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Paroxysmal tonic upgaze (PTU) of childhood is a rare and distinctive neuro-ophthalmological syndrome characterized by episodes of sustained upward deviation of the eyes. Symptoms normally appear in babies under one year of age and are characterized by an upward stare or gaze, with the eyes rolled back, while the chin is typically held low.[1]
## Contents
* 1 Presentation
* 2 Genetics
* 3 Treatment
* 4 History
* 5 References
## Presentation[edit]
Babies suffering from PTU may exhibit normal or slightly jerky side-to-side eye movement, nausea, irritability, frequent sleep, developmental and language delays, vertigo and loss of muscle tone.
The condition is generally regarded as having a benign outcome, in the sense that it improves, rather than worsens over time. The average age of recovery is at about 2.5 years.
## Genetics[edit]
This condition has been associated with mutations in the following genes: CACNA1A, GRID2 and SEPSECS.[2]
## Treatment[edit]
Because of the rarity of this condition there are few reports of successful treatment. Carbonic anhydrase inhibition has been reported to work in a small series. [3]
## History[edit]
PTU was first described in 1988. As of 2002, approximately fifty cases had been diagnosed. Because the condition is so rare, the majority of physicians have never seen it, and thus may not recognize it. Videotaping a child both in and out of the upgaze state can be vital for reaching a diagnosis.[4]
## References[edit]
1. ^ Hayman, M.; Harvey, A. S.; Hopkins, I. J.; Kornberg, A. J.; Coleman, L. T.; Shield, L. K. (1998). "Paroxysmal tonic upgaze: A reappraisal of outcome". Annals of Neurology. 43 (4): 514–520. doi:10.1002/ana.410430416. PMID 9546334.
2. ^ Quade A, Thiel A, Kurth I, Holtgrewe M, Elbracht M, Beule D, Eggermann K, Scholl UI, Häusler M (2019) Paroxysmal tonic upgaze: A heterogeneous clinical condition responsive to carbonic anhydrase inhibition. Eur J Paediatr Neurol
3. ^ Quade A, Thiel A, Kurth I, Holtgrewe M, Elbracht M, Beule D, Eggermann K, Scholl UI, Häusler M (2019) Paroxysmal tonic upgaze: A heterogeneous clinical condition responsive to carbonic anhydrase inhibition. Eur J Paediatr Neurol
4. ^ "PTU: A Summary". Retrieved 11 June 2013.
*[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-hydroxybutyric 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
|
Paroxysmal tonic upgaze
|
c1868576
| 25,700 |
wikipedia
|
https://en.wikipedia.org/wiki/Paroxysmal_tonic_upgaze
| 2021-01-18T18:58:00 |
{"gard": ["4176"], "mesh": ["C566817"], "umls": ["C1868576"], "orphanet": ["1179"], "wikidata": ["Q7139591"]}
|
Van der Woude syndrome
SpecialtyMedical genetics
Van der Woude syndrome (VDWS) is a genetic disorder characterized by the combination of lower lip pits, cleft lip with or without cleft palate (CL/P), and cleft palate only (CPO).[1] The frequency of orofacial clefts ranges from 1:1000 to 1:500 births worldwide, and there are more than 400 syndromes that involve CL/P.[2] VWS is distinct from other clefting syndromes due to the combination of cleft lip and palate (CLP) and CPO within the same family. Other features frequently associated with VWS include hypodontia in 10-81% of cases, narrow arched palate, congenital heart disease, heart murmur and cerebral abnormalities, syndactyly of the hands, polythelia, ankyloglossia, and adhesions between the upper and lower gum pads.[3]
The association between lower lip pits and cleft lip and/or palate was first described by Anne Van der Woude in 1954. The worldwide disease incidence ranges from 1:100,000 to 1:40,000.[4]
## Contents
* 1 Genetics
* 2 Pathophysiology
* 3 Diagnosis
* 3.1 Genetic Counseling
* 4 Treatment
* 5 References
* 6 External links
## Genetics[edit]
Van der Woude syndrome is inherited as an autosomal dominant disease caused by a mutation in a single gene with equal distribution between the sexes. The disease has high penetrance at about 96% but the phenotypic expression varies from lower lip pits with cleft lip and cleft palate to no visible abnormalities.[2][4] Approximately 88% of VWS patients display lower lip pits, and in about 64% of cases lip pits are the only visible defect. Reported clefting covers a wide range including submucous cleft palate, incomplete unilateral CL, bifid uvula, and complete bilateral CLP. VWS is the most common orofacial clefting syndrome, accounting for 2% of CLP cases.[3]
The majority of VWS cases are caused by haploinsufficiency due to mutations in the interferon regulatory factor 6 gene (IRF6) on chromosome 1 in the 1q32-q41 region known as VWS locus 1. A second, less common, causative locus is found at 1p34, known as VWS locus 2 (VWS2). More recent work has shown that GRHL3 is the VWS2 gene. Grhl3 is downstream of Irf6 in oral epithelium, suggesting a common molecular pathway leading to VWS. Prior work also suggested WDR65 as a candidate gene.[4][5] IRF6 contains two non-coding and seven coding exons and is part of a family of nine transcription factors with a highly conserved helix-turn-helix DNA binding domain called the Smad-interferon regulatory factor binding domain (SMIR). Mutations in coding or non-coding IRF6 exons can result in Van der Woude syndrome.[2] Due to the wide range of expressivity, it is also believed that other unidentified loci contribute to disease development.[4]
An example of the clear phenotypic variability is a monozygotic twin study conducted by Jobling et al. (2010). Two monozygotic female twins had the same IRF6 mutation; however Twin A was born with a bilateral cleft lip, whereas Twin B had bilateral lip pits and no orofacial clefting. Both twins were diagnosed with VWS. The twins' father had lip pits alone and a family history of CLP, CP, CL, and/or lip pits. Both twins were diagnosed with VWS. Polymerase chain reaction (PCR) amplification was done for all exons of IRF6, and a missense mutation was discovered in exon 4. The tyrosine in the normal protein at this position is conserved across mammals, frogs, and chickens, so despite the fact that it was a previously unreported mutation, it was expected to be deleterious. This study is not the first case of different phenotypes occurring between monozygotic twins. Possible causes of phenotypic variability include variations in the intrauterine environment, epigenetic differences, or chance effects.[6]
## Pathophysiology[edit]
Lip pits were first reported in 1845 by Demarquay who thought they were indentations made by the upper incisors. Today it is known that they occur during embryogenesis due to IRF6 mutations. On day 32 of embryonic development there are four growth centers of the lower lip divided by two lateral grooves and one median. By day 38 of normal development, the grooves have disappeared. However, when growth of the mandibular process is impeded, a lip pit occurs. Lip pits begin to develop on day 36. Cleft lip begins to develop on day 40, and cleft palate emerges on day 50 of development.[3]
There are three types of lip pits, which are classified according to their location: midline upper, comissural, and lower lip. The most common phenotype is two symmetrical lower lip pits flanking both sides of the midline in the bilateral paramedial sinuses. Lower lip pits may also be bilaterally, unilaterally, or medially asymmetrical. The occurrence of a single lip pit is considered incomplete expression, and it typically occurs on the left side of the lower lip. There are also three different shapes for lip pits, the most common being circular or oval; less common forms include slit-like or transverse. The lip pits extend into the orbicularis oris muscle, ending in blind sacs surrounded by mucous glands. In some cases mucous is excreted when the muscles contract.[3]
## Diagnosis[edit]
Clinical diagnosis based on orofacial clefts and lip pits typically occurs shortly after birth. Certain defects may be difficult to diagnose, particularly a submucous cleft palate. This form of CP may not be detected except through finger palpation, as the mucosa covering the palate is intact, but the muscles underneath have lost their proper attachments. Feeding problems, impaired speech, and hearing loss are symptoms of a submucous cleft palate.[4] Furthermore, approximately 15% of VWS cases with orofacial clefts, in the absence of prominent lip pits, cannot be easily distinguished from non-syndromic forms of orofacial clefting.[7] Therefore, it is very important to closely examine these patients as well as their relatives for lip pits, especially when there is a family history of mixed clefting, in order to make the VWS diagnosis.[3] Dentists may also play an important role in diagnosing cases not detected at birth, as they detect hypodontia commonly associated with VWS. The patients most commonly lack the upper second premolars followed by the lower second premolars and upper lateral incisors. The absence of these teeth might play a role in the constricting of the dental arches.[3][4]
The clinical signs seen in VWS are similar to those of popliteal pterygium syndrome (PPS), which is also an autosomal dominant disease. Approximately 46% of affected individuals have lip pits; other features include genital abnormalities, abnormal skin near nails, syndactyly of fingers and toes, and webbed skin. The disease is also caused by mutations in IRF6; however, they occur in the DNA-binding domain of IRF6 and result in a dominant negative effect in which the mutated IRF6 transcription factor interferes with the ability of the wild type copy to function, in the case of a heterozygous individual.[2]
### Genetic Counseling[edit]
Genetic counseling for VWS involves discussion of disease transmission in the autosomal dominant manner and possibilities for penetrance and expression in offspring.[3] Autosomal dominance means affected parents have a 50% chance of passing on their mutated IRF6 allele to a their child. Furthermore, if a cleft patient has lip pits, he or she has a ten times greater risk of having a child with cleft lip with or without cleft palate than a cleft patient who does not have lip pits.[4] Types of clefting between parents and affected children are significantly associated; however, different types of clefts may occur horizontally and vertically within the same pedigree. In cases where clefting is the only symptom, a complete family history must be taken to ensure the patient does not have non-syndromic clefting.[3]
## Treatment[edit]
Lip pits may be surgically removed either for aesthetic reasons or discomfort due to inflammation caused by bacterial infections or chronic saliva excretion, though spontaneous shrinkage of the lip pits has occurred in some rare cases. Chronic inflammation has also been reported to cause squamous-cell carcinoma. It is essential to completely remove the entire lip pit canal, as mucoid cysts can develop if mucous glands are not removed. A possible side effect of removing the lip pits is a loose lip muscle. Other conditions associated with VWS, including CL, CP, congenital heart defects, etc. are surgically corrected or otherwise treated as they would be if they were non-syndromic.[3]
## References[edit]
1. ^ "Van der Woude syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17.
2. ^ a b c d Malik S, Kakar N, Hasnain S, Ahmad J, Wilcox ER, Naz S (2010). "Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan". Clinical Genetics. 78 (3): 247–256. doi:10.1111/j.1399-0004.2010.01375.x. PMID 20184620.
3. ^ a b c d e f g h i Rizos M, Spyropoulos MN (2004). "Van der Woude syndrome: a review. Cardinal signs, epidemiology, associated features, differential diagnosis, expressivity, genetic counselling, and treatment". European Journal of Orthodontics. 26 (1): 17–24. doi:10.1093/ejo/26.1.17. PMID 14994878.
4. ^ a b c d e f g Lam AK, David DJ, Townsend GC, Anderson PJ (2010). "Van der Woude syndrome: dentofacial features and implications for clinical practice". Australian Dental Journal. 55 (1): 51–58. doi:10.1111/j.1834-7819.2009.01178.x. PMID 20415912.
5. ^ [1], OMIM Van der Woude Syndrome 2
6. ^ Jobling R, Ferrier RA, McLeod R, Petrin AL, Murray JC, Thomas MA (2011). "Monozygotic twins with variable expression of Van der Woude syndrome". American Journal of Medical Genetics. 155A (8): 2008–2010. doi:10.1002/ajmg.a.34022. PMC 3140610. PMID 21739575.
7. ^ Salahshourifar I, Sulaiman WA, Halim AS, Zilfalil BA (2012). "Mutation screening of IRF6 among families with non-syndromic oral clefts and identification of two novel variants: review of the literature". European Journal of Medical Genetics. 55 (6–7): 389–393. doi:10.1016/j.ejmg.2012.02.006. PMID 22440537.
## External links[edit]
Classification
D
* ICD-10: Q38.0
* OMIM: 119300 606713
* MeSH: C563529 C536528, C563529
* DiseasesDB: 31926
External resources
* eMedicine: ped/2753
* Orphanet: 888
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Van der Woude syndrome
|
c0175697
| 25,701 |
wikipedia
|
https://en.wikipedia.org/wiki/Van_der_Woude_syndrome
| 2021-01-18T18:53:59 |
{"gard": ["8414"], "mesh": ["C563529", "C536528"], "umls": ["C0175697"], "orphanet": ["888"], "wikidata": ["Q2033532"]}
|
A number sign (#) is used with this entry because nephronophthisis-1 (NPHP1) is caused by homozygous or compound heterozygous mutation in or deletion of the gene encoding nephrocystin (607100) on chromosome 2q13.
Description
Nephronophthisis is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. It is the most frequent genetic cause of renal failure in children. NPHP may be combined with extrarenal manifestations, such as liver fibrosis, situs inversus, or cardiac malformations. When nephronophthisis is combined with retinitis pigmentosa, the disorder is known as Senior-Loken syndrome (SLSN1; 266900); when it is combined with cerebellar vermis hypoplasia, the disorder is known as Joubert syndrome (JBTS1; 213300); and when it is combined with multiple developmental and neurologic abnormalities, the disorder is often known as Meckel-Gruber syndrome (MKS1; 249000). Because most NPHP gene products localize to the cilium or its associated structures, nephronophthisis and the related syndromes have been termed 'ciliopathies' (summary by Hoff et al., 2013).
Clinical features of familial juvenile nephronophthisis include anemia, polyuria, polydipsia, isosthenuria, and death in uremia. Simms et al. (2009) provided a detailed review of nephronophthisis, including a discussion of clinical features and molecular genetics.
### Genetic Heterogeneity of Nephronophthisis
NPHP2 (602088) is caused by mutation in the INVS gene (243305) on chromosome 9q31; NPHP3 (604387) is caused by mutation in the NPHP3 gene (608002) on chromosome 3q22; NPHP4 (606966) is caused by mutation in the NPHP4 gene (607215) on chromosome 1p36; NPHP7 (611498) is caused by mutation in the GLIS2 gene (608539) on chromosome 16p13; NPHP9 (613824) is caused by mutation in the NEK8 gene (609799) on chromosome 17q11; NPHP11 (613550) is caused by mutation in the TMEM67 gene (609884) on chromosome 8q22; NPHP12 (613820) is caused by mutation in the TTC21B gene (612014) on chromosome 2q24; NPHP13 (614377) is caused by mutation in the WDR19 gene (608151) on chromosome 4p14; NPHP14 (614844) is caused by mutation in the ZNF423 gene (604557) on chromosome 16; NPHP15 (614845) is caused by mutation in the CEP164 gene (614848) on chromosome 11q; NPHP16 (615382) is caused by mutation in the ANKS6 gene (615370) on chromosome 9q22; NPHP18 (615862) is caused by mutation in the CEP83 gene (615847) on chromosome 12q22; NPHP19 (616217) is caused by mutation in the DCDC2 gene (605755) on chromosome 6p22; and NPHP20 (617271) is caused by mutation in the MAPKBP1 gene (616786) on chromosome 15q13.
Nomenclature
The disorder symbol NPHP1 was suggested to distinguish this locus from NPHL1 (nephrolithiasis, X-linked; 310468) and NPHS1 (congenital nephrosis, Finnish type; 256300) (Hildebrandt, 1997).
Clinical Features
Like several other mendelizing disorders, this one was first described by Fanconi et al. (1951). In the various reports, anemia, polyuria, polydipsia, isosthenuria, and death in uremia have been features. Hypertension and proteinuria are conspicuous in their absence. Symmetrical destruction of the kidneys involving both tubules and glomeruli (which were hyalinized) are observed. The age at death ranges from about 4 to 15 years.
Mangos et al. (1964) thought decreased urine concentrating ability might be a manifestation of heterozygotes. Herdman et al. (1967) described medullary cystic disease in 7- and 5-year-old sibs and in a 7-year-old boy whose sister had died of the disease. They were impressed with the probable identity of medullary cystic disease and familial nephronophthisis. Mongeau and Worthen (1967) came to the same conclusion, as did Strauss and Sommers (1967) who with humor commented that those who gave the name of medullary cysts of the kidney focused 'attention on the hole as the characteristic feature of the doughnut rather than on the kind of dough enclosing the hole.' Even though one form of medullary cystic disease may be the same as juvenile nephronophthisis, it is clear that a separate form of polycystic kidney, medullary type (174000), inherited as a dominant, also exists. The sibship reported by Meier and Hess (1965) had first-cousin parents and apparently independent inheritance of 2 recessive disorders, retinitis pigmentosa and nephronophthisis. (More likely this was the syndrome described in entry 266900.)
Sworn and Eisinger (1972) reported 3 affected sibs in one of whom there was biopsy demonstration of medullary cystic disease whereas in another, nephronophthisis was found at autopsy. They suggested that the morphologic findings in the kidney may be a function of age, i.e., that longer-surviving patients are more likely to show the changes of medullary cystic disease. This is the second most common cause of childhood chronic renal failure. Excessive urinary loss of sodium accounts for the rarity of hypertension. Excessive urinary loss of potassium is thought to be the 'cause' of the cystic change.
Boichis et al. (1973) described an association of nephronophthisis and congenital hepatic fibrosis in sibs. Five had demonstrated renal disease. Two died of renal failure at ages 7 and 15. A third was maintained on hemodialysis. The nosologic relation to the usual nephronophthisis on the one hand and polycystic renal disease on the other is unclear. It may be a distinct entity. Steele et al. (1980) reviewed 21 patients. In 10, there was a 'familial incidence,' consistent with autosomal recessive inheritance for the series as a whole. In 7 patients an associated and characteristic retinal degeneration dated from infancy. Renal cysts were uncommon. The authors listed 12 other designations that have been used.
In the retinal dysplasia of nephronophthisis, the classic paravenous 'bone spicule' pigmentation of retinitis pigmentosa is not seen. Pale optic nerve head and attenuated blood vessels are seen, as in other forms of chorioretinal degeneration. Cohen and Hoyer (1986) studied renal tissues from 4 patients with nephronophthisis, using immunofluorescence with antibodies to laminin, type IV collagen, and tubular basement membranes. They found constant morphologic changes affecting tubular basement membranes of all segments of the nephron, with or without cysts. These included extreme thinning and attenuation, layering, and thickening. Laminin and type IV collagen were present in normal intensity and distribution. Cohen and Hoyer (1986) compared the changes in the tubular basement membrane to the changes that occur in glomerular basement membrane in the Alport syndrome (301050). Khoury et al. (1988) described a family in which 3 of 4 sibs with congenital absence of permanent teeth (206780) were shown to have familial medullary sponge kidney; the fourth refused to be examined. Phenotypically, the autosomal dominant type of medullary cystic disease was suggested.
Hallmarks of familial nephronophthisis are tubular basement membrane disruption, interstitial lymphohistiocytic cell infiltration, and development of cysts at the corticomedullary border of the kidneys (Waldherr et al., 1982). The histology in later stages of NPH always merges into a chronic sclerosing tubulointerstitial nephropathy, which is found in chronic renal failure of all origins.
Ala-Mello et al. (1999) reviewed the clinical features of 59 nephronophthisis patients identified by a nationwide survey in Finland. The incidence was 1:61,800 live births over a 20-year period. Seventeen patients came from 4 families showing dominant inheritance and 37 from 28 apparently recessive families. Two patients were considered to have new dominant mutations; 3 sporadic patients could not be classified. About two-thirds of the recessive patients were found to be homozygous for a deletion at 2q13. The most significant difference between recessive patients with deletions, recessive patients without deletions, and dominant patients was the age at onset of disease, at the start of dialysis, and at renal transplantation, which showed a significant increase from one group to the next. These findings will help to determine the mode of inheritance in a sporadic patient without a deletion as well as the prognosis.
Inheritance
Autosomal recessive inheritance has been observed. Von Sydow and Ranstrom (1962) observed parental consanguinity.
Chamberlin et al. (1977) arrived at the following conclusion concerning the relation of juvenile nephronophthisis and medullary cystic disease: 'These diseases...very likely are a single disease entity and occur as a juvenile-onset, autosomal recessive form and as an adult-onset, autosomal dominant form.' There is an inconsistency in this sentence. In the strict genetic sense the disorders are unlikely to be the same entity if they have different modes of autosomal inheritance. There are rather abundant examples of disorders that are caused by different mutations in the same gene, some with a dominant-negative effect resulting in dominant inheritance, others with recessive inheritance due to inactivation of both alleles of the gene; see Table 15 in McKusick (1998). Actually, despite the similarity in phenotype (except for age of onset), distinctness of the autosomal recessive familial juvenile nephronophthisis and the autosomal dominant medullary cystic kidney disease (autosomal dominant nephronophthisis) is indicated by the fact that the disorders map to different chromosomal sites, 2q13 and 1q21, respectively (see later).
Mapping
By family linkage studies in 22 multiplex families (18 without and 4 with ocular abnormalities), Antignac et al. (1993) localized the mutant gene for this disorder to chromosome 2p in a region between D2S48 and D2S51. The microsatellite marker at the D2S160 locus gave a lod score of 4.78 at theta = 0.05 in 18 families with isolated NPH, whereas the same marker excluded linkage in the 4 families with associated ocular abnormalities (thus corroborating the view that Senior-Loken syndrome (266900) is a distinct entity). The markers used in mapping the locus had been shown to be tightly linked to several probes, all located on chromosome 2p and more centromeric than NMYC (164840) at 2p24.1 or APOB (107730) at 2p24; thus, the NPH1 locus can be assigned to the 2p23-cen region. However, in situ hybridization of YAC clones isolated with 2 closely linked markers led Medhioub et al. (1994) to assign the NPH1 gene to 2q13. Furthermore, based on haplotype analysis and specific recombination events, the NPH1 gene was placed between D2S293/D2S340 and D2S121, a genetic interval of about 5 to 7 cM. Hildebrandt et al. (1995) likewise concluded that the NPH1 gene is probably located in 2q13 in an interval of 6.9 cM between D2S293 and D2S363.
Medhioub et al. (1994) studied 4 NPH families in which haplotype analyses showed unequivocally that the disorder was not linked to the chromosome 2 markers, thus indicating genetic heterogeneity.
Molecular Genetics
Familial nephronophthisis that maps to chromosome 2q13 is associated with mutation in and/or deletion of the NPHP1 gene (see 607100.0001-607100.0005) (Saunier et al., 1997; Hildebrandt et al., 1997). For a complete discussion of the molecular genetics of nephronophthisis-1, see 607100.
In a worldwide cohort of 1,056 patients diagnosed with a nephronophthisis-related ciliopathy (NPHP-RC), including 447 patients with isolated nephronophthisis and 609 patients with additional extrarenal manifestations, Halbritter et al. (2013) performed a high-throughput mutation analysis of 13 genes known to cause these disorders. Biallelic mutations were found in 127 patients (12%), and heterozygous truncating mutations were found in 31 patients (2.9%). A total of 159 different mutations were found in 11 of the 13 genes, 99 of which were novel. The most common mutations occurred in the following genes: NPHP1 (23 patients), NPHP4 (22 patients), CEP290 (609237; 20 patients), NPHP3 (17 patients), and IQCB1 (610743; 16 patients).
### Genetic Modifiers
Louie et al. (2010) identified a 2488C-T (arg830-to-trp; R830W) hypomorphic SNP in the WD40 repeat domain of the AHI1 gene (608894) that was associated with retinal degeneration in patients with nephronophthisis. Among 153 Italian NPHP individuals, the T allele was found at a higher frequency among those with retinal degeneration compared to those without retinal degeneration (25% compared to 1.8%, p = 5.36 x 10(-6)) and to controls, yielding a relative risk of 7.5. The findings were irrespective of the mutations causing NPHP, and suggested that variation in AHI1 may explain some of the variability in retinal phenotypes. A similar association was not observed for 155 patients with Joubert syndrome (JBTS; see, e.g., 213300).
### Associations Pending Confirmation
For discussion of a possible association between NPHP-related ciliopathies and variation in the IFT81 gene, see 605489.0001 and 605489.0002.
For discussion of a possible association between nephronophthisis and variation in the INTU gene, see 610621.0005.
Animal Model
Lyon and Hulse (1971) described the mouse mutation 'kd' (kidney disease), which seems to cause a homologous disorder.
Simon et al. (1994) concluded that NPH1 is not homologous to cpk in the mouse because it appears to map to a different region of homology between 2p and mouse chromosome 12.
Jiang et al. (2009) used Nphp1-mutant mice carrying an exon 20 deletion and transgenic mice expressing EmGFP-tagged nephrocystin to demonstrate that nephrocystin was localized to the connecting cilium axoneme, where it affected the sorting mechanism and transportation efficiency of the intraflagellar transport between inner and outer segments of photoreceptors.
INHERITANCE \- Autosomal recessive GROWTH Other \- Growth retardation GENITOURINARY Kidneys \- Nephronophthisis \- End stage renal disease \- Tubular atrophy \- Tubular basement membrane disintegration \- Interstitial fibrosis \- Corticomedullary renal cysts METABOLIC FEATURES \- Polyuria \- Polydipsia \- Absence of hypertension HEMATOLOGY \- Anemia LABORATORY ABNORMALITIES \- Hyposthenuria (inability to concentrate urine normally) MISCELLANEOUS \- Medial onset of end stage renal disease 13 years \- Allelic to Senior-Loken syndrome 1 ( 266900 ) and Joubert syndrome 4 ( 609583 ) MOLECULAR BASIS \- Caused by mutation in the nephrocystin 1 gene (NPHP1, 607100.0001 ) ▲ Close
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NEPHRONOPHTHISIS 1
|
c1855681
| 25,702 |
omim
|
https://www.omim.org/entry/256100
| 2019-09-22T16:24:26 |
{"doid": ["0111112"], "omim": ["256100"], "orphanet": ["93592", "655"], "synonyms": ["Alternative titles", "NEPHRONOPHTHISIS, FAMILIAL JUVENILE", "NPH1"], "genereviews": ["NBK368475"]}
|
## Summary
### Clinical characteristics.
Adenosine deaminase (ADA) deficiency is a systemic purine metabolic disorder that primarily affects lymphocyte development, viability, and function. The clinical phenotypic spectrum includes:
* Severe combined immunodeficiency disease (SCID), often diagnosed by age six months and usually by age 12 months;
* Less severe "delayed" onset combined immune deficiency (CID), usually diagnosed between age one and ten years;
* "Late/adult onset" CID, diagnosed in the second to fourth decades;
* Benign "partial ADA deficiency" (very low or absent ADA activity in erythrocytes but greater ADA activity in nucleated cells), which is compatible with normal immune function.
Infants with typical early-onset ADA-deficient SCID have failure to thrive and opportunistic infections associated with marked depletion of T, B, and NK lymphocytes, and an absence of both humoral and cellular immune function. If immune function is not restored, children with ADA-deficient SCID rarely survive beyond age one to two years. Infections in delayed- and late-onset types (commonly, recurrent otitis, sinusitis, and upper respiratory) may initially be less severe than those in individuals with ADA-deficient SCID; however, by the time of diagnosis these individuals often have chronic pulmonary insufficiency and may have autoimmune phenomena (cytopenias, anti-thyroid antibodies), allergies, and elevated serum concentration of IgE. The longer the disorder goes unrecognized, the more immune function deteriorates and the more likely are chronic sequelae of recurrent infection.
### Diagnosis/testing.
The diagnosis of ADA deficiency is established in a proband:
* With <1% of normal ADA catalytic activity in hemolysates (in untransfused individuals) or in extracts of other cells (e.g., blood mononuclear cells, fibroblasts); AND/OR
* By the identification of biallelic pathogenic variants in ADA by molecular genetic testing.
### Management.
Treatment of manifestations: Infections are treated with specific antibiotic, antifungal, and antiviral agents and administration of intravenous immunoglobulin (IVIg); prophylaxis is provided for Pneumocystis jiroveci infection.
Prevention of primary manifestations: Restoration of a functional immune system is essential. The preferred treatment is bone marrow/stem cell transplantation (BMT/SCT) from an HLA-identical healthy sib or close relative. However, most individuals with ADA-deficient SCID lack an HLA-identical related donor. For these individuals, alternative therapies can be considered:
* BMT/SCT from a "non-ideal" donor, which may be an HLA-matched unrelated donor, an HLA-haploidentical donor (usually a parent), or umbilical cord-derived stem cells
* Enzyme replacement therapy (ERT) with polyethylene glycol-modified bovine adenosine deaminase (PEG-ADA)
* Gene therapy, which is currently experimental
Surveillance: Annual or more frequent evaluation of lymphocyte counts, serum immunoglobulin levels, and various in vitro tests of cellular and humoral immune function following BMT/SCT and during ERT (more frequent monitoring and other specialized testing would be required for participants in gene therapy trials). Individuals on ERT also require periodic monitoring of PEG-ADA levels in plasma and metabolite levels in erythrocytes, and under some circumstances testing for anti-ADA antibodies.
Agents/circumstances to avoid: The use of adenine arabinoside (a substrate for ADA) as an antiviral agent or for chemotherapy of malignancies should be avoided; pentostatin, a potent ADA inhibitor used to treat some lymphoid malignancies, would be ineffective in persons who lack ADA, and would interfere with PEG-ADA.
Evaluation of relatives at risk: In the newborn sibs of a proband, it is appropriate to either assay ADA catalytic activity or perform molecular genetic testing (if the family-specific pathogenic variants are known), so that morbidity and mortality can be reduced by early diagnosis and treatment.
### Genetic counseling.
ADA deficiency 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 testing for pregnancies at increased risk are possible once the pathogenic variants have been identified in the family.
## Diagnosis
### Suggestive Findings
Adenosine deaminase (ADA) deficiency should be suspected in individuals with the following newborn screening results, clinical findings (by age), and supportive laboratory findings.
Newborn screening
* In newborns found to have reduced T cell receptor excision circles (TRECs), particularly if follow-up lymphocyte subset analysis reveals a deficiency of T, B, and NK lymphocytes (T-B- NK- phenotype), biochemical testing for ADA deficiency should be performed.
* Historically, about 15% of all cases of SCID result from ADA deficiency, but the frequency among newborns identified as having SCID by screening for a reduced number of TRECs is not yet known.
Note: (1) Individuals with delayed or late/adult ADA deficiency may have TRECs in the normal range. (2) Reduced levels of a B lymphocyte marker, kappa-deleting recombination excision circles (KRECs), have also been found in DNA from dried blood spots (DBS) of individuals with delayed- or late-onset ADA deficiency [Speckmann et al 2012].
Clinical findings
* Infancy (severe combined immunodeficiency disease or SCID phenotype):
* Failure to thrive
* Absence of lymphoid tissues (tonsils, lymph nodes)
* Opportunistic infections
* Persistent diarrhea
* Extensive dermatitis
* Recurrent pneumonia
* Childhood ("delayed" onset combined immune deficiency [CID]) and adulthood ("late/adult onset" CID):
* Recurrent otitis media
* Sinusitis
* Upper respiratory infections
* Chronic pulmonary insufficiency
* Allergies or autoimmunity
Supportive laboratory findings
* Immune function
* Lymphopenia is present at birth. The total blood lymphocyte count is usually <500/µL (normal for neonates: 2,000 to >5,000).
* All major lymphoid lineages (T-, B-, and NK-cells) are depleted as demonstrated by flow cytometry.
* In vitro lymphocyte function, as measured by proliferative response to mitogens and antigens, is low or absent.
* Serum immunoglobulins are low and no specific antibody response to infections and immunizations is observed. However, those with a delayed or late-onset phenotype may have elevated serum IgE levels.
* Elevated deoxyadenosine (dAdo) triphosphate (dATP) or total dAdo nucleotides (dAXP, measured as the sum of dAMP+dADP+dATP) in erythrocytes
* Marked increase in dATP and total dAXP, a finding pathognomonic for ADA deficiency.
