reflex that can best be seen in photos or on red reflex testing. Other common presentations include the onset of strabismus or failure of a school vision screening examination. Ophthalmoscopy reveals unilateral retinal telangiectasia and aneurysms of the retinal vasculature. This is followed by exudation of fluids producing yellow subretinal deposits. The most advanced stages of CD include total retinal detachment, leukocoria and painful glaucoma secondary to angle closure. ## Etiology An abnormal permeability of capillary endothelial cells in the retina, along with abnormal pericytes, causes the retinal vascular leakage that is the hallmark of CD. CD is not heritable, however, somatic mutations in the Norrie Disease Pseudoglioma, NDP, gene have been hypothesized to play a role in the pathogenesis of CD. ## Diagnostic methods Diagnostic methods include indirect ophthalmoscopy, fluorescein angiography, ultrasonography, computerized tomography scanning and magnetic resonance imaging. ## Differential diagnosis Retinoblastoma (see this term) is the most important differential diagnosis. B-scan ultrasound and MRI with gadolinium contrast aid in distinguishing between late stage CD and solid tumors. Others include familial exudative vitreoretinopathy, Von Hippel-Lindau disease, intermediate uveitis and incontinentia pigmenti which are more often bilateral, as well as the more typically unilateral conditions such as ocular toxocariasis and persistent hyperplastic primary vitreous (see these terms). ## Management and treatment Treatment depends on severity of disease. Mild peripheral vascular abnormalities may be followed with serial fundus photography. When exudation is present, ablation of incompetent vessels and avascular retina should be performed using laser or less often, cryotherapy. More advanced cases can require surgical intervention for retinal reattachment, such as scleral buckling, or laser photocoagulation combined with pars plana vitrectomy and removal of the vitreous membrane. Intravitreal corticosteroid as well as anti-VEGF agents have been used as adjuvant therapies. ## Prognosis The majority of cases stabilize with proper therapy, although exudation and macular scarring commonly compromise vision. A retrospective study showed that 16% of patients had a final visual acuity of 20/50 or better and 47% had hand motions to no light perception in the affected eye. Approximately 20% of eyes may require enucleation. [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	Coats disease	c0154832	27,286	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=190	2021-01-23T18:09:21	{"gard": ["6121"], "mesh": ["D058456"], "omim": ["300216"], "umls": ["C0154832"], "icd-10": ["H35.0"], "synonyms": ["Congenital retinal telangiectasia", "Leber miliary aneurysm"]}
In a brother and sister, Skre and Loken (1970) described a disorder with clinical features of Friedreich ataxia and, in the late stages, myoclonic epilepsy and progressive dementia. Neuropathologic studies showed spinocerebellar degeneration as in Friedreich ataxia, cerebral involvement as in subacute presenile dementia, and peripheral neuropathy as in Charcot-Marie-Tooth disease. Neuro \- Ataxia \- Myoclonus epilepsy \- Seizures \- Dementia \- Peripheral neuropathy 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	ATAXIA WITH MYOCLONIC EPILEPSY AND PRESENILE DEMENTIA	c1859646	27,287	omim	https://www.omim.org/entry/208700	2019-09-22T16:30:39	{"mesh": ["C565933"], "omim": ["208700"]}
A rare genetic disease characterized by early-onset severe obesity due to mutations in single genes acting on the development and function of the hypothalamus or the leptin-melanocortin pathway, leading to disruption of energy homeostasis and endocrine dysfunction. Patients present with a body mass index over three standard deviations above normal at less than five years of age, accompanied by a variety of signs and symptoms according to the mutated gene, including hyperphagia, insulin resistance, reduced basal metabolic rate, or hypogonadism, among others. [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	Genetic non-syndromic obesity	None	27,288	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98267	2021-01-23T18:45:33	{"synonyms": ["Monogenic obesity due to a leptin-melanocortin pathway anomaly"]}
This article needs attention from an expert in psychology. See the talk page for details. WikiProject Psychology may be able to help recruit an expert. (January 2015) Zou huo ru mo (Chinese: 走火入魔; pinyin: zǒuhuǒrùmó) or qigong deviation (Chinese: 氣功偏差; pinyin: qìgōngpiānchā; lit. 'qigong deviation/error' or Chinese: 气功出偏),[clarification needed] is a Chinese-culture concept traditionally used to indicate that something has gone wrong in spiritual or martial arts training. The qigong community uses this term to describe a physiological or psychological disorder believed to result during or after qigong practice, due to "improper practice" of qigong and other self-cultivation techniques. The concept was highlighted in the social and political context of mass popularization of qigong in China. ## Contents * 1 Background * 2 Symptoms * 3 Diagnosis * 3.1 Chinese psychiatry * 3.2 Western psychiatry * 4 Medical causes * 4.1 Latent psychosis * 5 Qigong community perspective * 5.1 Treatment * 6 Social and political context * 7 References ## Background[edit] The Chinese word zǒuhuǒrùmó (Chinese: 走火入魔 "①be obsessed with sth. ②possessed by the Devil") combines zǒuhuǒ(r) ("①〈elec.〉 ⓐspark ⓑhave a short circuit ②〈coll.〉 discharge (a firearm) accidentally ③overstate ④catch fire; be on fire") and rùmó ("①be spellbound ②be infatuated/obsessed").[1] In recent times this syndrome has been known as qìgōngpiānchā (Chinese: 氣功偏差 "qigong deviation/error").[clarification needed][citation needed] The term has traditionally been applied to indicate that something has gone wrong in one's martial arts training, interpreted as "imbalance of qi (life energy)". In more recent history, the term has been applied to refer to undesirable somatic or psychological effects experienced during or after the practice of the broad range of Chinese self-cultivation exercises known as qigong.[2][3] Most cases do not last for an extended period of time, and are never brought to medical attention.[4] While qigong could potentially act as a stressor in some vulnerable individuals, relations between qigong and disorders are manifold, and causal relationships have not been demonstrated.[5] Similar syndromes have been observed in other forms of self-cultivation practices such as yoga (Kundalini syndrome),[6] meditation,[7] and hypnosis.[8] ## Symptoms[edit] Symptoms are often identified as being in one of three categories: 1. panic, discomfort, and uncontrolled spontaneous movement; 2. sensory problems, such as visual or auditory hallucination; and 3. irrational beliefs.[2] Somatic symptoms can include sensations and pain in head, chest and back, abdomen, limbs, or whole body; whereas, mental and emotional symptoms can include neurasthenia, affective disorder, self-consciousness, hallucination, and paranoia.[9]:165–167 ## Diagnosis[edit] While the Chinese Society of Psychiatry prefers the term "qigong deviation", the American Psychiatric Association uses psychosis terminology.[10] Some physicians believe that this disease can be categorized as a culture-bound syndrome, but this point is debated.[3] ### Chinese psychiatry[edit] In the second edition of the Chinese Classification of Mental Disorders (CCMD-2) published by the Chinese Society of Psychiatry[11] the diagnosis of “Qigong Deviation Syndrome” is based upon the following criteria:[12] * The subject being demonstrably normal before doing qigong exercises * Psychological and physiological reactions appearing during or after qigong exercises (suggestion and autosuggestion may play an important role in these reactions) * Complaints of abnormal sensations during or after qigong exercises * Diagnostic criteria do not meet other mental disorders such as schizophrenia, affective disorder, and neurosis. ### Western psychiatry[edit] In the West, there was no equivalent experience until the adoption of qigong practices by the public became more common. When the Western medical community encountered abnormal conditions presenting in patients practicing qigong, they used the term "Qi-gong psychotic reaction" and classified the disorder as a culture-bound syndrome in the 4th edition of the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association. It is described as > [a] term describing an acute, time-limited episode characterized by disassociative, paranoid, or other psychotic or non-psychotic symptoms that may occur after participation in the Chinese folk health-enhancing practice of qigong. Especially vulnerable are individuals who become overly involved in the practice.[13][14][15][16] In order to diagnose this disease in the West, practitioners determine the cultural formation of the patient; this includes their cultural reference group and how that culture might explain their illness.[17] The DSM-IV classification has been criticized by other Western psychiatrists on the grounds that > [i]t is not clear how the architects of the DSM-IV can logically defend labeling a syndrome as aberrant in the context of a diagnostic system while simultaneously placing that syndrome outside of conventional Western nosologic categories that serve as basis for determining whether a syndrome is or is not aberrant and therefore a disorder.[18] ## Medical causes[edit] The appearance of symptoms during or after qigong practice has been explained in various ways by the psychiatric community, in severe cases as an indication of latent psychosis. The Chinese medical literature includes a wider variety of symptoms associated with qigong deviation; the non-psychotic symptoms correspond to conversion disorder and histrionic personality disorder in Western classifications.[19] ### Latent psychosis[edit] In cases of psychosis, a Western psychiatric belief is that qigong could be a precipitating stressor of a latent psychotic disorder to which the patient is predisposed, rather than erroneous qigong practice;[19] a type of reactive psychosis or the precipitation of an underlying mental illness, such as schizophrenia, bipolar disorder, or posttraumatic stress disorder.[20] ## Qigong community perspective[edit] Within the qigong community, Zou huo ru mo is believed to be caused by improper practice:[21] * Inexperienced or unqualified instructor * Incorrect instructions * Impatience * Becoming frightened, irritated, confused, or suspicious during the course of qigong practice * Inappropriate focus, interpreted as "inappropriate channeling of qi (life energy)." ### Treatment[edit] Within the qigong community, there are specific treatments believed to be effective for addressing different forms of Zou huo ru mo.[21] In particular, depending upon somatic versus psychological symptoms, and whether the condition is considered temporary or an intrinsic mental disorder, self-correction treatments can involve relaxation, walking, self-vibrating, self-patting, and self-massage. Clinical treatments can involve psychological counseling, expert guidance of practice, acupuncture, massage, "external qi" treatments, and symptomatic correction.[9]:164–173 ## Social and political context[edit] Qigong deviation became part of political controversy during the 1990s, when the Chinese government became concerned about loss of state control due to widespread popularity of qigong, mass practice, and rise to power of charismatic qigong "grandmasters".[2][22] ## References[edit] 1. ^ Translation equivalents from Wenlin, Version 4.2.2, 2015. 2. ^ a b c Chen, Nancy N. (2003). "Chapter 4. Qiqong Deviation or Psychosis". Breathing spaces: qigong, psychiatry, and healing in China. Columbia University Press. pp. 77–107. ISBN 978-0-231-12804-9. 3. ^ a b Shan, HH (2000). "Culture-bound psychiatric disorders associated with qigong practice in China" (PDF). Hong Kong J Psychiatry: 10–14. 4. ^ Lee, Sing (December 1996). "Cultures in psychiatric nosology: the CCMD-2-R and international classification of mental disorders". Culture, Medicine and Psychiatry. 20 (4): 421–472. doi:10.1007/bf00117087. PMID 8989986. S2CID 25418717. 5. ^ Ng BY. 1998. "Qigong-induced mental disorders: a review." Australian & New Zealand Journal of Psychiatry 33(2):197-206. 6. ^ Upadhyaya, Pt.Rajnikant (2006). Awake Kundalini. Lotus Press. p. 26. ISBN 978-81-8382-039-4. 7. ^ Nelson, James M. (2009). Psychology, Religion, and Spirituality. Springer. p. 470. ISBN 978-0-387-87572-9. 8. ^ Gibson, Hamilton Bertie (1991). Hypnosis in therapy. Psychology Press. ISBN 978-0-86377-155-2. 9. ^ a b Liu, Tian Jun; Qiang, Xiao Mei, eds. (2013). Chinese Medical Qigong, Third Edition. Singing Dragon. ISBN 978-1848190962. 10. ^ Liu, Lydia He (1999). Tokens of exchange: the problem of translation in global circulations. Durham, North Carolina: Duke University Press. p. 315. ISBN 978-0-8223-2424-9. 11. ^ The Chinese Society of Psychiatry (1989). "66. Qigong deviation syndrome". Chinese Classification and Diagnostic Criteria of Mental Disorders (CCMD-2). CCMD-2. 12. ^ Human Rights Watch (2002). Dangerous minds: political psychiatry in China today and its origins in the Mao era. New York, New York: Human Rights Watch. ISBN 978-1-56432-278-4. 13. ^ DSM-IV-TR, American Psychiatric Association, p. 902 14. ^ Schatzberg, Alan F.; Hales, Robert E. (2008). American Psychiatric Publishing Textbook of Psychiatry. American Psychiatric Publishing, Inc. p. 1551. ISBN 978-1-58562-257-3. 15. ^ Vuong, Ngan Kim (2006). "Cultural Bound Syndromes: Qigong Psychotic Reaction". In Jackson, Yo (ed.). Encyclopedia of Multicultural Psychology. Sage Publications. pp. 142–143. ISBN 978-1-4129-0948-8. 16. ^ Sandhu, Daya Singh (1999). Asian and Pacific Islander Americans : issues and concerns for counseling and psychotherapy. Commack, New York: Nova Science Publishers. p. 231. ISBN 978-1-56072-663-0. 17. ^ Hwang, Wei-Chin (1 December 2007). "Qi-gong Psychotic Reaction in a Chinese American Woman". Culture, Medicine and Psychiatry. 31 (4): 547–560. doi:10.1007/s11013-007-9065-z. PMID 17932733. S2CID 31958321. 18. ^ Robinson, Bruce H. (2007). Biomedicine: A Textbook for Practitioners of Acupuncture & Oriental Medicine. Blue Poppy Press. p. 434. ISBN 978-1-891845-38-3. 19. ^ a b Robinson, Bruce H. (2007). Biomedicine: A Textbook for Practitioners of Acupuncture & Oriental Medicine. Blue Poppy Press. p. 435. ISBN 978-1-891845-38-3. 20. ^ Sing, Lee, & Kleinman, Arthur (2002). "Psychiatry in its Political and Professional Contexts: A Response to Robin Munro" (PDF). J Am Acad Psychiatry Law. 30:120–5: 122.CS1 maint: multiple names: authors list (link) 21. ^ a b Xu, Xiangcai (2000). Qigong for Treating Common Ailments. YMAA Publication Center. ISBN 978-1-886969-70-4. 22. ^ Ownby, David (2008). Falun Gong and the future of China. Oxford, England, UK: Oxford University Press. pp. 181–186. ISBN 978-0-19-532905-6. [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	Zou huo ru mo	None	27,289	wikipedia	https://en.wikipedia.org/wiki/Zou_huo_ru_mo	2021-01-18T19:09:57	{"wikidata": ["Q8074613"]}