* In untreated affected individuals, the level of dAXP in hemolysates or dried blood spot (DBS) extracts correlates with clinical phenotype (SCID > "delayed/late" onset > "partial ADA deficiency").
* Even after transfusion, some elevation in erythrocyte dAXP persists and strongly indicates underlying ADA deficiency.
* Reduced S-adenosylhomocysteine hydrolase (AdoHcyase, SAHase) activity in erythrocytes, typically <5% of normal
* Elevated urinary dAdo in untreated affected individuals
* Elevated levels of adenosine (Ado) and dAdo in extracts of dried blood spots (DBS), quantified using tandem mass spectrometry [Azzari et al 2011, Speckmann et al 2012, la Marca et al 2013]
### Establishing the Diagnosis
The diagnosis of ADA deficiency is established in a proband:
* With <1% of normal ADA catalytic activity in hemolysates or in extracts of dried blood spots (DBS) prepared with EDTA or heparin-anticoagulated blood; AND/OR
* By the identification of biallelic pathogenic variants in ADA on molecular genetic testing (see Table 1).
Note: (1) In recently transfused individuals, a deficiency of ADA catalytic activity can be demonstrated in extracts of non-erythroid cells (e.g., blood mononuclear cells, fibroblasts). (2) Analysis of ADA enzymatic activity in plasma is not useful for diagnosis because ADA activity is much lower in plasma than in cells, even in normal (non ADA-deficient) individuals. Additionally, plasma contains adenosine deaminase activity as a result of another enzyme known as ADA2 (see Differential Diagnosis).
Molecular genetic testing approaches can include single-gene testing and use of a multigene panel:
* Single-gene testing. Sequence analysis of ADA is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.
* Multigene panel. A panel that includes ADA 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.
### Table 1.
Molecular Genetic Testing Used in Adenosine Deaminase Deficiency
View in own window
Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
ADASequence analysis 3>90% 4
Gene-targeted deletion/duplication analysis 5~3% 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 individuals with biochemically documented ADA deficiency
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used 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\.
Hirschhorn [1999], Hershfield & Mitchell [2001], Vihinen et al [2001]
## Clinical Characteristics
### Clinical Description
Adenosine deaminase (ADA) deficiency is a systemic purine metabolic disorder that primarily affects lymphocyte development, viability, and function; various effects on several non-lymphoid organs are also observed in some affected individuals [Hirschhorn 1999, Hershfield & Mitchell 2001, Hershfield 2004, Whitmore & Gaspar 2016]. The phenotypic spectrum associated with ADA deficiency includes early-onset SCID diagnosed in infancy; less severe "delayed/late" -onset combined immune deficiency (CID) diagnosed in older children and adults; and benign "partial ADA deficiency," which is discovered by screening populations or relatives of individuals with SCID for deficiency of erythrocyte ADA activity.
#### ADA-Deficient Severe Combined Immunodeficiency Disease (SCID)
The clinical picture in infants with typical early-onset ADA-deficient SCID is similar to that associated with SCID resulting from other genetic defects [Dvorak et al 2013, Shearer et al 2014]. Affected individuals present in the first weeks to months of life with failure to thrive and opportunistic infections associated with marked lymphocytopenia and the absence of both humoral and cellular immune function. The diagnosis of SCID is often made within the first six months of life and usually by age 12 months.
Persistent diarrhea, extensive dermatitis, recurrent pneumonia, and other life-threatening illnesses caused by opportunistic infections occur frequently. The initial hospitalization is often for pneumonitis, which may result from viral or Pneumocystis jiroveci infection. However, a causative agent often cannot be identified.
Noninfectious lung disease appears to occur more frequently in individuals with ADA deficiency than with other genetic forms of SCID [Booth et al 2012]. Pulmonary alveolar proteinosis has also been found more frequently in individuals with ADA-deficient SCID than in those with other forms of SCID [Grunebaum et al 2012]. Pulmonary dysfunction in those with ADA deficiency has also been identified using the effort-independent technique of impulse oscillometry [Komarow et al 2015].
Physical findings include growth failure, the absence of lymphoid tissues (tonsils, lymph nodes), and the effects of specific infections. Thymus shadow is absent on x-ray. Characteristic anterior rib cupping, scapular spurring, and other skeletal abnormalities are present at diagnosis in about half of individuals with ADA deficiency. These abnormalities appear to resolve after a few months of treatment [Manson et al 2013].
Other organ involvement. In addition to marked depletion of T, B, and NK lymphocytes, some individuals with ADA deficiency may show reduced neutrophil counts and bone marrow abnormalities including myeloid dysplasia and hypocellularity [Sokolic et al 2011]. In some cases, abnormal liver function tests or various neurologic abnormalities (including sensorineural deafness) also occur and may be clinically significant [Bollinger et al 1996, Tanaka et al 1996, Rogers et al 2001, Albuquerque & Gaspar 2004, Nofech-Mozes et al 2007]. It is often unclear whether these hepatic and neurologic abnormalities are caused by the metabolic effects of ADA deficiency itself or are secondary to the immunodeficiency (i.e., to infections or to their treatment – e.g., with aminoglycoside antibiotics). However, in some individuals, hepatic and neurologic abnormalities have improved or resolved with institution of enzyme replacement therapy. If immune function is not restored, individuals with ADA-deficient SCID rarely survive beyond age one to two years.
* A rare malignant skin tumor, dermatofibrosarcoma protuberans (DFSP) has been identified in several individuals with ADA deficiency [Kesserwan et al 2012]. The natural history of DFSP in people with ADA deficiency is unknown at this time; surveillance is recommended.
* Presentation of ADA-deficient SCID as atypical hemolytic uremic syndrome has recently been reported [Nikolajeva et al 2015].
#### Delayed-/Late-Onset ADA Deficiency
Approximately 15%-20% of children with ADA deficiency have a "delayed" onset of clinical symptoms, usually diagnosed between age one and ten years. Rarely, individuals are diagnosed in the second to fourth decades ("late/adult" onset). The immunologic abnormalities are less pronounced than in SCID and these affected individuals are usually referred to as having CID, or sometimes "leaky SCID" [Shearer et al 2014]. Infections in delayed- and late-onset types may initially be less severe than in those individuals with full-blown SCID, and growth may be less severely affected. Recurrent otitis, sinusitis, and upper respiratory infections are common. Palmar and plantar warts may be persistent, and older individuals have presented with unusual papilloma viral infections [Antony et al 2002, Artac et al 2010]. By the time of diagnosis, these individuals often have chronic pulmonary insufficiency and possibly autoimmune phenomena, including cytopenias and anti-thyroid antibodies [Sauer et al 2012]. Allergies and elevated serum concentration of IgE are common.
Individuals with a delayed- or late-onset phenotype may survive undiagnosed into the first decade of life or beyond. However, the longer the disorder goes unrecognized, the more immune function deteriorates and the more likely are chronic sequelae of recurrent respiratory and other types of infection.
#### Partial ADA Deficiency
Screening of populations and families of probands with ADA-deficient SCID has identified some healthy individuals with very low or absent ADA activity in erythrocytes, but greater levels of ADA activity (2%-50% of normal) in nucleated cells. This benign condition, which is compatible with normal immune function, has been called "partial ADA deficiency."
### Genotype-Phenotype Correlations
Most known ADA pathogenic variants have been discovered through research into the relationship of genotype to phenotype [Hirschhorn et al 1990, Santisteban et al 1993, Arredondo-Vega et al 1994, Ozsahin et al 1997].
* A good correlation has been established between the effect of pathogenic variants on ADA activity and both clinical and metabolic phenotype [Arredondo-Vega et al 1998].
* In several individuals, the relationship of genotype to phenotype was modulated by mosaicism in lymphoid cells for reversion of deleterious pathogenic variants [Hirschhorn et al 1994, Hirschhorn et al 1996, Ariga et al 2001a, Arredondo-Vega et al 2002, Liu et al 2009, Moncada-Vélez et al 2011].
Systematic expression in E coli of more than 30 cDNAs with single missense variants identified in ADA-deficient individuals has shown that the total ADA activity expressed by both of an individual's mutated alleles correlates with age at diagnosis and the level of erythrocyte dAXP measured prior to treatment [Arredondo-Vega et al 1998]. A system for ranking the severity of genotypes has been proposed based on these data and the potential of other alleles to provide ADA activity. For this purpose, individual pathogenic ADA alleles are clustered in groups, as follows:
* Group 0. "Null" alleles (deletion, frameshifting, or nonsense variants)
* Groups I-IV. Missense variants ranked in order of increasing activity expressed in the E coli system
* Splice site variants. A separate group, as a low level of normal splicing may result in variable levels of ADA activity
Phenotype correlation with pathogenic variant type was assessed for 52 clinically diverse individuals with 43 genotypes composed of 42 different pathogenic alleles [Arredondo-Vega et al 1998]:
* ADA-deficiency SCID. Both alleles scored as Group 0 or I.
* Delayed-/late-onset ADA deficiency. At least one allele in Group II or III was detected.
* Partial ADA deficiency. At least one Group IV allele was detected.
Discordance in phenotype among first-degree ADA-deficient relatives in several families has been attributed to the following:
* Individual differences in "leakiness" of a splice site variant [Arredondo-Vega et al 1994]
* Mosaicism for reversion of a pathogenic allele in lymphoid cells [Arredondo-Vega et al 2002]
* The segregation of both alleles that cause a severe phenotype and a mild phenotype in a family [Santisteban et al 1995, Ozsahin et al 1997, Ariga et al 2001b]
### Prevalence
ADA deficiency has been estimated to occur in from 1:200,000 to 1:1,000,000 births. As information from newborn screening becomes available, estimates of the incidence of ADA deficiency may change.
All racial and ethnic groups are affected. Prevalence is higher in some geographic areas where a high degree of consanguinity exists in certain population groups.
## Differential Diagnosis
Purine nucleoside phosphorylase (PNP) deficiency (OMIM 613179) is an inborn error of purine metabolism that causes autosomal recessive immunodeficiency, which in some respects is similar clinically and pathophysiologically to adenosine deaminase (ADA) deficiency [Hershfield 2004]. Biochemical testing for both ADA and PNP deficiency should be performed in individuals with immunodeficiency who are suspected of having either disorder.
The SCID phenotype can also result from pathogenic variants in other genes [Buckley 2004, Fischer et al 2005, Dvorak et al 2013, Shearer et al 2014]. These disorders are similar clinically, but some have characteristic patterns of lymphocyte depletion that can be determined by flow cytometric enumeration of T, B, and natural killer (NK) cells in peripheral blood. The "T- B- NK-" pattern of lymphopenia in ADA deficiency differs from the "T- B+ NK-" pattern of the more common X-linked SCID, but it is not so well differentiated from "T- B-" patterns found in SCID caused by mutation of RAG1, RAG2, DCLRE1C, PRKDC, NHEJ1, and AK2 [Buckley 2004, Fischer et al 2005].
An inherited deficiency of the enzyme adenosine deaminase 2 (DADA2) caused by biallelic pathogenic variants in ADA2 (CECR1) was reported recently [Navon Elkan et al 2014, Zhou et al 2014]. The initial individuals identified with DADA2 deficiency had clinical features of an autoinflammatory condition associated with vasculopathy, but many also had immunodeficiency, usually manifested by reduced serum IgM and abnormalities of the B lymphocyte lineage. However, individuals with DADA2 deficiency have not had classic features of SCID or combined immune deficiency. At the biochemical level, DADA2 deficiency can be distinguished from ADA-SCID by the findings in DADA2 deficiency of: absent ADA2 activity in plasma but normal ADA activity in red cells; the absence of any elevation of adenosine or deoxyadenosine in plasma and urine; and the absence of elevated dATP and total dAXP in red blood cells. See Adenosine Deaminase 2 Deficiency.
HIV-AIDS should be considered in individuals with T lymphopenia and opportunistic infections, but the retroviral infection can be identified by specific testing.
For older individuals with delayed- and late-onset phenotypes, cystic fibrosis, common variable immunodeficiency (OMIM PS607594), and PNP deficiency could also be considered. Measurement of cellular ADA activity definitively distinguishes ADA deficiency from all other disorders associated with compatible clinical features.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with adenosine deaminase (ADA) deficiency, the following evaluations are recommended, some of which may be performed as part of the diagnostic evaluation:
* Identification of specific disease-causing viral, fungal, or bacterial organisms (both normal pathogens and opportunistic agents)
* Complete blood count (CBC)
* Flow cytometry to quantify lymphocyte subsets (T-, B-, NK-cells)
* Assessment of humoral immune function by measuring serum immunoglobulins and the titer of specific antibodies related to infections and immunizations
* Evaluation of cellular immune function by in vitro response of blood mononuclear cells to mitogens and antigens
* Measurement of erythrocyte dAXP concentration to evaluate metabolic severity
* Liver function testing to assess for metabolic hepatitis
* Auditory testing
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
The following are appropriate:
* Treatment of infections with specific antibiotic, antifungal, and antiviral agents
* Prophylaxis for Pneumocystis jiroveci
* Intravenous immunoglobulin (IVIg)
### Prevention of Primary Manifestations
Restoring a functional immune system is essential and can be achieved in several ways. The choice of therapy is complex and depends on a number of factors, including the affected person’s age and clinical status, the expectations and desires of the parents, and the specific experience and expertise of physicians in treating ADA-deficient SCID. A workshop held in 2008 developed consensus guidelines for therapy [Gaspar et al 2009] (full text).
Bone marrow/stem cell transplantation (BMT/SCT) from an HLA-identical healthy sib is the method of choice for treating all forms of SCID.
* This can be performed without cytoreductive conditioning of the affected individual, and without depletion of donor T-cells.
* Results vary among transplant centers, but the procedure is curative in approximately 70% or more of affected individuals.
* The main risks are graft-versus-host disease and delayed or incomplete recovery of humoral immune function, requiring continued immunoglobulin replacement.
For the majority of individuals with ADA-deficient SCID who lack an HLA-identical related donor, the following two forms of treatment can be considered [Gaspar et al 2009, Gaspar 2010, Candotti et al 2012, Baffelli et al 2015].
BMT/SCT from a "non-ideal" donor
* Donor-derived T-cells are depleted to minimize the risk of graft-versus-host disease.
* Pre-transplant cytoreductive "conditioning" of the recipient (individual with SCID) is often performed to prevent graft loss, which occurs with relative frequency in those with ADA-deficient SCID who are not conditioned.
Note: Some transplant centers do not perform conditioning of the recipient prior to a haploidentical transplant because of the risk of peri-transplant morbidity [Buckley et al 1999]. However, this latter approach has frequently been associated with a failure to achieve stable engraftment [Gaspar et al 2009, Gaspar 2010, Hassan et al 2012].
Following a T-cell-depleted transplant, return of functional T-cells requires three to four months. B-cell reconstitution is delayed longer, or may not be adequately achieved, requiring long-term immunoglobulin replacement therapy.
Note: Universal agreement regarding the best methods for performing partially mismatched BMT/SCT does not exist [Cancrini et al 2010, Gaspar 2010, Hassan et al 2012]. When considering therapeutic options, it is therefore important for parents to obtain specific information about prior experience and long-term results of transplants for ADA-deficient SCID at the center where their child will be treated.
Enzyme replacement therapy (ERT) has been used as a primary therapy in individuals who lack an HLA-identical marrow/stem cell donor when the risks associated with a partially mismatched transplant are deemed too great or when the risk of graft failure is high, as in older individuals with a delayed- or late-onset phenotype.
* Polyethylene glycol-modified bovine adenosine deaminase (PEG-ADA) is composed of purified bovine ADA covalently linked to multiple strands of PEG (average mass: 5 kd) in order to prolong circulating life and reduce immunogenicity. It is administered by intramuscular injection once or twice a week (~15-60 U/kg per week).
* By maintaining a high level of ADA activity in plasma, PEG-ADA eliminates extracellular Ado and dAdo, preventing the toxic metabolic effects that interfere with lymphocyte viability and function and that may injure other organs (liver, lung, brain) [Hershfield et al 1987, Hershfield & Mitchell 2001, Hershfield 2004, Gaspar et al 2009].
* ERT is not curative; PEG-ADA must be given regularly and at a sufficient dose to maintain a nontoxic metabolic environment.
* PEG-ADA has also been used as a secondary therapy in affected individuals who have failed to engraft following an unconditioned BMT/SCT, or in whom an acceptable recovery of immune function has not been achieved following experimental gene therapy.
Most individuals treated with PEG-ADA recover partial immune function that is sufficient to prevent opportunistic infections and other clinical manifestations of SCID. A lag of approximately two to four months occurs before T-cell function appears, but B-cells often increase earlier than after BMT/SCT. Lymphocyte counts and in vitro lymphocyte function usually increase during the first year of ERT, but beyond the first year or two most PEG-ADA-treated individuals remain lymphopenic and in vitro lymphocyte function fluctuates widely. Most individuals remain clinically well, but over time both T and B lymphocytes gradually decline in number and display various functional abnormalities [Chan et al 2005, Malacarne et al 2005, Serana et al 2010, Brigida et al 2014]. Approximately half of those maintained on ERT were continuing to receive immunoglobulin replacement.
More than 300 affected individuals have received PEG-ADA. Survival of PEG-ADA-treated individuals beyond five years and through approximately ten years is approximately 75%-80%, comparable or superior to that achieved with BMT/SCT (i.e. in individuals who lack an HLA-identical donor). Most deaths occurred during the first six months of treatment, with the majority in the first month due to life-threatening infections present at diagnosis.
Lymphoproliferative disorders have developed in eight individuals who received PEG-ADA for eight to 22 years [Hershfield 2004; Chan et al 2005; Kaufman et al 2005; Husain et al 2007; Author, unpublished data]. Hepatocellular carcinoma developed in one affected individual after 13 years of ERT, and was present in another at the time ERT was initiated following an unsuccessful stem cell transplant. A third affected individual died of hepatoblastoma after 2.5 years of ERT; the tumor was thought to have been present but undetected prior to ERT. Several other affected individuals have developed persistent hemolytic anemia, which in some cases began in association with a viral infection or with central catheter sepsis [Hershfield 2004, Lainka et al 2005].
The limitations of PEG-ADA therapy include primary failure to recover protective immune function, the development of neutralizing antibodies that reduce or eliminate efficacy, immune dysregulation (particularly in the first few months of therapy), and a risk that immune function will eventually (i.e., beyond 10-15 years) decline to an inadequate level. Approximately 20% of affected individuals have discontinued ERT in order to undergo BMT/SCT. In most of these cases, the transplant had been intended at the time of diagnosis but not performed because a suitable donor was not available or the affected individual had been too ill to undergo the procedure. In a minority of individuals, the transplant was performed because of declining immune function while receiving PEG-ADA. Overall, approximately half of these secondary transplants have been successful [Hershfield 2004, Gaspar et al 2009].
Most individuals treated with PEG-ADA for longer than a year develop antibodies that bind specifically to bovine ADA and are detectable by an enzyme-linked immunosorbent assay (ELISA); these are of no clinical significance. Neutralizing antibodies that inhibit catalytic activity and enhance clearance of PEG-ADA (and which do compromise efficacy) have developed in fewer than 10% of treated individuals [Chaffee et al 1992, Hershfield 1997]. No allergic or hypersensitivity reactions to PEG-ADA have occurred, and the treatment has generally been well tolerated.
Gene therapy, while still technically experimental, is still another treatment option for those who have failed all other options (see Therapies Under Investigation).
### Prevention of Secondary Complications
As noted under Treatment of Manifestations, affected individuals receive antibiotic prophylaxis for Pneumocystis, and also IVIG, prior to immune reconstitution. The use of such prophylaxis following transplantation and while receiving ERT varies and depends on the level of immune reconstitution achieved.
### Surveillance
Annual or more frequent evaluation of lymphocyte counts, serum immunoglobulin levels, and various in vitro tests of cellular and humoral immune function (i.e., as listed above for the evaluation of individuals suspected of having SCID) should be performed following BMT/SCT and during ERT [Gaspar et al 2009].
Individuals on ERT also require periodic monitoring as follows:
* Plasma levels of PEG-ADA activity
* Erythrocyte dAXP concentration
* Development of neutralizing antibodies, particularly if plasma ADA activity or clinical or immunologic status declines unexpectedly
* Monitoring for the appearance or recurrence of dermatofibrosarcoma protuberans
### Agents/Circumstances to Avoid
The use of adenine arabinoside (a substrate for ADA) as an antiviral agent or for chemotherapy of malignancies should be avoided.
Pentostatin, a potent ADA inhibitor used to treat some lymphoid malignancies, would be ineffective in persons who lack ADA, and would interfere with PEG-ADA.
### Evaluation of Relatives at Risk
It is appropriate to evaluate newborn sibs of a proband so that morbidity and mortality can be reduced by early diagnosis and treatment. Evaluations can include:
* Molecular genetic testing if the pathogenic variants in the family are known;
* Assay of ADA catalytic activity if the pathogenic variants in the family are not known.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Experimental gene therapy for ADA-deficient SCID employing gamma retroviral vectors has been under clinical investigation for more than 20 years [Engel et al 2003, Cavazzana-Calvo et al 2005]. Clinical trials since about 2000 have employed an approach that was first reported for two affected individuals treated in Milan, Italy and later updated for ten others [Aiuti et al 2002, Aiuti et al 2009]. This strategy involved discontinuing PEG-ADA (in those receiving ERT) and administering non-myeloablative conditioning prior to the infusion of vector carrying human ADA cDNA in order to transduce autologous CD34+ stem cells. Variations on this protocol have also been under investigation in the UK, US, and Japan. More than 40 affected individuals (most of whom had been receiving PEG-ADA) have been treated at these centers [Aiuti et al 2002, Gaspar et al 2006, Engel et al 2007, Aiuti et al 2009, Cappelli & Aiuti 2010, Selleri et al 2011, Candotti et al 2012, Sauer et al 2012, Gaspar et al 2013]. In most treated individuals, stable ADA expression in lymphoid cells has been achieved, along with correction of metabolic abnormalities in erythrocytes, which has been accompanied by reconstitution of both T and B cell immune function, although this reconstitution may take a year or more. Good health has been maintained without the need for ERT.
In contrast to the experience with gene therapy for X-linked SCID, no individuals with ADA deficiency have developed leukemia as a result of vector-associated insertional mutagenesis, and at this time no deaths have been reported [Cicalese et al 2016]. In May of 2016, GlaxoSmithKline announced that the European Commission had approved the gamma retroviral vector developed in Milan for use in treatment of SCID due to ADA deficiency. However, because of remaining concerns about potential insertional mutagenesis, and in order to achieve more effective ADA expression, clinical investigation of gene therapy using lentiviral vectors has now begun [Farinelli et al 2014, Candotti 2016].
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.
*[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
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*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
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*[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-hydroxybutyric 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
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*[SDPD]: Self-Defeating Personality Disorder
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*[m.]: married
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*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
|
Adenosine Deaminase Deficiency
|
c0268124
| 25,703 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1483/
| 2021-01-18T20:47:02 |
{"synonyms": ["ADA Deficiency", "ADA-SCID"]}
|
## Summary
### Clinical characteristics.
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with high risks for a diverse spectrum of childhood- and adult-onset malignancies. The lifetime risk of cancer in individuals with LFS is ≥70% for men and ≥90% for women. Five cancer types account for the majority of LFS tumors: adrenocortical carcinomas, breast cancer, central nervous system tumors, osteosarcomas, and soft-tissue sarcomas. LFS is associated with an increased risk of several additional cancers including leukemia, lymphoma, gastrointestinal cancers, cancers of head and neck, kidney, larynx, lung, skin (e.g., melanoma), ovary, pancreas, prostate, testis, and thyroid. Individuals with LFS are at increased risk for cancer in childhood and young adulthood; survivors are at increased risk for multiple primary cancers.
### Diagnosis/testing.
The diagnosis of LFS is established in a proband who meets ALL THREE classic clinical criteria and/or has a heterozygous germline pathogenic variant in TP53. Classic clinical criteria:
* A proband with a sarcoma diagnosed before age 45 years
* A first-degree relative with any cancer diagnosed before age 45 years
* A first- or second-degree relative with any cancer diagnosed before age 45 years or a sarcoma diagnosed at any age
### Management.
Treatment of manifestations: Routine oncologic management is recommended for malignancies, with the exception of breast cancer, in which bilateral mastectomy rather than lumpectomy is recommended in order to reduce the risks of a second primary breast cancer and avoid radiation therapy. Concerns about increased risk for radiation-induced second primary tumors has led to more cautious use of therapeutic radiation in general, but most experts recommend that treatment efficacy be prioritized above concerns about late effects after careful analysis of risks and benefits.
Prevention of primary manifestations: Prophylactic bilateral mastectomy to reduce the risk for breast cancer is an option for women with a germline TP53 pathogenic variant. Colonoscopy may be considered surveillance as well as primary prevention of colorectal cancer. Avoidance of sun exposure, tobacco use, and exposure to other known or suspected carcinogens is encouraged.
Surveillance: Comprehensive physical examination and ultrasound of abdomen and pelvis every 3-4 months from birth to age 18 years, annual neurologic exam and whole-body MRI including brain MRI from the time of diagnosis. In individuals 18 years or older, complete physical exam every 6 months, ultrasound of abdomen and pelvis and dermatologic exam annually. Women should have a clinical breast examination every 6-12 months beginning at age 20-25 years, annual breast MRI beginning at age 20-30 years, annual mammogram and breast MRI from age 30 to age 75 years. Upper endoscopy and colonoscopy are recommended every 2-5 years in individuals from age 25 years.
Agents/circumstances to avoid: Minimize exposure to diagnostic and therapeutic radiation; avoid known carcinogens including sun exposure, tobacco use, occupational exposures, and excessive alcohol use.
Evaluation of relatives at risk: It is appropriate to offer genetic counseling and testing to all relatives who are at risk of having a familial TP53 pathogenic variant.
### Genetic counseling.
LFS is inherited in an autosomal dominant manner. Most individuals diagnosed with LFS inherited a TP53 pathogenic variant from a parent. The proportion of individuals with a de novo germline TP53 pathogenic variant is estimated to be between 7% and 20%. Offspring of an individual with an established diagnosis of LFS (i.e., an individual who meets classic LFS criteria and/or has a heterozygous germline TP53 pathogenic variant) have a 50% risk of inheriting an LFS-causative pathogenic variant and having the cancer risks associated with LFS. Predictive testing for at-risk family members, prenatal testing, and preimplantation genetic testing are possible if a TP53 germline pathogenic variant in the family has been identified.
## Diagnosis
Clinical diagnostic criteria for Li-Fraumeni syndrome (LFS) have been published [Mai et al 2012].
### Suggestive Findings
LFS should be suspected in individuals who meet the Chrompret criteria [Bougeard et al 2015, Valdez et al 2017], have early-onset hypodiploid acute lymphoblastic leukemia (ALL), or have suggestive findings on somatic tumor tissue testing.
* 2015 Chompret criteria (~30% will have a germline TP53 pathogenic variant) [Mai et al 2012]:
* A proband with a tumor belonging to the LFS tumor spectrum (e.g., premenopausal breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system (CNS) tumor, adrenocortical carcinoma) before age 46 years AND at least one first- or second-degree relative with an LFS tumor (except breast cancer if the proband has breast cancer) before age 56 years or with multiple tumors; OR
* A proband with multiple tumors (except multiple breast tumors), two of which belong to the LFS tumor spectrum and the first of which occurred before age 46 years; OR
* A proband with adrenocortical carcinoma, choroid plexus tumor, or rhabdomyosarcoma of embryonal anaplastic subtype, irrespective of family history; OR
* A female proband with breast cancer before age 31 years.
* Hypodiploid acute lymphoblastic leukemia (ALL) diagnosed in a proband <age 21 years (~50% will have a germline TP53 pathogenic variant) [Holmfeldt et al 2013]
Note: To date, a germline TP53 pathogenic variant has not been reported in an individual with adult-onset hypodiploid ALL.
* Somatic tumor tissue testing identifies one of the following:
* A TP53 pathogenic variant with an allele frequency of ~50% or >50%
* Absent or decreased staining of p53 by immunohistochemistry
Note: The LFSPRO prediction tool, based on a Mendelian model, can also be used to estimate the likelihood of identifying a germline TP53 pathogenic variant [Peng et al 2017].
### Establishing the Diagnosis
The diagnosis of LFS is established in a proband who meets ALL THREE classic LFS criteria AND/OR has a germline pathogenic variant in TP53 identified by molecular genetic testing (see Table 1).
Classic LFS criteria (~60%-80% will have a germline TP53 pathogenic variant) [Mai et al 2012]:
* A proband with a sarcoma diagnosed before age 45 years
* A first-degree relative with any cancer diagnosed before age 45 years
* A first- or second-degree relative with any cancer diagnosed before age 45 years or a sarcoma diagnosed at any age
Note: Identification of low-level (<20%) mosaicism for a TP53 pathogenic variant in leukocytes is suggestive of a postzygotic (acquired) pathogenic variant due to clonal hematopoiesis of indeterminate potential (CHIP) related to aging, cytotoxic treatments, underlying hematologic malignancy or premalignancy, or circulating tumor cells [Weitzel et al 2018]. There are no standardized approaches to distinguish a TP53 pathogenic variant due to CHIP from a germline TP53 pathogenic variant, but evaluations may include the following [Weitzel et al 2018]:
* Analysis of cultured skin fibroblasts for the identified TP53 pathogenic variant
* Molecular genetic testing of all offspring to determine if the TP53 pathogenic variant was transmitted
* Molecular genetic testing of other affected family members to determine if the TP53 pathogenic variant is segregating with cancer in the family
Molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of TP53 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
* A multigene panel that includes TP53 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Multigene panels typically include additional inherited cancer genes, which are not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1).
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
### Table 1.
Molecular Genetic Testing Used in Li-Fraumeni Syndrome
View in own window
Gene 1MethodProportion of Probands with a Pathogenic
Variant 2 Detectable by Method
TP53Sequence analysis 391% 4
Gene-targeted deletion/duplication analysis 51% 6
Unknown 7NA8%
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\.
Sequence analysis of the entire TP53 coding region (exons 2-11) detects about 95% of TP53 pathogenic variants, most of which are missense variants. It is estimated that about 91% of individuals with LFS will have TP53 pathogenic / likely pathogenic variants detected by sequence analysis [Guha & Malkin 2017].
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\.
LFS can be caused by a deletion involving the coding region of TP53 or the promoter and noncoding exon [Guha & Malkin 2017].
7\.
To date, TP53 is the only gene known to be associated with LFS. However, a germline pathogenic variant is identified in only 92% of individuals with LFS [Guha & Malkin 2017].
## Clinical Characteristics
### Clinical Description
Li-Fraumeni syndrome (LFS) is associated with high risks for a diverse spectrum of childhood- and adult-onset malignancies. The lifetime risk of cancer in individuals with LFS is ≥70% for men and ≥90% for women [Mai et al 2016, Guha & Malkin 2017]. Five cancer types account for the majority of LFS tumors: adrenocortical carcinomas, breast cancer, central nervous system tumors, osteosarcomas, and soft-tissue sarcomas [Guha & Malkin 2017].
* Adrenocortical carcinomas (ACC) develop in 6%-13% of individuals with individuals with LFS with most diagnoses occurring before age five years. ACC also occurs in adults with LFS, typically before age 40 years [Mai et al 2016]. The southern Brazilian TP53 founder variant, p.Arg337His, is associated with a high risk of ACC, especially in childhood. In one series of individuals with pathogenic variant p.Arg337His, ACC accounted for 55% of the childhood cancers and 23% of the adult-onset cancers observed [Ferreira et al 2019]. For individuals with pathogenic variant p.Arg337His, the penetrance of childhood ACC is one in 30 to 40 [Achatz & Zambetti 2016].
* Breast cancer. Female breast cancer accounts for 27%-31% of LFS cancers, making it the most common cancer in women with LFS [Id Said et al 2016]. In one series, the cumulative incidence of breast cancer in females by age 70 was 54% [Mai et al 2016]. LFS-associated breast cancers occur at a younger age (median age: 33 years), with almost all breast cancers in women with LFS occurring prior to menopause [Bougeard et al 2015]. LFS-associated breast cancers are more likely to be ductal, estrogen receptor and progesterone receptor positive, and show HER2 amplification [Bougeard et al 2015, Mai et al 2016, Packwood et al 2019]. Malignant phyllodes tumors of the breast are also associated with LFS [Villani et al 2016]. In two series of families with LFS, no instances of male breast cancer were observed [Bougeard et al 2015, Mai et al 2016].
* Central nervous system (CNS) tumors account for 9%-14% of LFS cancers [Bougeard et al 2015]. In one series, the cumulative incidence of brain cancer by age 70 was 6% for women and 19% for men [Mai et al 2016]. The age of onset of brain tumors is biphasic with both childhood and adult onset, typically before age 40 years (median age: 16 years) [Valdez et al 2017]. Glioblastomas and astrocytomas are the most common CNS tumor types in individuals with LFS, although many other CNS tumor types have been reported, including ependymomas, choroid plexus carcinomas, and supratentorial primitive neuroectodermal tumors [Bougeard et al 2015, Valdez et al 2017]. Medulloblastomas in individuals with LFS are more likely to be of the sonic hedgehog subtype [Taylor et al 2012] and display chromothripsis (numerous clustered chromosome rearrangements occurring in malignant cells) [Zhukova et al 2013].
* Osteosarcomas account for 3%-16% of LFS cancers and typically occur prior to age 30 years (median age: 14 years), although later diagnoses up to age 55 years have been reported [Bougeard et al 2015, Mirabello et al 2015]. In one series, the cumulative incidence of bone cancers by age 70 was 5% for women and 11% for men [Mai et al 2016].
* Soft-tissue sarcomas. Rhabdomyosarcomas and other soft-tissue sarcomas are the most common LFS cancers in children and account for 17%-27% of the total cancers occurring in individuals with LFS [Bougeard et al 2015]. In one series, the cumulative incidence of soft-tissue sarcoma was 15% for women and 22% for men [Mai et al 2016]. Rhabdomyosarcomas often occur before age five years [Ognjanovic et al 2012] and are often nonalveolar tumors with diffuse anaplasia [Hettmer et al 2014].
Additional cancers. LFS is associated with an increased risk of several additional cancer types including the following:
* Leukemias and lymphomas. Primary and secondary leukemias, especially acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) represent about 2%-4% of LFS cancers. In one series, leukemia occurred between ages two and 35 years (median age: 12 years) [Bougeard et al 2015]. ALL often exhibits a low hypodiploid state with 32-39 chromosomes [Holmfeldt et al 2013, Qian et al 2018, Swaminathan et al 2019]. Hodgkin and non-Hodgkin lymphomas account for approximately 2% of cancers reported in individuals with LFS [Bougeard et al 2015]. Lifetime risk estimates for developing leukemia or lymphoma in LFS are not established but are likely to be lower than the risks for developing any of the five most common cancers reported in individuals with LFS.
* Gastrointestinal cancers. Colorectal cancers account for about 3% of the cancers diagnosed in individuals with LFS [Guha & Malkin 2017]. A recent series reported that 8.6% of individuals with LFS were diagnosed with colorectal cancer or a polyp with high-grade dysplasia; 3.2% of these occurred before age 25 years and 4.3% before age 35 years [Rengifo-Cam et al 2018]. Additional gastrointestinal cancers have also been reported including gastric cancer [Bougeard et al 2015, Mai et al 2016]. A higher incidence of gastric cancer is reported in individuals younger than age 40 years in Asian kindreds [Ariffin et al 2015]. Lifetime risk estimates for developing gastrointestinal cancer in LFS are not established but are likely to be lower than the risks for developing any of the five most common cancers reported in individuals with LFS.
* Other cancers. Additional cancers reported in families with an identified TP53 pathogenic variant or a clinical diagnosis of LFS have included cancers of the head and neck, kidney, larynx, lung, skin (e.g., melanoma), ovary, pancreas, prostate, testis, and thyroid [Mai et al 2016, Valdez et al 2017].
* Gestational choriocarcinoma in female partners. The pregnant mother of a fetus heterozygous for a paternally inherited TP53 pathogenic variant is at risk for choriocarcinoma or another gestational trophoblastic disease (i.e., the occurrence of cancer in placental tissue, which may spread to other maternal organs) [Cotter et al 2018].
Excess of early-onset cancers. In one series, the average onset of first cancer for men with LFS was age 17 years; the average onset of first cancer for women was age 28 years when including breast cancer and age 13 years when excluding breast cancer [Bougeard et al 2015]. In another series, it was estimated that 50% of LFS-associated malignancies occurred by age 30-31 years for women and age 46 for men [Mai et al 2016].
Excess of multiple primary cancers. Individuals with LFS have a 40%-49% risk of developing a second cancer (median onset: 10 years after the first cancer diagnosis). Radiation and chemotherapy treatment of an LFS-related cancer may increase the risk for a second malignancy [Bougeard et al 2015, Churpek et al 2016, Mai et al 2016, Schon & Tischkowitz 2018].
Prognosis. In a series of 89 individuals with LFS who either selected or declined surveillance including rapid whole-body MRI, breast imaging, brain imaging, blood tests, and other targeted interventions, including upper and lower endoscopies in adults, the five-year overall survival rate was 88.8% for individuals in the surveillance group and 59.6% for those in the non-surveillance group [Villani et al 2016].
With the utilization of multigene panel testing, the number of individuals identified with a germline TP53 pathogenic variant has substantially increased. Individuals who had germline TP53 pathogenic variants identified on multigene panel testing appear to have had cancer diagnoses at older ages and less striking family histories of cancer, and were less likely to meet classic LFS or Chompret criteria compared to individuals who had a TP53 pathogenic variant identified on single-gene testing [Rana et al 2018]. Thus, there may be a broader phenotypic spectrum in LFS than was previously recognized.
### Genotype-Phenotype Correlations
There continues to be debate regarding genotype-phenotype correlations in LFS.
A recent study reported that individuals with germline TP53 pathogenic variants resulting in p53 loss of function appeared to have a more severe phenotype than individuals with pathogenic variants that caused partial deficiency of p53. Individuals with loss-of-function variants had an earlier onset of first cancer, higher incidences of breast cancer before age 35 and of sarcoma, and greater likelihood of meeting classic LFS and/or Chompret criteria [Rana et al 2019].
These findings are in contrast with another series, which reported that individuals with LFS who carry dominant-negative pathogenic variants (in which the mutated p53 protein interferes with the function of the wild type p53 protein) appeared to have more clinically severe phenotypes than did individuals with other TP53 pathogenic variants [Bougeard et al 2015]. A laboratory study also reported that dominant-negative pathogenic variants appear to cause a more profound alteration of p53 DNA binding than other pathogenic variants [Zerdoumi et al 2017].
The TP53 founder variant p.Arg337His common in southern Brazil is associated with a high risk of childhood-onset ACC, up to 55% in one series [Ferreira et al 2019]. This variant is associated with an increased risk of breast cancer, as well as other LFS-associated cancers, although at older ages and with lower lifetime risks (50%-60%) compared to other TP53 pathogenic variants [Ferreira et al 2019]. Maternal inheritance of p.Arg337His was identified in 72% of individuals, suggesting preferential selection. One individual homozygous for p.Arg337His whose clinical phenotype did not appear to differ from p.Arg337His heterozygotes, has been identified [Ferreira et al 2019].
### Penetrance
LFS is typically considered to be a highly penetrant cancer syndrome with a 70% or higher lifetime risk of cancer in men and a 90% or higher lifetime risk of cancer in women [Mai et al 2016, Guha & Malkin 2017]. Another study reported an 80% risk of cancer by age 70, with 22% of the cancers occurring between ages 0 and15 years, 51% between ages 16 and 50 years, and 27% between ages 51 and 80 years [Amadou et al 2018].
However, the penetrance of LFS may be overestimated as more individuals recently identified with a germline TP53 pathogenic variant do not meet classic LFS or Chompret criteria due to a less striking family and personal history of cancer [Rana et al 2018].
Individuals with TP53 pathogenic variant p.Arg337His appear to have a lower lifetime risk of cancer than those with other TP53 pathogenic variants [Ferreira et al 2019].
### Genetic Modifiers
Genetic modifiers of LFS-associated cancer risk include the following:
* TP53 p.Arg72 polymorphism. The p.Arg72 polymorphism causes increased affinity toward MDM2, resulting in higher levels of p53 degradation and earlier onset of first cancer [Guha & Malkin 2017].
* MDM2 c.14+309T>G variant. The presence of the NM_002392.2:c.14+309G>T variant (also termed SNP309T>G) in the MDM2 promoter region (rs2279744) leads to increased MDM2 expression resulting in higher levels of p53 degradation and earlier onset of first cancer [Guha & Malkin 2017, Amadou et al 2018].
* microRNA R-605 variant. The presence of a variant in miR-605, which regulates the p53-MDM2 loop, resulted in a ten-year accelerated mean age of tumor onset [Guha & Malkin 2017, Amadou et al 2018].
* 16 base pair duplication polymorphism in intron 3 (PIN3). The presence of the PIN3 polymorphism appears to be protective, with older ages of first cancer compared to individuals who do not have this polymorphism [Guha & Malkin 2017, Amadou et al 2018].
* Shortened telomere length. Shortened telomere length over subsequent generations has been associated with accelerated tumor development (anticipation) in families with LFS [Guha & Malkin 2017]. The association between telomere erosion and earlier cancer onset continues to be studied.
### Nomenclature
LFS was referred to as SBLA (sarcoma, breast, leukemia, and adrenal gland) syndrome in earlier publications.
### Prevalence
The frequency of germline TP53 pathogenic variants in the general population is not well established. One group places the prevalence at 1:3,555 to 1:5,476 [de Andrade et al 2019].
TP53 pathogenic variant p.Arg337His is a founder variant in southern Brazil with a prevalence of 0.3% (1:375 individuals) [Achatz & Zambetti 2016, Valdez et al 2017].
## Differential Diagnosis
### Table 2.
Other Genes of Interest in the Differential Diagnosis of Li-Fraumeni Syndrome
View in own window
Gene(s)DisorderMOICore Cancer(s)Age at Cancer OnsetComments
BRCA1
BRCA2BRCA1\- and BRCA2-associated hereditary breast and ovarian cancerADBreast; ovary; pancreas; prostate; melanomaTypically in adulthoodA BRCA1 or BRCA2 pathogenic variant is more likely in individuals w/:
* Premenopausal breast cancer, especially ER/PR/HER2-negative tumors
* Personal or family history of ovarian, pancreatic, male breast, or prostate cancer
* Ashkenazi Jewish ancestry
* No family history of adrenocortical carcinomas, CNS tumors, osteosarcomas, or soft-tissue sarcomas
CHEK2CHEK2 cancer susceptibility (OMIM 609265)ADBreast; colorectal; prostateTypically in adulthoodCHEK2 pathogenic variants are more likely to explain personal & family histories of predominantly breast, colon, prostate, or other adult-onset cancers.
MLH1
MSH2
MSH6
PMS2Constitutional mismatch repair deficiency (a variant of Lynch syndrome)ARColorectal; small bowel; hematologic; brainEarly childhoodCMMRD should be considered in individuals w/childhood-onset gastrointestinal cancer or polyps, malignant brain tumor, hematologic cancer, &/or café au lait macules.
AD = autosomal dominant; AR = autosomal recessive; CMMRD = constitutional mismatch repair deficiency; CNS = central nervous system; ER = estrogen receptor; MOI = mode of inheritance; PR = progesterone receptor
Somatic mosaicism for TP53 pathogenic variant. Low-level (<20%) mosaicism for a TP53 pathogenic variant due to clonal hematopoiesis of indeterminate potential (CHIP) can be identified in leukocytes of individuals due to aging, cytotoxic treatments, underlying hematologic malignancy or premalignancy, or circulating tumor cells [Weitzel et al 2018]. Medical history should include assessment of exposure to cigarette smoke or cytotoxic chemotherapy, the possibility of circulating malignant clones (leukemia, lymphoma, or other tumor), and allelic fraction [Weitzel et al 2018]. It is important to distinguish individuals with CHIP from those with Li-Fraumeni syndrome (LFS), as screening for LFS-related tumors is not recommended for individuals with CHIP [Weitzel et al 2018].
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Li-Fraumeni syndrome (LFS), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended.
Due to the lifelong increased cancer risk and the diversity of tumors associated with LFS, evaluations for cancer in individuals with LFS need to be ongoing and comprehensive. Cancer monitoring can include physical examinations, blood counts, imaging studies, endoscopies, and/or biopsies (see Surveillance). Individuals with or suspected of having LFS based on clinical or molecular criteria should seek a cancer genetics consultation to review the diagnosis and medical management recommendations.
### Treatment of Manifestations
In individuals with LFS, radiation therapy is avoided if possible to reduce the risk of secondary malignancies. However, treatment efficacy should be prioritized above concerns regarding risk of subsequent malignancies (e.g., radiation treatment may be necessary to provide the best chance of cure).
Women with LFS who develop breast cancer are encouraged to consider bilateral mastectomy (rather than lumpectomy) in order to reduce the risk of developing a second primary breast cancer and avoid exposure to radiation therapy [Schon & Tischkowitz 2018].
Aside from avoiding radiation therapy if possible, LFS tumors are typically treated according to standard protocols.
### Prevention of Primary Manifestations
Women with LFS have the option of bilateral mastectomy to reduce the risk of breast cancer [Schon & Tischkowitz 2018].
Adults with LFS should have screening colonoscopy examinations, which can be considered surveillance as well as primary prevention of colorectal cancer [MacFarland et al 2019].
Avoidance of sun exposure, tobacco use, and exposure to other known or suspected carcinogens is encouraged.
### Surveillance
Surveillance guidelines for adults and children with LFS have been developed, largely based on the "Toronto protocol" [Villani et al 2016, Kratz et al 2017, NCCN 2019].
### Table 3.
Recommended Surveillance for Individuals with Li-Fraumeni Syndrome
View in own window
System/ConcernEvaluationFrequency
All cancersComplete physical exam w/high index of suspicion for cancer 1
* Every 3-4 mos, birth to 18 yrs
* Every 6 mos, ≥18 yrs
Whole-body MRI 2, 3Annually, all ages
ACCUltrasound of abdomen & pelvisEvery 3-4 mos, birth to age 18 yrs (not done on same visit as whole-body MRI)
Serum total testosterone, dehydroepiandrosterone sulfate, & androstenedioneIf ultrasound is unsatisfactory 4
Breast cancerClinical breast examEvery 6-12 mos, age ≥20-25 yrs
Breast MRI w/& w/out contrastAnnually, age 20-30 yrs
Mammogram + breast MRI w/ & w/out contrastAnnually, age 30-75 yrs
CNS tumorsNeurologic examAnnually, all ages
Brain MRI 5Annually
Gastrointestinal
cancersUpper endoscopy & colonoscopyEvery 2-5 yrs, age ≥25 yrs 6
Leukemia/
LymphomaNone recommended 7N/A
MelanomaDermatologic examAnnually, age ≥18 yrs
SarcomasWhole-body MRIAnnually, all ages
Ultrasound of abdomen & pelvisAnnually, age ≥18 yrs
1\.
Complete physical examination should include blood pressure, full neurologic exam, and assessment of growth, sudden weight gain or loss, Cushingoid appearance, or signs of virilization in a child [Kratz et al 2017].
2\.
MRI preferably within a clinical trial [NCCN 2019]. A meta-analysis of baseline whole-body (WB)-MRI reported cancers in 7% of individuals screened [Ballinger et al 2017]. Risks of WB-MRI include the high false positive rate (requiring further evaluation to rule out malignancy) and the need for sedation in young children.
3\.
Participants with LFS in a WB-MRI screening program reported significant reductions in anxiety following WB-MRI exam. Some individuals with LFS reported an increased sense of control and hope due to participation in a surveillance program, while others reported an increased burden due to multiple visits, extra surveillance, and concerns regarding false positive results [McBride et al 2017].
4\.
Kratz et al [2017]
5\.
The first brain MRI should be done with contrast, and subsequent brain MRIs may be done without contrast if the previous MRI was normal and there is no new abnormality [Kratz et al 2017].
6\.
Colonoscopy examinations starting at age 25 or five years prior to earliest case of colorectal cancer in the family [NCCN 2019]
7\.
Periodic blood tests, such as complete blood count, erythrocyte sedimentation rate, and lactate dehydrogenase, are not generally recommended for individuals with LFS, but can be considered in those at increased risk for MDS or leukemia due to prior cancer treatments [Kratz et al 2017].
### Agents/Circumstances to Avoid
There is some evidence that TP53 pathogenic variants confer an increased sensitivity to ionizing radiation [Churpek et al 2016, Schuler et al 2017, Kasper et al 2018]. Thus, when possible, individuals with a germline TP53 pathogenic variant should avoid or minimize exposure to diagnostic and therapeutic radiation. Radiation-induced tumors and leukemias have been reported among individuals with LFS [Churpek et al 2016, Schuler et al 2017]. However, there remains limited information regarding the extent of risk posed by radiation in terms of the dosage, age of the person, or other factors [Valdez et al 2017].
Individuals with LFS are also encouraged to avoid or minimize exposures to known or suspected carcinogens, including sun exposure, tobacco use, occupational exposures, and excessive alcohol use, because the effects of carcinogenic exposures and germline TP53 pathogenic variants may be cumulative.
Cytotoxic chemotherapy agents may also increase the risk of treatment-related leukemias or other cancers in individuals with LFS [Churpek et al 2016, Kasper et al 2018].
### Evaluation of Relatives at Risk
If a TP53 pathogenic variant has been identified in a family, molecular genetic testing of at-risk relatives can identify those family members who also have LFS and thus need increased cancer monitoring with attention to symptoms or signs of cancer and early intervention when a cancer or precancer is identified. Since the risks of LFS-related cancers are increased at all ages, including infancy and childhood, it is recommended that predictive testing be offered to individuals at birth (via cord blood analysis) or soon after birth.
If a TP53 pathogenic variant has not been identified in a family but the family meets classic criteria for LFS, all at-risk family members should be counseled regarding their potential increased risks for LFS-related cancers and options for surveillance and risk reduction.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Female with LFS. Women with LFS who are pregnant should bring any potential signs or symptoms of cancer to the attention of their physicians. Women with LFS who are pregnant can continue to have clinical breast exams and/or breast imaging studies if indicated.
Heterozygous fetus. There are no special recommendations for screening a fetus identified as having a germline TP53 pathogenic variant. Once the infant is born, he or she should begin screening for cancer (see Surveillance).
Reproductive partner of a male with LFS. The pregnant mother of a fetus heterozygous for a paternally inherited TP53 pathogenic variant is at risk for choriocarcinoma or another gestational trophoblastic disease (i.e., the occurrence of cancer in placental tissue, which may spread to other maternal organs) [Cotter et al 2018].
### Therapies Under Investigation
There are efforts to identify medications that can reduce the risk of cancer in individuals with LFS. The National Cancer Institute plans to begin a clinical trial with metformin based on encouraging preclinical models, which demonstrated lower cancer incidence when mitochondrial metabolism was inhibited [Wang et al 2017].
Several trials utilizing cell-free DNA for early cancer detection are also under way in LFS cohorts.
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.
### Other
The Li-Fraumeni Exploration (LiFE) Research Consortium, formed in 2010, is a collaborative group of clinicians, scientists, genetic counselors, and psychologists who work with individuals and families with LFS [Mai et al 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-hydroxybutyric 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
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Li-Fraumeni Syndrome
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c0085390
| 25,704 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1311/
| 2021-01-18T21:14:33 |
{"mesh": ["D016864"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that progressive supranuclear palsy-1 (PSNP1) is caused by heterozygous mutation in the gene encoding microtubule-associated protein tau (MAPT; 157140) on chromosome 17q21.
Description
Progressive supranuclear palsy (PSP) is the second most frequent cause of degenerative parkinsonism. In addition to parkinsonism, the clinical symptoms include early postural instability, supranuclear gaze palsy, and cognitive decline. Neuropathologically, the disorder is characterized by abundant neurofibrillary tangles, which differ in both distribution and composition from those associated with Alzheimer disease. In progressive supranuclear palsy, the tangles are primarily localized to subcortical regions and are found in both neurons and glia, whereas in Alzheimer disease they are more widespread, largely cortical, and limited to neurons. They also have different characteristics at the ultrastructural level (Baker et al., 1999).
Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of frontotemporal dementia (FTD; 600274), primary progressive aphasia (PPA), corticobasal degeneration (CBD), progressive supranuclear palsy, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease,' and that the term 'Pick disease' (172700) should be restricted to the pathologic finding of Pick bodies.
### Genetic Heterogeneity of Progressive Supranuclear Palsy
Other loci for PSP have been mapped to chromosome 1q31 (PSNP2; 609454) and 11p12-p11 (PSNP3; 610898).
See also Parkinson-dementia syndrome and atypical progressive supranuclear palsy (260540).
Clinical Features
Rojo et al. (1999) reported 12 pedigrees of familial progressive supranuclear palsy, confirmed by pathology in 4 probands. Pathologic diagnosis was confirmed by internationally agreed criteria. The spectrum of the clinical phenotypes in these families was variable, including 34 typical cases of PSP (12 probands plus 22 secondary cases), 3 patients with postural tremor, 3 with dementia, 1 with parkinsonism, 2 with tremor, dystonia, gaze palsy, and tics, and 1 with gait disturbance. Ros et al. (2005) provided an update on 1 of the families reported by Rojo et al. (1999). Three family members were affected. At 37 years of age, the proband developed an akinetic-rigid syndrome, gait disturbance, frequent falls, micrographia, dysarthria, eyelid apraxia, abolition of upgaze, and hyperreflexia with unilateral extensor plantar response. PET scan showed reduced striatal fluorodopa uptake. The patient showed disease progression, with axial dystonia, mutism, complete vertical gaze palsy, and dysphagia, leading to death at age 45 years. Neuropathologic examination showed atrophy of the mesencephalon, pons, striatum, and subthalamic nuclei, and depigmentation of the substantia nigra. There was tau protein accumulation in neurons and glia, primarily in the mesencephalon. Protein analysis of brain tissue detected hyperphosphorylated tau protein and overexpression of tau isoforms with 4 microtubule-binding repeats.
Nath et al. (2003) provided a detailed review of the clinical features of 187 patients with PSP in the United Kingdom. The most common symptoms included bradykinesia, falls, cognitive impairment, bulbar or language problems, and visual disturbances, such as diplopia. Other variable features included tremor, retrocollis, limb dystonia, and favorable response to levodopa. Average age at onset was 66 years, and the mean survival was 5 to 6 years.
Tuite et al. (2005) reported a family in which several members had clinical features consistent with PSP and others had features consistent with corticobasal degeneration. Neuropathologic examination of 2 affected sibs showed features of PSP in 1 sib and features of CBD in the other. Specifically, PSP features included tufted astrocytes, whereas CBD features included ballooned neurons and astrocytic plaques. Both patients had severe neuronal loss in the substantia nigra. Genetic studies of 4 affected family members demonstrated the H1/H1 tau haplotype, but no mutations in the MAPT gene were identified. There was a history of remote consanguinity, and Tuite et al. (2005) suggested a unifying genetic etiology in this family.
Donker Kaat et al. (2009) reported 176 patients who fulfilled the diagnostic criteria for PSP, including 65 possible, 91 probable, and 20 definite. The mean age at PSP onset was 66.5 years. Presenting symptoms included gait disorder with falls (65%), behavioral changes (21%), bradykinesia (20%), cognitive decline (16%), stiffness (14%), speech problems (9%), visual complaints (6%), and tremor (4%). Tremor at disease onset occurred significantly more frequently in patients with PSP who had a positive family history compared to patients who did not (9% vs 1%, p = 0.02). Neuropathologic examination of 20 patients were consistent with the diagnosis. Detailed results of 5 patients showed mild frontal atrophy and depigmentation of the substantia nigra and locus ceruleus. There was severe neuronal loss and gliosis in the pallidum, subthalamic nucleus, and substantia nigra. Immunohistochemistry with the MAPT AT8 antibody (which stains 4-repeat tau) showed neurofibrillary tangles, tufted astrocytes, and coiled bodies with threads in the striatum and caudate; a variable number of these were found in the subthalamic nucleus and thalamus. The neocortex showed a few pre-tangles and tufted astrocytes in the frontal, temporal, and parietal cortex.
### Neuroradiologic Studies
Piccini et al. (2001) studied regional cerebral dopaminergic function and glucose metabolism in members of 2 large kindreds with familial PSP in an effort to identify subclinical cases. They studied 3 clinically affected PSP patients who showed significant reduction in caudate and putamen uptake of (18)F-dopa in positron emission tomography (PET) studies, along with a significant reduction in striatal, lateral, and medial premotor area and dorsal prefrontal cortex glucose metabolism. In 4 of 15 asymptomatic relatives, caudate and putamen (18)F-dopa uptake was 2.5 SDs lower than the normal mean. These 4 subjects and a fifth asymptomatic relative with normal (18)F-dopa uptake showed a significant reduction of cortical and striatal glucose metabolism in a pattern similar to that of their affected relatives.
To calculate the rate of brain atrophy in 6 patients with PSP, Josephs et al. (2006) used serial MRI scans and a technique called the 'boundary shift integral,' which calculates the integral change in the brain/CSF fluid boundary over the interior and exterior surfaces of the brain. The mean interval between baseline and final MRI scan was 3.1 years. PSP Patients had a rate of cerebral atrophy and ventricular expansion of 1.3% and 7% per year, respectively, compared to 0.4% and 1.8%, respectively, in control individuals. Josephs et al. (2006) suggested that these benchmark rates and the boundary shift integral technique could be used to monitor disease progression and response to therapy in PSP.
### Clinical Variability
Nicholl et al. (2003) described a form of PSP characterized by fatal respiratory hypoventilation in 2 sibs from a consanguineous marriage. The authors called the disorder 'tauopathy and respiratory failure.' The 29-year-old pregnant sister developed dyspnea with stridor, and later had a generalized seizure that left her unconscious. Despite therapy, she died after 9 days. Her 30-year-old brother developed cough syncope, dyspnea, and central apnea, which progressed over 40 months, leading to death at age 34 years. During the illness, he showed slow smooth pursuit and impaired saccades, mild rigidity and bradykinesia, and myoclonic jerks. Neuropathologic examination showed widespread neuronal eosinophilia and pyknosis with gliosis in multiple brain regions, consistent with hypoxic brain damage. There was pervasive tau pathology in neuronal perikarya, neurites, and threads in the gray matter of the hippocampus, thalamus, and pons, but not in the cerebral cortex. Functional studies indicated that the mutated protein showed reduced binding to microtubules as well as increased fibrillization and aggregation. Both sibs carried the H1/H1 haplotype associated with PSP. Nicholl et al. (2003) commented on the unusual apparent autosomal recessive inheritance of this tauopathy. In a review of the role of tau in neurodegenerative diseases, Quadros et al. (2007) classified the disorder in the sibs reported by Nicholl et al. (2003) as PSP.
Pathogenesis
Van Leeuwen et al. (2006) detected aberrant frameshifted proteins, APP+1 (APP; 104760) and UBB+1 (UBB; 191339), within the neuropathologic hallmarks of Alzheimer disease (AD; 104300) and other MAPT-related dementias, including Pick disease, progressive supranuclear palsy, and less commonly frontotemporal dementia. Van Leeuwen et al. (2006) postulated that accumulation of APP+1 and UBB+1, which represents defective proteasome function, contributes to various forms of dementia.
Botella-Lopez et al. (2006) found increased levels of a 180-kD reelin (RELN; 600514) fragment in CSF from 19 patients with AD compared to 11 nondemented controls. Western blot and PCR analysis confirmed increased levels of reelin protein and mRNA in tissue samples from the frontal cortex of AD patients. Reelin was not increased in plasma samples, suggesting distinct cellular origins. The reelin 180-kD fragment was also increased in CSF samples of other neurodegenerative disorders, including frontotemporal dementia, PSP, and Parkinson disease (PD; 168600).
Inheritance
De Yebenes et al. (1995) described 7 families with multiple affected individuals. These included 3 suggesting autosomal dominant inheritance (see 609454) and 1 family in which there was parental consanguinity, suggesting recessive inheritance. Although the majority of cases of progressive supranuclear palsy appear to be sporadic, there may be rare genetically determined forms.
Golbe et al. (1996) failed to demonstrate substantial contribution of heredity to the cause of progressive supranuclear palsy in a study of 91 personally examined patients (75 were age-matched with controls). They pointed out that the size of their study may not have been sufficient to demonstrate a subtle familial aggregation in progressive supranuclear palsy.
The presence of affected members in at least 2 generations in 8 of the 12 families reported by Rojo et al. (1999) and the absence of consanguinity suggested autosomal dominant transmission with incomplete penetrance. Rojo et al. (1999) concluded that hereditary PSP is more frequent than previously thought and that the scarcity of familial cases may be related to a lack of recognition of the variable phenotypic expression of the disease.
Donker Kaat et al. (2009) found that 57 (33%) of 172 probands with PSP had at least 1 first-degree relative who had dementia or parkinsonism, compared to 131 (25%) of the control subjects (odds ratio of 1.5). In addition, patients with PSP had more first-degree relatives with parkinsonism compared to controls, (OR of 3.9). Twelve patients with PSP (7%) fulfilled the criteria for autosomal dominant transmission of PSP, dementia, tremor, or parkinsonism. One patient was found to have a P301L mutation in the MAPT gene (157140.0001). The findings supported familial aggregation of parkinsonism in progressive supranuclear palsy.
Molecular Genetics
Conrad et al. (1997) demonstrated an association between progressive supranuclear palsy and a dinucleotide (TG) polymorphic repeat between exons 9 and 10 of the microtubule-associated protein tau gene (MAPT; 157140). This association was subsequently confirmed by several other studies (Oliva et al., 1998; Higgins et al., 1998; Bennett et al., 1998). In each case, an overrepresentation of the most common allele (a0) and genotype (a0a0) was reported for the progressive supranuclear palsy group. However, due to the nature of the dinucleotide polymorphism, it was considered unlikely that this variation was biologically significant in the disease process, but was in fact in disequilibrium with other polymorphisms. Baker et al. (1999) described 2 extended haplotypes, H1 and H2, that cover the human tau gene, and showed that the most common haplotype, H1, was significantly overrepresented in patients with PSP, extending earlier reports of the association between the intronic dinucleotide polymorphism a0 and the disorder.
Using an autosomal recessive model, Higgins et al. (1998) found that progressive supranuclear palsy was in linkage disequilibrium with the tau gene, but not with the alpha-synuclein (163890) gene.
Higgins et al. (1999) found that 22 unrelated patients with PSP had a common extended haplotype of the tau gene, designated HapA, characterized by a homozygous polymorphism in the 5-prime splice site untranslated region of exon 1, 2 missense mutations in exon 4A, and a nonsense mutation in the 5-prime splice site of exon 8. Higgins et al. (2000) found that 51 of 52 patients with PSP had the HapA haplotype.
In 25 unrelated individuals with PSP and 6 individuals with corticobasal degeneration, Higgins et al. (1999) failed to demonstrate the R406W tau mutation (157140.0003) that had been reported by Hutton et al. (1998) in a family segregating an atypical form of progressive supranuclear palsy in an autosomal dominant manner.
Morris et al. (2000) analyzed alpha-synuclein, tau, synphilin (603779), and APOE (107741) genotypes in 50 patients with PSP. They confirmed the predisposing effect of the tau H1 haplotype described by Baker et al. (1999) and others, and found no association between PSP and alpha-synuclein, synphilin, or APOE.