A rare, inherited disorder characterized by non-malignant lymphoproliferation, multilineage cytopenias, and a lifelong increased risk of Hodgkin's and non-Hodgkin's lymphoma. ## Epidemiology The prevalence of ALPS is unknown. It has been characterized in more than 500 patients to date and has been reported worldwide in various ethnic groups. ## Clinical description ALPS is clinically heterogeneous with the following primary clinical signs: lymphoproliferation, manifesting as lymphadenopathy and hepatosplenomegaly with or without hypersplenism, often improving with age, autoimmune disease, mostly involving blood cells, and an increased risk of lymphoma lifelong. Many patients develop non-malignant lymphoproliferation during the first years of life. Clinical manifestations of autoimmunity in the form of hemolytic anemia, thrombocytopenia, neutropenia, or autoimmune hepatitis are of variable severity but these signs are often absent at the time of diagnosis. Autoimmunity has been reported to potentially affect almost any organ, leading to uveitis, pulmonary fibrosis, gastritis, colitis, nephritis, urticaria, arthritis, or rarely autoimmune neurological complications. The disease course is also variable. Several genetic subtypes based on the causative genes and types of mutations have been proposed and result in often similar clinical presentations and outcomes. These include ALPS-FAS, ALPS-FASLG (FASgene), ALPS-CASP10 (CASP10), and ALPS-U (undetermined genetic defect). ## Etiology ALPS is caused by defective lymphocyte homeostasis. Germline mutations in the FAS (10q24.1), FASLG (1q23), or CASP10 (2q33-q34) genes are known to be associated with ALPS. 75% of cases are associated with heterozygous mutations in FAS. The second largest group (10%) has somatic mutations in FAS, while CASP10 (2-3%) and FASLG (<1%) mutations are extremely rarely reported. Some patients do not have mutations in any of these genes (ALPS-U). More recently one case of an ALPS-like disorder due to mutation in the PRKCD gene (3p21.31) was reported. This patient however did not have elevated DNT cells and hence does not fit the diagnostic criteria. ## Diagnostic methods Diagnosis is based on clinical, laboratory and genetic findings. A definitive diagnosis is established in the presence of both of the required diagnostic criteria, i.e. chronic non-malignant, non-infectious lymphadenopathy and/or splenomegalyand elevated TCR alpha/beta-double-negative T cells (DNTs) with normal or elevated lymphocyte counts, along with one primary accessory criterion, including defective lymphocyte apoptosis, and germline or somatic mutations in FAS, FASLG or CASP10. ## Genetic counseling Depending on the specific genetic mutation, inheritance may be autosomal dominant or autosomal recessive. ## Management and treatment Some patients may require chronic immunosuppressive therapies with sirolimus and mycophenolate mofetil. ## Prognosis The prognosis for ALPS patients remains guarded. ALPS-FAS patients have a significantly increased risk of non-Hodgkin's and Hodgkin's lymphoma which can occur at any age and responds to conventional chemotherapy. [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 lymphoproliferative syndrome	c1328840	27,290	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3261	2021-01-23T18:56:37	{"gard": ["8686"], "mesh": ["D056735"], "omim": ["601859", "603909", "615559", "618534"], "umls": ["C1328840"], "icd-10": ["D47.9"], "synonyms": ["ALPS", "Canale-Smith syndrome"]}
A number sign (#) is used with this entry because hypogonadotropic hypogonadism-19 with or without anosmia (HH19) can be caused by heterozygous mutation in the DUSP6 gene (602748) on chromosome 12q22, sometimes in association with mutations in other genes, e.g., FGFR1 (136350) and SPRY4 (607984). 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 as well as a discussion of oligogenicity of this disorder, see 147950. Molecular Genetics In a cohort of 386 unrelated individuals with congenital hypogonadotropic hypogonadism, 199 of whom were anosmic and 187 normosmic, many of whom were known to harbor mutations in previously identified HH-associated genes, Miraoui et al. (2013) analyzed 7 genes involved in the FGF8 (600483)-FGFR1 (136350) network and identified 5 HH probands with heterozygous missense mutations in the DUSP6 gene (602748.0001-602748.0004). In 3 of the patients, the DUSP6 mutation was accompanied by a heterozygous missense mutation in another HH-associated gene, including FGFR1 (136350.0028; see HH2, 147950) and SPRY4 (607984.0001 and 607984.0003; see HH17, 615266). Additional features present in the 5 probands with DUSP6 mutations included abnormal dentition in 2, low bone mass in 2, and hearing loss in 1. Miraoui et al. (2013) concluded that mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH. INHERITANCE \- Autosomal dominant (see MISCELLANEOUS below) HEAD & NECK Ears \- Hearing loss (in some patients) Nose \- Hyposmia/anosmia (in some patients) Teeth \- Abnormal dentition (in some patients) GENITOURINARY \- Delayed or absent puberty SKELETAL \- Osteopenia (in some patients) \- Osteoporosis (in some patients) \- Fractures (in some patients) NEUROLOGIC Central Nervous System \- Hyposmia/anosmia (in some patients) ENDOCRINE FEATURES \- Delayed or absent puberty MISCELLANEOUS \- Phenotypic variability within families and among patients carrying the same mutation appears to be due to the oligogenic nature of the disorder, with some patients having mutations in more than 1 neuroendocrine-related gene MOLECULAR BASIS \- Caused by mutation in the dual-specificity phosphatase-6 gene (DUSP6, 602748.0001}) ▲ 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 19 WITH OR WITHOUT ANOSMIA	c0162809	27,291	omim	https://www.omim.org/entry/615269	2019-09-22T15:52:43	{"doid": ["0090090"], "mesh": ["D017436"], "omim": ["615269"], "orphanet": ["432", "478"], "synonyms": ["Gonadotropic deficiency", "Isolated congenital gonadotropin deficiency", "Normosmic idiopathic hypogonadotropic hypogonadism", "nIHH"], "genereviews": ["NBK1334"]}
Aspiration pneumonia Microscopic image of aspiration pneumonia in an elderly person with a neurologic illness. Note foreign-body giant cell reaction. SpecialtyEmergency medicine, pulmonology SymptomsFever, cough[1] ComplicationsLung abscess[1] Usual onsetElderly[2] Risk factorsDecreased level of consciousness, problems with swallowing, alcoholism, tube feeding, poor oral health[1] Diagnostic methodBased on presenting history, symptoms, chest X-ray, sputum culture[2][1] Differential diagnosisChemical pneumonitis, tuberculosis[1][2] MedicationClindamycin, meropenem, ampicillin/sulbactam, moxifloxacin[1] Frequency~10% of pneumonia cases requiring hospitalization[1] Aspiration pneumonia is a type of lung infection that is due to a relatively large amount of material from the stomach or mouth entering the lungs.[1] Signs and symptoms often include fever and cough of relatively rapid onset.[1] Complications may include lung abscess.[1] Some include chemical induced inflammation of the lungs as a subtype, which occurs from acidic but non-infectious stomach contents entering the lungs.[1][2] Infection can be due to a variety of bacteria.[2] Risk factors include decreased level of consciousness, problems with swallowing, alcoholism, tube feeding, and poor oral health.[1] Diagnosis is typically based on the presenting history, symptoms, chest X-ray, and sputum culture.[1][2] Differentiating from other types of pneumonia may be difficult.[1] Treatment is typically with antibiotics such as clindamycin, meropenem, ampicillin/sulbactam, or moxifloxacin.[1] For those with only chemical pneumonitis, antibiotics are not typically required.[2] Among people hospitalized with pneumonia, about 10% are due to aspiration.[1] It occurs more often in older people, especially those in nursing homes.[2] Both sexes are equally affected.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Risk factors * 2.2 Bacteria * 3 Pathophysiology * 3.1 Location * 4 Diagnosis * 5 Prevention * 5.1 Oral hygiene * 5.2 Enhanced swallow * 5.3 After surgery * 6 Treatment * 7 Prognosis * 8 Elderly * 8.1 Microaspirations * 8.2 Choking * 8.3 Parkinson's disease * 8.4 Dementia * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] The person may have an insidious course with increased respiratory rate, foul-smelling sputum, hemoptysis, and fever. Complications may occur, such as exudative pleural effusion, empyema, and lung abscesses.[3] If left untreated, aspiration pneumonia can progress to form a lung abscess.[4] Another possible complication is an empyema, in which pus collects inside the lungs.[5] If continual aspiration occurs, the chronic inflammation can cause compensatory thickening of the insides of the lungs, resulting in bronchiectasis.[5] ## Causes[edit] Aspiration pneumonia is often caused by a defective swallowing mechanism, such as a neurological disease or as the result of an injury that directly impairs swallowing or interferes with consciousness. Impaired consciousness can be intentional, such as the use of general anesthesia for surgery. For many types of surgical operations, people preparing for surgery are therefore instructed to take nothing by mouth (nil per os, abbreviated as NPO) for at least four hours before surgery. These conditions enable the entry of bacteria into the lungs, thus allowing the development of an infection.[citation needed] ### Risk factors[edit] * Impaired swallowing: Conditions that cause dysphagia worsen the ability of people to swallow, causing an increased risk of entry of particles from the stomach or mouth into the airways. While swallowing dysfunction is associated with aspiration pneumonia, dysphagia may not be sufficient unless other risk factors are present.[3] Neurologic conditions that can directly impact the nerves involved in the swallow mechanism include stroke, Parkinson's disease, and multiple sclerosis.[1] Anatomical changes in the chest can also disrupt the swallow mechanism.[1] For example, patients with advanced COPD tend to develop enlarged lungs, resulting in compression of the esophagus and thus regurgitation.[1] * Altered mental status: Changes in levels of consciousness affect the swallow mechanism by both disabling the body's natural protective measures against aspiration as well as possibly causing nausea and vomiting.[1] Altered mental status can be caused by medical conditions such as seizures.[1] However, many other agents can be responsible as well, including general anesthesia and alcohol.[1] * Bacterial colonization: Poor oral hygiene can result in colonization of the mouth with excessive amounts of bacteria, which is linked to increased incidence of aspiration pneumonia.[1] * Ethnicity: Asians diagnosed with aspiration pneumonia have a lower risk of death compared to other ethnic groups while African Americans and whites share a relatively similar risk of death. Hispanics have a lower risk of death than non-Hispanics.[6] * Others: Age, male gender, diabetes mellitus, malnutrition, use of antipsychotic drugs, proton pump inhibitors, and angiotensin-converting enzyme inhibitors.[7] Residence in an institutional setting, prolonged hospitalization or surgical procedures, gastric tube feeding,[8] mechanical airway interventions, immunocompromised, history of smoking, antibiotic therapy, advanced age, reduced pulmonary clearance, diminished cough reflex, disrupted normal mucosal barrier, impaired mucociliary clearance, alter cellular and humoral immunity, obstruction of the airways, and damaged lung tissue.[9] ### Bacteria[edit] Bacteria involved in aspiration pneumonia may be either aerobic or anaerobic.[10] Common aerobic bacteria involved include: * Streptococcus pneumoniae[11] * Staphylococcus aureus[11] * Haemophilus influenzae[11] * Pseudomonas aeruginosa[11] * Klebsiella: often seen in aspiration lobar pneumonia in alcoholics Anaerobic bacteria also play a key role in the pathogenesis of aspiration pneumonia.[12] They make up the majority of normal oral flora and the presence of putrid fluid in the lungs is highly suggestive of aspiration pneumonia secondary to an anaerobic organism.[12] While it is difficult to confirm the presence of anaerobes through cultures, the treatment of aspiration pneumonia typically includes anaerobic coverage regardless.[12] Potential anaerobic bacteria are as follows: * Bacteroides[11] * Prevotella[11] * Fusobacterium[11] * Peptostreptococcus[11] ## Pathophysiology[edit] Aspiration is defined as inhalation of oropharyngeal or gastric contents into the pulmonary tree. Depending on the composition of the aspirate, three complications have been described:[3] * Chemical pneumonitis may develop whose severity depends on the pH value and quantity of aspirate. The two lung changes after acid aspiration are: a) direct toxic damage to the respiratory epithelium resulting in interstitial pulmonary edema and b) a few hours later, inflammatory response with production of cytokines, neutrophil infiltration, and macrophage activation. Oxygen-free radicals are generated which, in turn, lead to further lung damage. Patients may remain asymptomatic after acid aspiration. Others may develop dyspnea, pleuritic chest pain, cough, fever, bloody or frothy sputum, and respiratory failure. * Aspiration pneumonia may develop. * The third complication occurs after inhalation of particulate matter that obstructs airways. The patients will have sudden arterial hypoxemia with development of lung atelectasis. ### Location[edit] The location is often gravity dependent, and depends on the person's position. Generally, the right middle and lower lung lobes are the most common sites affected, due to the larger caliber and more vertical orientation of the right mainstem bronchus. People who aspirate while standing can have bilateral lower lung lobe infiltrates. The right upper lobe is a common area of consolidation, where liquids accumulate in a particular region of the lung, in alcoholics who aspirate in the supine position.