Litvan et al. (2001) examined 63 patients with PSP and found that the presence of the tau H1/H1 genotype was significantly greater in patients compared to controls, as previously reported. There was no difference between PSP cases with one H1 or two H1 alleles in the age of onset, severity, or survival of patients, thus showing that tau genotyping does not predict the prognosis of PSP. However, Litvan et al. (2001) noted that the majority of the PSP patients carried the H1/H1 genotype (88.9%) and none of the patients carried the H2/H2 genotype, thus limiting the conclusions of the study.
Among 96 patients with PSP, Poorkaj et al. (2002) identified 1 patient with a mutation in a highly conserved position in exon 1 of the MAPT gene (157140.0019).
In 2 sibs from a consanguineous marriage who presented with a form of progressive supranuclear palsy designated 'tauopathy and respiratory failure,' Nicholl et al. (2003) identified a homozygous 1291C-T transition in exon 12 of the MAPT gene, resulting in a nonconserved ser352-to-leu (S352L) substitution in the N-terminal repeat of the tau protein. Both sibs carried the H1/H1 haplotype associated with PSP.
De Silva et al. (2003) presented evidence suggesting that the Q7R polymorphism of the saitohin gene (607067), which is located within intron 9 of the MAPT gene, is associated with PSP: 47 of 49 (95.9%) affected patients had the QQ genotype, whereas 37 of 62 (59.7%) controls had the QQ genotype. However, the authors noted that the Q allele, which represents the tau H1 haplotype, was also the most common haplotype in normal controls.
Using single-nucleotide polymorphisms, Pittman et al. (2004) mapped linkage disequilibrium (LD) in the regions flanking MAPT and established the maximum extent of the haplotype block on chromosome 17q21.31 as a region covering approximately 2 Mb. The gene-rich region extended centromerically beyond the corticotropin-releasing hormone receptor-1 gene (CRHR1; 122561) to a region of approximately 400 kb, where there was a complete loss of LD. The telomeric end was defined by an approximately 150-kb region just beyond the WNT3 (165330) gene. The authors showed that the entire, fully extended H1 haplotype was associated with PSP, which implicates several other genes in addition to MAPT as candidate pathogenic loci.
Rademakers et al. (2005) and Pittman et al. (2005) used a large collection of pathologically confirmed PSNP samples to fine map PSNP risk on H1 chromosomes in PSNP cases and controls. PSNP risk was associated with an extended subhaplotype (H1c), and the risk for PSNP was narrowed to a 22-kb region in intron 0 of MAPT by examining younger patients with, presumably, a larger genetic component to their disease. The most likely explanation of the association of the MAPT H1 haplotype and PSNP is that variants in the H1 (and H2) haplotypes confer risk of (protect against) disease by altering expression at the locus, with the risky H1 haplotype expressing higher levels of MAPT.
In affected members of the family reported by Rojo et al. (1999), Ros et al. (2005) identified a heterozygous mutation in the MAPT gene (157140.0025).
### Associations Pending Confirmation
For discussion of a possible association of PSP with repeat expansion in the ATXN2 gene, see 601517.0002.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Blurred vision \- Diplopia \- Photophobia \- Eyelid apraxia \- Supranuclear gaze palsy ABDOMEN Gastrointestinal \- Dysphagia NEUROLOGIC Central Nervous System \- Parkinsonism \- Bradykinesia \- Akinesia \- Rigidity \- Axial dystonia \- Poor mobility \- Gait imbalance \- Falls \- Supranuclear gaze palsy \- Dysarthria \- Retrocollis \- Tremor (30%) \- Limb dystonia (18%) \- Mutism \- Frontolimbic dementia \- Neuropathology shows neuronal loss in basal ganglia, brainstem, and cerebellum \- Tau-immunoreactive inclusions in neurons and astrocytes \- Tau inclusions are 'flame-shaped' or 'tuft-like' \- Granulovacuolar degeneration \- Gliosis \- Neurofibrillary tangles Behavioral Psychiatric Manifestations \- Forgetfulness \- Irritability \- Apathy \- Frontal release signs (45%) MISCELLANEOUS \- Autosomal dominant with incomplete penetrance \- Average age at onset 66 years although earlier onset may occur \- Median survival 5.7 years \- May show good response to levodopa \- Genetic heterogeneity (see PSNP2 609454 ) \- Phenotypic overlap with frontotemporal dementia ( 600274 ) \- Associated with the tau ( 157140 ) H1 haplotype MOLECULAR BASIS \- Caused by mutation in the microtubule-associated protein tau gene (MAPT, 157140.0019 ) ▲ 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-hydroxybutyric 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
|
SUPRANUCLEAR PALSY, PROGRESSIVE, 1
|
c0038868
| 25,705 |
omim
|
https://www.omim.org/entry/601104
| 2019-09-22T16:15:25 |
{"doid": ["678"], "mesh": ["D013494"], "omim": ["601104"], "orphanet": ["240071", "683"], "synonyms": ["Alternative titles", "PSP", "STEELE-RICHARDSON-OLSZEWSKI SYNDROME"]}
|
Basidiobolomycosis
SpecialtyInfectious disease
Basidiobolomycosis is a fungal disease.[1][2]
It is caused by Basidiobolus ranarum.
Treatment with itraconazole has been described.[3]
## References[edit]
1. ^ van den Berk GE, Noorduyn LA, van Ketel RJ, van Leeuwen J, Bemelman WA, Prins JM (2006). "A fatal pseudo-tumour: disseminated basidiobolomycosis". BMC Infect. Dis. 6: 140. doi:10.1186/1471-2334-6-140. PMC 1574330. PMID 16978407.
2. ^ Singh R, Xess I, Ramavat AS, Arora R (2008). "Basidiobolomycosis: a rare case report". Indian J Med Microbiol. 26 (3): 265–267. doi:10.4103/0255-0857.42044. PMID 18695330.
3. ^ Mathew R, Kumaravel S, Kuruvilla S, et al. (July 2005). "Successful treatment of extensive basidiobolomycosis with oral itraconazole in a child". Int. J. Dermatol. 44 (7): 572–575. doi:10.1111/j.1365-4632.2004.02419.x. PMID 15985026.
## External links[edit]
Classification
D
* ICD-10: B46.8
* ICD-9-CM: 117.7
* DiseasesDB: 33790
* v
* t
* e
Fungal infection and mesomycetozoea
Superficial and
cutaneous
(dermatomycosis):
Tinea = skin;
Piedra (exothrix/
endothrix) = hair
Ascomycota
Dermatophyte
(Dermatophytosis)
By location
* Tinea barbae/tinea capitis
* Kerion
* Tinea corporis
* Ringworm
* Dermatophytids
* Tinea cruris
* Tinea manuum
* Tinea pedis (athlete's foot)
* Tinea unguium/onychomycosis
* White superficial onychomycosis
* Distal subungual onychomycosis
* Proximal subungual onychomycosis
* Tinea corporis gladiatorum
* Tinea faciei
* Tinea imbricata
* Tinea incognito
* Favus
By organism
* Epidermophyton floccosum
* Microsporum canis
* Microsporum audouinii
* Trichophyton interdigitale/mentagrophytes
* Trichophyton tonsurans
* Trichophyton schoenleini
* Trichophyton rubrum
* Trichophyton verrucosum
Other
* Hortaea werneckii
* Tinea nigra
* Piedraia hortae
* Black piedra
Basidiomycota
* Malassezia furfur
* Tinea versicolor
* Pityrosporum folliculitis
* Trichosporon
* White piedra
Subcutaneous,
systemic,
and opportunistic
Ascomycota
Dimorphic
(yeast+mold)
Onygenales
* Coccidioides immitis/Coccidioides posadasii
* Coccidioidomycosis
* Disseminated coccidioidomycosis
* Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis
* Histoplasma capsulatum
* Histoplasmosis
* Primary cutaneous histoplasmosis
* Primary pulmonary histoplasmosis
* Progressive disseminated histoplasmosis
* Histoplasma duboisii
* African histoplasmosis
* Lacazia loboi
* Lobomycosis
* Paracoccidioides brasiliensis
* Paracoccidioidomycosis
Other
* Blastomyces dermatitidis
* Blastomycosis
* North American blastomycosis
* South American blastomycosis
* Sporothrix schenckii
* Sporotrichosis
* Talaromyces marneffei
* Talaromycosis
Yeast-like
* Candida albicans
* Candidiasis
* Oral
* Esophageal
* Vulvovaginal
* Chronic mucocutaneous
* Antibiotic candidiasis
* Candidal intertrigo
* Candidal onychomycosis
* Candidal paronychia
* Candidid
* Diaper candidiasis
* Congenital cutaneous candidiasis
* Perianal candidiasis
* Systemic candidiasis
* Erosio interdigitalis blastomycetica
* C. auris
* C. glabrata
* C. lusitaniae
* C. tropicalis
* Pneumocystis jirovecii
* Pneumocystosis
* Pneumocystis pneumonia
Mold-like
* Aspergillus
* Aspergillosis
* Aspergilloma
* Allergic bronchopulmonary aspergillosis
* Primary cutaneous aspergillosis
* Exophiala jeanselmei
* Eumycetoma
* Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa
* Chromoblastomycosis
* Geotrichum candidum
* Geotrichosis
* Pseudallescheria boydii
* Allescheriasis
Basidiomycota
* Cryptococcus neoformans
* Cryptococcosis
* Trichosporon spp
* Trichosporonosis
Zygomycota
(Zygomycosis)
Mucorales
(Mucormycosis)
* Rhizopus oryzae
* Mucor indicus
* Lichtheimia corymbifera
* Syncephalastrum racemosum
* Apophysomyces variabilis
Entomophthorales
(Entomophthoramycosis)
* Basidiobolus ranarum
* Basidiobolomycosis
* Conidiobolus coronatus/Conidiobolus incongruus
* Conidiobolomycosis
Microsporidia
(Microsporidiosis)
* Enterocytozoon bieneusi/Encephalitozoon intestinalis
Mesomycetozoea
* Rhinosporidium seeberi
* Rhinosporidiosis
Ungrouped
* Alternariosis
* Fungal folliculitis
* Fusarium
* Fusariosis
* Granuloma gluteale infantum
* Hyalohyphomycosis
* Otomycosis
* Phaeohyphomycosis
This mycology-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-hydroxybutyric 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
|
Basidiobolomycosis
|
c0343965
| 25,706 |
wikipedia
|
https://en.wikipedia.org/wiki/Basidiobolomycosis
| 2021-01-18T19:10:26 |
{"icd-9": ["117.7"], "icd-10": ["B46.8"], "wikidata": ["Q4867062"]}
|
Tuberculosis cutis orificialis
Other namesOrificial tuberculosis[1]
SpecialtyDermatology
Tuberculosis cutis orificialis (also known as "acute tuberculous ulcer"[1]) is a form of cutaneous tuberculosis that occurs at the mucocutaneous borders of the nose, mouth, anus, urinary meatus, and vagina, and on the mucous membrane of the mouth or tongue.[2]:335
## See also[edit]
* Scrofuloderma
* Skin lesion
* List of cutaneous conditions
## References[edit]
1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. Chapter 74. ISBN 978-1-4160-2999-1.
2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
* v
* t
* e
Gram-positive bacterial infection: Actinobacteria
Actinomycineae
Actinomycetaceae
* Actinomyces israelii
* Actinomycosis
* Cutaneous actinomycosis
* Tropheryma whipplei
* Whipple's disease
* Arcanobacterium haemolyticum
* Arcanobacterium haemolyticum infection
* Actinomyces gerencseriae
Propionibacteriaceae
* Propionibacterium acnes
Corynebacterineae
Mycobacteriaceae
M. tuberculosis/
M. bovis
* Tuberculosis: Ghon focus/Ghon's complex
* Pott disease
* brain
* Meningitis
* Rich focus
* Tuberculous lymphadenitis
* Tuberculous cervical lymphadenitis
* cutaneous
* Scrofuloderma
* Erythema induratum
* Lupus vulgaris
* Prosector's wart
* Tuberculosis cutis orificialis
* Tuberculous cellulitis
* Tuberculous gumma
* Lichen scrofulosorum
* Tuberculid
* Papulonecrotic tuberculid
* Primary inoculation tuberculosis
* Miliary
* Tuberculous pericarditis
* Urogenital tuberculosis
* Multi-drug-resistant tuberculosis
* Extensively drug-resistant tuberculosis
M. leprae
* Leprosy: Tuberculoid leprosy
* Borderline tuberculoid leprosy
* Borderline leprosy
* Borderline lepromatous leprosy
* Lepromatous leprosy
* Histoid leprosy
Nontuberculous
R1:
* M. kansasii
* M. marinum
* Aquarium granuloma
R2:
* M. gordonae
R3:
* M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP
* MAI infection
* M. ulcerans
* Buruli ulcer
* M. haemophilum
R4/RG:
* M. fortuitum
* M. chelonae
* M. abscessus
Nocardiaceae
* Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica
* Nocardiosis
* Rhodococcus equi
Corynebacteriaceae
* Corynebacterium diphtheriae
* Diphtheria
* Corynebacterium minutissimum
* Erythrasma
* Corynebacterium jeikeium
* Group JK corynebacterium sepsis
Bifidobacteriaceae
* Gardnerella vaginalis
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-hydroxybutyric 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
|
Tuberculosis cutis orificialis
|
c2711686
| 25,707 |
wikipedia
|
https://en.wikipedia.org/wiki/Tuberculosis_cutis_orificialis
| 2021-01-18T18:44:10 |
{"umls": ["C2711686"], "wikidata": ["Q7850844"]}
|
Dumont-Herskowitz et al. (1978) reported ovarian fibromata in 6 women in 5 sibships of 4 generations of a family. In most, presentation was in childhood. The pedigree was consistent with either autosomal or X-linked dominant inheritance with, of course, sex limitation. Ovarian tumors occur with the Peutz-Jeghers syndrome (175200) and with the basal cell nevus syndrome (109400). In the latter condition the ovarian tumors are fibromata and undergo calcification. No stigmata of basal cell nevus syndrome was found in the family reported by Dumont-Herskowitz et al. (1978).
GU \- Ovarian fibroma Inheritance \- Autosomal dominant ▲ 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-hydroxybutyric 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
|
OVARIAN FIBROMATA
|
c0149951
| 25,708 |
omim
|
https://www.omim.org/entry/166970
| 2019-09-22T16:36:48 |
{"mesh": ["C562391"], "omim": ["166970"]}
|
A number sign (#) is used with this entry because of evidence that mitochondrial complex II deficiency is caused by homozygous or compound heterozygous mutation in the nuclear-encoded SDHA gene (600857) on chromosome 5p, the nuclear-encoded SDHAF1 gene (612848) on chromosome 19q, or the nuclear-encoded SDHD gene (602690) on chromosome 11q23.
Complex II, also known as succinate dehydrogenase (EC 1.3.5.1), is part of the mitochondrial respiratory chain.
Description
Mitochondrial complex II deficiency is an autosomal recessive disorder with a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Measurement of complex II activity in muscle is the most reliable means of diagnosis; however, there is no clear correlation between residual complex II activity and severity or clinical outcome. In some cases, treatment with riboflavin may have clinical benefit (summary by Jain-Ghai et al., 2013).
Clinical Features
Riggs et al. (1984) described 2 sibs with deficiency of complex II. A 7-year-old boy and his 9-year-old sister had progressive encephalomyopathy with dementia, myoclonic seizures, and short stature. A muscle biopsy showed mitochondrial aggregates and excessive lipid droplets in muscle fibers. In muscle mitochondria, the activity of succinate cytochrome c reductase was deficient. The activities of NADH-cytochrome c reductase and cytochrome oxidase were normal. The defect was thought to lie somewhere between succinate dehydrogenase and coenzyme Q10 in complex II.
Rivner et al. (1989) reported a 25-year-old woman with Kearns-Sayre syndrome (530000) and isolated complex II deficiency. She had short stature, complete external ophthalmoplegia, pigmentary retinopathy, ataxia, and cardiac conduction defects. Muscle biopsy showed ragged-red fibers and increased number of mitochondria with abnormal structure and paracrystalline inclusions. A patient with complex II deficiency reported by Rustin et al. (1993) had isolated hypertrophic cardiomyopathy. Reichmann and Angelini (1994) reported 2 brothers with hypertrophic cardiopathy and skeletal muscle myopathy associated with complex II deficiency.
Bourgeois et al. (1992) reported 2 sisters with a degenerative neurologic disorder presenting clinically as a leukodystrophy. Brain imaging showed symmetric foci of necrosis in the substantia nigra and basal ganglia typical of Leigh syndrome (256000). Mitochondria isolated from skeletal muscle, fibroblasts, and lymphocytes showed complex II deficiency. The heart was not involved in these sisters.
Arpa et al. (1994) reviewed 10 previously published cases of succinate dehydrogenase deficiency and reported another case. Their patient was a 22-year-old woman, the daughter of consanguineous parents, with generalized muscle weakness and easy fatigability. She had mild proximal muscle weakness with distal wasting and an elevation of creatine kinase. Histopathologically, there were no ragged-red fibers, but there was a mild excess of neutral lipids and subsarcolemmal granular accumulations. Enzymatic analysis of isolated muscle mitochondria showed mild diminution of all respiratory complexes, most markedly of succinate-cytochrome c reductase. Free carnitine was also reduced.
Brockmann et al. (2002) reported 3 patients, 2 Turkish sibs and an unrelated Norwegian boy, with isolated complex II deficiency with decreased activities of succinate dehydrogenase and succinate:cytochrome c oxidoreductase. The patients presented in infancy and very early childhood with neurologic symptoms, including loss of motor skills and spastic paresis, and leukoencephalopathy on MRI. Proton MRS showed strongly elevated concentrations of succinate in white matter and CSF.
Ghezzi et al. (2009) provided follow-up of the consanguineous Turkish family reported by Brockmann et al. (2002) and an Italian family reported by Bugiani et al. (2006). The 3 Italian patients originated from a small village in Lombardy, Italy. Two of the patients were clearly related and the other was believed to be related. Onset of the disorder became apparent in the first year of life, manifest as acute psychomotor regression and poor growth with lack of speech development. All patients developed severe spastic quadriplegia with partial loss of postural control and dystonia. Brain imaging studies showed leukoencephalopathy with sparing of the peripheral U-fibers and basal ganglia and increased lactate and succinate. Lactate and pyruvate were variably elevated in blood. Most had relative stabilization of their clinical conditions, with survival beyond the first decade of life in several cases, although growth was consistently and severely impaired. Biochemical analysis of mitochondrial respiratory chain complexes in muscle and fibroblasts showed 20 to 30% residual activity of SDH and succinate-CoQ reductase (SCoQR) and decreased protein levels.
Alston et al. (2012) reported a boy who presented at 3 months of age with symptoms of dilated cardiomyopathy after a normal neonatal period. He later showed delayed motor development with hypertonia, hyperreflexia, and joint contractures. Speech was delayed. Brain MRI at age 2.5 years showed cystic changes and abnormal symmetric signals in the central cerebral white matter, as well as abnormal signals in the corpus callosum, ventral pons, medulla, and throughout the majority of the gray matter of the spinal cord. Laboratory studies showed normal plasma lactate, but evidence of ketosis and increased urinary lactate and urinary tricarboxylic acid cycle metabolites. Skeletal muscle biopsy showed severe deficiency of mitochondrial complex II activity. Western blot analysis of patient fibroblasts showed decreased amounts of fully assembled complex II with almost complete absence of SDHA. Genetic analysis identified compound heterozygosity for 2 mutations in the SDHA gene (600857.0006 and 600857.0007).
Jain-Ghai et al. (2013) reported a female infant, born of unrelated parents of Middle Eastern descent, with complex II deficiency. She was born at 28 weeks' gestation due to preeclampsia. Echocardiogram showed dilated cardiomyopathy and left ventricular noncompaction, and laboratory studies showed increased serum lactate. The patient later showed developmental delay, failure to thrive, and hypotonia. She died at age 13 months. Electron microscopic analysis of muscle biopsy showed mitochondria with a dense array of parallel cristae and matrix granules, isolated complex II deficiency, and low levels of SDHA protein (24%) compared to controls. However, genetic analysis did not reveal mutations in the SDHA, SDHAF1, or ISCU (611911) genes. Jain-Ghai et al. (2013) postulated that this patient had a novel genetic defect.
Jain-Ghai et al. (2013) reviewed 36 cases of complex II deficiency from the literature. The phenotype was highly variable: some patients had multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others had only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Neurologic findings, although variable, included developmental delay or regression following infection, hypotonia, hypertonia, and spasticity. Ophthalmologic features included ophthalmoplegia, retinopathy, nystagmus, optic atrophy, and blindness. Measurement of complex II activity in muscle was the most reliable means of diagnosis; however, there was no correlation between residual complex II activity and severity or clinical outcome. In some cases, treatment with riboflavin had some clinical benefit.
Jackson et al. (2014) reported a girl, born of unrelated Swiss parents, with encephalomyopathy and biochemical evidence of isolated mitochondrial complex II deficiency. The patient showed developmental regression with reduced motor development at age 3 months of age after a respiratory infection. Thereafter, she showed severely delayed psychomotor development associated with hypotonia, nystagmus, secondary microcephaly, ataxia, dystonia, and deteriorating vision. Laboratory studies were normal, excluding severe catabolic episodes. After 4.5 years of age, she developed seizures and myoclonic movements. During an illness at age 7, the patient underwent laboratory studies that showed lactic acidosis, ketonuria, and Krebs cycle intermediates, suggesting a mitochondrial defect. Biochemical assays of skin fibroblasts and muscle homogenates indicated isolated mitochondrial complex II deficiency (5% residual activity) and defective oxygen consumption; immunoblotting showed impaired complex II assembly. Genetic analysis identified compound heterozygous mutation in the SDHD gene (602690.0029 and 602690.0030). Cellular complementation studies showed that the SDHD variants were unable to rescue the complex II assembly defect, whereas wildtype SDHD was able to rescue it.
Alston et al. (2015) reported an infant, born of unrelated Irish parents, with fatal cardiomyopathy associated with mitochondrial complex II deficiency. The patient was noted prenatally to have dilated cardiomyopathy with mitral regurgitation and left ventricular systolic dysfunction. He died on the first day of life. Postmortem examination showed noncompaction of the hypertrophic left ventricle and an underdeveloped right ventricle. Genetic analysis identified a homozygous missense mutation in the SDHD gene (D92G; 602690.0031). Patient skeletal muscle sample showed isolated complex II deficiency (30% residual activity), as well as a significant decrease in SDHD protein levels and a decrease in fully assembled complex II. Complementation studies in yeast deficient in the homologous SDH4 gene showed that the mutation was unable to rescue the oxidative growth defect, consistent with a loss of function.
Clinical Management
Bugiani et al. (2006) reported favorable results with oral riboflavin treatment in 2 Italian patients with complex II deficiency. The patients showed acute psychomotor regression in the first year of life, followed by rapidly progressive neurologic deterioration, spastic quadriparesis with dystonic posturing, and mental impairment. One patient was blind. Complex II deficiency was demonstrated in muscle and fibroblasts. Treatment with oral riboflavin resulted in stabilization of the clinical condition and moderate improvement in cognitive and communicative abilities. Riboflavin supplementation to the growth medium of cultured fibroblasts resulted in a 2-fold increase of complex II activity in patient cells but not control cells.
Molecular Genetics
In 2 sibs with complex II deficiency presenting as Leigh syndrome reported by Bourgeois et al. (1992), Bourgeron et al. (1995) identified a homozygous mutation in the SDHA gene (600857.0001). Bourgeron et al. (1995) claimed that this was the first report of a nuclear gene mutation causing a mitochondrial respiratory chain deficiency in humans.
In affected members of an Italian and Turkish family with mitochondrial complex II deficiency, Ghezzi et al. (2009) identified 2 different homozygous mutations in the SDHAF1 gene (612848.0001 and 612848.0002, respectively). Some of patients had been reported by Brockmann et al. (2002) and Bugiani et al. (2006).
### Associations Pending Confirmation
For discussion of a possible association between mitochondrial complex II deficiency and variation in the SDHB gene, see 185470.0020; for discussion of a possible association with variation in the SDHD gene, see 602690.0029.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Poor growth HEAD & NECK Eyes \- Ptosis \- Ophthalmoplegia \- Pigmentary retinopathy \- Optic atrophy \- Nystagmus \- Impaired vision CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy \- Dilated cardiomyopathy \- Left ventricular noncompaction SKELETAL \- Joint contractures MUSCLE, SOFT TISSUES \- Hypotonia, neonatal \- Muscle weakness \- Exercise intolerance \- Ragged red fibers seen on muscle biopsy \- Abnormal mitochondria with paracrystalline inclusions seen on muscle biopsy \- Accumulated lipid droplets seen on muscle biopsy NEUROLOGIC Central Nervous System \- Psychomotor regression in infants \- Spasticity \- Hyperreflexia \- Extensor plantar responses \- Ataxia \- Cognitive impairment \- Dystonia \- Myoclonus \- Seizures \- Leukoencephalopathy, progressive \- Spongiform encephalomyelopathy \- Leigh syndrome ( 245000 ), in a subset of patients \- Kearns-Sayre syndrome ( 530000 ), in a subset of patients METABOLIC FEATURES \- Lactic acidosis may occur with stress or infection LABORATORY ABNORMALITIES \- Decreased activity of mitochondrial complex II (succinate dehydrogenase) \- Mildly increased serum lactate MISCELLANEOUS \- Onset in first year of life \- Highly variable phenotype MOLECULAR BASIS \- Caused by mutation in the flavoprotein subunit of succinate dehydrogenase complex gene (SDHA, 600857.0001 ) \- Caused by mutation in the succinate dehydrogenase complex assembly factor 1 gene (SDHAF1, 612848.0001 ) \- Caused by mutation in the succinate dehydrogenase complex, subunit D, integral membrane protein gene (SDHD, 602690.0029 ) ▲ 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-hydroxybutyric 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
|
MITOCHONDRIAL COMPLEX II DEFICIENCY
|
c1855008
| 25,709 |
omim
|
https://www.omim.org/entry/252011
| 2019-09-22T16:25:00 |
{"doid": ["0060537"], "mesh": ["C565375"], "omim": ["252011"], "orphanet": ["3208"], "synonyms": ["Alternative titles", "SUCCINATE CoQ REDUCTASE DEFICIENCY"]}
|
Hyoid bone fracture
SpecialtyOrthopedics
The hyoid bone fracture is a very rare fracture of the hyoid bone, accounting for 0.002% of all fractures in humans. It is commonly associated with strangulation and rarely occurs in isolation. The fracture may be associated with gunshot injury, car accidents or induced vomiting. In 50% of strangulations and 27% of hangings, hyoid fractures occur.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 3.1 Classification
* 4 Treatment
* 5 Epidemiology
* 6 References
* 7 External links
## Signs and symptoms[edit]
The main symptoms of a hyoid bone fracture include pain when the affected person rotates their neck, trouble swallowing (dysphagia), and painful swallowing (odynophagia). Other symptoms can be crepitus or tenderness over the bone, suffocation when sticking out the tongue, dyspnea, dysphonia, and subcutaneous emphysema. On laryngoscope examination, lacerations on the pharynx, bruises, swelling, and/or hyoid bone fragments can be seen. If the hyoid bone is fractured, there is a high likelihood that the larynx, pharynx, mandible, and/or cervical spine may be injured as well. Common co-occurring injuries include Le Fort III fractures, mandibular or cervical vertebra fractures, and mandibular dislocation.[1]
## Causes[edit]
* Position of hyoid bone (shown in red).
* Shape of hyoid bone.
* Hyoid bone — anterior surface, enlarged.
* Anterolateral view of head and neck.
Neck trauma, commonly by strangulation, athletic activities, and car accidents, is the cause of a hyoid bone fracture.[1] Other causes include violent vomiting, gunshot wounds, and hanging.[2]
## Diagnosis[edit]
A diagnosis can be made using clinical examination, laryngoscope examination, and/or radiographic studies.[1]
### Classification[edit]
Hyoid bone fractures are classified into three different types:[2]
* Inward compression fractures with outside periosteal tears
* Antero-posterior compression fractures with inside periosteal tears
* Avulsion fractures
## Treatment[edit]
Treatment options vary from very conservative to aggressive. Conservative options include rest, observation, pain control, diet changes, use of a nasopharyngeal tube or oropharyngeal tube, and antibiotic therapy. More aggressive options include surgical repair of the hyoid bone and/or tracheotomy. Surgical treatment was used in 10.9% of cases in a 2012 meta-analysis.[1]
## Epidemiology[edit]
Hyoid bone fractures represent 0.002% of all fractures; they are rare because the hyoid bone is well-protected by its location in the neck behind the mandible and in front of the cervical spine, as well as its mobility. 91.3% of hyoid bone fractures occur in men.[1]
## References[edit]
1. ^ a b c d e Ramchand, Tekchand; Choudhry, Osamah J.; Shukla, Pratik A.; Tomovic, Senja; Kuperan, Arjuna B.; Eloy, Jean Anderson (2012-08-01). "Management of hyoid bone fractures: a systematic review". Otolaryngology–Head and Neck Surgery. 147 (2): 204–208. doi:10.1177/0194599812451409. ISSN 1097-6817. PMID 22691692.
2. ^ a b Dalati, T. (2005). "Isolated hyoid bone fracture". International Journal of Oral and Maxillofacial Surgery. 34 (4): 449–452. doi:10.1016/j.ijom.2004.09.004. PMID 16053860.
## External links[edit]
Classification
D
* ICD-10: S12.8
* ICD-9-CM: 807.5
*[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-hydroxybutyric 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
|
Hyoid bone fracture
|
c0347591
| 25,710 |
wikipedia
|
https://en.wikipedia.org/wiki/Hyoid_bone_fracture
| 2021-01-18T19:05:45 |
{"umls": ["C0347591"], "wikidata": ["Q25036697"]}
|
## Summary
### Clinical characteristics.
Cytochrome P450 oxidoreductase deficiency (PORD) is a disorder of steroidogenesis with a broad phenotypic spectrum including cortisol deficiency, altered sex steroid synthesis, disorders of sex development (DSD), and skeletal malformations of the Antley-Bixler syndrome (ABS) phenotype. Cortisol deficiency is usually partial, with some baseline cortisol production but failure to mount an adequate cortisol response in stress. Mild mineralocorticoid excess can be present and causes arterial hypertension, usually presenting in young adulthood. Manifestations of altered sex steroid synthesis include ambiguous genitalia/DSD in both males and females, large ovarian cysts in females, poor masculinization and delayed puberty in males, and maternal virilization during pregnancy with an affected fetus. Skeletal malformations can manifest as craniosynostosis, mid-face retrusion with proptosis and choanal stenosis or atresia, low-set dysplastic ears with stenotic external auditory canals, hydrocephalus, radiohumeral synostosis, neonatal fractures, congenital bowing of the long bones, joint contractures, arachnodactyly, and clubfeet; other anomalies observed include urinary tract anomalies (renal pelvic dilatation, vesicoureteral reflux). Cognitive impairment is of minor concern and likely associated with the severity of malformations; studies of developmental outcomes are lacking.
### Diagnosis/testing.
The diagnosis of PORD can be established by urinary steroid profiling using gas chromatography / mass spectrometry (GC/MS), which documents combined impairment of 17α-hydroxylase (CYP17A1) and 21-hydroxylase (CYP21A2) enzymatic activity located at key branch points of cortisol, aldosterone, and sex steroid synthesis. Identification of biallelic POR pathogenic variants on molecular genetic testing confirms the diagnosis. Molecular genetic testing is desirable for all individuals affected by PORD to confirm the diagnosis, but is mandatory if clinical and laboratory features are inconclusive.
### Management.
Treatment of manifestations: Glucocorticoid replacement therapy for cortisol deficiency including stress-dose cover in intercurrent illness; surgery as needed for craniosynostosis, hypospadias, and cryptorchidism in males and clitoromegaly and vaginal hypoplasia in females; dihydrotestosterone treatment has been successful in some males with micropenis; testosterone replacement in males in whom testosterone levels remain relatively low after onset of puberty; females with absent pubertal development may require estrogen replacement therapy; treatment with estradiol to reduce the size of ovarian cysts; endotracheal intubation, nasal stints or tracheotomy, and tracheostomy as needed; physical and occupational therapy for joint contractures and help with fine and gross motor skills.
Prevention of secondary complications: Supplementation with appropriate steroid hormones in individuals who are deficient has helped alleviate adrenal crisis, lack of or poor pubertal development in males and females, sleepiness, and fatigue. Early intervention services may improve the outcome for individuals at risk for developmental delays and learning difficulties.
Surveillance: Evaluations with a specialist tertiary pediatric endocrine service throughout childhood to closely monitor development and adjust steroid supplementation. Periodic formal developmental assessments in centers with expertise and experience in developmental testing.
Evaluation of relatives at risk: It is appropriate to evaluate apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures.
### Genetic counseling.
PORD 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 genetic testing for pregnancies at increased risk are possible if the POR pathogenic variants have been identified in the family. In addition, noninvasive testing of maternal urine steroid excretion by GC/MS can indicate whether the unborn child is affected by PORD from gestational week 12 onwards.
## Diagnosis
### Suggestive Findings
Cytochrome P450 oxidoreductase deficiency (PORD) is an autosomal recessive disorder with a broad phenotypic spectrum including skeletal malformations resembling the Antley-Bixler syndrome (ABS) phenotype and abnormalities in adrenal steroid biosynthesis resulting in congenital adrenal hyperplasia (CAH).
#### Clinical Findings
Skeletal abnormalities. PORD should be suspected in individuals with features of ABS. Affected individuals may present with the following congenital craniofacial and skeletal anomalies:
* Midface retrusion
* Craniosynostosis (i.e. brachycephaly or turricephaly)
* Hand and feet malformations (arachnodactyly, clinodactyly, camptodactyly, metacarpal and metatarsal synostoses, wrist deviation, rocker-bottom feet, talipes)
* Large joint synostosis, predominantly radiohumeral or radioulnar synostosis, in severely affected individuals. Other large joints (e.g., knees, ankles) can also be affected.
* Femoral bowing
Ambiguous genitalia at birth. The majority of individuals with PORD have disordered sex development (DSD) and present with ambiguous genitalia at birth. DSD can occur in both sexes:
* Females may present with masculinized genitalia (46,XX DSD; e.g., enlarged clitoris, labial fusion).
* Males can present undermasculinized (46,XY DSD; e.g., hypospadias, micropenis).
#### Laboratory Findings
Because POR is required for normal enzymatic function at various steps within the cholesterol and steroid synthesis pathways, individuals with PORD exhibit characteristic abnormalities in both sterol and steroid metabolism (see Figures 1, 2, and 3).
#### Figure 1.
Steroid synthesis Principal intermediates of steroidogenesis illustrating the location of multiple partial biochemical blocks at steps that rely on cytochrome p450 oxidoreductase. These partial blocks lead to increased serum pregnenolone, progesterone, (more...)
#### Figure 2.
Steroid anomalies and pregnancy Partial blockages, which occur at each step catalyzed by cytochrome p450 (CYP) dependent enzymes, presumably explain the finding of low maternal serum unconjugated estriol (uE3) during pregnancies with an affected fetus. (more...)
#### Figure 3.
Cholesterol synthesis pathway (distal portion) Evidence for a partial biochemical block in sterol synthesis at the level of 14- α-demethylase comes from the finding of significantly increased levels of lanosterol and dihydrolanosterol when lymphoblasts (more...)
Serum steroid abnormalities
* ACTH plasma concentration is normal or elevated at baseline.
* Cortisol serum concentration is normal or low at baseline, and may not increase as expected following ACTH stimulation.
* Pregnenolone, progesterone, 17-OH pregnenolone, and 17-OH progesterone serum concentrations are often elevated at baseline and/or after ACTH stimulation.
* Dehyroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione serum concentrations are normal or decreased before and/or after ACTH stimulation.
* Androgen serum concentration may be low and unresponsive to ACTH or hCG stimulation.
Urinary steroid anomalies detected by gas chromatography / mass spectrometry (GC/MS). Steroid abnormalities in individuals with PORD are consistent with attenuated activity of 21-hydroxylase (encoded by CYP21A2) and 17α-hydroxlyase/17,20 lyase activities (encoded by CYP17A1) [Krone et al 2012] and are characterized by:
* Increased concentration of pregnenediol (metabolite of pregnenolone) and pregnanediol (metabolite of progesterone);
* Significantly elevated ratio of metabolites associated with:
* Deficiency of 17α-hydroxylase (5α-tetrahydrocorticosterone, tetrahydrocorticosterone, and 11-dehydro metabolites);
* Deficiency of 21-hydroxylase (17α-hydroxypregnanolone, pregnanetriol, and pregnanetriolone).
Note: The term "apparent pregnene hydroxylation deficiency (APHD)" refers to individuals with this unique urinary steroid profile [Shackleton & Malunowicz 2003]. Despite sharing common characteristics, steroid profiles vary somewhat among affected individuals, presumably because of differences in how the various POR pathogenic variants affect different enzymatic reactions [Pandey et al 2007, Huang et al 2008, Dhir et al 2009, Miller et al 2009].
Evidence of steroid anomalies during pregnancy. Low or undetectable maternal serum unconjugated estriol (uE3) and/or failure of urinary E3 excretion to increase have been noted during pregnancies in which fetuses have PORD [Cragun et al 2004, Shackleton et al 2004]. Prenatal testing for PORD by maternal urinary steroid profiling (GC/MS) has been developed as a sensitive tool to establish the diagnosis in the fetus [Reisch et al 2013] (see Prenatal Testing and Preimplantation Genetic Diagnosis).
Newborn screening for congenital adrenal hyperplasia. In some individuals with PORD, newborn screening for CAH may be positive with moderately elevated serum 17-OH progesterone [Fukami et al 2005]. However, newborn screening does not appear to be sensitive enough to detect all individuals with PORD.
Cholesterol abnormalities. Subtle sterol abnormalities consistent with a partial block in cholesterol synthesis at the level of CYP51 may be present (Figure 3) [Kelley et al 2002, Cragun et al 2004, Fukami et al 2005]. CYP51 catalyzes the conversion of lanosterol into principal intermediates of the distal portion of the cholesterol biosynthesis pathway. Although serum concentrations of cholesterol are grossly normal in individuals with ABS [Fukami et al 2005], lanosterol and dihydrolanosterol accumulate when cells from affected individuals are grown in cholesterol-depleted medium. Sterol profiling of amniotic fluid in an affected pregnancy may reveal di- and trimethylated sterols, but this finding is not unique to PORD [Chevy et al 2005].
### Establishing the Diagnosis
The diagnosis of PORD is established in a proband with the characteristic urinary steroid profile:
* Increased concentration of metabolites of pregnenolone (pregnenediol) and progesterone (pregnanediol)
* Significantly elevated metabolites associated with:
* Deficiency of 17α-hydroxylase (5α-tetrahydrocorticosterone, tetrahydrocorticosterone, and 11 dehydrometabolites)
* Deficiency of 21-hydroxylase (17α-hydroxypregnanolone, pregnanetriol, and pregnanetriolone)
Identification of biallelic pathogenic variants in POR on molecular genetic testing confirms the diagnosis (see Table 1). Molecular genetic testing is desirable for all individuals affected by PORD to confirm the diagnosis, but mandatory if clinical and laboratory features are inconclusive.
Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:
* Single-gene testing. Sequence analysis of POR 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 POR and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
* More comprehensive genomic testing (when available) including exome sequencing, mitochondrial sequencing, and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Cytochrome P450 Oxidoreductase Deficiency
View in own window
Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
PORSequence analysis 392% 4
Gene-targeted deletion/duplication analysis 52.5% 4
Unknown 6NA5.5%
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\.
The results of POR molecular genetic testing in 140 individuals with PORD have been reported (see Molecular Genetics). Homozygous or compound heterozygous pathogenic variants were detected by sequence analysis of POR in 266 alleles. In seven individuals, a large deletion or insertion was detected on one allele by gene-targeted deletion/duplication analysis [Soneda et al 2011, Krone et al 2012].
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\.
Affected individuals have been reported with a single pathogenic variant and nearly complete absence of mRNA made from the allele in which no pathogenic variant was found [Fukami et al 2009]. Also reported: a pathogenic variant in a different gene involved in steroidogenesis: a female with a single POR pathogenic variant in addition to pathogenic variants in both copies of CYP21 [Scott et al 2007]; and, as part of a larger PORD cohort, three individuals (5 alleles) in whom a pathogenic sequence variant could not be found following direct sequencing and MLPA [Krone et al 2012].
## Clinical Characteristics
### Clinical Description
The natural history of cytochrome P450 oxidoreductase deficiency (PORD) varies because it encompasses a wide phenotypic spectrum. However, steroid abnormalities, which occur in all individuals with PORD, can be associated with a number of characteristics.
The summary of clinical characteristics is based on 26 studies on 140 individuals with molecularly confirmed PORD published to date (June 2017).
Cortisol deficiency found in PORD varies, but is present in the majority of individuals.
Based on ACTH stimulation tests, Krone et al [2012] reported severe cortisol deficiency (requiring permanent hydrocortisone replacement) in 43% of individuals, and partial cortisol deficiency (requiring glucocorticoid replacement during stress only) in 40%; no replacement was required in 10% of the cohort.
Mineralocorticoid excess due to inhibition of 17α-hydroxylase activity can result in hypertension, which typically manifests in young adulthood.
Disorders of sex development (DSD) occur in approximately 75% of individuals with molecularly confirmed PORD. DSD can occur in both sexes: 46,XY DSD (e.g., small penis, undescended testes) and 46,XX DSD (e.g., enlarged clitoris, fused and hypoplastic labia). The unusual finding that both sexes can present with DSD (e.g., virilized genitalia in 46,XX and undermasculinized genitalia in 46,XY) was suggested to be caused by the presence of an alternative pathway to dihydrotestosterone [Arlt et al 2004] (see Molecular Genetics). The manifestation of DSD is related to genotype, with some pathogenic variants leading to normal male virilization and 46,XX DSD in girls while other pathogenic variants result in normal female genital appearance and 46,XY DSD in boys (see Genotype-Phenotype Correlations).
Primary amenorrhea was the presenting feature in at least one woman with PORD (milder phenotype) [Scott et al 2007].
Large ovarian cysts with a tendency to spontaneous rupture are present in a number of adolescent and adult females with PORD [Scott et al 2007, Fukami et al 2009, Idkowiak et al 2011].
Poor masculinization and delayed puberty have been reported in some males, but spontaneous progression during puberty has also been observed [Fukami et al 2005, Hershkovitz et al 2008, Idkowiak et al 2011]. Hypospermatogenesis was documented on testicular biopsy in a male with PORD [Fukami et al 2005].
Fertility may be a concern. No reports describe reproduction in individuals with PORD; thus, the prevalence of infertility among individuals with PORD remains uncertain.
Signs of maternal virilization during pregnancy with an affected fetus, including hirsutism, enlargement of the nose and lips, deepening of the voice, and acne, have been reported in women during pregnancies in which fetuses were later found to have PORD [Fukami et al 2009, Krone et al 2012, Reisch et al 2013].
Skeletal abnormalities of the Antley-Bixler syndrome (ABS) phenotype are frequently observed in individuals with PORD. The severity of malformations varies from mild to moderate and severe. Functional studies are currently lacking but individuals with milder skeletal features similar to those in classic ABS probably have moderate PORD. Those with mild PORD tend to have few if any notable physical characteristics. Krone et al have introduced a clinical scoring system rating the severity of the skeletal and craniofacial malformations in PORD (Table 2) [Krone et al 2012], which is useful for systematic assessment of malformations in PORD.
* Skeletal malformations occur in approximately 85% of individuals with molecularly confirmed PORD. Elbow ankylosis, often from radiohumeral synostosis, causes fixation of the elbow in a flexed position. Elbow extension may be restricted in the absence of radiohumeral synostosis. Neonatal fractures and congenital bowing of the long bones (especially the femurs) are common. Other common malformations of the limbs include long palms, camptodactyly, other joint contractures, arachnodactyly, clubfeet, irregularly positioned toes, and rocker-bottom feet. Vertebral and rib anomalies, hypoplasia of the scapula, scoliosis, and narrow chest and/or pelvis have been reported. Other skeletal anomalies reported in individuals with PORD include diastases of the radioulnar joint, ulnar deviation of the wrists, marfanoid habitus, flattened metacarpal epiphyses, cubitus valgus, brachymetacarpia, and brachytelephalangy.
* Craniofacial anomalies. Craniosynostosis is usually severe and most commonly involves the coronal and lambdoid sutures, resulting in turricephaly; synostosis of other cranial sutures has also been reported. Other craniofacial anomalies include frontal bossing, enlarged anterior fontanelle, severe midface retrusion, choanal stenosis or atresia, short bulbous nose, depressed nasal bridge, narrow mouth, high arched narrow palate, and dysplastic ears that may be low-set with stenotic external auditory canals. In milder forms, the craniofacial features – if present – may not be as easily identified at birth and/or tend to be less severe than those in individuals with severe disease. Although craniosynostosis and/or brachycephaly may be observed, surgical treatment may not require as many procedures. Individuals may have conductive hearing loss.
* Hydrocephalus requiring ventriculoperitoneal shunt insertion has been reported in a number of affected individuals [Krone et al 2012].
### Table 2.
PORD Skeletal Malformation Scoring System Classifying the Major Features of the Antley-Bixler Syndrome Phenotype
View in own window
ScoreMidface HypoplasiaCraniosynostosisHand & Feet MalformationsLarge-Joint SynostosisFemoral BowingAdditional Malformations
0NoneNoneNoneNoneNoneNone
1Mild (low-set ears, pear-shaped nose)Mild (1 suture affected, e.g. brachycephaly)1 hand/feet malformationExtension deficitPresent1
2Severe (compressed midface skeletal structure, proptosis)Severe (≥2 sutures affected, e.g. turricephaly)2 hand/feet malformationsFixed synostosis, joint contractures of 1 large jointComplicated by neonatal fractures≥2
3Complicated by choanal stenosis/ atresiaComplicated by hydrocephalus, w/VP-shunt requirement≥3 hand/feet malformationsFixed synostosis, joint contractures of several large joints--
Proposed in Krone et al [2012]
The maximum score is 16. A score of 1-4 has been proposed as "mild," 5-8 as "moderate," and >9 as "severe."
VP = ventriculoperitoneal
Associated anomalies, presumably not related to the disruption of sterol or steroid synthesis, are rare in individuals with PORD. These include urinary tract anomalies including several individuals with renal pelvic dilatation and vesicoureteral reflux [Krone et al 2012, Bonamichi et al 2016] and one individual with unilateral renal agenesis [Krone et al 2012]. Gastrointestinal conditions are reported in one individual with PORD who developed severe gastroesophageal reflux and constipation [Williamson et al 2006] and another individual with an anteriorly placed anus [Krone et al 2012]. Other observations include a two vessel umbilical cord in two individuals with PORD; Arnold-Chiari malformation and a frontal capillary hemangioma have each been reported in one individual [Krone et al 2012].
Cognitive function and development. There is a paucity of data on cognitive function and developmental outcomes in individuals with PORD. Developmental delays have been reported in a number of children with PORD, mainly delayed speech and language development and fine motor skills, presumably secondary to conductive hearing loss, skeletal abnormalities, multiple surgical procedures with anesthesia, and prolonged hospitalization with immobility [Williamson et al 2006, Sahakitrungruang et al 2009]. Early and effective management of upper airway obstruction, craniosynostosis, hydrocephalus, and hearing loss appear to be a prerequisite for good cognitive development.
Prognosis is primarily determined by the severity of the skeletal and craniofacial malformations. Stillbirth has been reported in infants with very severe skeletal malformations [Krone et al 2012, Reisch et al 2013]. In individuals with mild to moderate clinical features, the prognosis is guarded in infancy and improves with age. Early death caused by respiratory complications is a concern. However, with careful airway management, many children with ABS survive and the prognosis may be reasonably good. Prospective follow-up studies describing the natural course of PORD are currently lacking.
### Genotype-Phenotype Correlations
While individuals with the same pathogenic variants (even sibs) can show phenotypic variations, some commonalities are observed among individuals with the same genotype. The broad phenotypic spectrum of PORD may be caused by the effect of various POR pathogenic variants on different enzymatic reactions [Huang et al 2005, Dhir et al 2007, Pandey et al 2007, Huang et al 2008, Burkhard et al 2017].
Three studies report the investigation of genotype-phenotype correlations in larger cohorts of individuals with PORD [Huang et al 2005, Fukami et al 2009, Krone et al 2012]. The observations from these studies include the following.
Skeletal malformations
* The overall reported frequency of skeletal malformations in genetically confirmed PORD is about 85%.
* Homozygotes for p.Arg457His tend to have less severe skeletal abnormalities.
* Compound heterozygosity for p.Arg457His and a severe loss-of-function pathogenic variant on the other allele is associated with a more severe skeletal phenotype.
* Homozygotes for p.Ala287Pro have moderate skeletal malformations.
* Compound heterozygosity for p.Ala287Pro and a severe loss-of-function pathogenic variant on the other allele is associated with a severe skeletal phenotype.
Disorders of sex development (DSD). Homozygosity for either pathogenic variant p.Arg457His or p.Ala287Pro causes 46,XX DSD (virilized females at birth) but undermasculinization occurs less frequently in 46,XY individuals.
Adrenal steroid biosynthesis
* An abnormal urinary steroid pattern has been found in all persons with genetically confirmed PORD investigated; however, not all reported patients have had a urinary steroid profile as part of their work-up.
* Adrenal insufficiency is present in most persons with PORD: based on ACTH stimulation tests, Krone et al [2012] reported hydrocortisone replacement in 43%, stress dose cover only in 40%, and no replacement in 10% of his cohort; Fukami et al [2009] found the prevalence of adrenal crisis was increased in individuals with pathogenic variant p.Arg457His combined with a severe loss-of-function pathogenic variant.
* However, a prediction of the overall severity of glucocorticoid deficiency based on genotype is not possible.
### Nomenclature
Peterson et al [1985] first reported a male with ambiguous genitalia and apparent combined partial 21-hydroxylase (P450c21, CYP21A2) deficiency and partial 17-hydroxylase (P450c17, CYP17A1) deficiency, and referred to this condition as "mixed oxidase disease" [Peterson et al 1985]. This condition, also known as congenital adrenal hyperplasia due to apparent combined CYP21A1 and CYP17A1 deficiency, has been shown to be caused by biallelic POR pathogenic variants [Arlt et al 2004, Flück et al 2004].
### Prevalence
The prevalence of PORD has yet to be determined, however it is a very rare condition. Since POR pathogenic variants were first reported in 2004, approximately 140 individuals with PORD have been reported in the literature (June 2017).
The most prevalent pathogenic variant in individuals with PORD of Japanese ancestry is p.Arg457His. In individuals of European background with PORD, p.Ala287Pro is the most prevalent pathogenic variant.
## Differential Diagnosis
Congenital adrenal hyperplasia (CAH) is a heterogeneous group of autosomal recessive conditions that result in impaired synthesis of cortisol, mineralocorticoids, and/or sex steroids. Based on this definition, the term CAH can be used to describe cytochrome P450 oxidoreductase deficiency (PORD). PORD and the following etiologies of CAH may be distinguished by differences in urinary steroid profiles, molecular genetic testing, and/or the presence of skeletal anomalies, as skeletal anomalies are never found in other forms of CAH, but may occur in PORD. POR acts as an electron donor to two major steroidogenic enzymes, CYP21A2 and CYP17A1. Therefore, individuals with POR show biochemical features of both 21-hydroxylase and 17α-hydroxylase deficiency.
* 21-hydroxylase deficiency (21-OHD, CYP21A2 deficiency), the most common form of CAH, is associated with glucocorticoid and, in most cases, mineralocorticoid deficiency as well as with sex steroid excess resulting in masculinization of the external genitalia in females (46,XX DSD). Unlike PORD, 21-OHD is characterized by increased circulating androgens and progressive virilization of females after birth.
* 17α-hydroxylase/17,20-lyase deficiency (CYP17A1 deficiency) (OMIM 202110) is associated with mineralocorticoid excess, glucocorticoid deficiency and sex steroid deficiency, which is clinically associated with ambiguous genitalia in males (46,XY DSD) and lack of pubertal progression in both sexes. Milder pathogenic variants on the other end of a broad phenotypic spectrum might affect sex steroid production only ("isolated 17,20-lyase deficiency").
* 11β-hydroxylase deficiency (OMIM 202010) is associated with glucocorticoid deficiency but excess of both mineralocorticoids and sex steroids – therefore, with hypertension and ambiguous genitalia in females (46,XX DSD).
* 3β-hydroxysteroid dehydrogenase deficiency (OMIM 201810) is associated with glucocorticoid and mineralocorticoid deficiency and leads to ambiguous genitalia in males (46,XY DSD), but in rare cases also in females (46,XX DSD).
Antley-Bixler syndrome (ABS) without genital anomalies or disordered steroidogenesis (OMIM 207410) is characterized by the skeletal features of ABS including craniosynostosis, radioulnar and radiohumeral synostosis, midface hypoplasia with narrowing of the upper airway, frontal bossing, arachnodactyly and camptodactyly, femoral bowing, irregular positioned toes, and rocker-bottom feet. Pathogenic variants in FGFR2 are causative. Inheritance is autosomal dominant.
Autosomal dominant craniosynostosis syndromes. Craniosynostosis occurs in the autosomal dominant FGFR-related craniosynostosis syndromes that include Pfeiffer syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Apert syndrome, and Beare-Stevenson syndrome (see FGFR-Related Craniosynostosis).
* Pfeiffer and Crouzon syndromes. Some individuals with severe FGFR-related craniosynostosis have clinical features that overlap ABS. Individuals with FGFR pathogenic variants may have more severe proptosis compared to those with PORD. Although common in PORD, a short bulbous nose, low-set and dysplastic ears, arachnodactyly, and rocker-bottom feet are not usually described in FGFR-related craniosynostosis syndromes. In Pfeiffer syndrome, limb deformities are part of the spectrum (e.g., broad thumbs and toes, brachydactyly, tarsal fusion). FGFR1 and FGFR2 pathogenic variants are causative.
* Apert syndrome can usually be distinguished from ABS by the presence of the typical syndactyly. FGFR2 pathogenic variants are causative.
* Muenke syndrome is caused by FGFR3 pathogenic variant p.Pro250Arg. Muenke syndrome is characterized by uni-or bilateral synostosis of the coronal suture. Deformities of the hand and feet (e.g., broad toes, carpal/tarsal fusions) can be part of the spectrum.
* Saethre-Chotzen syndrome is characterized by uni-or bilateral coronal synostosis, facial asymmetry, ptosis, ear anomalies, and syndactyly in some individuals. Pathogenic variants of TWIST1 are causative.
Cytochrome P450 26B1 (CYP26B1) deficiency (OMIM 614416) is characterized by craniosynostosis, oligodactyly, femoral bowing, radiohumeral synostosis, narrow thorax, and small pelvic bones [Laue et al 2011, Morton et al 2016]. The spectrum of severity in the small number of individuals reported has included perinatal lethal, early infant demise, and a milder phenotype in a female age 22 years, which resembled ABS and Pfeiffer syndrome [Morton et al 2016]. Individuals with cytochrome P450 26B1 deficiency are not reported to have features consistent with abnormal steroid metabolism. Biallelic CYP26B1 pathogenic variants are causative.
Thanatophoric dysplasia. The combination of femoral bowing and craniosynostosis may be seen in thanatophoric dysplasia, but genital anomalies do not occur in this condition. Unlike ABS, thanatophoric dysplasia is characterized by severe rhizomelia. Brain malformations and severe intellectual disability are also universal features of thanatophoric dysplasia but are not reported as part of PORD [Wang et al 2014, Weaver et al 2014]. Thanatophoric dysplasia is caused by pathogenic variants in FGFR3 and is inherited in an autosomal dominant manner; the majority of probands have a de novo pathogenic variant.
Shprintzen-Goldberg syndrome (SGS) overlaps with PORD skeletal malformations in that both can have camptodactyly, arachnodactyly, femoral bowing, craniosynostosis, and a marfanoid habitus. However, individuals with SGS do not have ambiguous genitalia or the distinctive facial features of PORD. SGS is associated with significant cognitive disability and brain malformations. At least two individuals with PORD without ABS-like malformations were originally classified as having SGS. Pathogenic variants in SKI are causative.
Bent-bone dysplasias, which include campomelic dysplasia, kyphomelic dysplasia (OMIM 211350), and Stüve-Wiedemann syndrome (OMIM 601559), are commonly associated with long-bone bowing, primarily of the femora. These conditions are distinguished from PORD by the lack of craniosynostosis or radiohumeral synostosis. Long-bone fractures occur in campomelic dysplasia, but usually after the neonatal period, whereas fractures in PORD usually occur during the neonatal period. Campomelic dysplasia is often associated with abnormal sexual development (e.g., hypospadias to phenotypic female with a 46,XY karyotype) and is caused by pathogenic variants in SOX9. Campomelic dysplasia is inherited in an autosomal dominant manner but is most commonly the result of a de novo pathogenic variant.
Osteogenesis imperfecta (OI; see COLA1/2-Related Osteogenesis Imperfecta) is associated with neonatal fractures, but lacks the characteristic craniofacial, limb, and urogenital anomalies of PORD. Unlike OI, PORD is not associated with osteoporosis or Wormian bones.
Teratogen exposure. Early prenatal exposure to oral, high-dose fluconazole has resulted in an ABS-like phenotype in five reported individuals [Aleck & Bartley 1997, Lopez-Rangel & Van Allen 2005]. However, frontal bossing, choanal stenosis/atresia, genital abnormalities, and camptodactyly were not observed. Pregnancy history is important in identifying this exposure.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with PORD, the following evaluations are recommended:
* Evaluations by appropriate specialists in endocrinology, clinical genetics, neurosurgery, otolaryngology, and cardiology
* Assessment for airway problems in individuals with skeletal malformations
* Functional adrenal studies (cosyntropin test) to assess glucocorticoid deficiency, regardless of the presence or absence of genital abnormalities
* Additional studies that may be indicated:
* Cranial CT scan and/or MRI to determine the degree of craniosynostosis, hydrocephaly, choanal stenosis, and orbital depth
* Radiographs to identify long-bone fractures and/or bowing, bony synostoses, and/or joint contractures
* Echocardiogram if a heart defect is suspected
* Abdominal and pelvic ultrasound examination to identify internal sex organs, detect any renal anomalies, and detect and monitor ovarian cysts in adolescent girls.
### Treatment of Manifestations
Cortisol deficiency
* Regular hydrocortisone replacement therapy is indicated if baseline serum cortisol concentrations are low.
* Stress-dose steroids should be provided perioperatively and during times of physiologic stress in individuals in whom cortisol response to ACTH stimulation (cosyntropin test) is below normal [Krone et al 2012].
Genital abnormalities
* Hypospadias and cryptorchidism may be corrected with surgery.
* When clitoromegaly is severe, surgical reduction and plastic reconstruction of the clitoris may be considered.
* Vaginal reconstruction may be performed in females with vaginal hypoplasia.
* Dihydrotestosterone treatment has been successful in some males with micropenis [Fukami et al 2005].
* Testosterone replacement has been initiated in males in whom testosterone levels remained relatively low after onset of puberty [Hershkovitz et al 2008, Idkowiak et al 2011]. Similarly, females with absent pubertal development may require estrogen replacement therapy.
Ovarian cysts. Treatment with estradiol appeared to successfully reduce the size of ovarian cysts in females with PORD [Fukami et al 2009, Idkowiak et al 2011]. Ovarian cysts in females can be a significant problem as they tend to be large and prone to spontaneous rupture; cases of girls treated with GnRH agonists and potent steroids have been reported [Idkowiak et al 2011].
Craniosynostosis. Treatment for craniosynostosis is similar to that for other syndromes associated with premature fusion of cranial sutures. Although surgical correction can be performed at any age, it is generally believed that earlier surgical correction results in better cognitive outcome.
Airway management is often a primary concern in individuals with ABS as a result of choanal stenosis or atresia, small chest, narrow trachea, and/or shortening of the larynx.
* Endotracheal intubation is often required in the first minutes after delivery.
* Nasal stints or tracheotomy may be required.
* Tracheostomy may be necessary until age three to five years when the pharyngeal encroachment can be corrected.
Hydrocephalus. If present, hydrocephalus may be treated by surgical placement of a ventriculoperitoneal shunt.
Joint contractures and elbow synostosis. Physical and occupational therapy can help individuals with contractures and elbow synostosis develop fine and gross motor skills.
### Prevention of Secondary Complications
Supplementation with appropriate steroid hormones in individuals who are deficient has helped alleviate:
* Adrenal crisis
* Lack of or poor pubertal development in males and females
* Sleepiness and fatigue
Early intervention services may improve the outcome for individuals at risk for developmental delays and learning difficulties.
### Surveillance
Individuals with PORD should be seen by a specialist tertiary pediatric endocrine service throughout childhood to closely monitor their development and adjust steroid supplementation.
Because of the presence of developmental delays in many individuals with ABS, periodic formal developmental assessments may be indicated. However, interpretation of these assessments may be complicated by the physical limitations of the disorder. Screening evaluations are likely to underestimate cognitive abilities. Therefore, evaluations should be done in centers with expertise and experience in developmental testing.
### Evaluation of Relatives at Risk
It is appropriate to evaluate apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures. Evaluations can include:
* Molecular genetic testing if the pathogenic variants in the family are known;
* Urinary steroid profiling using gas chromatography / mass spectrometry (GC/MS) can be done if the pathogenic variants in the family are not known. The characteristic urinary steroid profile:
* Increased coancentration of metabolites of pregnenolone (pregnenediol) and progesterone (pregnanediol)
* Significantly elevated metabolites associated with:
* Deficiency of 17α-hydroxylase (5α-tetrahydrocorticosterone, tetrahydrocorticosterone, and 11 dehydrometabolites)
* Deficiency of 21-hydroxylase (17α-hydroxypregnanolone, pregnanetriol, and pregnanetriolone)
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Fertility may be a concern. No reports describe reproduction in individuals with PORD; thus, the prevalence of infertility among individuals with PORD remains uncertain.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
### Other
Hepatic drug metabolism. NADPH--cytochrome P450 reductase (POR) plays an important role in the metabolism of various drugs and endogenous metabolites/hormones by hepatic microsomal (type 2) P450 cytochromes. Initial studies using bacterially expressed POR pathogenic variants and two hepatic P450 enzymes suggest that pathogenic variants in POR may alter drug metabolism [Miller et al 2009]. In these studies different pathogenic variants resulted in different effects, ranging from no apparent activity to elevated activity of the hepatic P450 enzymes; these activities were not correlated with their activity in CYP17A1 assays.
In vitro activity assays on major drug-metabolizing enzymes and in vivo investigations to assess the impact of various pathogenic and non-pathogenic variants of POR have been performed by various groups [Agrawal et al 2008, Hart & Zhong 2008, Kranendonk et al 2008, Gomes et al 2009, Oneda et al 2009, Agrawal et al 2010, Flück et al 2010, Tomalik-Scharte et al 2010]. For comprehensive reviews on the pharmacogenetics of POR see Pandey & Sproll [2014] and Burkhard et al [2017].