[13] ## Diagnosis[edit] Aspiration pneumonia in a ventilated person with a central line and nasogastric tube Evaluation of aspiration is generally performed with a video fluoroscopic swallowing study involving radiologic evaluation of the swallowing mechanism via challenges with liquid and solid food consistencies. These studies allow for evaluation of penetration to the vocal folds and below but are not a sensitive and specific marker for aspiration.[14] Additionally, it is difficult to distinguish between aspiration pneumonia and aspiration pneumonitis.[15] Aspiration pneumonia is typically diagnosed by a combination of clinical circumstances (people with risk factors for aspiration) and radiologic findings (an infiltrate in the proper location).[1] A chest x-ray is typically performed in cases where any pneumonia is suspected, including aspiration pneumonia.[16] Findings on chest x-ray supportive of aspiration pneumonia include localized consolidation depending on the patient's position when the aspiration occurred.[17] For example, people that are supine when they aspirate often develop consolidation in the right lower lobe of the lung.[17] Sputum cultures are not used for diagnosing aspiration pneumonia because of the high risk of contamination.[18] Clinical symptoms may also increase suspicion of aspiration pneumonia, including new difficulty breathing and fever after an aspiration event.[5] Likewise, physical exam findings such as altered breath sounds heard in the affected lung fields may also be suggestive of aspiration pneumonia.[5] Some cases of aspiration pneumonia are caused by aspiration of food particles or other particulate substances like pill fragments; these can be diagnosed by pathologists on lung biopsy specimens.[19] While aspiration pneumonia and chemical pneumonitis may appear similar, it is important to differentiate between the two due to major differences in management of these conditions. Chemical pneumonitis is caused by damage to the inner layer of lung tissue, which triggers an influx of fluid.[18] The inflammation caused by this reaction can rapidly cause similar findings seen in aspiration pneumonia, such as an elevated WBC (white blood cell) count, radiologic findings, and fever.[18] However, it is important to note that the findings of chemical pneumonitis are triggered by inflammation not caused by infection, as seen in aspiration pneumonia. Inflammation is the body's immune response to any perceived threat to the body. Thus, treatment of chemical pneumonitis typically involves removal of the inflammatory fluid and supportive measures, notably excluding antibiotics.[20] The use of antimicrobials is reserved for chemical pneumonitis complicated by secondary bacterial infection.[18] ## Prevention[edit] There have been several practices associated with decreased incidence and decreased severity of aspiration pneumonia as detailed below. ### Oral hygiene[edit] Studies showed that the net reduction of oral bacteria was associated with a decrease in both incidence of aspiration pneumonia as well as mortality from aspiration pneumonia.[21] One broad method of decreasing the number of bacteria in the mouth involves the use of antimicrobials, ranging from topical antibiotics to intravenous antibiotic use.[21] Whereas the use of antibiotics focuses on destroying and hindering the growth of bacteria, mechanical removal of oral bacteria by a dental professional also plays a key role in reducing the bacterial burden.[21] By reducing the amount of bacteria in the mouth, the likelihood of infection when aspiration occurs is reduced as well.[21] For people who are critically ill that require a feeding tube, there is evidence suggesting that the risk of aspiration pneumonia may be reduced by inserting the feeding tube into the duodenum or the jejunum (post-pyloric feeding), when compared to inserting the feeding tube into the stomach (gastric feeding).[8] ### Enhanced swallow[edit] Many people at risk for aspiration pneumonia have an impaired swallowing mechanism, which may increase the chance of aspiration of food particles with meals.[21] There is some evidence to indicate that training of various parts of the body involved in the act of swallowing, including the tongue and lips, may reduce episodes of aspiration and aspiration pneumonia; however, further research is required to confirm this benefit.[21] Other simple actions during feeding can improve the swallowing capability of a person and thus reduce the risk of aspiration, including changes in position and feeding assistance.[22] ### After surgery[edit] Many instances of aspiration occur during surgical operations, especially during anesthesia induction.[23] The administration of anesthesia causes suppression of protective reflexes, most importantly the gag reflex. As a result, stomach particles can easily enter the lungs. Certain risk factors predispose individuals to aspiration, especially conditions causing dysfunction of the upper gastrointestinal system.[23] Identifying these conditions before the operation begins is essential for proper preparation during the procedure.[23] It is recommended that patients fast prior to procedures as well.[23] Other practices that may be beneficial but have not been well-studied include medication that reduce the acidity of gastric contents and rapid sequence induction.[23] On the other hand, regarding reducing acidity of the stomach, an acid environment is needed to kill the organisms that colonize the gastrointestinal tract; agents, such as proton pump inhibitors, that decrease the acidity of the stomach, may favor the growth of bacteria and increase the risk of pneumonia.[3] ## Treatment[edit] The main treatment of aspiration pneumonia revolves around the use of antibiotics to remove the bacteria causing the infection.[1] Broad antibiotic coverage is required to account for the diverse types of bacteria possibly causing the infection.[1] Currently recommended antibiotics include clindamycin, meropenem, ertapenem, ampicillin/sulbactam, and moxifloxacin.[1] Treatment with piperacillin/tazobactam, cefepime, levofloxacin, imipenem, or meropenem is recommended in cases of potential antibiotic resistance.[24] The typical duration of antibiotic therapy is about 5 to 7 days.[24] If there is a large accumulation of fluid within the lungs, drainage of the fluid may also aid in the healing process.[12] ## Prognosis[edit] Dysphagia clinicians often recommend alteration of dietary regimens, altered head positioning, or removal of all oral intake. While studies have suggested that thickening liquids can decrease aspiration through slowed pharyngeal transit time, they have also demonstrated increased pharyngeal residues with risk for delayed aspiration. The ability of clinical interventions to reduce pneumonia incidence is relatively unknown. Dietary modifications or nothing-by-mouth status also have no effect on a patient's ability to handle their own secretions. A patient's individual vigor may impact the development of pulmonary infections more than aspiration. Also increased pneumonia risk exists in patients with esophageal dysphagia when compared to stroke patients because patients with stroke will improve as they recover from their acute injury, whereas esophageal dysphagia is likely to worsen with time. In one cohort of aspiration pneumonia patients, overall three-year mortality was 40%.[14] Studies have shown that aspiration pneumonia has been associated with an overall increased in-hospital mortality as compared with other forms of pneumonia.[25] Further studies investigating differing time spans including 30-day mortality, 90-day mortality, and 1-year mortality.[25] Individuals diagnosed with aspiration pneumonia were also at increased risk of developing future episodes of pneumonia. In fact, these individuals were also found to be at higher risk for readmission after being discharged from the hospital.[25] Lastly, one study found that individuals diagnosed with aspiration pneumonia were more likely to fail treatment compared to other types of pneumonia.[25] ## Elderly[edit] Aging increases the risk of dysphagia. The prevalence of dysphagia in nursing homes is approximately 50%, and 30% of the elderly with dysphagia develop aspiration. For individuals older than 75, the risk of pneumonia due to dysphagia, is six times greater than those 65.[26] Owing to multiple factors, such as frailty, impaired efficacy of swallowing, decreased cough reflex and neurological complications, dysphagia can be considered as a geriatric syndrome.[27] Atypical presentation is common in the elderly. Older patients may have impaired T cell function and hence, they may be unable to mount a febrile response. The mucociliary clearance of older people is also impaired, resulting in diminished sputum production and cough. Therefore, they can present non-specifically with different geriatric syndromes.[3] ### Microaspirations[edit] In the elderly, dysphagia is a significant risk factor for the development of aspiration pneumonia. Aspiration pneumonia most often develops due to micro-aspiration of saliva, or bacteria carried on food and liquids, in combination with impaired host immune function.[28] Chronic inflammation of the lungs is a key feature in aspiration pneumonia in elderly nursing home residents and presents as a sporadic fever (one day per week for several months). Radiological review shows chronic inflammation in the consolidated lung tissue, linking chronic micro-aspiration and chronic lung inflammation. ### Choking[edit] After falls, choking on food presents as the second highest cause of preventable death in aged care.[28] Although food choking risk is commonly associated with young children, data shows that individuals over 65 years of age have a choking incidence that is seven times higher than children aged 1–4 years. ### Parkinson's disease[edit] The reported prevalence of dysphagia in patients with Parkinson's disease ranges from 20% to 100% due to variations in the methods of assessing the swallowing function.[29] Unlike some medical problems, such as stroke, dysphagia in Parkinson's Disease degenerates with disease progression. Aspiration pneumonia was the most common reason for the emergency admission of patients with Parkinson's Disease whose disease duration was >5 years and pneumonia was one of the main causes of death. ### Dementia[edit] The familiar model of care for people with advanced dementia and dysphagia is the revolving door of recurrent chest infections, frequently associated with aspiration and related readmissions. Many individuals with dementia resist or are indifferent to food and fail to manage the food bolus. There are also many contributory factors such as poor oral hygiene, high dependency levels for being positioned and fed, as well as the need for oral suctioning. While tube feeding might therefore be considered a safer option, tube feeding has not been shown to be beneficial in people with advanced dementia. The preferred option therefore is to continue eating and drinking orally despite the risk of developing chest infections.[26] ## See also[edit] * Dysphagia * Meconium aspiration syndrome * Nosocomial pneumonia * Chemical pneumonitis ## 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 DiBardino DM, Wunderink RG (February 2015). "Aspiration pneumonia: a review of modern trends". Journal of Critical Care. 30 (1): 40–8. doi:10.1016/j.jcrc.2014.07.011. PMID 25129577. 2. ^ a b c d e f g h i Ferri, Fred F. (2017). Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 1006. ISBN 9780323529570. Archived from the original on 2017-07-31. 3. ^ a b c d e Luk JK, Chan DK (Jul 2014). "Preventing aspiration pneumonia in older people: do we have the 'know-how'?". Hong Kong Med J. 20 (5): 421–7. doi:10.12809/hkmj144251. PMID 24993858. 4. ^ Brown TG, Kemp WL, Burns DK (2008). Pathology: The Big Picture. New York: McGraw-Hill Medical. ISBN 978-0-07-147748-2. 5. ^ a b c d Hay WW, Levin MJ, Deterding RR, Abzug MJ (2016-05-02). Current diagnosis & treatment : pediatrics (Twenty-third ed.). New York, NY. ISBN 978-0-07-184854-1. OCLC 951067614. 6. ^ Oliver MN, Stukenborg GJ, Wagner DP, Harrell FE, Kilbridge KL, Lyman JA, Einbinder J, Connors AF (November 2004). "Comorbid disease and the effect of race and ethnicity on in-hospital mortality from aspiration pneumonia". Journal of the National Medical Association. 96 (11): 1462–9. PMC 2568617. PMID 15586650. 7. ^ van der Maarel-Wierink CD, Vanobbergen JN, Bronkhorst EM, Schols JM, de Baat C (June 2011). "Risk factors for aspiration pneumonia in frail older people: a systematic literature review". Journal of the American Medical Directors Association. 12 (5): 344–54. doi:10.1016/j.jamda.2010.12.099. PMID 21450240. 8. ^ a b Alkhawaja S, Martin C, Butler RJ, Gwadry-Sridhar F (August 2015). "Post-pyloric versus gastric tube feeding for preventing pneumonia and improving nutritional outcomes in critically ill adults". The Cochrane Database of Systematic Reviews (8): CD008875. doi:10.1002/14651858.CD008875.pub2. PMC 6516803. PMID 26241698. 9. ^ Taylor GW, Loesche WJ, Terpenning MS (2000). "Impact of oral diseases on systemic health in the elderly: diabetes mellitus and aspiration pneumonia". Journal of Public Health Dentistry. 60 (4): 313–20. doi:10.1111/j.1752-7325.2000.tb03341.x. PMID 11243053. 10. ^ Son YG, Shin J, Ryu HG (March 2017). "Pneumonitis and pneumonia after aspiration". Journal of Dental Anesthesia and Pain Medicine. 17 (1): 1–12. doi:10.17245/jdapm.2017.17.1.1. PMC 5564131. PMID 28879323. 11. ^ a b c d e f g h Table 13-7 in: Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). Robbins Basic Pathology: With Student Consult Online Access (8th ed.). Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 12. ^ a b c d Bartlett JG (March 2013). "How important are anaerobic bacteria in aspiration pneumonia: when should they be treated and what is optimal therapy". Infectious Disease Clinics of North America. 27 (1): 149–55. doi:10.1016/j.idc.2012.11.016. PMID 23398871. 13. ^ "Aspiration Pneumonitis and Pneumonia: Overview of Aspiration Pneumonia, Predisposing Conditions for Aspiration Pneumonia, Pathophysiology of Aspiration Pneumonia". 3 February 2019. Retrieved 26 June 2019. 14. ^ a b Bock M, Varadarajan V, Brawley M, Blumin J (2017). "Evaluation of the Natural History of Patients Who Aspirate". Laryngoscope. 127 (8): S1–S10. doi:10.1002/lary.26854. PMC 5788193. PMID 28884823. 15. ^ Lanspa M, Peyrani P, Wiemkwn T, Wilson E, Ramirez J, Dean N (2015). "Characteristics associated with clinician diagnosis of aspiration pneumonia; a descriptive study of afflicted patients and their outcomes". J Hosp Med. 10 (2): 90–6. doi:10.1002/jhm.2280. PMC 4310822. PMID 25363892. 