In brief, the different pathogenic variations have different effects on microsomal P450 drug metabolizing enzymes. The common pathogenic variant p.Ala287Pro reduces the activity of the major P450 cytochrome CYP3A4 (which metabolizes ~50% of clinically used drugs) by more than 75% [Nicolo et al 2010]. In vivo cocktail phenotyping in an individual homozygous for the p.Ala287Pro pathogenic variant confirmed altered hepatic detoxification of a variety of drugs due to impaired activity of various hepatic CYP enzymes, including CYP3A4, CYP1A1, CYP2C9, and CYP2D6; the heterozygous mother of this individual also showed impaired activities of CYP1A1 and CYP2C9 [Tomalik-Scharte et al 2010]. In addition, in vitro assays suggest that some variants cause a substrate-specific modulation of CYP3A4 [Agrawal et al 2010].
*[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-hydroxybutyric 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
|
Cytochrome P450 Oxidoreductase Deficiency
|
c1860042
| 25,711 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1419/
| 2021-01-18T21:32:20 |
{"mesh": ["D054882"], "synonyms": ["POR Deficiency", "PORD"]}
|
Stomatitis
An infant with stomatitis due to kwashiorkor and an accompanying Vitamin B deficiency.
SpecialtyDermatology
Stomatitis is inflammation of the mouth and lips.[1] It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration.[2]
In its widest meaning, stomatitis can have a multitude of different causes and appearances. Common causes include infections, nutritional deficiencies, allergic reactions, radiotherapy, and many others.
When inflammation of the gums and the mouth generally presents itself, sometimes the term gingivostomatitis is used, though this is also sometimes used as a synonym for herpetic gingivostomatitis.
The term is derived from the Greek stoma (στόμα), meaning "mouth", and the suffix -itis (-ῖτις), meaning "inflammation".
## Contents
* 1 Causes
* 1.1 Nutritional deficiency
* 1.2 Aphthous stomatitis
* 1.3 Angular stomatitis
* 1.4 Denture-related stomatitis
* 1.5 Allergic contact stomatitis
* 1.6 Migratory stomatitis
* 1.7 Herpetic gingivostomatitis
* 1.8 Irradiation and chemotherapy
* 1.9 Necrotizing ulcerative gingivostomatitis
* 1.10 Stomatitis nicotina
* 1.11 Chronic ulcerative stomatitis
* 1.12 Plasma cell gingivostomatitis
* 1.13 Other forms of stomatitis
* 2 References
* 3 External links
## Causes[edit]
### Nutritional deficiency[edit]
Malnutrition (improper dietary intake) or malabsorption (poor absorption of nutrients into the body) can lead to nutritional deficiency states, several of which can lead to stomatitis. For example, deficiencies of iron, vitamin B2 (riboflavin),[3]:490 vitamin B3 (niacin), vitamin B6 (pyridoxine), vitamin B9 (folic acid) or vitamin B12 (cobalamine) may all manifest as stomatitis. Iron is necessary for the upregulation of transcriptional elements for cell replication and repair. Lack of iron can cause genetic downregulation of these elements, leading to ineffective repair and regeneration of epithelial cells, especially in the mouth and lips. Many disorders which cause malabsorption can cause deficiencies, which in turn causes stomatitis. Examples include tropical sprue.[3]:49
### Aphthous stomatitis[edit]
Main article: Aphthous stomatitis
Aphthous stomatitis (canker sores) is the recurrent appearance of mouth ulcers in otherwise healthy individuals. The cause is not completely understood, but it is thought that the condition represents a T cell mediated immune response which is triggered by a variety of factors. The individual ulcers (aphthae) recur periodically and heal completely, although in the more severe forms new ulcers may appear in other parts of the mouth before the old ones have finished healing. Aphthous stomatitis is one of the most common diseases of the oral mucosa, and is thought to affect about 20% of the general population to some degree.[4] The symptoms range from a minor nuisance to being disabling in their impact on eating, swallowing and talking, and the severe forms can cause people to lose weight. There is no cure for aphthous stomatitis,[5] and therapies are aimed at alleviating the pain, reducing the inflammation and promoting healing of the ulcers, but there is little evidence of efficacy for any treatment that has been used.
### Angular stomatitis[edit]
Main article: Angular cheilitis
Inflammation of the corners (angles) of the lips is termed angular stomatitis or angular cheilitis. In children a frequent cause is repeated lip-licking, and in adults it may be a sign of underlying iron deficiency anemia, or vitamin B deficiencies (e.g., B2-riboflavin, B9-folate, or B12-cobalamin, which in turn may be evidence of poor diets or malnutrition such as celiac disease).
Also, angular cheilitis can be caused by a patient's jaws at rest being 'overclosed' due to edentulousness or tooth wear, causing the jaws to come to rest closer together than if the complete/unaffected dentition were present. This causes skin folds around the angle of the mouth which are kept moist by saliva, which in turn favours infection; mostly by Candida albicans or similar species. Treatment usually involves the administration of topical nystatin or similar antifungal agents. Another treatment can be to correct the jaw relationship with dental treatment (e.g., dentures or occlusal adjustment).
### Denture-related stomatitis[edit]
Main article: Denture-related stomatitis
This is a common condition present in denture wearers. It appears as reddened but painless mucosa beneath the denture. 90% of cases are associated with Candida species, and it is the most common form of oral candidiasis. Treatment is by antifungal medication and improved dental hygiene, such as not wearing the denture during sleep.
### Allergic contact stomatitis[edit]
Allergic contact stomatitis (also termed "allergic gingivostomatitis" or "allergic contact gingivostomatitis")[6] is a type IV (delayed) hypersensitivity reaction that occurs in susceptible atopic individuals when allergens penetrate the skin or mucosa.[7]
Allergens, which may be different for different individuals, combine with epithelial-derived proteins, forming haptens which bind with Langerhans cells in the mucosa, which in turn present the antigen on their surface to T lymphocytes, sensitizing them to that antigen and causing them to produce many specific clones. The second time that specific antigen is encountered, an inflammatory reaction is triggered at the site of exposure.[7] Allergic contact stomatitis is less common than allergic contact dermatitis because the mouth is coated in saliva, which washes away antigens and acts as a barrier.[7] The oral mucosa is also more vascular (has a better blood supply) than skin, meaning that any antigens are more quickly removed from the area by the circulation.[7] Finally, there is substantially less keratin in oral mucosa, meaning that there is less likelihood that haptens will form.[7]
Allergic contact stomatitis appears as non-specific inflammation, so it may be mistaken for chronic physical irritation.[7] There may be burning or soreness of the mouth and ulceration.[7] Chronic exposure to the allergen may result in a lichenoid lesion.[7] Plasma cell gingivitis may also occur, which may be accompanied by glossitis and cheilitis.[7]
Patch test
Allergens that may cause allergic contact stomatitis in some individuals include cinnamaldehyde, Balsam of Peru, peppermint, mercury, gold, pyrophosphates, zinc citrate, free acrylic monomer, nickel, fluoride, and sodium lauryl sulfate.[7][8][9][10][11][12][13] These allergens may originate from many sources, including various foods and drink, chewing gum, toothpaste, mouthwash, dental floss, dental fillings, dentures, orthodontic bands or wires, and many other sources.[7] If the substance containing the allergen comes into contact with the lips, allergic contact cheilitis can occur, together with allergic contact stomatitis.
The diagnosis is confirmed by patch test, and management is by avoidance of exposure to the allergen.[7]
### Migratory stomatitis[edit]
Main article: Geographic tongue
Migratory stomatitis (or geographic stomatitis) is an atypical presentation of a condition which normally presents on the tongue, termed geographic tongue. Geographic tongue is so named because there are atrophic, erythematous areas of depapillation that migrate over time, giving a map-like appearance.
In migratory stomatitis, other mucosal sites in the mouth, such as the ventral surface (undersurface) of the tongue, buccal mucosa, labial mucosa, soft palate, or floor of mouth may be afflicted with identical lesions, usually in addition to the tongue.[14] Apart from not being restricted to the tongue, migratory stomatitis is an identical condition in every regard to geographic tongue. Another synonym for geographic tongue which uses the term stomatitis is "stomatitis areata migrans".
### Herpetic gingivostomatitis[edit]
Herpetic stomatitis (herpetic gingivostomatitis)
Main article: Herpetic gingivostomatitis
This is inflammation of the mouth caused by herpes simplex virus.
### Irradiation and chemotherapy[edit]
Stomatitis may also be caused by chemotherapy, or radiation therapy of the oropharyngeal area.[15] The term mucositis is sometimes used synonymously with stomatitis, however the former usually refers to mucosal reactions to radiotherapy or chemotherapy, and may occur anywhere in the gastrointestinal tract and not just in the mouth.[16]
### Necrotizing ulcerative gingivostomatitis[edit]
See Necrotizing periodontal diseases
The term necrotizing ulcerative gingivostomatitis is sometimes used as a synonym of the necrotizing periodontal disease more commonly termed necrotizing ulcerative gingivitis, or a more severe form (also termed necrotizing stomatitis). The term necrotizing gingivostomatitis is also sometimes used.[17]
### Stomatitis nicotina[edit]
Main article: Stomatitis nicotina
Also called smoker's palatal keratosis,[18]:176 this condition may occur in smokers, especially pipe smokers. The palate appears dry and cracked, and white from keratosis. The minor salivary glands appear as small, red and swollen bumps. It is not a premalignant condition, and the appearance reverses if the smoking is stopped.[18]:176
### Chronic ulcerative stomatitis[edit]
Chronic ulcerative stomatitis is a recently discovered condition with specific immunopathologic features.[19] It is characterized by erosions and ulcerations which relapse and remit. Lesions are located on the buccal mucosa (inside of the cheeks) or on the gingiva (gums).[20][21] The condition resembles Oral lichen planus when biopsied.
The diagnosis is made with Immunofluorescence techniques, which shows circulating and tissue-bound autoantibodies (particulate stratified squamous-epithelium-specific antinuclear antibody) to DeltaNp63alpha protein, a normal component of the epithelium. Treatment is with hydroxychloroquine.[19]
### Plasma cell gingivostomatitis[edit]
Main article: plasma cell gingivitis
Terms such as plasma cell gingivostomatitis,[22] atypical gingivostomatitis and idiopathic gingivostomatitis[23][24] are sometimes a synonym for plasma cell gingivitis, or specifically to refer to a severe form of plasma cell gingivitis.
### Other forms of stomatitis[edit]
* Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome—occurs in children.
* Uremic stomatitis—a rare form of stomatitis that occurs with kidney failure.[25]
* Pyostomatitis vegetans
* Bovine papular stomatitis
## References[edit]
1. ^ Zaoutis, [edited by] Jeffrey M. Bergelson, Samir S. Shah, Theoklis E. (2008). Pediatric infectious diseases. Philadelphia: Mosby/Elsevier. ISBN 9780323076333.CS1 maint: extra text: authors list (link)
2. ^ Michael G. Stewart, Samuel Selesnick (editors) (2010-10-04). "35". Differential diagnosis in otolaryngology – head and neck surgery. New York: Thieme. ISBN 9781604062793.CS1 maint: extra text: authors list (link)
3. ^ a b Yamada T, Alpers DH, et al. (2009). Textbook of gastroenterology (5th ed.). Chichester, West Sussex: Blackwell Pub. ISBN 978-1-4051-6911-0.
4. ^ Neville BW, Damm DD, Allen CM, Bouquot JE (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. pp. 253–284. ISBN 978-0721690032.
5. ^ Brocklehurst, P; Tickle, M; Glenny, AM; Lewis, MA; Pemberton, MN; Taylor, J; Walsh, T; Riley, P; Yates, JM (Sep 12, 2012). Brocklehurst, Paul (ed.). "Systemic interventions for recurrent aphthous stomatitis (mouth ulcers)". The Cochrane Database of Systematic Reviews. 9 (9): CD005411. doi:10.1002/14651858.CD005411.pub2. PMID 22972085.
6. ^ Kanerva, L.; Alanko, K.; Estlander, T. (1 December 1999). "Allergic contact gingivostomatitis from a temporary crown made of methacrylates and epoxy diacrylates". Allergy. 54 (12): 1316–1321. doi:10.1034/j.1398-9995.1999.00074.x. PMID 10688437. S2CID 11805635.
7. ^ a b c d e f g h i j k l Greenberg MS, Glick M (2003). Burket's oral medicine diagnosis & treatment (10th ed.). Hamilton, Ont.: BC Decker. pp. 60, 61. ISBN 978-1550091861.
8. ^ Gottfried Schmalz; Dorthe Arenholt Bindslev (2008). Biocompatibility of Dental Materials. Springer. ISBN 9783540777823. Retrieved March 5, 2014.
9. ^ Thomas P. Habif (2009). Clinical Dermatology. Elsevier Health Sciences. ISBN 978-0323080378. Retrieved March 6, 2014.
10. ^ Edward T. Bope; Rick D. Kellerman (2013). Conn's Current Therapy 2014: Expert Consult. Elsevier Health Sciences. ISBN 9780323225724. Retrieved March 6, 2014.
11. ^ "Balsam of Peru contact allergy". Dermnetnz.org. December 28, 2013. Retrieved March 5, 2014.
12. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. p. 63. ISBN 0-7216-2921-0.
13. ^ J. J. Shea, M.D., F.A.C.A., S. M. Gillespie, M.D., G. L. Waldbott, M.D. Allergy to Fluoride. Annals of Allergy, Volume 25, July, 1967
14. ^ Treister NS, Bruch JM (2010). Clinical oral medicine and pathology. New York: Humana Press. pp. 20, 21. ISBN 978-1-60327-519-4.
15. ^ Berger, Ann M.; Shuster, John L.; von Roenn, Jamie H. (2007). Principles and Practice of Palliative Care and Supportive Oncology. ISBN 9780781795951. Retrieved 2014-03-20.
16. ^ Zeppetella, Giovambattista (2012-06-14). Palliative care in clinical practice. London: Springer. p. 132. ISBN 9781447128434.
17. ^ Horning, GM (October 1996). "Necotizing gingivostomatitis: NUG to noma". Compendium of Continuing Education in Dentistry. 17 (10): 951–4, 956, 957–8 passim, quiz 964. PMID 9533316.
18. ^ a b Coulthard P, Horner K, Sloan P, Theaker E (2008). Master dentistry volume 1, oral and maxillofacial surgery, radiology, pathology and oral medicine (2nd ed.). Edinburgh: Churchill Livingstone/Elsevier. ISBN 9780443068966.
19. ^ a b Solomon, LW (July 2008). "Chronic ulcerative stomatitis". Oral Diseases. 14 (5): 383–9. doi:10.1111/j.1601-0825.2008.01446.x. PMID 18593454.
20. ^ Scully, Crispian (2008). Oral and maxillofacial medicine : the basis of diagnosis and treatment (2nd ed.). Edinburgh: Churchill Livingstone. ISBN 9780443068188.
21. ^ Fourie J, van Heerden WF, McEachen SC, van Zyl A (April 2011). "Chronic ulcerative stomatitis: a distinct clinical entity?". South African Dental Journal. 66 (3): 119–21. PMID 21874892.
22. ^ Neville BW, Damm DD, Allen CA, Bouquot JE (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. pp. 141, 142. ISBN 978-0721690032.
23. ^ Janam, P; Nayar, BR; Mohan, R; Suchitra, A (January 2012). "Plasma cell gingivitis associated with cheilitis: A diagnostic dilemma!". Journal of Indian Society of Periodontology. 16 (1): 115–9. doi:10.4103/0972-124X.94618. PMC 3357019. PMID 22628976.
24. ^ Kerr, DA; McClatchey, KD; Regezi, JA (September 1971). "Idiopathic gingivostomatitis. Cheilitis, glossitis, gingivitis syndrome; atypical gingivostomatitis, plasma-cell gingivitis, plasmacytosis of gingiva". Oral Surgery, Oral Medicine, and Oral Pathology. 32 (3): 402–23. doi:10.1016/0030-4220(71)90201-5. PMID 5285187.
25. ^ Laskaris, George (2006). Pocket atlas of oral diseases (2nd ed.). Stuttgart: Thieme. p. 12. ISBN 9781588902498.
## External links[edit]
Classification
D
* ICD-10: K12
* ICD-9-CM: 528.0
* MeSH: D013280
* DiseasesDB: 27158
* SNOMED CT: 95361005
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
* Microcheilia
* Nasolabial cyst
* Sun poisoning
* Trumpeter's wart
Tongue
* Ankyloglossia
* Black hairy tongue
* Caviar tongue
* Crenated tongue
* Cunnilingus tongue
* Fissured tongue
* Foliate papillitis
* Glossitis
* Geographic tongue
* Median rhomboid glossitis
* Transient lingual papillitis
* Glossoptosis
* Hypoglossia
* Lingual thyroid
* Macroglossia
* Microglossia
* Rhabdomyoma
Palate
* Bednar's aphthae
* Cleft palate
* High-arched palate
* Palatal cysts of the newborn
* Inflammatory papillary hyperplasia
* Stomatitis nicotina
* Torus palatinus
Oral mucosa – Lining of mouth
* Amalgam tattoo
* Angina bullosa haemorrhagica
* Behçet's disease
* Bohn's nodules
* Burning mouth syndrome
* Candidiasis
* Condyloma acuminatum
* Darier's disease
* Epulis fissuratum
* Erythema multiforme
* Erythroplakia
* Fibroma
* Giant-cell
* Focal epithelial hyperplasia
* Fordyce spots
* Hairy leukoplakia
* Hand, foot and mouth disease
* Hereditary benign intraepithelial dyskeratosis
* Herpangina
* Herpes zoster
* Intraoral dental sinus
* Leukoedema
* Leukoplakia
* Lichen planus
* Linea alba
* Lupus erythematosus
* Melanocytic nevus
* Melanocytic oral lesion
* Molluscum contagiosum
* Morsicatio buccarum
* Oral cancer
* Benign: Squamous cell papilloma
* Keratoacanthoma
* Malignant: Adenosquamous carcinoma
* Basaloid squamous carcinoma
* Mucosal melanoma
* Spindle cell carcinoma
* Squamous cell carcinoma
* Verrucous carcinoma
* Oral florid papillomatosis
* Oral melanosis
* Smoker's melanosis
* Pemphigoid
* Benign mucous membrane
* Pemphigus
* Plasmoacanthoma
* Stomatitis
* Aphthous
* Denture-related
* Herpetic
* Smokeless tobacco keratosis
* Submucous fibrosis
* Ulceration
* Riga–Fede disease
* Verruca vulgaris
* Verruciform xanthoma
* White sponge nevus
Teeth (pulp, dentin, enamel)
* Amelogenesis imperfecta
* Ankylosis
* Anodontia
* Caries
* Early childhood caries
* Concrescence
* Failure of eruption of teeth
* Dens evaginatus
* Talon cusp
* Dentin dysplasia
* Dentin hypersensitivity
* Dentinogenesis imperfecta
* Dilaceration
* Discoloration
* Ectopic enamel
* Enamel hypocalcification
* Enamel hypoplasia
* Turner's hypoplasia
* Enamel pearl
* Fluorosis
* Fusion
* Gemination
* Hyperdontia
* Hypodontia
* Maxillary lateral incisor agenesis
* Impaction
* Wisdom tooth impaction
* Macrodontia
* Meth mouth
* Microdontia
* Odontogenic tumors
* Keratocystic odontogenic tumour
* Odontoma
* Dens in dente
* Open contact
* Premature eruption
* Neonatal teeth
* Pulp calcification
* Pulp stone
* Pulp canal obliteration
* Pulp necrosis
* Pulp polyp
* Pulpitis
* Regional odontodysplasia
* Resorption
* Shovel-shaped incisors
* Supernumerary root
* Taurodontism
* Trauma
* Avulsion
* Cracked tooth syndrome
* Vertical root fracture
* Occlusal
* Tooth loss
* Edentulism
* Tooth wear
* Abrasion
* Abfraction
* Acid erosion
* Attrition
Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures
* Cementicle
* Cementoblastoma
* Gigantiform
* Cementoma
* Eruption cyst
* Epulis
* Pyogenic granuloma
* Congenital epulis
* Gingival enlargement
* Gingival cyst of the adult
* Gingival cyst of the newborn
* Gingivitis
* Desquamative
* Granulomatous
* Plasma cell
* Hereditary gingival fibromatosis
* Hypercementosis
* Hypocementosis
* Linear gingival erythema
* Necrotizing periodontal diseases
* Acute necrotizing ulcerative gingivitis
* Pericoronitis
* Peri-implantitis
* Periodontal abscess
* Periodontal trauma
* Periodontitis
* Aggressive
* As a manifestation of systemic disease
* Chronic
* Perio-endo lesion
* Teething
Periapical, mandibular and maxillary hard tissues – Bones of jaws
* Agnathia
* Alveolar osteitis
* Buccal exostosis
* Cherubism
* Idiopathic osteosclerosis
* Mandibular fracture
* Microgenia
* Micrognathia
* Intraosseous cysts
* Odontogenic: periapical
* Dentigerous
* Buccal bifurcation
* Lateral periodontal
* Globulomaxillary
* Calcifying odontogenic
* Glandular odontogenic
* Non-odontogenic: Nasopalatine duct
* Median mandibular
* Median palatal
* Traumatic bone
* Osteoma
* Osteomyelitis
* Osteonecrosis
* Bisphosphonate-associated
* Neuralgia-inducing cavitational osteonecrosis
* Osteoradionecrosis
* Osteoporotic bone marrow defect
* Paget's disease of bone
* Periapical abscess
* Phoenix abscess
* Periapical periodontitis
* Stafne defect
* Torus mandibularis
Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities
* Bruxism
* Condylar resorption
* Mandibular dislocation
* Malocclusion
* Crossbite
* Open bite
* Overbite
* Overeruption
* Overjet
* Prognathia
* Retrognathia
* Scissor bite
* Maxillary hypoplasia
* Temporomandibular joint dysfunction
Salivary glands
* Benign lymphoepithelial lesion
* Ectopic salivary gland tissue
* Frey's syndrome
* HIV salivary gland disease
* Necrotizing sialometaplasia
* Mucocele
* Ranula
* Pneumoparotitis
* Salivary duct stricture
* Salivary gland aplasia
* Salivary gland atresia
* Salivary gland diverticulum
* Salivary gland fistula
* Salivary gland hyperplasia
* Salivary gland hypoplasia
* Salivary gland neoplasms
* Benign: Basal cell adenoma
* Canalicular adenoma
* Ductal papilloma
* Monomorphic adenoma
* Myoepithelioma
* Oncocytoma
* Papillary cystadenoma lymphomatosum
* Pleomorphic adenoma
* Sebaceous adenoma
* Malignant: Acinic cell carcinoma
* Adenocarcinoma
* Adenoid cystic carcinoma
* Carcinoma ex pleomorphic adenoma
* Lymphoma
* Mucoepidermoid carcinoma
* Sclerosing polycystic adenosis
* Sialadenitis
* Parotitis
* Chronic sclerosing sialadenitis
* Sialectasis
* Sialocele
* Sialodochitis
* Sialosis
* Sialolithiasis
* Sjögren's syndrome
Orofacial soft tissues – Soft tissues around the mouth
* Actinomycosis
* Angioedema
* Basal cell carcinoma
* Cutaneous sinus of dental origin
* Cystic hygroma
* Gnathophyma
* Ludwig's angina
* Macrostomia
* Melkersson–Rosenthal syndrome
* Microstomia
* Noma
* Oral Crohn's disease
* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Stomatitis
|
c1568868
| 25,712 |
wikipedia
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https://en.wikipedia.org/wiki/Stomatitis
| 2021-01-18T19:01:58 |
{"mesh": ["D013280"], "umls": ["C1568868"], "icd-9": ["528.0"], "icd-10": ["K1212."], "wikidata": ["Q911386"]}
|
Platypnea-orthodeoxia syndrome
Differential diagnosisintracardiac shunting
Platypnea–orthodeoxia syndrome is a condition in which a person has shortness of breath and low oxygen saturations when upright (platypnea and orthodeoxia), but no symptoms when lying down. It can be caused by ventilation-perfusion mismatch, intracardiac shunting, or pulmonary shunting. In some cases, the cause is multifactorial.[1][2]
## References[edit]
1. ^ Henkin, Stanislav; Negrotto, Sara; Pollak, Peter M.; Cullen, Michael W.; O'Cochlain, D. Fearghas; Wright, R. Scott (2015-10-01). "Platypnea-Orthodeoxia Syndrome: Diagnostic Challenge and the Importance of Heightened Clinical Suspicion". Texas Heart Institute Journal. 42 (5): 498–501. doi:10.14503/THIJ-14-4596. ISSN 0730-2347. PMC 4591898. PMID 26504452.
2. ^ De Vecchis, Renato; Baldi, Cesare; Ariano, Carmelina (2016-09-23). "Platypnea–Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea". Journal of Clinical Medicine. 5 (10): 85. doi:10.3390/jcm5100085. ISSN 2077-0383. PMC 5086587. PMID 27669319.
This medical symptom 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-hydroxybutyric 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
|
Platypnea-orthodeoxia syndrome
|
None
| 25,713 |
wikipedia
|
https://en.wikipedia.org/wiki/Platypnea-orthodeoxia_syndrome
| 2021-01-18T18:54:39 |
{"wikidata": ["Q30753528"]}
|
Schilder's disease is a progressive demyelinating disorder of the central nervous system.
## Epidemiology
Less than 20 sporadic cases (predominantly males) have been reported so far.
## Clinical description
The onset is usually in childhood (age 5-14 years). The disease often occurs shortly after an infectious illness and may manifest with headache, malaise and fever. Variable neurological abnormalities progressively develop and include personality changes, poor attention, dementia, aphasia, headache, vomiting, tremor, seizures, balance instability, incontinence, muscle weakness. Deafness, paralysis of eye movements, nystagmus, optic neuritis and optic atrophy are common. Malnutrition and cachexia are reported in the later chronic stages of illness. Schilder's disease is considered as a variant or borderline form of multiple sclerosis.
## Etiology
Pathologically, it is characterized by bilateral widespread demyelination of the brain hemispheres with varying degrees of axonal injury. Etiology remains unclear.
## Diagnostic methods
Diagnosis is based on sequential neuroimaging (consistent with subacute or chronic myelinoclastic diffuse sclerosis) and electroencephalographic studies.
## Differential diagnosis
Differential diagnosis includes a wide range of neurodegenerative disorders such as multiple sclerosis, acute disseminated encephalomyelitis, subacute sclerosing panencephalitis, progressive rubella panencephalitis, brucellosis, metachromatic leukoencephalopathy, Churg-Strauss disease, Wegener granulomatosis (see these terms). Schilder's disease often mimics intracranial neoplasm or abscess.
## Management and treatment
Management is mainly symptomatic and supportive (physiotherapy, occupational therapy, nutritional support in the later stages). Corticosteroids have been shown effective in some patients. Additional treatments include beta-interferon and/or immunosuppressive drugs.
## Prognosis
Prognosis of Schilder's disease is variable. The clinical course is usually progressive, but significant improvement and remissions have also been described. Survival has been reported to be less than ten years after the onset. Patients with a good response to corticosteroids and those with smaller lesions may have a better prognosis.
*[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-hydroxybutyric 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
|
Schilder disease
|
c0007795
| 25,714 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=59298
| 2021-01-23T17:24:37 |
{"mesh": ["D002549"], "omim": ["272100"], "umls": ["C0007795"], "icd-10": ["G37.0"], "synonyms": ["Myelinoclastic diffuse sclerosis"]}
|
A number sign (#) is used with this entry because of evidence that Schmid-type metaphyseal chondrodysplasia (MCDS) is caused by heterozygous mutation in the COL10A1 gene (120110) on chromosome 6q22.
Description
Schmid-type metaphyseal chondrodysplasia is characterized by short stature and bowing of the long bones; radiographic features include widening and irregularity of the growth plates, especially in the distal and proximal femora (summary by Makitie et al., 2005).
Clinical Features
Stephens (1943) reported a Mormon kindred in which over 40 members of 4 generations were affected with what he considered to be achondroplasia. The x-ray findings as demonstrated in his figures and as reviewed by Caffey and Christensen (1963) were, however, those of metaphyseal chondrodysplasia. In a 3-year-old child the interpediculate distances and greater sciatic groove were normal and the typical metaphyseal changes were demonstrated. Affected women went through vaginal deliveries successfully and were usually accompanied only by a midwife. Stephens (1943) suggested that the original mutation could be identified. The first affected ancestor, born in 1833, was said to have normal parents and 11 unaffected sibs.
Rosenbloom and Smith (1965) described 24 affected persons in 1 kindred. In a girl with metaphyseal chondrodysplasia said to be intermediate in phenotype between the Jansen (156400) and Schmid types, Cooper et al. (1973) demonstrated distention of the rough-surfaced endoplasmic reticulum cisternae of chondrocytes due to accumulation of what appeared to be a protein. Cooper and Ponseti (1973) studied an affected girl. Electron microscopy of her chondrocytes from the iliac crest area and ulnar epiphyseal plate revealed dilated rough endoplasmic reticulum (RER) cisternae containing a granular material. Cartilage matrix collagen and osteoid appeared to be normal. Osteoblasts and osteocytes showed a slight degree of RER dilatation. Gorlin (1985) suggested that the true diagnosis in the family reported by David and Palmer (1958) was oculodentoosseous dysplasia (164200).
Lachman et al. (1988) analyzed 20 cases and reviewed the literature. They suggested that the condition was often overdiagnosed. Significant radiologic features included an enlarged capital femoral epiphysis in early childhood, coxa vara, greater involvement of the distal femoral metaphysis than the proximal, anterior rib changes, and a normal spine. Chondroosseous morphology is not specific. Presentation in nonfamilial cases is no earlier than the second year of life.
Hasegawa et al. (1994) reported a Japanese family in which 5 members (3 males, 2 females) had a spondylometaphyseal dysplasia (SMD) characterized clinically by short stature and bowed legs and radiographically by severe coxa vara, moderately severe metaphyseal changes, normal hands, and mild platyspondyly. The platyspondyly was observed only in the males, and the younger 2 boys (aged 11 and 6) had greater platyspondyly than that in their 43-year-old father. Hasegawa et al. (1994) considered this a novel form of SMD, which they called the Japanese type. Ikegawa et al. (1998) identified a mutation in the COL10A1 gene (120110.0016), which had previously been found in a family with Schmid metaphyseal chondrodysplasia, in the family reported by Hasegawa et al. (1994).
Because of clinical, radiographic, and molecular similarities between the Japanese type of SMD reported by Hasegawa et al. (1994) and Schmid MCD, Savarirayan et al. (2000) reviewed 33 cases of of 'typical' MCDS and found that 3 cases had radiographic evidence of spinal involvement comprising mild platyspondyly, vertebral body abnormalities, and end-plate irregularity. Savarirayan et al. (2000) concluded that spinal changes are an uncommon but variable component of MCDS and that MCDS and the Japanese type of SMD are identical collagen type X disorders.
Elliott et al. (2005) reviewed radiographs of 15 'classic' MCDS patients and found hand involvement in 7 cases (47%). The findings were subtle and consisted of shortening of the tubular bones and metaphyseal cupping of the proximal phalanges and metacarpals; these changes were more marked in younger patients. Elliott et al. (2005) concluded that mild hand involvement that appears to resolve with age is a common feature of MCDS and should not exclude the diagnosis in young patients.
Molecular Genetics
In the Mormon kindred reported by Stephens (1943) and studied by Caffey and Christensen (1963), Warman et al. (1993) identified a 13-bp deletion in heterozygous state in COL10A1 gene (120110.0001). The mutation produced a frameshift that altered the highly conserved C-terminal domain of the alpha-1(X) chain and reduced the length of the peptide by 9 residues. Type X collagen is a homotrimeric molecule. Its restricted expression in hypertrophic chondrocytes and studies in transgenic mice with a dominant-negative mutation in type X collagen support its role in endochondral ossification (Jacenko et al., 1993).