16. ^ Principles and practice of hospital medicine. McKean, Sylvia C.,, Ross, John J. (John James), 1966-, Dressler, Daniel D.,, Scheurer, Danielle (Second ed.). New York. 2016-12-05. ISBN 9780071843133. OCLC 950203123.CS1 maint: others (link) 17. ^ a b McKean SC, Ross JJ, Dressler DD, Scheurer D (2016-12-05). Principles and practice of hospital medicine (Second ed.). New York. ISBN 978-0-07-184313-3. OCLC 950203123. 18. ^ a b c d Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J (2015-04-08). Harrison's principles of internal medicine (19th ed.). New York. ISBN 978-0-07-180215-4. OCLC 893557976. 19. ^ Mukhopadhyay S, Katzenstein AL (May 2007). "Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens". The American Journal of Surgical Pathology. 31 (5): 752–9. doi:10.1097/01.pas.0000213418.08009.f9. PMID 17460460. S2CID 45207101. 20. ^ Grippi MA, Elias JA, Fishman JA, Pack AI (2015-04-14). Fishman's pulmonary diseases and disorders (Fifth ed.). New York. ISBN 978-0-07-180728-9. OCLC 904408460. 21. ^ a b c d e f Tada A, Miura H (July 2012). "Prevention of aspiration pneumonia (AP) with oral care". Archives of Gerontology and Geriatrics. 55 (1): 16–21. doi:10.1016/j.archger.2011.06.029. PMID 21764148. 22. ^ Williams BA, Chang A, Ahalt C, Conant R, Ritchie CS (2014-04-15). Current diagnosis and treatment. Geriatrics (Second ed.). New York. ISBN 978-0-07-179208-0. OCLC 885407197. 23. ^ a b c d e Nason KS (August 2015). "Acute Intraoperative Pulmonary Aspiration". Thoracic Surgery Clinics. 25 (3): 301–7. doi:10.1016/j.thorsurg.2015.04.011. PMC 4517287. PMID 26210926. 24. ^ a b Mandell, Lionel A.; Niederman, Michael S. (2019-02-14). Longo, Dan L. (ed.). "Aspiration Pneumonia". New England Journal of Medicine. 380 (7): 651–663. doi:10.1056/NEJMra1714562. ISSN 0028-4793. PMID 30763196. S2CID 73428526. 25. ^ a b c d Komiya K, Rubin BK, Kadota JI, Mukae H, Akaba T, Moro H, Aoki N, Tsukada H, Noguchi S, Shime N, Takahashi O, Kohno S (December 2016). "Prognostic implications of aspiration pneumonia in patients with community acquired pneumonia: A systematic review with meta-analysis". Scientific Reports. 6: 38097. Bibcode:2016NatSR...638097K. doi:10.1038/srep38097. PMC 5141412. PMID 27924871. 26. ^ a b Hansjee, Djaromee (2018). "An Acute Model of Care to Guide Eating & Drinking Decisions in the Frail Elderly with Dementia and Dysphagia". Geriatrics. 3 (4): 65. doi:10.3390/geriatrics3040065. PMC 6371181. PMID 31011100. 27. ^ Hollaar V, Putten G, Maarel-Wierink C, Bronkhorst E, Swart B, Creugers N (2017). "The effect of a daily application of a 0.05% chlorhexidine oral rinse solution on the incidence of aspiration pneumonia in nursing home residents: a multicenter study". Geriatrics. 17 (128): 128. doi:10.1186/s12877-017-0519-z. PMC 5477106. PMID 28629318. 28. ^ a b Cichero, Julie (2018). "Age-Related Changes to Eating and Swallowing Impact Frailty: Aspiration, Choking Risk, Modified Food Texture and Autonomy of Choice". Geriatrics. 3 (4): 69–79. doi:10.3390/geriatrics3040069. PMC 6371116. PMID 31011104. 29. ^ Umemoto G, Furuya H (2019). "Management of Dysphagia in Patients with Parkinson's Disease and Related Disorders". Intern Med. 59 (1): 7–14. doi:10.2169/internalmedicine.2373-18. PMC 6995701. PMID 30996170. ## External links[edit] Classification D * ICD-10: J69.0, P24.9 * ICD-9-CM: 507,770.18 997.32 * MeSH: D011015 External resources * MedlinePlus: 000121 * eMedicine: emerg/464 * 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 Pneumonia Infectious pneumonias * Bacterial pneumonia * Viral pneumonia * Fungal pneumonia * Parasitic pneumonia * Atypical pneumonia * Community-acquired pneumonia * Healthcare-associated pneumonia * Hospital-acquired pneumonia * Ventilator-associated pneumonia * Severe acute respiratory syndrome Pneumonias caused by infectious or noninfectious agents * Aspiration pneumonia * Lipid pneumonia * Eosinophilic pneumonia * Bronchiolitis obliterans organizing pneumonia Noninfectious pneumonia * Chemical pneumonitis * Idiopathic pneumonia syndrome * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal [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	Aspiration pneumonia	c0032290	27,292	wikipedia	https://en.wikipedia.org/wiki/Aspiration_pneumonia	2021-01-18T18:57:17	{"mesh": ["D011015"], "umls": ["C0032290"], "icd-9": ["506.0", "507", "770.18"], "wikidata": ["Q677449"]}
A medical emergency that afflicts the penis Penile injury frameless\|upright=1.36 A fractured penis with extensive bruising. A penile injury is a medical emergency that afflicts the penis. Common injuries include fracture, avulsion, strangulation, entrapment, and amputation.[1] ## Contents * 1 Epidemiology * 2 Types * 2.1 Fracture * 2.2 Degloving and avulsion * 2.3 Soft-tissue injuries * 2.3.1 Strangulation * 2.3.2 Entrapment * 2.3.3 Other * 2.4 Amputation * 2.5 Penetration * 3 Classification * 4 Causes * 5 Diagnosis * 6 Treatment * 7 Complications * 8 References ## Epidemiology[edit] Penetrating and blunt traumas combined make up approximately 90% of all civilian penile injuries (45% each), with burns and other accidents making up the remaining 10%.[1] ## Types[edit] ### Fracture[edit] Main article: Penile fracture A still from a 3D medical animation showing tunica albuginea. Penile fractures are the result of rupture of the tunica albuginea. They are fairly rare and can co-occur with partial or complete urethral rupture, though this is rare.[2][3][4] Urethral damage occurs in 10–38% of cases.[1] Fractures are treated with emergency surgery, and can be diagnosed with ultrasound, especially in pediatric cases.[2][3][4] Penile fractures are caused by trauma to the erect penis, typically by suddenly bending it laterally during penetrative intercourse with the receptive partner on top of the penetrating partner, or during masturbation. Characterized by a loud popping sound at the time of the injury, the result of the tunica albuginea rupturing. Other symptoms include severe pain, loss of erection, and swelling.[5] Symptoms of urethral injury include hematuria, blood at the meatus, and dysuria.[1] If left untreated, complications result in 28–53% of cases; these include permanent curvature of the penis, fistula, urethral diverticulum, priapism, and erectile dysfunction.[5] ### Degloving and avulsion[edit] 3D medical animation still showing skin grafting in case of Penile injury. Degloving and avulsion injuries involve the removal of the penis skin, which is a serious medical emergency. Treatment of these injuries involves either closure of the torn skin, or a skin graft to replace the skin lost in the injury. Skin grafts are constructed to attempt to preserve erectile function and sensation.[1] ### Soft-tissue injuries[edit] #### Strangulation[edit] Strangulation injuries to the penis, also called incarceration injuries, caused by hair, rubber bands, or other objects are the second most common soft tissue injury in children.[6][7] Hair strangulation may be hard to diagnose due to the anatomy of the penis; the hair causing the strangulation may be hidden under the coronal sulcus if it is swollen.[8] In adults, strangulation injuries that require medical treatment can be caused by a variety of objects typically used for the purpose of sexual gratification, extending the time of an erection, or enuresis, including metal rings, which must be removed by specialized cutting instruments. The object can also be removed by decompressing the penis.[6][7] Because the vasculature of the penis is compressed, a variety of complications can result from strangulation injuries, depending on whether the veins, arteries, or both are compressed, including mild, reversible vascular obstruction; ischemic necrosis; gangrene and kidney damage; lymphedema; ulceration; urethrocutaneous fistula, loss of sensation; urethral injury; sepsis; and autoamputation.[7] Penile strangulation injuries that require medical attention are rare: since their first description in 1755, there have been approximately 60–120 reported cases. Though usually acute, cases of chronic strangulation and acute cases lasting up to one month have been reported.[7][9] Various objects have been involved in cases of strangulation: * Wedding ring [10][11] * Steel ring [12][13][14] * Bottle [15] * Chastity belt #### Entrapment[edit] The most common soft-tissue injury is an entrapment injury involving the penis caught in a zipper; these injuries are particularly common in young children who are uncircumcised and are always superficial. They are treated by removing the zipper with local anesthesia using a bone cutter, lubrication, or hacksaw, dismantling the zipper, or removing the affected tissue, and can be prevented in most situations by circumcision.[5][6] If not treated promptly, the affected tissue can swell and become infected.[6] In some cases, emergency circumcision is necessary.[8] #### Other[edit] Other soft-tissue injuries to the penis can be caused by burns, animal bites, and human bites.[5] Animal bites are common in children, and dogs are the most common animals involved. Though typically not severe, animal bites can cause amputation or infection.[1][6] Treatment for animal bites and human bites involves antibiotic treatment and closure of the wounds by secondary intention because they are contaminated.[1] Penis burns can be very severe and often require specialized care in a burn unit to prevent contractures, severe scarring, or other complications including lymphedema, hypospadias, or necrosis.[8] This treatment can involve debridement, skin grafts, antibiotics, and the use of a suprapubic catheter. Because of its thin skin, the penis is susceptible to full-thickness, third-degree burns. Burns to the penis typically co-occur with other severe burns. Most thermal penis burns are first or second degree burns caused by flame; some are caused by grease or boiling water. Electrical burns are typically deeper than thermal burns and require more extensive tissue removal.[1] ### Amputation[edit] Amputation of the penis can be either partial or complete. Often self-inflicted by people with psychiatric disorders, it may be occur with other trauma, such as in an assault or a mechanical accident. These injuries are treated by re-implantation if possible, with or without anastomosis of the vasculature to restore erectile function; skin necrosis and loss of sensation are common complications after treatment. Microsurgery on the vasculature decreases the risk of necrosis significantly.[5] Klingsor syndrome is a psychiatric disorder that causes self-harm, which can involve the penis. Paranoid schizophrenia, eating disorders, and psychotic breaks can also be associated with penile injury.[6] In some cases, transgender people who are not able to access genital surgery may self-amputate their penis.[1] Favorable prognostic factors for replantation of amputated penises include short ischemic time and a clean incision (as opposed to a crush injury or ragged incision).[16] Replantation of an amputated penis can be done up to 24 hours after the injury, though fewer than 16 hours of cold ischemia or 6 hours of warm ischemia leads to the best outcomes. If replantation is not possible or desired, a penile stump can be closed and phalloplasty could be performed later.[1] ### Penetration[edit] Penetrating injuries can be caused by accidents during sexual activities (typically, by foreign objects inserted into the urethra), by weapons (i.e. bullets) during wartime, or by stabbing. These injuries can have varying severity and be superficial, affect the corpora cavernosa, other soft tissue, and/or urethra.[4][5][6] In 50% of cases, the urethra is injured.[1] Some foreign objects may be removed like any other penetrating object in soft tissue; using forceps and gentle traction. However, if the foreign object was inserted into the urethra or has damaged the urethra transversely, urethography is used to avoid further injury to the urinary tract while removing the object.[8] Penetrating injuries make up approximately 45% of civilian penile injuries.[1] ## Classification[edit] Organ Injury Scale[5] Grade Description of injury I Superficial injury to the skin (laceration or contusion) II Injury to the cavernosa/Buck's fascia, no tissue loss III Avulsion or laceration through the urethral meatus, glans, or cavernosa, or urethral damage less than 2 cm in size IV Partial penectomy (amputation) or a cavernosal/urethral injury more than 2 cm in size V Complete penectomy (amputation or replacement) ## Causes[edit] The causes of penile injury are mostly the same as other causes of trauma; however, penile injury is more likely to occur during sexual intercourse and masturbation than other traumas. Nocturnal erections and sleeping positions can be another cause of penile injury. Industrial and automobile accidents can also cause penile injury. Self-injury may also affect the penis.[5][6] abnormally curved shape, buised, penis. Eggplant sign ## Diagnosis[edit] Most penile trauma can be diagnosed by history and physical examination, hearing 'snapping' or 'popping' sound, immediate penile pain, swollen, bruised (often known as eggplant deformity), some may notice blood over the urethral meatus.[17] But in some cases, ultrasonography can indicate the extent of the injury and help a clinician decide if the injured person needs surgical treatment.[18] It is important to rule out urethral injury in those with penile injury, as it is a urological emergency that may result in significant morbidity if left untreated. [19] ## Treatment[edit] The type of injury dictates the treatment; however, surgery is a common treatment. Most traumatic penile injury warrant an emergency repairing surgery to prevent complications and maintain functionality of the penis sexually and urologically. Catheterization is usually a part of treatment for penis injuries; when the urethra is intact, urethral catheterization may be used, but if it has been injured, suprapubic catheterization is used. Some injuries, including animal bites, are also treated with antibiotics, irrigation, and rabies prophylaxis.[6] ## Complications[edit] Common complications from penile injury are erectile dysfunction, abnormal penile curvature, penile abscess, formation of fibrotic plaques, painful erection, urethral stricture, uretherocutaneous or corporourethral fistula.[20] ## References[edit] 1. ^ a b c d e f g h i j k l Chang, Andrew J.; Brandes, Steven B. (2013-08-01). "Advances in diagnosis and management of genital injuries". The Urologic Clinics of North America. 40 (3): 427–438. doi:10.1016/j.ucl.2013.04.013. ISSN 1558-318X. PMID 23905941. 2. ^ a b Garofalo, Marco; Bianchi, Lorenzo; Gentile, Giorgio; Borghesi, Marco; Vagnoni, Valerio; Dababneh, Hussam; Schiavina, Riccardo; Franceschelli, Alessandro; Romagnoli, Daniele (2015-09-01). "Sex-related penile fracture with complete urethral rupture: A case report and review of the literature". Archivio Italiano di Urologia e Andrologia. 87 (3): 260–261. doi:10.4081/aiua.2015.3.260. ISSN 1124-3562. PMID 26428656. 3. ^ a b Lam, Samuel H. F. (2015-02-01). "Use of point-of-care ultrasound to evaluate for penile fracture in a child". Pediatric Emergency Care. 31 (2): 157–158. doi:10.1097/PEC.0000000000000358. ISSN 1535-1815. PMID 25651388. 4. ^ a b c Lehnert, Bruce E.; Sadro, Claudia; Monroe, Eric; Moshiri, Mariam (2014-02-01). "Lower male genitourinary trauma: a pictorial review". Emergency Radiology. 21 (1): 67–74. doi:10.1007/s10140-013-1159-z. ISSN 1438-1435. PMID 24052083. 5. ^ a b c d e f g h Krishna Reddy, S. V.; Shaik, Ahammad Basha; Sreenivas, K. (2014-09-01). "Penile injuries: A 10-year experience". Canadian Urological Association Journal. 8 (9–10): E626–631. doi:10.5489/cuaj.1821. ISSN 1911-6470. PMC 4164551. PMID 25295134. 6. ^ a b c d e f g h i Kim, Jae Heon; Park, Jae Young; Song, Yun Seob (2014-01-01). "Traumatic penile injury: from circumcision injury to penile amputation". BioMed Research International. 2014: 375285. doi:10.1155/2014/375285. ISSN 2314-6141. PMC 4164514. PMID 25250318. 7. ^ a b c d Ivanovski, Ognen; Stankov, Oliver; Kuzmanoski, Marjan; Saidi, Skender; Banev, Saso; Filipovski, Vanja; Lekovski, Ljupco; Popov, Zivko (2007-11-01). "Penile strangulation: two case reports and review of the literature". The Journal of Sexual Medicine. 4 (6): 1775–1780. doi:10.1111/j.1743-6109.2007.00601.x. ISSN 1743-6095. PMID 17888068. 8. ^ a b c d Dubin, Jeffrey; Davis, Jonathan E. (2011). "Penile Emergencies". Emergency Medicine Clinics of North America. 29 (3): 485–499. doi:10.1016/j.emc.2011.04.006. PMID 21782070. 9. ^ Li, Chao; Xu, Yue-Min; Chen, Rong; Deng, Chen-Liang (2013-07-01). "An effective treatment for penile strangulation". Molecular Medicine Reports. 8 (1): 201–204. doi:10.3892/mmr.2013.1456. ISSN 1791-3004. PMID 23652299. 10. ^ Osborne, Hannah (2016-11-16). "Doctors report rare case of penile strangulation after man puts wedding ring on penis". International Business Times UK. Retrieved 2017-01-28. 11. ^ "Man with penis stuck in ring suffered three days of pain - Nation \| The Star Online". www.thestar.com.my. Retrieved 2017-01-28. 12. ^ 11:24, 10 Feb 2016 at; tweet_btn(), Lester Haines. "Firemen free chap's todger from four-ring chokehold". Retrieved 2017-01-28.CS1 maint: numeric names: authors list (link) 13. ^ "Inhaled Condoms And Vacuum Cleaner Hose Mishaps: The Wackiest Sex Injuries In Medical Literature". Retrieved 2017-01-28. 14. ^ Nuzzo, Regina. "Good Vibrations: U.S. Consumer Web Site Aims to Enhance Sex Toy Safety". Scientific American. Retrieved 2017-01-28. 15. ^ Mirror.co.uk (2016-10-16). "Man tries pleasuring himself with a bottle - things go horrifically wrong". mirror. Retrieved 2017-01-28. 16. ^ Riyach, Omar; El Majdoub, Aziz; Tazi, Mohammed Fadl; El Ammari, Jalal Eddine; El Fassi, Mohammed Jamal; Khallouk, Abdelhak; Farih, Moulay Hassan (2014-01-01). "Successful replantation of an amputated penis: a case report and review of the literature". Journal of Medical Case Reports. 8: 125. doi:10.1186/1752-1947-8-125. ISSN 1752-1947. PMC 4000145. PMID 24716477. 17. ^ Metzler, Ian S.; Reed-Maldonado, Amanda B.; Lue, Tom F. (2017-09-16). "Suspected penile fracture: to operate or not to operate?". Translational Andrology and Urology. 6 (5): 981–986. ISSN 2223-4691. 18. ^ Nicola, Refky; Carson, Nancy; Dogra, Vikram S. (2014-06-01). "Imaging of traumatic injuries to the scrotum and penis". AJR. American Journal of Roentgenology. 202 (6): W512–520. doi:10.2214/AJR.13.11676. ISSN 1546-3141. PMID 24848844. 19. ^ Nelson, Quentin; Leslie, Stephen W.; Baker, Jeff (2020), "Urethral Injury", StatPearls, StatPearls Publishing, PMID 32119462, retrieved 2020-05-05 20. ^ "Penile Fracture and Trauma: Practice Essentials, Background, Relevant Anatomy". 2019-11-09. Cite journal requires `\|journal=` (help) [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	Penile injury	c0149751	27,293	wikipedia	https://en.wikipedia.org/wiki/Penile_injury	2021-01-18T19:06:27	{"umls": ["C0149751"], "wikidata": ["Q23749262"]}
A number sign (#) is used with this entry because of evidence that spondyloepimetaphyseal dysplasia with joint laxity type 2 (SEMDJL2) is caused by heterozygous mutation in the KIF22 gene (603213) on chromosome 16p11. Description Spondyloepimetaphyseal dysplasia with joint laxity type 2 (SEMDJL2) is characterized by short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalized ligamentous laxity, and mild spinal deformity. Intellectual development is not impaired. Radiographic characteristics include significantly retarded epiphyseal ossification that evolves into epiphyseal dysplasia and precocious osteoarthritis, metaphyseal irregularities and vertical striations, constricted femoral neck, slender metacarpals and metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or mild platyspondyly (summary by Min et al., 2011). For a discussion of genetic heterogeneity of SEMD with joint laxity, see SEMDJL1 (271640). Nomenclature The International Nosology and Classification of Constitutional Disorder of Bone initially described two disorders of SEMD with dislocation and joint laxity: SEMDJL (Beighton type) and SEMD with multiple dislocations, the Hall or leptodactylic type (Hall et al., 1998). However, in the 2006 revision of Nosology and Classification of Genetic Skeletal Disorders, the Nosology Group of the International Skeletal Dysplasia Society proposed the use of the united term 'joint laxity' instead of the term 'multiple dislocations' (Superti-Furga et al., 2007). These included 2 conditions: SEMDJL-Beighton type (designated SEMDJL1 (271640) in OMIM) and SEMDJL-leptodactylic or Hall type (designated SEMDJL2 in OMIM). Clinical Features Hall et al. (1998) described 3 children from unrelated families who presented in infancy with hip dislocation and joint laxity and developed progressive deformity, particularly involving the knees, spine, and hips. Clinically, the facial appearance was normal in 2 of the 3 cases; in the third case, there was mild midface hypoplasia. Cleft palate and ocular or auditory abnormalities were not present. Cognitive development was normal. Height measurements were available for only 1 individual, who was below the 3rd centile at age 5.5 years. Radiographically, the epiphyses were small, flattened, irregular, and fragmented. The metaphyses showed widening, irregularity, and streaky sclerosis. The dorsal vertebral bodies showed posterior decrease in height with scalloping of the posterior aspects of the lumbar vertebral bodies, vertebral endplate irregularity, and progressive chordal narrowing of the interpedicular distances. Scoliosis was not present at birth, but developed in the first years of life. Hall et al. (1998) regarded the hand changes as being particularly characteristic. The metacarpals were gracile, the phalanges were long and slender with squared ends, and the distal phalangeal tufts were prominent. Carpal bones were individually small, irregular, and flattened, and the overall size of the carpals was reduced. There was gross delay in the appearance of the phalangeal epiphyses. All 3 cases showed absent or severely delayed ossification of the patellae. Hall et al. (1998) noted that 2 cases with virtually identical findings, one reported by Camera et al. (1994) and one (case 5) by Langer et al. (1997), had been considered examples of sponastrime dysplasia (271510). Hall et al. (1998) argued, however, that the striking epiphyseal changes, specific hand findings, and joint laxity with dislocations, in addition to narrow interpedicular distances and posterior scalloping of the vertebrae, allowed differentiation of this condition from sponastrime dysplasia. Hall et al. (1998) also differentiated this condition from the form of spondyloepimetaphyseal dysplasia with joint laxity described by Beighton and Kozlowski (1980) (SEMDJL1; 271640), since SEMDJL1 is associated with kyphoscoliosis at birth, progressing to severe deformity and talipes equinovarus, cleft palate, congenital heart disease, and a specific facial dysmorphism. In addition, the particular radiographic findings in the spine and hands described by Hall et al. (1998) are absent in SEMDJL1. Hall et al. (2002) reported 3 additional patients with spondyloepimetaphyseal dysplasia with multiple dislocations, including a father with mild manifestations and his daughter who was severely affected. All of the patients showed facial dysmorphism with a short, broad, upturned nose. There were striking epiphyseal and metaphyseal changes of the long bones and joint laxity with multiple dislocations of the large joints, which were particularly incapacitating at the knees. Megarbane et al. (2003) reported a 6-year-old male with congenital hip dislocation, short stature, macrocephaly, low-set ears, short neck, and hyperlaxity of the wrists and fingers. A broad thorax and limitation of extension of the elbow were seen. X-rays showed severe delay of ossification of the epiphyses and carpal bones and a generalized osteoporosis. There was thoracic scoliosis, mild changes of vertebral endplates, right hip dislocation, and subluxation of the elbows. The epiphyses were small, flattened, and irregular. The femoral neck was slender with flattened femoral epiphyses. Metaphyses of the knees were irregular, squared with vertical striations. Tarsal bones were normally ossified. Delay in early development was noted in this case, as in those reported by Camera et al. (1994) and Hall et al. (2002). Macrocephaly, frontal bossing, midface hypoplasia with saddle-nose, low-set ears, and short neck were thought to be common findings. Holder-Espinasse et al. (2004) reported a patient with a mild form of spondyloepimetaphyseal dysplasia with persistent inspiratory stridor secondary to laryngeal stenosis. Nishimura et al. (2003) described 4 patients with spondyloepimetaphyseal dysplasia with multiple dislocations, 2 of whom had previously been diagnosed with sponastrime dysplasia by Masuno et al. (1996) and Nishimura et al. (1998). Clinical findings included midface hypoplasia, micromelic short stature, and generalized joint laxity leading to thoracolumbar scoliosis and multiple joint subluxations. Laryngotracheomalacia was present in 2 patients, an increased serum creatine kinase with transient, mild muscle weakness was noted in another, and pronounced developmental delay was present in 1 patient. Radiologic findings included mild platyspondyly and stellar ossification of the calcaneus (both notable in infancy), narrow interpediculate distances and posterior scalloping of the lumbar spine, constriction of the femoral neck, delayed epiphyseal ossification that evolved to epiphyseal dysplasia and degenerative joint disease, metaphyseal irregularities and striations, and slender, short tubular bones of the hands. Rossi et al. (2005) reported a father and son with the Hall type of spondyloepimetaphyseal dysplasia with multiple dislocations. The father had short stature and marked joint laxity, including multiple severe joint dislocations. The son had a milder phenotype. Park et al. (2007) reported a mother and son with the Hall type of SEMD. The son had persistent inspiratory stridor beginning at 4 months of age. Microlaryngoscopy at 22 months revealed laryngeal stenosis secondary to failure of abduction of the vocal cords. A tracheostomy was performed to provide an adequate airway. Park et al. (2007) noted that 5 of the 13 published cases of Hall-type SEMD had upper airway obstruction. They suggested that this is a clinically important diagnostic feature of the disorder. Kim et al. (2009) reported the clinical and radiologic findings in a Korean mother, daughter, and son with Hall-type SEMDJL and in 3 unrelated Korean patients and 1 Japanese patient. The major clinical features were short stature, midface hypoplasia, and multiple dislocations and/or ligamentous laxity of the large joints, particularly at the knees with genu valgum or varum deformity. One patient had mild mental retardation. No cleft palate was found, and there were no neurologic, ophthalmologic, or auditory abnormalities. One patient had undergone surgical correction of an atrial septal defect, and another had a tracheostomy for tracheomalacia. The main radiologic features included small, irregular epiphyses, metaphyseal irregularity with vertical striations that was a consistent finding at the knees, constricted femoral necks, delayed ossification of the carpal bones, and slender metacarpals. Progressive thoracolumbar scoliosis was evident with aging; however, the vertebral bodies appeared normal in height or showed mild platyspondyly. Kim et al. (2009) stated that the slender appearance of the metacarpals ('leptodactyly') is distinctive enough for a definitive diagnosis. Boyden et al. (2011) stated that the most distinctive features of leptodactylic SEMD are the slender metacarpals and phalanges and the progressive degeneration of carpal bones; however, these 2 features are evident only in older children and young adults. The soft consistency of cartilage in the airways leads to laryngotracheomalacia with proneness to respiratory obstruction and inspiratory stridor in infancy and childhood. Inheritance Hall et al. (2002) reported variable intrafamilial expressivity of the disorder and suggested autosomal dominant inheritance with the majority of cases being new mutations. Nishimura et al. (2003) and Megarbane et al. (2003) concurred, noting that all of the other cases had been sporadic, with no clinical differences between males and females, and none of the families had been consanguineous. Rossi et al. (2005) reported father-to-son transmission. Molecular Genetics In affected members of a Korean family and 2 unrelated Korean patients with Hall-type spondyloepimetaphyseal dysplasia and joint laxity, previously studied by Kim et al. (2009), as well as 3 additional unrelated Korean patients, Min et al. (2011) performed exome sequencing and identified sequence variants in the KIF22 gene (603213) in 7 of the 8 affected individuals. Sanger sequencing confirmed 3 heterozygous missense mutations in the 7 patients (603213.0001-603213.0003). The patient in whom no KIF22 mutation was found showed a relatively mild clinical phenotype, with moderate short stature and equivocal midface retrusion, suggesting the possibility of genetic heterogeneity. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Face \- Midface hypoplasia SKELETAL \- Spondyloepimetaphyseal dysplasia \- Joint laxity Spine \- Scoliosis \- Caudal narrowing of interpedicular distances \- Vertebral endplate irregularity \- Posterior vertebral body scalloping \- Sacral spinal dysraphism Pelvis \- Congenital hip dislocation \- Small flattened capital femoral epiphyses \- Narrow femoral necks \- Tapered ischia Limbs \- Large joint dislocations (especially knees) \- Small, flattened irregular epiphyses \- Irregular, flared metaphyses with streaky sclerosis \- Radial head dislocation \- Genu valgum \- Severely delayed patellae ossification Hands \- Gracile metacarpals \- Long, slender middle and proximal phalanges \- Broad, square ends of distal phalanges \- Prominent distal phalangeal tufts \- Small carpal bones \- Severe delay in phalangeal epiphyseal bone maturation SKIN, NAILS, & HAIR Skin \- Velvety skin \- Normal wound healing NEUROLOGIC Central Nervous System \- Hypotonia MOLECULAR BASIS \- Caused by mutation in the kinesin family member 22 gene (KIF22, 603213.0001 ) ▲ 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	SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2	c1863732	27,294	omim	https://www.omim.org/entry/603546	2019-09-22T16:13:01	{"mesh": ["C535784"], "omim": ["603546"], "orphanet": ["93360"], "synonyms": ["Alternative titles", "SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, HALL TYPE", "SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, LEPTODACTYLIC TYPE", "SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH MULTIPLE DISLOCATIONS, HALL TYPE"]}