Wallis et al. (1996) noted that at least 17 different point mutations and deletions in the region of the COL10A1 gene encoding the carboxy-terminal (NC1) domain had been reported in patients with MCDS. To determine whether mutations in other regions of the gene can cause MCDS or comparable phenotypes, Wallis et al. (1996) used PCR and SSCP techniques in the study of 5 patients with typical MCDS, 1 patient with atypical MCDS, and 9 patients with other forms of metaphyseal chondrodysplasia. Four new mutations in the NC1 domain were found in 4 patients with typical MCDS. Mutations in the COL10A1 gene were not found in 1 typical and 1 atypical case of MCDS or in cases of other metaphyseal chondrodysplasias. Wallis et al. (1996) contended that the restricted distribution of COL10A1 mutations in the region encoding the NC1 domain argues against haplotype insufficiency being the mutation mechanism in this disorder.
In 2 MCDS patients with COL10A1 nonsense mutations, trp611 to ter (120110.0019) and tyr632 to ter (120110.0015), Bateman et al. (2003) showed that the mutated alleles underwent complete nonsense-mediated mRNA decay (NMD) in cartilage, but not in lymphoblasts or bone cells. The authors suggested that novel RNA surveillance mechanisms may exist in cartilage, and that tissue specificity of NMD could be of importance in understanding the molecular pathology of nonsense mutations.
Makitie et al. (2005) reported 10 patients with MCDS and COL10A1 mutations in whom the most characteristic radiographic findings were found in the proximal femoral metaphysis, which showed metaphyseal irregularity, coxa vara, and a vertical growth plate in all the patients. One patient had a significantly milder presentation, characterized by normal height, late onset of symptoms, and lack of lower limb deformity. Makitie et al. (2005) suggested that the clinical variability in severity of COL10A1-associated skeletal dysplasia might be greater than previously thought.
In a 13-year-old boy with MCDS, Ho et al. (2007) identified heterozygosity for a nonsense mutation in the COL10A1 gene (Y663X; 120110.0020). Approximately 50% of mutant Y663X mRNA was translated into truncated alpha-1(X) chains that were misfolded, unable to assemble into trimers, and interfered with the assembly of normal alpha-1(X) chains into trimers.
Animal Model
Ho et al. (2007) studied transgenic mice bearing the equivalent of a human 1859delC frameshift mutation (120110.0005), which displayed typical characteristics of MCDS. The degree of expansion of the hypertrophic zones was transgene dosage-dependent, and transgenic chondrocytes in the lower region of the expanded hypertrophic zone expressed markers uncharacteristic of hypertrophic chondrocytes, indicating that differentiation was disrupted. Misfolded mutant alpha-1(X) chains were retained within the endoplasmic reticulum (ER) of hypertrophic chondrocytes, activating the unfolded protein response. Ho et al. (2007) suggested that a gain-of-function effect, linked to the activation of ER-stress response and altered chondrocyte differentiation, was a possible molecular pathogenetic mechanism for MCDS.
History
Schmid metaphyseal chondrodysplasia was formerly known as metaphyseal dysostosis. The disorder is not a true dysostosis (since it is not primarily a disorder of bone formation), nor is the primary defect in the metaphyses.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature, mild to moderate \- Adult height 130-160cm SKELETAL \- No osteoarthritic symptoms Spine \- Mild platyspondyly \- Endplate irregularity Pelvis \- Coxa vara \- Irregular acetabular roof \- Enlarged capital femoral epiphyses Limbs \- Femoral bowing \- Tibial bowing, especially at ankle \- Genu varum \- Metaphyseal abnormalities of distal and proximal femurs \- Metaphyseal abnormalities of proximal tibiae and fibulae \- Metaphyseal abnormalities of distal radius and ulna Hands \- Metaphyseal cupping of proximal phalanges \- Metaphyseal cupping of metacarpals \- Short/broad middle phalanges \- Hypoplastic distal phalanges MISCELLANEOUS \- Waddling gait, often presenting sign in second year \- Leg pain during childhood \- Hand involvement improves with age \- Spinal involvement improves with age MOLECULAR BASIS \- Caused by mutation in the collagen X, alpha-1 polypeptide gene (COL10A1, 120110.0001 ) ▲ 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-hydroxybutyric 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
|
METAPHYSEAL CHONDRODYSPLASIA, SCHMID TYPE
|
c0265289
| 25,715 |
omim
|
https://www.omim.org/entry/156500
| 2019-09-22T16:38:16 |
{"doid": ["0080021"], "mesh": ["C537352"], "omim": ["156500"], "orphanet": ["174"], "synonyms": ["Alternative titles", "SPONDYLOMETAPHYSEAL DYSPLASIA, JAPANESE TYPE"]}
|
A number sign (#) is used with this entry because of evidence that the aggrecan type of spondyloepimetaphyseal dysplasia (SEMDAG) is caused by homozygous or compound heterozygous mutation in the ACAN gene (155760) on chromosome 15q26.
Clinical Features
Tompson et al. (2009) described a Mexican family in which 2 brothers and a sister had a newly recognized autosomal recessive form of spondyloepimetaphyseal dysplasia characterized by severe short stature and a novel constellation of radiographic findings. The sibs, aged 16, 19, and 24 years, had a height ranging between 66 and 71 cm. Craniofacial abnormalities included relative macrocephaly, severe midface hypoplasia with almost absent nasal cartilage, relative prognathism, and slightly low-set, posteriorly rotated ears. They had short necks and barrel chests and exhibited a mild lumbar lordosis. Their extremities showed rhizomelia and mesomelia with no bowing of any segment. Hand findings included significant brachydactyly with short, broad thumbs, horizontal nails, and telescoping interphalangeal joints. Radiographic features included long bones with generalized irregular epiphyses with widened metaphyses, especially at the knees; platyspondyly; and multiple cervical-vertebral clefts. The mother and father were 150 cm and 152 cm tall, respectively. An unaffected half sister was 150 cm tall and an unaffected full sib was 178 cm tall. The authors raised the possibility of a carrier phenotype of mild proportionate short stature.
Fukuhara et al. (2019) reported a 45-year-old man with the aggrecan type of spondyloepimetaphyseal dysplasia. He was born to nonconsanguineous parents and his weight and length at birth were within the normal range. At age 6 years, he was noted to have short stature. When evaluated at 42 years of age, his height was 118.3 cm (-9.1 SD) and his head circumference was 59.4 cm (+2 SD). He had acromesomelic limb shortening and relative macrocephaly. No midface hypoplasia, prognathism, or low-set ears were noted. On radiologic examination, his phenotype was consistent with SEMD. He had moderate platyspondyly with cervical lordosis and thoracolumbar kyphosis. Vertebral bodies were rectangular in shape, except for a wedge-shaped deformity of L1. Acetabula were shallow and degenerative joint disease of the large joints, especially the hips, was significant. Long bones were short and relatively broad with metaphyseal flaring. Generalized brachydactyly was remarkable. The authors noted that his skeletal phenotype was milder than that previously reported with this phenotype.
Inheritance
The aggrecan type of SEMD is an autosomal recessive disorder (Tompson et al., 2009).
Mapping
Tompson et al. (2009) found homozygosity for a haplotype that was identical by descent between 2 of the 3 affected sibs in the Mexican family segregating SEMDAG and identified a locus for the disease within a 17.4 Mb interval on chromosome 15.
Molecular Genetics
In 3 sibs with SEMDAG, Tompson et al. (2009) identified homozygosity for a missense mutation in the ACAN gene (D2267N; 155760.0002) that affected the C-type lectin domain of the protein. The mutation segregated with the phenotype in the family.
In a 45-year-old male with SEMDAG, who was born to nonconsanguineous parents, Fukuhara et al. (2019) identified compound heterozygosity for missense mutations in the ACAN gene (S1687R, 155760.0014 and V1380F, 155760.0015) that affected chondroitin sulfate domains. No DNA from his parents was available for segregation analysis. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were not present in the ESP6500 or 1000 Genomes Project databases.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, disproportionate (adult height 26-28 inches) Other \- Upper/lower segment ratio 1.1-1.2 HEAD & NECK Head \- Macrocephaly, relative Face \- Prognathism, relative \- Midface hypoplasia Ears \- Low-set posteriorly rotated ears Nose \- Absent nasal bridge Neck \- Short neck RESPIRATORY Airways \- Bronchospasm (in 1 patient) CHEST External Features \- Barrel-shaped chest SKELETAL \- Spondyloepimetaphyseal dysplasia (SEMD) \- Joint laxity (especially hands) Spine \- Platyspondyly \- Multiple cervical-vertebral clefts \- Lumbar lordosis, mild Limbs \- Irregular epiphyses \- Widened metaphyses \- Mesomelia \- Rhizomelia Hands \- Brachydactyly \- Short, broad thumbs \- Telescoping interphalangeal joints \- Accessory carpal ossification centers SKIN, NAILS, & HAIR Nails \- Horizontal nail beds VOICE \- Hoarse voice MISCELLANEOUS \- One family from Zacatecas, Mexico has been described (last curated August 2017) MOLECULAR BASIS \- Caused by mutation in the aggrecan gene (ACAN, 155760.0002 ) ▲ 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-hydroxybutyric 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
|
SPONDYLOEPIMETAPHYSEAL DYSPLASIA, AGGRECAN TYPE
|
c2748544
| 25,716 |
omim
|
https://www.omim.org/entry/612813
| 2019-09-22T16:00:33 |
{"mesh": ["C567558"], "omim": ["612813"], "orphanet": ["171866"], "synonyms": ["Alternative titles", "SEMD, AGGRECAN TYPE"]}
|
Cluttering is a disorder that affects the way a person speaks. It is characterized by a rapid speaking rate and inability to maintain normally expected sound, syllable, phrase, and pausing patterns while speaking. Other symptoms may include stuttering; language or phonological errors (problems organizing sounds); and attention deficits. The disorder seems to result from disorganized speech planning, talking too fast or in spurts, or simply being unsure of what one wants to say. Therapy generally focuses on the symptoms present in each individual and may include slowing the rate of speech and clearly producing speech sounds (articulating). Articulation and language problems are often reduced if the affected individual can achieve a slower rate of speech.
*[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-hydroxybutyric 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
|
Cluttering
|
c0009090
| 25,717 |
gard
|
https://rarediseases.info.nih.gov/diseases/9272/cluttering
| 2021-01-18T18:01:15 |
{"mesh": ["D013064"], "synonyms": ["Speech disturbance - use of faulty phrasing and unrelated words", "Tachyphemia"]}
|
Darnborough et al. (1969) discovered a new antibody, anti-En(a), which reacted strongly with many cells tested, a total of 7000, but did not react with her own cells or those of 2 of her 8 sibs. The proposita, an English woman, was pregnant and had been transfused 2 years earlier. En of the notation stands for envelope; the authors summarized as follows: 'The reactions of various unrelated blood group antigens are modified, in some cases enhanced and in others depressed, the total picture being strongly reminiscent of the effects of proteolytic enzyme treatment. It is suggested that these effects can only be due to some factor affecting the red cell structure possibly by modifying the cell envelope.' Two further examples of En(a-) were found in Finland in unrelated persons. The great rarity of the phenotype is indicated by the fact that by 1975 only these 3 families had been discovered (Race and Sanger, 1975). The English case had parents from a small fishing port in Yorkshire. The parents of both Finnish probands were consanguineous. Because of the consanguinity, any locus for which the En(a-) persons were heterozygous cannot have been responsible for the En gene. Using this reasoning, ABO, MNSs, Rh, Duffy, Haptoglobin, Kidd, Gm, and Dombrock could be excluded (Race and Sanger, 1975). Although En is independent of MN, MN typing shows a profound derangement in En(a-) persons.
*[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-hydroxybutyric 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
|
BLOOD GROUP--En
|
None
| 25,718 |
omim
|
https://www.omim.org/entry/110720
| 2019-09-22T16:44:25 |
{"omim": ["110720"]}
|
The features are chronic swelling of the face, peripheral facial palsy that tends to relapse and may be bilateral, and in some cases lingua plicata ('scrotal' tongue). The disease often begins in childhood or youth. The swelling is localized especially to the lips. Kunstadter (1965) described a case with onset at 5.5 years of age. The maternal grandmother developed unilateral Bell palsy without facial edema at age 68. A maternal aunt developed unilateral Bell palsy with questionable edema at 10 years of age and recovered completely. Carr (1966) found at least 4 other reported families in which 2 generations were affected and 1 instance of 3 generations affected. In a Greek kindred, Lygidakis et al. (1979) observed 7 cases in 5 sibships of 4 generations, with 1 instance of male-to-male transmission and 1 instance of 'skipped generation.'
Smeets et al. (1994) described a 26-year-old female with typical clinical features of Melkersson-Rosenthal syndrome and a de novo t(9;21)(p11;p11) translocation, and suggested that the gene is located at 9p11. The patient's mother had normal chromosomes. The patient developed episodes of recurrent and transient swelling of the upper lip in late adolescence. The swelling gradually became persistent and more manifest, also involving the lower lip. Her tongue had been of the scrotal type since childhood. There had been no facial palsy, although she complained of loss of taste in the anterior part of the tongue. On physical examination, discrete swelling of her chin and eyelids was also noted.
Cockerham et al. (2000) reviewed the clinicopathologic features of eyelid involvement in Melkersson-Rosenthal syndrome. The 3 men and 1 woman studied ranged in age from 33 to 74 years. Each had insidious, painless, nonpitting eyelid edema: 3 had unilateral edema; 1 had bilateral, asymmetric involvement. Ipsilateral lip edema was present in 1 case. Computed tomography aided in the diagnosis. Histopathology of each eyelid biopsy in this study revealed granulomatous lymphangitis unique to Melkersson-Rosenthal syndrome. The authors recommended biopsy of all cases of unexplained nonpitting eyelid edema.
Caksen et al. (2002) described Melkersson-Rosenthal syndrome in association with Ehlers-Danlos syndrome and found 1 previously reported instance of the association.
INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Facial edema Eyes \- Insidious, painless, nonpitting eyelid edema \- Periorbital heterogeneous thickening on CT scan \- Granulomatous lymphangitis on eyelid biopsy Mouth \- Lip swelling \- Scrotal tongue \- Fissured tongue NEUROLOGIC Peripheral Nervous System \- Recurrent peripheral facial palsy MISCELLANEOUS \- Onset in childhood or youth ▲ 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-hydroxybutyric 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
|
MELKERSSON-ROSENTHAL SYNDROME
|
c0025235
| 25,719 |
omim
|
https://www.omim.org/entry/155900
| 2019-09-22T16:38:25 |
{"doid": ["1761"], "mesh": ["D008556"], "omim": ["155900"], "icd-10": ["G51.2"], "orphanet": ["2483"], "synonyms": ["Alternative titles", "MROS", "MELKERSSON SYNDROME"]}
|
Gibson et al. (1988) described a male fetus with bilateral radial aplasia, hydrocephalus, and penile hypospadias who had a similarly affected maternal uncle. The uncle, who died soon after birth, also had imperforate anus. The legs were normal in both. Gibson et al. (1993) published a full report on these patients and suggested that the complex is a distinct X-linked syndrome of absent radii and anogenital anomalies.
Limbs \- Radial aplasia \- Normal legs GU \- Penile hypospadias Head \- Hydrocephalus GI \- Imperforate anus 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-hydroxybutyric 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
|
RADIAL APLASIA, X-LINKED
|
c1839410
| 25,720 |
omim
|
https://www.omim.org/entry/312190
| 2019-09-22T16:17:20 |
{"mesh": ["C535281"], "omim": ["312190"], "orphanet": ["3016"], "synonyms": ["Alternative titles", "RADIAL APLASIA AND ANOGENITAL ANOMALIES"]}
|
## Description
Rupture of an intracranial aneurysm, an outpouching or sac-like widening of a cerebral artery, leads to a subarachnoid hemorrhage, a sudden-onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension, and excessive alcohol intake are associated with subarachnoid hemorrhage (summary by Krischek and Inoue, 2006).
For a discussion of genetic heterogeneity of intracranial berry aneurysms, see ANIB1 (105800).
Mapping
In a genomewide association study of 920 Finnish patients with intracranial aneurysm and 985 controls, Bilguvar et al. (2008) found a significant association with rs700651 on chromosome 2q. The association was replicated in a Dutch cohort of 781 cases and 6,424 controls and a Japanese cohort of 495 cases and 676 controls. The combined p value was 4.4 x 10(-8) with an odds ratio of 1.24.
Molecular Genetics
Berry aneurysm may have an increased frequency in persons with Ehlers-Danlos syndrome type IV (130050), which is caused by mutation in the type III collagen gene (COL3A1; 120180) on chromosome 2q. Ostergaard and Oxlund (1987) sampled the middle cerebral artery and brachial artery postmortem in 14 patients who died following rupture of intracranial saccular aneurysms and from a control group of 14 age- and sex-matched patients who died of causes unrelated to aneurysm rupture. In 6 of the 14 patients, deficiency of type III collagen was demonstrated in the specimens from the middle cerebral artery. De Paepe et al. (1988) proposed that a defect in type III collagen may be responsible for familial multiple intracranial aneurysms, perhaps with few signs suggesting Ehlers-Danlos syndrome type IV. The same suggestion had been made by Pope et al. (1981). The experience of Kuivaniemi et al. (1993), however, suggested that mutations in the COL3A1 gene are not a common cause of intracranial aneurysms or of cervical artery dissections. They studied type III collagen cDNA from 58 patients of 7 different nationalities with one or the other of these diagnoses. Among the patients studied were 3 pairs of relatives; among the others 29 had at least 1 blood relative with either an intracranial artery aneurysm or a cervical artery dissection. The age of the patients at the time of diagnosis ranged from 15 to 68 years. The study group consisted of 25 males and 33 females. Mutations in the coding sequence for the triple-helical domain were excluded in 40 individuals with intracranial aneurysms and 18 individuals with cervical artery dissections. Mutations that markedly decreased expression from 1 allele were also excluded in 42 of the 58 individuals.
*[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-hydroxybutyric 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
|
ANEURYSM, INTRACRANIAL BERRY, 9
|
c2675485
| 25,721 |
omim
|
https://www.omim.org/entry/612586
| 2019-09-22T16:01:06 |
{"doid": ["0060228"], "mesh": ["C567238"], "omim": ["612586", "105800"], "orphanet": ["231160"], "synonyms": ["Familial berry aneurysm", "Familial intracranial saccular aneurysm"]}
|
Adenine phosphoribosyltransferase (APRT) deficiency is an inherited condition that affects the kidneys and urinary tract. The most common feature of this condition is recurrent kidney stones; urinary tract stones are also a frequent symptom. Kidney and urinary tract stones can create blockages in the urinary tract, causing pain during urination and difficulty releasing urine.
Affected individuals can develop features of this condition anytime from infancy to late adulthood. When the condition appears in infancy, the first sign is usually the presence of tiny grains of reddish-brown material in the baby's diaper caused by the passing of stones. Later, recurrent kidney and urinary tract stones can lead to problems with kidney function beginning as early as mid- to late childhood. Approximately half of individuals with APRT deficiency first experience signs and symptoms of the condition in adulthood. The first features in affected adults are usually kidney stones and related urinary problems. Other signs and symptoms of APRT deficiency caused by kidney and urinary tract stones include fever, urinary tract infection, blood in the urine (hematuria), abdominal cramps, nausea, and vomiting.
Without treatment, kidney function can decline, which may lead to end-stage renal disease (ESRD). ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.
The features of this condition and their severity vary greatly among affected individuals, even among members of the same family. It is estimated that 15 to 20 percent of people with APRT deficiency do not have any signs or symptoms of the condition.
## Frequency
APRT deficiency is estimated to affect 1 in 27,000 people in Japan. The condition is rarer in Europe, where it is thought to affect 1 in 50,000 to 100,000 people. The prevalence of APRT deficiency outside these populations is unknown.
## Causes
Mutations in the APRT gene cause APRT deficiency. This gene provides instructions for making APRT, an enzyme that helps to convert a DNA building block (nucleotide) called adenine to a molecule called adenosine monophosphate (AMP). This conversion occurs when AMP is needed as a source of energy for cells.
APRT gene mutations lead to the production of an abnormal APRT enzyme with reduced function or prevent the production of any enzyme. A lack of functional enzyme impairs the conversion of adenine to AMP. As a result, adenine is converted to another molecule called 2,8-dihydroxyadenine (2,8-DHA). 2,8-DHA crystallizes in urine, forming stones in the kidneys and urinary tract. 2,8-DHA crystals are brownish in color, which explains why affected infants frequently have dark urine stains in their diapers. 2,8-DHA is toxic to kidneys, which may explain the possible decline in kidney function and the progression to ESRD.
### Learn more about the gene associated with Adenine phosphoribosyltransferase deficiency
* APRT
## 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-hydroxybutyric 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
|
Adenine phosphoribosyltransferase deficiency
|
c0268120
| 25,722 |
medlineplus
|
https://medlineplus.gov/genetics/condition/adenine-phosphoribosyltransferase-deficiency/
| 2021-01-27T08:25:40 |
{"gard": ["546"], "mesh": ["C538228"], "omim": ["614723"], "synonyms": []}
|
For a phenotypic description and a discussion of genetic heterogeneity of essential hypertension, see 145500.
One of the principal blood pressure loci identified in rat models of hereditary hypertension has been mapped to rat chromosome 10 (Hilbert et al., 1991). Julier et al. (1997) investigated the homologous region on human chromosome 17 in familial essential hypertension. Affected sib-pair analysis and parametric analysis with ascertainment correction gave significant evidence of linkage (P less than 0.0001 in some analyses) near 2 closely linked microsatellite markers, D17S183 and D17S934, that reside 18 cM proximal to the gene encoding angiotensin I converting enzyme (ACE; 106180). The authors concluded that 17q contains a susceptibility locus for human hypertension presumably separate from the ACE gene.
By testing a series of microsatellite markers in the region identified by Julier et al. (1997), Baima et al. (1999) confirmed the location of a blood pressure QTL on 17q in a collection of both white and black sib pairs in the U.S.
Knight et al. (2003) summarized data, gathered by various methods, suggesting that there is a gene or genes on chromosome 17 causing essential hypertension.
*[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-hydroxybutyric 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
|
HYPERTENSION, ESSENTIAL, SUSCEPTIBILITY TO, 1
|
c1858967
| 25,723 |
omim
|
https://www.omim.org/entry/603918
| 2019-09-22T16:12:33 |
{"omim": ["603918"], "synonyms": ["Alternative titles", "HYT1"]}
|
A number sign (#) is used with this entry because of evidence that brachyolmia type 3 (BCYM3) is caused by heterozygous mutation in the TRPV4 gene (605427) on chromosome 12q24.
For a discussion of heterogeneity of brachyolmia, see 271530.
Clinical Features
Lenz (1964) observed father and son with a very short spine and deformity of the anterior chest rather like that in Morquio disease. Except for marked changes in the femoral epiphyses, the extremities were normal. The vertebral bodies were small, irregular, and radiolucent. Perhaps the family of Lomas and Boyle (1959) in which 3 generations were affected had the same condition. See also the dominant type of spondyloepiphyseal dysplasia tarda (184100).
Kozlowski et al. (1982) stated that pure brachyolmia does not exist and that metaphyseal involvement may be minimal and scattered but always is present along with involvement of the spine in cases labeled brachyolmia. Shohat et al. (1989), however, described a mother and son with severe spinal changes with no metaphyseal or epiphyseal changes in the long bones. These patients showed the most severe scoliosis of the patients they studied, and demonstrated marked cervical vertebral flattening and irregularity.
Gardner and Beighton (1994) investigated the cases of a mother and son of South African Xhosa stock who presented with short-trunk dwarfism and kyphoscoliosis. Radiographs showed the marked platyspondyly and vertebral irregularity characteristic of brachyolmia. In the mother, the femoral necks were very short with a varus deformity; in the 6-year-old son, the femoral necks were likewise short and their metaphyseal regions were irregular, with areas of patchy lucency and sclerosis.
Rock et al. (2008) described type 3 brachyolmia as an autosomal dominant form with severe kyphoscoliosis and flattened, irregular cervical vertebrae. Paradoxically, although the limbs are mildly shortened in all 3 types of brachyolmia, they show only minimal epiphyseal and metaphyseal abnormalities on radiographs. Rock et al. (2008) characterized a large family with autosomal dominant brachyolmia. The clinical phenotype was characterized by moderately short-trunk short stature, mildly short limbs, mild brachydactyly, and no extraskeletal clinical findings. The most characteristic radiographic features were scoliosis with platyspondyly and overfaced pedicles, which were most prominent in the lumbar vertebrae. There were mild irregularities at the metaphyses of the proximal femora, and the hands showed delayed epiphyseal and carpal ossification.
Mapping
Using a 2-stage genome scan in a large family with autosomal dominant brachyolmia, Rock et al. (2008) mapped the phenotype to chromosome 12q24.1-q24.2, with a maximum lod score of 3.04 at a recombination fraction of zero for the marker D12S79. Recombination mapping limited the interval to 11.1 Mb.
Molecular Genetics
To narrow the search for the genes in the critical 11.1-Mb interval for a form of brachyolmia, Rock et al. (2008) searched for genes with higher expression in cartilage and identified TRPV4 (605427) as having about 10-fold higher cartilage selectivity than the average of all other genes in the interval. In the family in which the critical interval for autosomal dominant brachyolmia was mapped, and in another family with a similar phenotype, Rock et al. (2008) identified heterozygosity for single-base changes within exon 12 of the TRPV4 gene (605427.0001-605427.0002). No mutations in the TRPV4 gene were found in 2 additional families with autosomal dominant brachyolmia, suggesting that autosomal dominant brachyolmia may be genetically heterogeneous.
History
Brown (1933) described the condition in a mother and 2 daughters as Morquio disease (see 253000).
INHERITANCE \- Autosomal dominant GROWTH Height \- Normal birth length \- Short stature, disproportionate (short trunk), identifiable in childhood HEAD & NECK Eyes \- Hyperopia Neck \- Short neck CHEST External Features \- Barrel-shaped chest SKELETAL Spine \- Gibbus \- Kyphosis \- Scoliosis \- Marked platyspondyly Pelvis \- Short femoral neck \- Irregular proximal femoral metaphyses Hands \- Clinodactyly NEUROLOGIC Central Nervous System \- Normal intelligence \- Spinal cord compression MOLECULAR BASIS \- Caused by mutation in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4, 605427.0001 ). ▲ 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-hydroxybutyric 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
|
BRACHYOLMIA TYPE 3
|
c0432227
| 25,724 |
omim
|
https://www.omim.org/entry/113500
| 2019-09-22T16:43:57 |
{"doid": ["0050690"], "mesh": ["C562963"], "omim": ["113500"], "orphanet": ["93304"], "synonyms": ["Alternative titles", "BRACHYOLMIA, AUTOSOMAL DOMINANT", "BRACHYRACHIA"], "genereviews": ["NBK201366"]}
|
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Undervirilization" – news · newspapers · books · scholar · JSTOR (December 2009) (Learn how and when to remove this template message)
Undervirilization is a medical term describing the state of a male whose body, especially the genitalia, shows evidence of below-normal prenatal (less commonly pubertal) androgen effects.
See virilization for a more detailed description of the normal process and newborn status.
## See also[edit]
* Sexual differentiation
* Defeminization and masculinization
* Defeminization
* Feminization
## References[edit]
This article about an endocrine, nutritional, or metabolic disease 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-hydroxybutyric 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
|
Undervirilization
|
c0342533
| 25,725 |
wikipedia
|
https://en.wikipedia.org/wiki/Undervirilization
| 2021-01-18T19:08:12 |
{"umls": ["C0342533"], "wikidata": ["Q7883835"]}
|
## Clinical Features
Goldberg and Pashayan (1976) reported 10 members over 3 generations of a family with a syndrome involving syndactyly, polydactyly, and earlobe malformations. The syndactyly was an unusual complete cutaneous type involving toes 1 and 2. Ulnar polydactyly varied from postminimi nubbins to nearly complete sixth finger. The earlobes showed either a deep horizontal groove or a nodule. The feet also showed a broad or bifid great toe or in some a complete, separate, preaxial extra toe.
Inheritance
Goldberg and Pashayan (1976) stated that the pedigree pattern in the family they reported was compatible with autosomal dominant inheritance because there were 2 instances of male-to-male transmission.
Limbs \- Complete cutaneous syndactyly of toes 1 and 2 \- Ulnar polydactyly \- Broad/bifid great toe \- Complete, separate, preaxial extra toe Inheritance \- Autosomal dominant Ears \- Deep horizontal groove or nodule of earlobes ▲ 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-hydroxybutyric 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
|
SYNDACTYLY-POLYDACTYLY-EARLOBE SYNDROME
|
c1861347
| 25,726 |
omim
|
https://www.omim.org/entry/186350
| 2019-09-22T16:45:33 |
{"mesh": ["C566091"], "omim": ["186350"], "orphanet": ["3259"], "synonyms": ["Alternative titles", "SPEL SYNDROME"]}
|
Mendelian susceptibily to mycobacterial diseases (MSMD) due to complete interferon gamma receptor 2 (IFN-gammaR2) deficiency is a genetic variant of MSMD (see this term) characterized by a complete deficiency in IFN-gammaR2, leading to an undetectable response to IFN-gamma, and consequently, to severe and often fatal infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
## Epidemiology
The prevalence is unknown. Only ten children have been identified to date.
## Clinical description
Severe and often fatal BCG and EM infections begin in early childhood (before the age of 3). The most common pathogens seen in patients include Mycobacterium fortuitum, Mycobacterium bovis BCG, Mycobacterium abscessus and Mycobacterium avium. Infections are disseminated and can involve soft tissue, bone marrow, lungs, skin, bones and lymph nodes. Infections manifest with fever, weight loss, hepatosplenomegaly and lymphadenopathies and can be fatal.
## Etiology
This disease is caused by mutations in IFNGR2 on chromosome 21q22.1-22.2 which encodes the IFN-gamma receptor signal transducing chain, essential for IFN-gamma mediated immunity. Two clinically indistinguishable forms have been reportedly defined by the presence or absence of protein expression on the cell surface.
## Diagnostic methods
Diagnosis is made by laboratory analysis. IFN-gamma, IL-12p40 and IL-12p70 levels can be measured by ELISA, after whole blood activation by BCG, BCG+IL-12 and BCG+IFN-gamma. Leukocytes and fibroblasts from patients with this immunodeficiency do not respond to IFN-gamma in vitro. Genetic testing reveals mutations in IFNGR2.
## Differential diagnosis
Differential diagnosis includes the other variants of MSMD, especially complete IFN-gammaR1 deficiency (see this term). Chronic granulomatous disease, cystic fibrosis and severe combined immunodeficiency (see these terms) should also be excluded.
## Antenatal diagnosis
As this disease is often fatal, antenatal diagnosis is offered to families with a known IFNGR2 mutation.
## Genetic counseling
MSMD due to complete IFN-gammaR2 deficiency is inherited autosomal recessively and genetic counseling is recommended.
## Management and treatment
The only curative option for MSMD due to complete IFN-gammaR2 deficiency is hematopoietic stem cell transplantation (HSCT). Due to a lack of specific receptors, IFN-gamma treatment is not indicated. BCG vaccination should be avoided in those with a known IFNGR2 mutation.
## Prognosis
Prognosis is poor with most patients not living past 10 years of age.