Perforating granuloma annulare SpecialtyDermatology Perforating granuloma annulare is a skin condition of unknown cause, usually appearing on the dorsal hands, presenting as papules with a central keratotic core.[1]:704 These lesions are often seen on the hands, arms, and ankles. Granuloma Annulare is characterized by rings of closely set, small, smooth, firm papules, usually skin colored, but they also may be slightly erythematous or have a purplish hue. Lesions vary in size from 1cm to 5cm. They are generally asymptomatic and nonpruritic (Fairlie, 2004). Reports of associations between Granuloma Annulare and diabetes mellitus, thyroid disease, malignancies, drug allergies, hypertension, arthritis, AIDS, and other conditions are being evaluated, but to date, no consistent association has been found (Rigopoulos et al., 2005). ## See also[edit] * Granuloma annulare * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. ## External links[edit] Classification D * ICD-10: L92.0 (ILDS L92.020) * v * t * e Cutaneous keratosis, ulcer, atrophy, and necrobiosis Epidermal thickening * keratoderma: Keratoderma climactericum * Paraneoplastic keratoderma * Acrokeratosis paraneoplastica of Bazex * Aquagenic keratoderma * Drug-induced keratoderma * psoriasis * Keratoderma blennorrhagicum * keratosis: Seborrheic keratosis * Clonal seborrheic keratosis * Common seborrheic keratosis * Irritated seborrheic keratosis * Seborrheic keratosis with squamous atypia * Reticulated seborrheic keratosis * Dermatosis papulosa nigra * Keratosis punctata of the palmar creases * other hyperkeratosis: Acanthosis nigricans * Confluent and reticulated papillomatosis * Callus * Ichthyosis acquisita * Arsenical keratosis * Chronic scar keratosis * Hyperkeratosis lenticularis perstans * Hydrocarbon keratosis * Hyperkeratosis of the nipple and areola * Inverted follicular keratosis * Lichenoid keratosis * Multiple minute digitate hyperkeratosis * PUVA keratosis * Reactional keratosis * Stucco keratosis * Thermal keratosis * Viral keratosis * Warty dyskeratoma * Waxy keratosis of childhood * other hypertrophy: Keloid * Hypertrophic scar * Cutis verticis gyrata Necrobiosis/granuloma Necrobiotic/palisading * Granuloma annulare * Perforating * Generalized * Subcutaneous * Granuloma annulare in HIV disease * Localized granuloma annulare * Patch-type granuloma annulare * Necrobiosis lipoidica * Annular elastolytic giant-cell granuloma * Granuloma multiforme * Necrobiotic xanthogranuloma * Palisaded neutrophilic and granulomatous dermatitis * Rheumatoid nodulosis * Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction Foreign body granuloma * Beryllium granuloma * Mercury granuloma * Silica granuloma * Silicone granuloma * Zirconium granuloma * Soot tattoo * Tattoo * Carbon stain Other/ungrouped * eosinophilic dermatosis * Granuloma faciale Dermis/ localized CTD Cutaneous lupus erythematosus * chronic: Discoid * Panniculitis * subacute: Neonatal * ungrouped: Chilblain * Lupus erythematosus–lichen planus overlap syndrome * Tumid * Verrucous * Rowell's syndrome Scleroderma/ Morphea * Localized scleroderma * Localized morphea * Morphea–lichen sclerosus et atrophicus overlap * Generalized morphea * Atrophoderma of Pasini and Pierini * Pansclerotic morphea * Morphea profunda * Linear scleroderma Atrophic/ atrophoderma * Lichen sclerosus * Anetoderma * Schweninger–Buzzi anetoderma * Jadassohn–Pellizzari anetoderma * Atrophoderma of Pasini and Pierini * Acrodermatitis chronica atrophicans * Semicircular lipoatrophy * Follicular atrophoderma * Linear atrophoderma of Moulin Perforating * Kyrle disease * Reactive perforating collagenosis * Elastosis perforans serpiginosa * Perforating folliculitis * Acquired perforating dermatosis Skin ulcer * Pyoderma gangrenosum Other * Calcinosis cutis * Sclerodactyly * Poikiloderma vasculare atrophicans * Ainhum/Pseudo-ainhum 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	Perforating granuloma annulare	c1304165	27,295	wikipedia	https://en.wikipedia.org/wiki/Perforating_granuloma_annulare	2021-01-18T18:36:30	{"umls": ["C1304165"], "icd-10": ["L92.0"], "wikidata": ["Q7168176"]}
Combined immunodeficiency with skin granulomas is characterized by recurrent viral infections and the presence of granulomas in the skin, mucous membranes and/or internal organs. There is a gradual reduction in the number and function of B cells (a type of white blood cell that makes antibodies), and T lymphocytes (a type of white blood cell, that protect the body from infection attacking the infected cells directly), hypogammaglobulinemia (reduction in all types of gamma globulins, including antibodies that help fight infection.) and defective autoinmunity where the immune system attacks the body itself. Some people may develop associated auto-immune diseases such as myasthenia gravis, vitiligo, low blood red and white cells, psoriasis, and Guillain–Barré syndrome. It is caused by mutations in the RAG1 and/or RAG2 genes. These genes provide instructions for making a member of a group of proteins called the RAG complex, which is involved in the process, known as V(D)J recombination, needed for maintaining the diversity of the B and T cells so they can be able to recognize diverse foreign agents allowing the body to fight infections. The mutations can impair RAG complex formation and function, resulting in an impaired B and T cells' function. Depending on the residual activity of the RAG proteins the disease can be more or less severe. In less severe cases symptoms are milder and may appear later in life. Treatment is with bone marrow transplantation. [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 immunodeficiency with skin granulomas	c2673536	27,296	gard	https://rarediseases.info.nih.gov/diseases/13587/combined-immunodeficiency-with-skin-granulomas	2021-01-18T18:01:12	{"mesh": ["C567115"], "omim": ["233650"], "orphanet": ["157949"], "synonyms": ["CID due to RAG 1/2 deficiency", "Combined immunodeficiency due to RAG 1/2 deficiency", "Combined immunodeficiency with granulomatosis", "Combined cellular and humoral immune defects with granulomas"]}
Ford (1966) referred to this form as the subacute childhood type. It begins at age 8-10 years and is characterized by deafness, blindness, weakness and spasticity of the legs, and dementia. Survival is shorter after onset of symptoms. However, in the family reported by Scholz (1925), although the affected males in the youngest generation showed this picture, their maternal grandfathers, aged 65 and 60, had the picture of spastic paraplegia. Scholz (1925) used histologic techniques which would have removed metachromatic material. When the cases of Scholz were restudied by Peiffer (1959) using frozen sections, striking metachromasia was demonstrated. Walsh (1957) described under the heading of Schilder disease, or encephalitis periaxialis diffusa, a kindred in which 4 males, offspring of sisters, succumbed to an illness possibly of the type shown by Scholz's youngest patients. See also Addison disease and cerebral sclerosis (300100). It seems highly probable that Scholz's patients suffered from a form of adrenoleukodystrophy (300100); the family reported by Walsh (1957) should be restudied. Eyes \- Blindness Neuro \- Dementia \- Spastic paraplegia Inheritance \- X-linked Misc \- Onset in first decade Limbs \- Leg weakness and spasticity Ears \- Deafness ▲ 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	CEREBRAL SCLEROSIS, DIFFUSE, SCHOLZ TYPE	c0162309	27,297	omim	https://www.omim.org/entry/302700	2019-09-22T16:18:37	{"mesh": ["D000326"], "omim": ["302700"], "orphanet": ["43"]}
## Summary ### Clinical characteristics. Facioscapulohumeral muscular dystrophy (FSHD) typically presents with weakness of the facial muscles, the stabilizers of the scapula, or the dorsiflexors of the foot. Severity is highly variable. Weakness is slowly progressive and approximately 20% of affected individuals eventually require a wheelchair. Life expectancy is not shortened. ### Diagnosis/testing. The diagnosis of FSHD1 is established in a proband with characteristic clinical features by identification of a heterozygous pathogenic contraction of the D4Z4 repeat array in the subtelomeric region of chromosome 4q35 on a chromosome 4 permissive haplotype. The diagnosis of FSHD2 is established in a proband by identification of hypomethylation of the D4Z4 repeat array in the subtelomeric region of chromosome 4q35 on a chromosome 4 permissive haplotype. Hypomethylation of the D4Z4 repeat array can be due to a heterozygous pathogenic variant in SMCHD1 or DNMT3B. ### Management. Treatment of manifestations: Consultation with a physical therapist to establish appropriate exercise regimen; ankle/foot orthoses to improve mobility and prevent falls; occupational and speech therapy in individuals with infantile onset; surgical fixation of the scapula to the chest wall may improve range of motion of the arms over the short term; management of chronic pain by physical therapy and medication; monitoring respiratory function; lubricants to prevent drying of the sclera or taping the eyes shut during sleep to treat exposure keratitis; treatment for retinal vasculopathy as per ophthalmologist; standard treatment of sensorineural hearing loss. Surveillance: Annual physical therapy assessment; Pain should be assessed at regular visits to the primary care physician or physical therapist; screening for hypoventilation in individuals with abnormal PFTs, severe proximal weakness, kyphoscoliosis, wheelchair dependence, or comorbid disease affecting ventilation; pulmonary consultation for FVC <60%, excessive daytime somnolence or nonrestorative sleep, and prior to surgical procedures requiring anesthesia; annual dilated ophthalmoscopy in individuals with early childhood-onset FSHD with large pathogenic contraction of D4Z4 and adults with visual symptoms; audiometry in infants at each visit and annually in children. ### Genetic counseling. FSHD1 is inherited in an autosomal dominant manner. Approximately 70%-90% of individuals have inherited the disease-causing deletion from a parent, and approximately 10%-30% of affected individuals have FSHD as the result of a de novo deletion. Offspring of an affected individual have a 50% chance of inheriting the deletion. Prenatal testing for pregnancies at increased risk is possible if the D4Z4 pathogenic contraction has been identified in the family. FSHD2 is inherited in a digenic manner. ## Diagnosis Evidence-based guidelines for diagnosis of FSHD are available (see Figure 1) [Tawil et al 2015]. #### Figure 1. Molecular genetic testing for a heterozygous pathogenic variant in SMCHD1 or DNMT3B can be pursued in individuals with at least one permissive chromosome 4 haplotype (e.g., 4A161, 4A159, 4A168, 4A166H) and hypomethylation of D4Z4. ### Suggestive Findings Facioscapulohumeral muscular dystrophy (FSHD) should be suspected in individuals with the following: * Weakness that predominantly involves the facial, scapular stabilizer, or foot dorsiflexor muscles without associated ocular or bulbar muscle weakness. Weakness is often asymmetric. * Progression of weakness after pregnancy [Ciafaloni et al 2006] * Prior diagnosis with inflammatory myopathy that was refractory to immunosuppression * Family history of FSHD ### Supportive Findings Serum concentration of creatine kinase (CK) is normal to elevated in individuals with FSHD and usually does not exceed three to five times the upper limit of the normal range. Serum concentration of CK >1500 IU/L suggests an alternate diagnosis. EMG can show mild myopathic changes in symptomatic muscles. Muscle biopsy most often shows nonspecific chronic myopathic changes. Mononuclear inflammatory reaction, typically perivascular, is present in muscle biopsies in up to 40% of individuals with FSHD. Rarely, the inflammatory reaction is intense enough to suggest an inflammatory myopathy. Muscle biopsy is now performed only in individuals in whom FSHD is suspected but not confirmed by molecular genetic testing. ### Establishing the Diagnosis The diagnosis of FSHD is established in a proband who has one of the following identified on molecular genetic testing (see Table 1; Figure 1): * FSHD1 (~95% of FSHD). A heterozygous pathogenic contraction of the D4Z4 repeat array in the subtelomeric region of chromosome 4q35 on the permissive chromosome 4 haplotype * FSHD2 (~5% of FSHD). Hypomethylation of the D4Z4 repeat array in the subtelomeric region of chromosome 4q35 on the permissive chromosome 4 haplotype due to one of the following: * A heterozygous SMCHD1 pathogenic variant (<5% of individuals with FSHD; ~85% of individuals with FSHD2) [Lemmers et al 2015] * A heterozygous DNMT3B pathogenic variant (3 families reported) [van den Boogaard et al 2016] * Unknown cause of hypomethylation of D4Z4 repeat array at 4q35 (2 families) [Lemmers et al 2012a] Allele sizes * Normal alleles. A D4Z4 locus with ≥12 repeat units (i.e., fragments of ≥43 kb using EcoRI and the p13E-11 probe), or a D4Z4 locus with any number of repeat units on a non-permissive haplotype * Contracted, reduced-penetrance alleles. A D4Z4 locus that has ten or 11 repeat units AND is on a permissive haplotype * Contracted, full-penetrance alleles. A D4Z4 locus that has ≤9 repeat units AND is on a permissive haplotype Note: Penetrance of allele sizes is dependent on multiple factors (see Penetrance) and patient-specific manifestations may vary from the categories below. Molecular genetic testing approaches can include targeted analysis for the repeat size of D4Z4 repeat array in the subtelomeric region of chromosome 4q35 and haplotype analysis, DNA methylation studies, and single-gene testing. #### Targeted Analysis and Haplotype Analysis Targeted analysis. Testing is targeted for the abnormally contracted D4Z4 repeat array in the subtelomeric region of chromosome 4q35. Note: Contraction of an almost identical D4Z4 repeat array at 10q26 is not associated with FSHD (see Molecular Genetics). Note: Targeted testing is typically done by Southern blotting (Table 1); molecular combing techniques have also been described. Molecular combing has a higher resolution than Southern blotting: in individuals with a normal D4Z4 repeat array by Southern blot testing, molecular combing has been used to identify a short D4Z4 repeat array (5-6 repeat units), which may not be recognized by Southern blot [Lemmers et al 2018]. However, molecular combing may not be clinically available. Haplotype analysis. Haplotype analysis is recommended concurrently with testing for a D4Z4 contraction to determine if an abnormal allele is present on a permissive or non-permissive haplotype distal to the last D4Z4 repeat (see Molecular Genetics). In individuals with a contracted D4Z4 repeat array (see Allele sizes), a permissive haplotype is required to confirm FSHD1. Examples of chromosome 4q35 permissive (known as 4A or A) and non-permissive (known as 4B or B) haplotypes: * Permissive: 4A161, 4A159, 4A168, 4A166H * Non-permissive: 4A166, 4B Note: The presence of a typical FSHD clinical profile without a contracted repeat but with at least one allele with a permissive haplotype, raises the possibility of FSHD2. #### DNA Methylation Studies In individuals who do not have a contracted D4Z4 repeat array identified and have at least one repeat array with a permissive chromosome 4 haplotype, D4Z4 methylation analysis should be done next. D4Z4 hypomethylation suggests the presence of a heterozygous SMCHD1 or DNMT3B pathogenic variant. #### Single-Gene Testing Sequence analysis of SMCHD1 and DNMT3B should be done in individuals with D4Z4 hypomethylation to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. If no pathogenic variant is found perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. ### Table 1. Molecular Genetic Testing Used in Facioscapulohumeral Muscular Dystrophy View in own window Locus/ Gene 1MethodPathogenic Variants/Alterations 2 DetectedProportion of FSHD-Related Alterations Detected 3 D4Z4Targeted analysis for pathogenic variants 4Pathogenic contraction of number of D4Z4 repeats 5, 6, 7~95% Haplotype analysisAnalysis to confirm that the D4Z4 pathogenic contraction occurred on a permissive haplotype 8Not applicable Methylation analysisD4Z4 hypomethylation (<25% methylation) 9~5% SMCHD1Sequence analysis 10SMCHD1 sequence variants~4% 11 Gene-targeted deletion/duplication analysis 12SMCHD1 deletion/duplicationSee footnote 13. DNMT3BSequence analysis 10DNMT3B sequence variants3 families 14 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\. The ability of the test method used to detect a variant that is present in the indicated gene/locus 4\. Molecular genetic testing to determine the length or number of repeat units of the D4Z4 locus has typically relied on Southern blot analysis, typically with a probe (e.g., p13E-11) immediately proximal to D4Z4. Standard DNA diagnostic testing (defined here as linear gel electrophoresis and Southern blot analysis) uses the restriction enzyme EcoRI, which recognizes the D4Z4 locus on chromosomes 4 and 10. Pulsed-field gel electrophoresis and Southern blot analysis requires EcoRI/HindIII double digestion for a better resolution of DNA fragments between 20 and 50 kb. An EcoRI/BlnI double digestion further fragments the chromosome 10 array, allowing one to distinguish D4Z4 arrays located on chromosome 4 from the similar benign arrays on chromosome 10. Molecular combing, which has a higher resolution than Southern blotting [Nguyen et al 2017, Lemmers et al 2018, Nguyen et al 2019] has also been described, but may not be clinically available. 5\. Detection of the pathogenic contraction of the D4Z4 locus by Southern blot analysis requires high-quality DNA; a false negative test result can be caused by poor-quality DNA that was sheared into small fragments. 6\. In approximately 3% of the European families with FSHD1 the D4Z4 contraction on chromosome 4q35 is not visible using the standard genetic test because a deletion encompasses the region of the molecular diagnostic probe p13E-11. These individuals require additional testing to visualize the contracted D4Z4 repeat and resolve the size of the repeat [Lemmers et al 2003, Ehrlich et al 2007]. 7\. A combination of Southern blotting and molecular combing detected complex rearrangements of 4q35 with duplication of D4Z4 array [Nguyen et al 2017, Lemmers et al 2018] and a 4q deletion proximal to D4Z4 [Nguyen et al 2019]. 8\. 4A161 is most common permissive haplotype, but others are reported (4A159, 4A168, 4A166H) [Lemmers et al 2010a]. All individuals with FSHD carry a permissive haplotype. Because 66% of controls also carry a permissive haplotype, this analysis (without sizing of the repeat array) is often not informative. Lemmers et al developed a clinically available diagnostic test to discriminate both haplotype variants using HindIII-digested DNA and specific probes for 4A and 4B [Lemmers et al 2002, Lemmers et al 2007]. 9\. D4Z4 methylation values below the threshold of 25% are indicative of FSHD. However, the CpG methylation at the D4Z4 repeat array is also determined by the size of the D4Z4 arrays on chromosomes 4q and 10q. Contracted D4Z4 arrays on chromosomes 4q and 10 have a significantly lower level of methylation than normal-sized arrays. D4Z4 methylation levels should always be evaluated with respect to the repeat size. A Southern blot-based method has been developed that measures the total D4Z4 methylation at chromosomes 4q and 10q by using methylation-sensitive restriction enzyme (FseI) in the promoter region of DUX4 [Lemmers et al 2012b]. The average methylation of D4Z4 in control individuals is 45%, while in individuals with FSHD2 the methylation level drops below 25%, with an average of 11% [Lemmers et al 2012b]. 10\. 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. 11\. 51 families of 60 with FSHD2 were found to have an SMCHD1 pathogenic variant with D4Z4 DNA hypomethylation [Lemmers et al 2015]. 12\. 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. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. 13\. Deletions including SMCHD1 and other genes have been reported as 18p- syndrome [Lemmers et al 2015]. 14\. van den Boogaard et al [2016] ## Clinical Characteristics ### Clinical Description Facioscapulohumeral muscular dystrophy (FSHD) is characterized by progressive muscle weakness involving the face, scapular stabilizers, upper arm, lower leg (peroneal muscles), and hip girdle [Wang & Tawil 2016]. Asymmetry of facial, limb, and shoulder weakness is common [Kilmer et al 1995]. Typically, individuals with FSHD become symptomatic in their teens, but age of onset is variable. More than 50% of individuals with FSHD demonstrate findings by age 20 years. Individuals with severe infantile FSHD have muscle weakness at birth. In contrast, some individuals remain asymptomatic throughout their lives. Progression is usually slow; however, many affected individuals describe a stuttering course with periods of disease inactivity followed by periods of rapid deterioration. Eventually 20% of affected individuals require a wheelchair. Scapular winging is the most common initial finding; preferential weakness of the lower trapezius muscle results in characteristic upward movement of the scapula when attempting to flex or abduct the arms. The shoulders tend to slope forward with straight clavicles and pectoral muscle atrophy. Affected individuals show facial weakness, with symptoms more pronounced in the lower facial muscles than the upper. Some affected individuals recall having facial weakness before the onset of shoulder weakness. Earliest signs are often difficulty whistling or sleeping with eyes partially open in childhood. Individuals with FSHD are often unable to purse their lips, turn up the corners of their mouth when smiling, or bury their eyelashes when attempting to close their eyelids tightly. Extraocular, eyelid, and bulbar muscles are spared. The deltoids remain minimally affected until late in the disease; however, the biceps and triceps are selectively involved, resulting in atrophy of the upper arm and sparing of the forearm muscles. The latter results in the appearance of "Popeye arms." In more severely affected individuals, distal upper extremity weakness typically involves the wrist and finger extensors. Abdominal muscle weakness results in protuberance of the abdomen and exaggerated lumbar lordosis. The lower abdominal muscles are selectively involved, resulting in a Beevor's sign (upward displacement of the umbilicus upon flexion of the neck in a supine position). The legs are variably involved, with peroneal muscle weakness with or without weakness of the hip girdle muscles, resulting in foot drop. Sensation is preserved; reflexes are often diminished when the reflex involves weak muscles. Respiratory dysfunction is relatively uncommon. Individuals who had pulmonary function testing by spirometry showed a restrictive lung disease pattern in 38% [Moreira et al 2017], which was likely due to expiratory weakness. Respiratory support with noninvasive ventilation is uncommon (1%-3%) [Santos et al 2015]. Other manifestations. Retinal vasculopathy characterized by failure of vascularization of the peripheral retina, telangiectatic blood vessels, and microaneurysms can be demonstrated by fluorescein angiography in 40%-60% of affected individuals [Padberg et al 1995]. Vision is usually unaffected by this particular vascular malformation, but an exudative retinopathy clinically indistinguishable from Coats disease that can result in retinal detachment and vision loss has also been described. Bindoff et al [2006] reported two sisters with infantile-onset FSHD who had tortuous retinal vessels, small aneurysms, and yellow exudates. Approximately 15% of individuals with FSHD have an abnormal audiogram. An abnormal audiogram was identified in up to 32% of individuals with a large pathogenic contraction of D4Z4 (D4Z4 fragments <20 kb) [Lutz et al 2013]. Both the exudative retinopathy and symptomatic sensorineural hearing loss are seen almost exclusively in individuals with a large pathogenic contraction of D4Z4 (1-3) repeats) or in individuals with early-onset disease [Lutz et al 2013, Statland et al 2013]. A predilection for atrial tachyarrhythmias has been reported in about 5% of cases, but symptoms are rarely experienced [Laforêt et al 1998, Galetta et al 2005, Trevisan et al 2006]. Chronic pain is likely underrecognized in affected individuals, with a prevalence as high as 77% [van der Kooi et al 2007]. Atypical presentations. Clinical variants of typical FSHD in individuals with a pathogenic contraction of the D4Z4 locus in the subtelomeric region of chromosome 4q35 include the following: * Scapulohumeral dystrophy onset with facial sparing * Infantile onset with severe rapidly progressive disease and a large pathogenic contraction of D4Z4 (D4Z4 fragments in the 9-21 kb range) was observed in 4% of individuals studied [Klinge et al 2006]. Felice et al [2005] and Bindoff et al [2006] have also reported individuals with infantile onset and mild-to-moderate cognitive deficiency and possible epilepsy [Bindoff et al 2006, Hobson-Webb & Caress 2006, Quarantelli et al 2006]. Mosaicism for FSHD-associated alleles. Approximately half of de novo cases of FSHD (i.e., affected offspring of unaffected parents) show a mosaic distribution of D4Z4 repeat array lengths in peripheral blood. This mosaicism likely results from a postzygotic array contraction during the first few cell divisions in embryogenesis. In such cases, a proportion of cells have two normal-sized D4Z4 alleles, while the remaining cells have one normal-sized D4Z4 allele and one pathogenic contracted D4Z4 allele [Lemmers et al 2004]. Depending on when in embryogenesis the pathogenic contraction occurs at the D4Z4 locus and the proportion of cells with the contracted D4Z4 repeat, individuals with mosaicism can be affected or asymptomatic. FSHD with somatic mosaicism of D4Z4 array lengths is more penetrant in males than in females [van der Maarel et al 2000]. ### Genotype-Phenotype Correlations D4Z4 repeat array contraction size. Evidence-based guidelines published in 2015 recommend that a large pathogenic contraction of D4Z4 (D4Z4 fragments of 10-20 kb) should alert clinicians to the increased likelihood of significant disability, earlier onset of symptoms, and increased likelihood of extramuscular manifestations [Tawil et al 2015]. Allele size explains roughly 10% of variability in phenotype [Mul et al 2018]. A correlation has been reported between the degree of the pathogenic contraction of the D4Z4 locus and the age at onset of symptoms [Zatz et al 1995], age at loss of ambulation [Lunt & Harper 1991], and muscle strength as measured by quantitative isometric myometry [Tawil et al 1996], particularly in affected females [Tonini et al 2004a]. Individuals with a large contraction of D4Z4 (1-3 repeats) have a higher probability of earlier-onset disease and more rapid progression than those with smaller contractions of the D4Z4 locus [Bindoff et al 2006, Hobson-Webb & Caress 2006, Klinge et al 2006, Nikolic et al 2016, Goselink et al 2019]. However, significant variation exists even with small repeats, and others have not been able to confirm a correlation between disease severity and degree of D4Z4 pathogenic contractions [Butz et al 2003]. A study of Italy’s National Registry concluded that 76% of early-onset (age <10 years) disease was due to de novo pathogenic variants. However, neither de novo pathogenic variants nor earlier disease onset were associated with a more severe phenotype [Nikolic et al 2016], contrasting with other studies showing that earlier onset is associated with more severe symptoms [Mah et al 2018, Goselink et al 2019]. Caution must be noted as this correlation may represent an ascertainment bias, where more mild forms of FSHD are detected when inheritance of a known pathogenic variant in a family is suspected. Mosaicism. The phenotypic severity of individuals with mosaic distributions of one or more array sizes, which is typically less than that of individuals without mosaicism, may reflect the proportion of cells carrying the pathogenic contracted D4Z4 locus in addition to the degree of the contraction of the D4Z4 locus in those cells. Compound heterozygosity. Two unrelated affected individuals homozygous for a D4Z4 pathogenic contraction were reported by Wohlgemuth et al [2003], suggesting that the presence of two FSHD-associated alleles can be compatible with life. However, both families demonstrated reduced penetrance for FSHD, leaving open the possibility that in other genetic/environmental settings, compound heterozygosity could be a lethal condition. In support of this possibility, the authors report a phenotypic dosage effect in both of the compound heterozygotes, compared to other family members. Homozygosity. Tonini et al [2004b] reported an individual homozygous for the contraction on two D4Z4 4A alleles whose clinical phenotype is not more severe than those of some of his heterozygous relatives. Within the same family, the authors also observed a large number of asymptomatic or minimally affected heterozygotes, reflecting the wide range of clinical variability that can occur in a given kindred. ### Penetrance Penetrance is increased with smaller D4Z4 repeat arrays; however, significant variation exists. In one study, penetrance of FSHD was found to vary by age and gender; it was 83% by age 30 years, but significantly greater for males (95%) than for females (69%) [Zatz et al 1998, Wohlgemuth et al 2018]. The effect of gender on penetrance and disease variability is uncertain, with data showing a lack of significant effect of lifetime estrogen exposures [Mul et al 2018], or methylation status between genders [Lemmers et al 2015]. Effects from epigenetic factors such as methylation status (for both FSHD1 and 2) and other unknown environmental or genetic factors likely contribute [Mul et al 2018]. ### Anticipation Absence of anticipation in large multigenerational families has been reported [Flanigan et al 2001]. ### Nomenclature The term "Landouzy-Dejerine muscular dystrophy," used in the past for a syndrome similar or identical to FSHD, is no longer in use. Persons with FSHD are sometimes included under the descriptive terms "scapulo-humeral" or "scapulo-peroneal syndromes." ### Prevalence The estimated prevalence of FSHD is between four and ten per 100,000 population. Sposìto et al [2005] found a prevalence in central Italy of 4.6:100,000. Lunt and Harper noted reports of 1:435,000 population in Wisconsin and figures for Europe from 1:17,000 to 1:250,000 population [Lunt & Harper 1991]. In Wales, the prevalence was 4.4:100,000 population. In Netherlands, the prevalence of FSHD may be 2.4:20,000 population, higher than prior estimates [Deenen et al 2014]. ## Differential Diagnosis Disorders that are similar clinically to facioscapulohumeral muscular dystrophy (FSHD) but easily differentiated by their distinct muscle histopathology include the following: * Myofibrillar myopathy (previously called desmin-storage myopathy) * Inclusion body myositis including inclusion body myopathy 2 (See GNE-Related Myopathy.) * Mitochondrial myopathies * Adult acid maltase deficiency (See Pompe Disease.) * Congenital myopathies * Polymyositis More troublesome are the following disorders in which the distribution of weakness and pathologic findings can be difficult to distinguish easily from FSHD. Molecular genetic testing allows definitive diagnosis of these conditions: * Limb-girdle muscular dystrophies * Scapuloperoneal muscular dystrophy syndromes, including myotonic dystrophy type 1 and myotonic dystrophy type 2 (also known as PROMM), which have mild facial weakness and nonspecific histopathologic changes that cannot be differentiated from FSHD ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with facioscapulohumeral muscular dystrophy (FSHD), the evaluations summarized in Table 2 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 2. Recommended Evaluations Following Initial Diagnosis in Individuals with Facioscapulohumeral Muscular Dystrophy View in own window System/ConcernEvaluationComment MusculoskeletalPhysical examinationTo assess strength & functional limitations Evaluation for PT & need for assistive devices NeurodevelopmentalOT & speech therapy assessmentIn individuals w/infantile onset RespiratoryEvaluation for hypoventilation, screen for daytime somnolence, nonrestorative sleep * Baseline PFTs * Pulmonary/sleep evaluation if abnormal PFTs or sleep symptoms OphthalmologicOphthalmologic evaluation * In individuals w/large pathogenic contraction of D4Z4 (D4Z4 fragments of 10-20 kb) or visual symptoms * For presence of retinal vasculopathy AudiologicAssessment of hearing * In all affected infants & children * In adults w/symptomatic hearing loss OtherConsultation w/clinical geneticist &/or genetic counselor OT = occupational therapy; PFT = pulmonary function test; PT = physical therapy ### Treatment of Manifestations Standards of care and management of facioscapulohumeral muscular dystrophy were agreed upon at the 171st ENMC International Workshop. A consensus on the following topics and the recommendations from that conference [Tawil et al 2010] are outlined in Table 3. ### Table 3. Treatment of Manifestations in Individuals with Facioscapulohumeral Muscular Dystrophy View in own window Manifestation/ ConcernTreatmentConsiderations/Other WeaknessPT * Establish appropriate exercise regimens (e.g., moderate weight training, aerobic training) * Identify assistive devices that may ↑ mobility & ↓ risk of falls in home environment. Ankle/foot orthosesTo improve mobility &prevent falls in individuals with foot drop OT & speech therapyIn individuals w/infantile onset Limited range of motionSurgical fixation of the scapula to chest wallOffered cautiously w/careful consideration of risk & benefit in context of affected individual's symptoms PainPT; pain medication * NSAIDs for acute pain * Antidepressants or antiepileptics for chronic pain HypoventilationVentilatory support (e.g., BiPAP)As necessary Exposure keratitisOcular lubricantsIn severe cases taping the eyes shut during sleep may be required. Exudative retinopathyTreatment per ophthalmologistMay be prevented by early intervention w/laser treatment Hearing lossStandard therapiesIncl amplification if necessary OT = occupational therapy; PT = physical therapy ### Surveillance ### Table 4. Recommended Surveillance for Individuals with Facioscapulohumeral Muscular Dystrophy View in own window System/ConcernEvaluationFrequency MusculoskeletalPT assessmentAnnually or more frequently as determined by disease severity Pain assessmentW/each visit to primary care physician & PT RespiratoryScreening for hypoventilation * Regular monitoring for individuals w/abnormal PFTs, severe proximal weakness, kyphoscoliosis, wheelchair dependence, or comorbid disease affecting ventilation * Pulmonary consultation for FVC <60%, excessive daytime somnolence or nonrestorative sleep, & before surgical procedures requiring anesthesia OphthalmologicDilated ophthalmoscopy * Annually in individuals w/large pathogenic contraction of D4Z4 (D4Z4 fragments of 10-20 kb) * In adults only if visual symptoms develop AudiologyAudiometry * W/each visit in infants w/early-onset FSHD * Annually in children until starting school * In adults only if symptoms of hearing loss reported CardiologyCardiac evaluationIf overt signs or symptoms of cardiac disease (regular screening not required) FVC = forced vital capacity; PFT = pulmonary function test; PT = physical therapy/therapist ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Outcome of 105 pregnancies in 38 women with FSHD was generally favorable [Ciafaloni et al 2006]. However, rates for low-birth-weight infants, augmented extraction procedures such as forceps and vacuum assisted deliveries, delivery by cesarean section, and anesthetic complications were higher than for the general population. Worsening of weakness occurred in 24% of the pregnancies, beginning during the pregnancy and generally not resolving after delivery. ### Therapies Under Investigation Genetic treatments such as RNAi treatment to silence DUX4 have been evaluated in preclinical studies, though no human trials are currently underway [Wallace et al 2017]. Losmapimod is an inhibitor of p38α/β mitogen-activated protein kinase (MAPK) shown in preclinical studies to reduced DUX4 expression. The medication has been previously studied in Phase I trials in other diseases, and Phase II trials are currently enrolling for FSHD [Ino et al 2015, Oliva et al 2019]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. [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	Facioscapulohumeral Muscular Dystrophy	c0238288	27,298	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1443/	2021-01-18T21:27:12	{"mesh": ["D020391"], "synonyms": ["FSH Muscular Dystrophy"]}
A number sign (#) is used with this entry because of evidence that nephrotic syndrome type 11 (NPHS11) is caused by homozygous or compound heterozygous mutation in the NUP107 gene (607617) on chromosome 12q15. Biallelic mutation in the NUP107 gene can also cause Galloway-Mowat syndorme-7 (GAMOS7; 618348). Description Nephrotic syndrome type 11 is an autosomal recessive disorder of the kidney with onset in the first decade of life. The disorder is progressive and usually results in end-stage renal disease necessitating renal transplantation, although some patients may have a slightly milder phenotype (summary by Miyake et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300). Clinical Features Miyake et al. (2015) reported 9 patients from 5 unrelated families of East Asian descent with early-onset steroid-resistant nephrotic syndrome. Four of the families were of Japanese origin and 1 was of Korean origin; 3 of the families had previously been reported by Kitamura et al. (2006). In 4 families, the patients developed nephrotic syndrome between 2 and 3 years of age, and end-stage renal disease became apparent before age 10. Two sisters from a Korean family had a slightly later age at onset, around 10 to 11 years of age, and renal function was relatively well preserved to age 34 years. Renal biopsy showed focal segmental glomerulosclerosis and minimal-change nephrotic syndrome. Six patients who underwent renal transplant had no recurrence of disease after transplant. None of the patients had neurologic phenotypes. Braun et al. (2018) reported a boy, born of consanguineous Turkish parents (family A3825), with onset of NPHS11 at age 4.5 years, which progressed to end-stage renal disease at age 5. Renal biopsy showed diffuse mesangial sclerosis. The patient also had cleft lip and palate. Inheritance The transmission pattern of NPHS11 in the families reported by Miyake et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 9 affected individuals from 5 unrelated families of East Asian descent with NPHS11, Miyake et al. (2015) identified compound heterozygous mutations in the NUP107 gene (607617.0001-607617.0004). All patients carried a D831A mutation (607617.0001) on 1 allele, and haplotype analysis was consistent with a founder effect. In vitro studies showed that 3 of the 4 mutations impaired NUP107 binding to NUP133 and NUP107 incorporation into the nuclear pore complex. However, patient lymphoblastoid cells showed no apparent loss of the nuclear pore complex, suggesting residual NUP107 function. Miyake et al. (2015) hypothesized that defective NUP107 function could result in functional impairment of podocytes that are progressively destroyed by increased filtration pressure after birth, resulting in damage to the glomerulus. The authors postulated that NPHS11 is caused by a structural abnormality, since there is no recurrence of the disorder after renal transplant. In a boy with NPHS11 from a Turkish family (A3825), Braun et al. (2018) identified a homozygous missense mutation in the NUP107 gene (Y889C; 607617.0007). The patient also had cleft lip and palate. Animal Model Miyake et al. (2015) found that zebrafish with an in-frame deletion mimicking the human missense mutation D831A (607617.0001) had underdeveloped glomeruli with hypoplastic or poorly organized capillary vessels and mesangial regions. Electron microscopy showed abnormally shaped foot processes, collapse of the capillary lumen, and thickened basement membrane, suggesting that the mutation caused renal abnormalities. Mutant zebrafish developed edema and died around days 5 and 6. Braun et al. (2018) found that morpholino knockdown of nup107 in Xenopus embryos resulted in abnormal pronephros morphology, consistent with a defect in glomerulogenesis. Expression of human wildtype NUP107 rescued the defect. CRISPR/Cas9-mediated knockout of the nup107 gene in zebrafish embryos resulted in developmental abnormalities, including small eyes, body axis curvature, and edema, as well as early lethality. INHERITANCE \- Autosomal recessive GENITOURINARY Kidneys \- Nephrotic syndrome \- Focal segmental glomerulosclerosis \- Minimal change disease \- End-stage renal disease \- Diffuse mesangial sclerosis \- Effacement of podocyte foot processes \- Tubular atrophy \- Interstitial fibrosis LABORATORY ABNORMALITIES \- Proteinuria \- Decreased serum albumin \- Hypercholesterolemia MISCELLANEOUS \- Onset of renal disease in first decade \- Progressive disorder \- Not responsive to steroid treatment \- Most patients require renal transplantation \- No recurrence of nephrotic syndrome after transplantation MOLECULAR BASIS \- Caused by mutation in the 107-kD nucleoporin gene (NUP107, 607617.0001 ) ▲ 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	NEPHROTIC SYNDROME, TYPE 11	c1868672	27,299	omim	https://www.omim.org/entry/616730	2019-09-22T15:48:05	{"doid": ["0080385"], "mesh": ["C536404"], "omim": ["616730"], "orphanet": ["656", "93213"]}

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