*[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-hydroxybutyric 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
|
Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency
|
c4013947
| 25,727 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319547
| 2021-01-23T17:44:20 |
{"omim": ["614889"], "icd-10": ["D84.8"], "synonyms": ["MSMD due to complete IFNgammaR2 deficiency", "MSMD due to complete interferon gamma receptor 2 deficiency", "Mendelian susceptibility to mycobacterial diseases due to complete interferon gamma receptor 2 deficiency"]}
|
Acromicric dysplasia affects the growth and development of the bones. Signs and symptoms include short stature, short hands and feet, and distinctive facial features. Overtime, people with acromicric dysplasia may develop limited joint movement and hip dislocations. Acromicric dysplasia does not affect intelligence or learning. Acromicric dysplasia is caused by genetic variants in the FBN1 gene or the LTBP3 gene and is inherited in an autosomal dominant pattern. Diagnosis is based on the symptoms, clinical exam, and imaging studies. Diagnosis may be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Acromicric dysplasia
|
c0265287
| 25,728 |
gard
|
https://rarediseases.info.nih.gov/diseases/7/acromicric-dysplasia
| 2021-01-18T18:02:20 |
{"mesh": ["C535662"], "omim": ["102370"], "umls": ["C0265287"], "orphanet": ["969"], "synonyms": ["Acromicric skeletal dysplasia"]}
|
A number sign (#) is used with this entry because of evidence that deafness, congenital heart defects, and posterior embryotoxon is caused by heterozygous mutation in the JAG1 gene (601920). One such family has been reported.
Heterozygous mutation in JAG1 also results in Alagille syndrome-1 (118450) and tetralogy of Fallot (187500).
Clinical Features
Le Caignec et al. (2002) described a large kindred with hearing loss, congenital heart defects, and posterior embryotoxon, segregating as autosomal dominant traits. Of the 7 affected patients available for study, 6 manifested mild to severe combined hearing loss, predominantly affecting middle frequencies. Two patients had vestibular pathology. All patients had congenital heart defects, including tetralogy of Fallot, ventricular septal defect, or isolated peripheral pulmonic stenosis. No history of hepatic dysfunction was noted for any of the patients. No individual in the family met diagnostic criteria for any previously described clinical syndrome.
Molecular Genetics
Using linkage analysis followed by direct sequencing of the JAG1 gene, Le Caignec et al. (2002) identified a novel JAG1 missense mutation, cys234 to tyr (C234Y; 601920.0012), in the first cysteine of the first epidermal growth factor-like repeat domain of the protein.
JAG1 is a transmembrane protein that serves as a ligand for the Notch (see 190198) transmembrane receptors. In functional studies, Bauer et al. (2010) determined that the C234Y mutation resulted in a JAG1 protein that was not present at the cell surface, was not properly posttranslationally modified, and could not initiate Notch signaling. Bauer et al. (2010) predicted that the C234Y mutation led to JAG1 haploinsufficiency, with only the wildtype allele in carriers of the mutation appearing on the cell surface.
*[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-hydroxybutyric 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
|
DEAFNESS, CONGENITAL HEART DEFECTS, AND POSTERIOR EMBRYOTOXON
|
c1866053
| 25,729 |
omim
|
https://www.omim.org/entry/617992
| 2019-09-22T15:44:07 |
{"mesh": ["C566604"], "omim": ["617992"]}
|
A rare type of hereditary spastic paraplegia usually characterized by a pure phenotype of proximal weakness of the lower extremities with spastic gait and brisk reflexes, with a bimodal age of onset of either childhood or adulthood (>30 years). In some cases, it can present as a complex phenotype with additional associated manifestations including peripheral neuropathy, bulbar palsy (with dysarthria and dysphagia), distal amyotrophy, and impaired distal vibration sense.
*[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-hydroxybutyric 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
|
Autosomal dominant spastic paraplegia type 31
|
c1853247
| 25,730 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101011
| 2021-01-23T17:03:25 |
{"gard": ["10817"], "mesh": ["C565210"], "omim": ["610250"], "umls": ["C1853247"], "icd-10": ["G11.4"], "synonyms": ["SPG31"]}
|
A rare genetic syndrome with limb malformations as a major feature characterized by unilateral or bilateral split-foot malformation, nail abnormalities of the hand, and bilateral sensorineural hearing impairment. Mesoaxial polydactyly of the foot has also been described.
*[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-hydroxybutyric 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
|
Split-foot malformation-mesoaxial polydactyly syndrome
|
c4225167
| 25,731 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=488232
| 2021-01-23T17:08:19 |
{"omim": ["616890"], "synonyms": ["SFMMP", "Split-foot malformation-mesoaxial polydactyly-nail abnormalities-sensorineural hearing loss syndrome"]}
|
MASS syndrome
Other namesMitral valve-aorta-skeleton-skin syndrome[1]
This condition is inherited in an autosomal dominant manner
SpecialtyMedical condition
MASS syndrome is a medical disorder of the connective tissue similar to Marfan syndrome. MASS stands for: Mitral valve prolapse, Aortic root diameter at upper limits of normal for body size, Stretch marks of the skin, and Skeletal conditions similar to Marfan syndrome. It is caused by a mutation in the FBN1 gene, which encodes fibrillin-1.[2] Fibrillin-1 is an extracellular matrix protein that is found in microfibrils;[3] defects in the fibrillin-1 protein cause the malfunctioning of microfibrils,[4] which results in improper stretching[4] of ligaments, blood vessels, and skin.
Treatment options for MASS syndrome are largely determined on a case-by-case basis and generally address the symptoms as opposed to the actual disorder;[5] furthermore, due to the similarities between these two disorders, individuals with MASS syndrome follow the same treatment plans as those with Marfan syndrome.[6]
Other possible symptoms are mitral valve prolapse, a large aortic root diameter, and myopia.[2] The skeletal features found in MASS syndrome include curvature of the spine (scoliosis), chest wall deformities, and joint hypermobility.[2]
MASS syndrome and Marfan syndrome are overlapping connective tissue disorders. Both can be caused by mutations in the gene encoding a protein called fibrillin. These conditions share many of the same signs and symptoms including long limbs and fingers, chest wall abnormalities (indented chest bone or protruding chest bone), flat feet, scoliosis, mitral valve prolapse, loose or hypextensible joints, highly arched roof of the mouth, and mild dilatation of the aortic root. Unlike in Marfan syndrome, aneurysm is not present.[2]
Individuals with MASS syndrome do not have progressive aortic enlargement or lens dislocation, while people with Marfan syndrome do. Skin involvement in MASS syndrome is typically limited to stretch marks (striae distensae). Also, the skeletal symptoms of MASS syndrome are generally mild.[citation needed]
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: MASS syndrome". www.orpha.net. Retrieved 27 August 2019.
2. ^ a b c d "MASS PHENOTYPE". Marfan Foundation. Retrieved 19 February 2018.
3. ^ Jacobs AM, Toudjarska I, Racine A, Tsipouras P, Kilpatrick MW, Shanske A (November 2002). "A recurring FBN1 gene mutation in neonatal Marfan syndrome". Arch Pediatr Adolesc Med. 156 (11): 1081–5. doi:10.1001/archpedi.156.11.1081. PMID 12413333.
4. ^ a b "FBN1 gene". Genetics Home Reference. NIH. Retrieved 8 November 2017.
5. ^ "MASS phenotype". GARD. NIH. August 30, 2018. Retrieved October 28, 2018.
6. ^ Pyeritz RE (January 2012). "Evaluation of the adolescent or adult with some features of Marfan syndrome". Genet. Med. 14 (1): 171–7. doi:10.1038/gim.2011.48. ISSN 1098-3600. PMID 22237449.
## External links[edit]
Classification
D
* OMIM: 04308
* MeSH: C536030
External resources
* Orphanet: 99715
* v
* t
* e
Cytoskeletal defects
Microfilaments
Myofilament
Actin
* Hypertrophic cardiomyopathy 11
* Dilated cardiomyopathy 1AA
* DFNA20
* Nemaline myopathy 3
Myosin
* Elejalde syndrome
* Hypertrophic cardiomyopathy 1, 8, 10
* Usher syndrome 1B
* Freeman–Sheldon syndrome
* DFN A3, 4, 11, 17, 22; B2, 30, 37, 48
* May–Hegglin anomaly
Troponin
* Hypertrophic cardiomyopathy 7, 2
* Nemaline myopathy 4, 5
Tropomyosin
* Hypertrophic cardiomyopathy 3
* Nemaline myopathy 1
Titin
* Hypertrophic cardiomyopathy 9
Other
* Fibrillin
* Marfan syndrome
* Weill–Marchesani syndrome
* Filamin
* FG syndrome 2
* Boomerang dysplasia
* Larsen syndrome
* Terminal osseous dysplasia with pigmentary defects
IF
1/2
* Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1
* Striate palmoplantar keratoderma 3
* Epidermolytic hyperkeratosis
* IHCM
* KRT2E (Ichthyosis bullosa of Siemens)
* KRT3 (Meesmann juvenile epithelial corneal dystrophy)
* KRT4 (White sponge nevus)
* KRT5 (Epidermolysis bullosa simplex)
* KRT8 (Familial cirrhosis)
* KRT10 (Epidermolytic hyperkeratosis)
* KRT12 (Meesmann juvenile epithelial corneal dystrophy)
* KRT13 (White sponge nevus)
* KRT14 (Epidermolysis bullosa simplex)
* KRT17 (Steatocystoma multiplex)
* KRT18 (Familial cirrhosis)
* KRT81/KRT83/KRT86 (Monilethrix)
* Naegeli–Franceschetti–Jadassohn syndrome
* Reticular pigmented anomaly of the flexures
3
* Desmin: Desmin-related myofibrillar myopathy
* Dilated cardiomyopathy 1I
* GFAP: Alexander disease
* Peripherin: Amyotrophic lateral sclerosis
4
* Neurofilament: Parkinson's disease
* Charcot–Marie–Tooth disease 1F, 2E
* Amyotrophic lateral sclerosis
5
* Laminopathy: LMNA
* Mandibuloacral dysplasia
* Dunnigan Familial partial lipodystrophy
* Emery–Dreifuss muscular dystrophy 2
* Limb-girdle muscular dystrophy 1B
* Charcot–Marie–Tooth disease 2B1
* LMNB
* Barraquer–Simons syndrome
* LEMD3
* Buschke–Ollendorff syndrome
* Osteopoikilosis
* LBR
* Pelger–Huet anomaly
* Hydrops-ectopic calcification-moth-eaten skeletal dysplasia
Microtubules
Kinesin
* Charcot–Marie–Tooth disease 2A
* Hereditary spastic paraplegia 10
Dynein
* Primary ciliary dyskinesia
* Short rib-polydactyly syndrome 3
* Asphyxiating thoracic dysplasia 3
Other
* Tauopathy
* Cavernous venous malformation
Membrane
* Spectrin: Spinocerebellar ataxia 5
* Hereditary spherocytosis 2, 3
* Hereditary elliptocytosis 2, 3
Ankyrin: Long QT syndrome 4
* Hereditary spherocytosis 1
Catenin
* APC
* Gardner's syndrome
* Familial adenomatous polyposis
* plakoglobin (Naxos syndrome)
* GAN (Giant axonal neuropathy)
Other
* desmoplakin: Striate palmoplantar keratoderma 2
* Carvajal syndrome
* Arrhythmogenic right ventricular dysplasia 8
* plectin: Epidermolysis bullosa simplex with muscular dystrophy
* Epidermolysis bullosa simplex of Ogna
* plakophilin: Skin fragility syndrome
* Arrhythmogenic right ventricular dysplasia 9
* centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II)
Related topics: Cytoskeletal proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
MASS syndrome
|
c1858556
| 25,732 |
wikipedia
|
https://en.wikipedia.org/wiki/MASS_syndrome
| 2021-01-18T19:10:48 |
{"gard": ["8489"], "mesh": ["C536030"], "omim": ["604308"], "icd-10": ["Q87.5"], "orphanet": ["99715"], "synonyms": ["Mitral valve-aorta-skeleton-skin syndrome"], "wikidata": ["Q3508570"]}
|
A rare, isolated, diffuse palmoplantar keratoderma disorder characterized by red-yellow, moderate to severe hyperkeratosis of the palms and soles, extending to the dorsal aspects of the hands, feet and/or wrists and involving the skin over the Achilles' tendon (transgrediens), gradually worsening with age (progrediens) to include patchy hyperkeratosis over the shins, knees, elbows and, sometimes, skin flexures. Hyperhidrosis is usually associated. Histologically, either epidermolytic or nonepidermolytic changes may be seen.
*[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-hydroxybutyric 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
|
Transgrediens et progrediens palmoplantar keratoderma
|
c1851479
| 25,733 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=495
| 2021-01-23T18:34:27 |
{"gard": ["3096"], "mesh": ["C536154"], "omim": ["133200"], "umls": ["C1851479", "C1851480"], "icd-10": ["Q82.8"], "synonyms": ["Greither disease", "Keratosis extremitatum hereditaria progrediens", "Keratosis palmoplantaris transgrediens et progrediens", "Progressive diffuse PPK", "Progressive diffuse palmoplantar keratoderma", "Transgrediens et progrediens PPK"]}
|
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-6 (ATFB6) is caused by heterozygous mutation in the NPPA gene (108780) on chromosome 1p36.
Description
Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997).
For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
Clinical Features
Hodgson-Zingman et al. (2008) reported a 3-generation Caucasian family of northern European ancestry in which 11 members were diagnosed with atrial fibrillation at a mean age of 40 years, in 3 cases during pregnancy. There was a transition from paroxysmal to chronic AF in 3 affected individuals and to arrest of atrial activation in 4 of them, suggesting progressive electrical remodeling. Tachycardia-induced cardiomyopathy was found in 5 subjects, which improved or resolved with effective pharmacologic rate control; subsequent echocardiography ruled out cardiac hypertrophy and contractile dysfunction, but showed dilation of the left atrial chamber in 7 patients and of the left ventricular chamber in 4 patients.
Abraham et al. (2010) studied a Caucasian kindred in which a mother and 2 children had relatively early-onset atrial fibrillation, with symptoms first appearing between 36 and 46 years of age. The proband developed palpitations, lightheadedness, and dizziness at age 36 years, and was diagnosed with paroxysmal lone AF at age 42, when an event recorder documented an episode of AF associated with rapid ventricular response. Family history revealed that his mother and older sister had been diagnosed with paroxysmal AF at the relatively young ages of 44 and 50 years. His mother subsequently developed hypertension and sick sinus syndrome, necessitating a permanent pacemaker at age 58. Two of the proband's children also reported occasional palpitations, but AF had not been documented.
Mapping
In a 3-generation family segregating autosomal dominant atrial fibrillation, Hodgson-Zingman et al. (2008) performed genomewide linkage analyses that ruled out known loci for atrial fibrillation. They obtained a peak 2-point lod score of 3.56 at marker D1S2667, and fine mapping identified a disease-associated haplotype spanning 24 Mb on chromosome 1p36-p35; a recombination event within this interval further narrowed the critical region to 11 Mb.
Molecular Genetics
Hodgson-Zingman et al. (2008) sequenced the candidate gene NPPA in a 3-generation family with atrial fibrillation and identified heterozygosity for a 2-bp deletion (108780.0001) that segregated with the disease and was not found in 560 controls.
In a cohort of 231 patients with atrial fibrillation, Abraham et al. (2010) analyzed the KCNQ1 (607542) and NPPA genes and identified heterozygosity for a missense mutation in NPPA (S64R; 108780.0002) in the proband of a Caucasian kindred segregating early-onset lone AF. The missense mutation segregated with disease in the family and was not found in Caucasian, Han Chinese, Asian, or African American population controls. Abraham et al. (2010) noted that ANP levels were not significantly different between family members with AF who were mutations carriers and those who were unaffected and did not carry the mutation. The authors also identified a mutation in the KCNQ1 gene (607542.0041) in another AF family (ATFB3; 607554) in the cohort; functional analysis revealed strikingly similar gain-of-function defects associated with the mutants, with atrial action potential shortening and altered calcium current as a common mechanism.
In a cohort of 384 Chinese AF patients and 844 controls, Ren et al. (2010) analyzed the NPPA SNP rs5063 but found no significant association. However, separate analysis involving only the 160 patients who were known to have lone AF showed significant association (p = 0.015; p = 0.003 after adjusting for age, gender, hypertension, diabetes, and smoking). The minor 'A' allele of rs5063 was found to confer a risk of lone AF with an odds ratio of 1.63, which increased to 1.89 after adjustment. Analysis of genotyping data under an additive, dominant, or recessive model showed significant association with lone AF for both an additive (p = 0.005) and a dominant (p = 0.007) model. Screening of the NPPA gene by direct sequencing revealed 3 probands with mutations that were not found in 844 controls, including 2 mutations in the 3-prime untranslated region and a missense mutation (I138T); however, all 3 families declined further genetic analysis. Ren et al. (2010) concluded that in addition to being a disease-causing gene, NPPA is a susceptibility gene for lone AF.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Atrial fibrillation \- Dilation of left atrial chamber \- Dilation of left ventricular chamber MISCELLANEOUS \- Mean age of diagnosis 40 years MOLECULAR BASIS \- Caused by mutation in the natriuretic peptide precursor A gene (NPPA, 108780.0001 ) ▲ 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-hydroxybutyric 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
|
ATRIAL FIBRILLATION, FAMILIAL, 6
|
c2677294
| 25,734 |
omim
|
https://www.omim.org/entry/612201
| 2019-09-22T16:02:09 |
{"doid": ["0050650"], "mesh": ["C567400"], "omim": ["612201", "608583"], "orphanet": ["334"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that infantile liver failure syndrome-1 (ILFS1) is caused by homozygous mutation in the LARS gene (151350) on chromosome 5q32. One such family has been reported.
### Genetic Heterogeneity of Infantile Liver Failure Syndrome
See also ILFS2 (616483), caused by mutation in the NBAS gene (608025) on chromosome 2p24.
A transient form of infantile liver failure (613070) is caused by mutation in the TRMU gene (610230) on chromosome 22q13.
Clinical Features
Casey et al. (2012) reported a 4-generation Irish Traveller family in which 6 individuals in 3 generations were affected with an infantile hepatopathy characterized by acute liver failure in the first year of life. The patients showed signs of intermittent improvement and developed acute symptoms only when their bodies were under physiologic stress due to illness. Earliest age at presentation was 2 months; the oldest affected family member was 33 years old at the time of the report. Liver biopsy performed in 3 family members showed steatosis and fibrosis. Patients also had microcytic anemia. Abnormal liver function tests, elevated lactates, abnormal brain MRIs, failure to thrive, developmental delay, and seizures were suggestive of a mitochondrial disorder. However, known causes of childhood liver failure and mitochondrial disease were excluded by biochemical, metabolic, and genetic analyses.
Population Genetics
Casey et al. (2012) stated that the estimated prevalence of infantile liver failure is less than 1 in 1 million.
Molecular Genetics
Using homozygosity mapping and whole-exome sequencing in a consanguineous Irish Traveller family with acute infantile liver failure, Casey et al. (2012) identified mutations in the LARS gene. All affected individuals were homozygous for 2 missense mutations. One was determined to be a rare nonpathogenic variant (c.245A-G, K82R, rs112954500). The other (Y373C; 151350.0001) was predicted to be highly deleterious, was highly conserved across eukaryotic species (89%), and was not present in 186 control chromosomes or in the dbSNP or 1000 Genomes Project databases. This mutation occurred in the editing domain of LARS, known as connective peptide-1, and was predicted to destabilize the protein structure. LARS knockdown achieved by siRNA in HEK293 cells had no effect on mitochondrial function even when cells were under physiologic stress.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Head \- Microcephaly (in one patient) Face \- Frontal bossing (in one patient) \- Chubby cheeks (in one patient) Ears \- Hearing loss, sensorineural (in one patient) ABDOMEN Liver \- Steatosis \- Fibrosis \- Hepatocyte ballooning \- Enlarged liver \- Liver failure \- Abnormal liver function tests GENITOURINARY Kidneys \- Renal dysfunction SKELETAL Hands \- Long fingers (in one patient) \- Abnormal thumbs (in one patient) Feet \- Long toes (in one patient) MUSCLE, SOFT TISSUES \- Decreased muscle bulk (in one patient) \- Congenital myopathy (in one patient) NEUROLOGIC Central Nervous System \- Abnormal MRI findings \- Gross motor delay (in some patients) \- Learning difficulties, mild to moderate (in some patients) \- Hypotonia \- Developmental delay \- Seizures METABOLIC FEATURES \- Lactic acidosis HEMATOLOGY \- Coagulopathy \- Macrocytic anemia MISCELLANEOUS \- Patients develop acute symptoms under physiologic stress due to illness \- Patients may show intermittent signs of improvement \- Clinical features other than liver findings may vary \- One family of Irish Traveller descent described (last curated September 2013) MOLECULAR BASIS \- Caused by mutation in the leucyl tRNA synthetase 1 gene (LARS1, 151350.0001 ) ▲ 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-hydroxybutyric 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
|
INFANTILE LIVER FAILURE SYNDROME 1
|
c3809522
| 25,735 |
omim
|
https://www.omim.org/entry/615438
| 2019-09-22T15:52:07 |
{"omim": ["615438"], "orphanet": ["370088"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that aortic valve disease-3 (AOVD3) is caused by heterozygous mutation in the ROBO4 gene (607528) on chromosome 11q24.
Description
Aortic valve disease-3 (AOVD3) is characterized by aortic stenosis and/or bicuspid aortic valve (BAV), associated in some patients with aneurysm of the aortic root and/or ascending aorta. Atrial septal defect (ASD) has also been observed in some individuals (Gould et al., 2019).
For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Clinical Features
Gould et al. (2019) studied a family (family 1) in which 7 males and 1 female over 3 generations had aortic root aneurysm, which was isolated in 4 patients and associated with aneurysm of the distal ascending aorta as well as aortic valve stenosis (AS) in 3; the remaining patient had associated bicuspid aortic valve with a right noncoronary cusp fusion pattern, as did 1 of the patients with AS and ascending aortic aneurysm. Three family members had undergone aortic valve replacement. In addition, the authors studied a mother and son (family 2) with aortic valve stenosis and atrial septal defect; the son also exhibited BAV with a left-to-right fusion pattern.
Molecular Genetics
By whole-exome sequencing in a cohort of 9 families with bicuspid aortic valve and/or thoracic aortic aneurysm (AAT), who were negative for mutation in AAT-associated genes, Gould et al. (2019) identified 2 families with heterozygous mutations in the ROBO4 gene: in family 1, a splicing mutation (607528.0001) was present in 8 affected individuals as well as in 2 unaffected family members; in family 2, an affected mother and son were heterozygous for a missense mutation (R64C; 607528.0002). Targeted sequencing of ROBO4 showed enrichment for rare variants in probands with BAV and ascending aortic aneurysm compared with controls: collectively, among familial and individual probands, 13 (1.77%) of 736 had a ROBO4 variant that passed a priori filtering constraints, whereas 1 rare missense variant was observed among 376 'rigorously phenotyped' controls (2-tailed Fisher exact test, p = 0.0432). One of the independent probands carried the same R64C missense variant that was identified in family 2; clinical details were not reported for that patient.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Aortic valve stenosis \- Bicuspid aortic valve \- Atrial septal defect (in some patients) Vascular \- Aortic root aneurysm \- Aneurysm of ascending aorta MISCELLANEOUS \- Reduced penetrance has been observed MOLECULAR BASIS \- Caused by mutation in the roundabout guidance receptor 4 gene (ROBO4, 607528.0001 ) ▲ 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-hydroxybutyric 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
|
AORTIC VALVE DISEASE 3
|
None
| 25,736 |
omim
|
https://www.omim.org/entry/618496
| 2019-09-22T15:41:39 |
{"omim": ["618496"]}
|
Leucostoma canker
Scientific classification
Kingdom:
Fungi
Division:
Ascomycota
Class:
Sordariomycetes
Order:
Diaporthales
Family:
Valsaceae
Genus:
Leucostoma
Species:
L. persoonii
Binomial name
Leucostoma persoonii
(Nitschke) Höhn. (1928)
Synonyms
Valsa persoonii Nitschke (1870)
Leucostoma canker is a fungal disease that can kill stone fruit (Prunus spp.).[1] The disease is caused by the plant pathogens Leucostoma persoonii[2] and Leucostoma cinctum[3] (teleomorph) and Cytospora leucostoma and Cytospora cincta[4] (anamorphs). The disease can have a variety of signs and symptoms depending on the part of the tree infected. One of the most lethal symptoms of the disease are the Leucostoma cankers. The severity of the Leucostoma cankers is dependent on the part of the plant infected. The fungus infects through injured, dying or dead tissues of the trees. Disease management can consist of cultural management practices such as pruning, late season fertilizers or chemical management through measures such as insect control. Leucostoma canker of stone fruit can cause significant economic losses due to reduced fruit production or disease management practices. It is one of the most important diseases of stone fruit tree all over the world.
## Contents
* 1 Hosts and symptoms
* 2 Disease cycle
* 3 Environment
* 4 Management
* 4.1 Cultural management
* 4.2 Genetic resistance
* 5 Importance
* 6 References
## Hosts and symptoms[edit]
Leukostoma Canker on Prunus Spp.
The hosts for Leucostoma canker include stone fruits such as cultivated peach, plum, prune, cherry (Prunus spp.), or other wild Prunus spp. It can also be found on apple (Malus domestica). Stone fruits are referred to as drupe, which are fruits containing a seed encased by a hard endocarp, surrounded by a fleshy outer portion.
Leucostoma canker symptoms differ depending on where on the tree infection takes place.[5] Discoloration occurs in sunken patches on infected twigs. Light and dark concentric circles of narcotic tissue characterize this symptom, occurring near buds killed by cold or on leaf scars. Infections on the nodes are seen 2–4 weeks after bud break.[6] As time passes, darkening occurs within diseased tissues, and eventually, amber gum ooze may seep from infected tissue.[7] Nodal infections are particularly vulnerable in one-year-old shoots that develop within the center of the tree. If fungal growth persists without treatment, scaffold limbs and large branches will likely become invaded within a short time frame. Cankers occurring on branches that are the product of such infections will contain dead twigs or twig stubs at the canker’s center.
The most striking symptom of infection includes cankers located on the main trunk, branch crotches, scaffold limbs, and older branches.[3] A symptom called “flagging” can be found on necrotic scaffold limbs. The cankers are parallel to the long axis of the stem and take on an oval shape. Normally, large-scale production of amber colored gum marks the first external symptom of such cankers. While gum production is the typical plant response to irritation, the gum secretion of Leucostoma occurs in bulk amounts. This gum darkens as time passes, gradually leading to the drying and cracking of bark; thus exposing the blackened tissue below.
As the tree continues to mature in the early growing season, the tree resists additional fungal penetration through the formation of callus rings surrounding the canker. However, the Leucostoma generally reinvades the tissue late in the growing season while the tree switches into dormancy. Due to the alteration of callus production and canker formation, cankers with circular callus rings are usually observed.
Foliar symptoms might develop from branch or twig infections. Symptoms include chlorosis, wilting, and necrosis. Signs include small black structures on dead bark which contain pycnidia.[7]
## Disease cycle[edit]
Leucostoma Canker of Stone Fruits Disease Cycle
Although the Leucostoma pathogen can undergo sexual stages, the asexual cycle is far more important for disease development.
The fungus that causes disease overwinters in cankers or previously invaded dead wood. Environmental cues, such as cool, moist weather in the early spring, cause conidia to be released from pycnidia in sticky masses. The conidia are then spread via wind or water splashes. Conidia then germinate and the fungi begins to colonize provided that the environment is wet. The fungus is incapable of invading healthy bark and must enter the tree through injured, dying, or dead tissues.[3] Leucostoma commonly enters through weak, winter-killed twigs in the center of the tree. Moreover, it gains entry through winter-injured wood on limbs and trunks. It also can enter through short, dead pruning stubs, leaf scars, winter-killed buds on small twigs, and on poorly healed pruning cuts.
Upon invasion, fungal growth moves into healthy adjacent tissue. This fungal growth is slow, but the expansion continues even at temperatures just above freezing. As the temperature rises above 50 degrees Fahrenheit, the tree actively starts to grow and a callus is usually formed around the canker. The defense mechanism, however, is outmatched in the fall and following spring when the dormant tree is unable to defend itself. The repeated tree growth eventually forms a new callus, and an annual pattern of callus formation and canker expansion leads to the development of concentric callus rings around the first infection site.
Pycnidia develop throughout the growing season within the colonized tissues. Conidia are then produced inside the pycnidia and can be released when conditions are favorable: i.e. humid weather. As a result, vulnerable tissues are at risk of initial invasion throughout most parts of the year, although it most commonly occurs in autumn and spring following winter injury and leaf scars.
## Environment[edit]
Leucostoma canker can be found in the Northeastern United States, from the cooler regions surrounding Lake Ontario to the warmer areas in the lower Hudson Valley. It can also be found the Southeastern United States on peaches. In California and Idaho, it has been found on plum and prune trees. In Europe, the disease can be found on apricot, peach, and cherry. Leucostoma canker has also been witnessed in South America and Japan.[1]
The spread of disease is favored in cool, wet, and humid conditions in late fall or early spring when conidia are most abundant. Regions with irrigation are particularly vulnerable to disease, for conidia thrive whenever water is available. Studies have shown that there are positive correlations between the number of disease causing agents (conidia), and the number of hours that temperatures are between 10 and 15 degrees Celsius. These data also correlate to the duration of moisture and amount of time humidity conditions are above 90 percent. These conditions are all optimal for disease. Without humidity and wet conditions, disease does not occur.
## Management[edit]
Control of Leucostoma Canker is possible through a combination of pest and crop management techniques following life cycles of the trees. The strategy is implemented following techniques aimed at reducing number of pathogenic inoculum, minimizing dead or injured tissues to prevent infection, and improving tree health to improve rapid wound healing. Chemical controls have not been very effective at controlling this disease with no fungicides registered specifically for control of Leucostoma spp., and demethylation-inhibiting (DMI) fungicides having almost no effect on L. persoonii.[1]
### Cultural management[edit]
There are many strategies to cultural management. Establishment of new trees that are disease free by trying to plant trees as soon as they are received from the nursery to reduce the amount of stress the tree undergoes to reduce the amount of dead tissue. Apply insecticides to prevent insects such as, peach tree borer to prevent disease causing conidia from entering wounded parts of the tree that the insects create. Prune trees appropriately and at the correct time when buds start to break to promote wide angled branching. Infection at pruning sites is less common when done during late spring because of the smaller amount of inoculum present at this time. Inspect trees occasionally and removed any dead branches to prevent infection at these sites. Training trees properly also helps foster decreased amount of disease. Training trees during the first season to have branches develop wide crotch angles to sustain long orchard life. Avoid excessive and late fertilization during cold season to avoid low temperature injury. Fertilize trees during the early spring to prevent cold-susceptible growth.[1]
### Genetic resistance[edit]
Selecting cultivars is important and the best ones are the cultivars resistant to cold temperatures. As plant pathologists have learned better ways to develop more efficient resistance to the Leucostoma canker pathogens, there have been many really effective cultivars developed that can be used. However, the cultivars that offer the best resistance to cold temperatures have a higher ability to resist infection due to injury or wounding. A peach cultivar resistant to cold temperatures would be Redhaven one that is especially, recommended for Missouri and some nectarine cultivars include RedGold, Crimson Snow, Crimson Gold, Sunglo and many more.[8]
## Importance[edit]
Cankers
Leucostoma canker[9] is one of the most important diseases on stone fruit. Leucostoma persoonii[10] is most significant on peaches, nectarines, and cherries in regions with cold winters. The first records of peach tree cankers caused by this pathogen were documented in western New York in 1900. The disease was then sighted in southern Ontario twelve years later.[1] Leucostoma canker decreases the bearing surface of fruiting trees and shortens the tree’s lifespan. Additionally, it considerably raises the costs of disease management.
As limbs with cankers die or break off due to the stress of holding fruit, economic losses add. Parts of the branch distal to the canker often become less fruitful, and eventually the canker will enlarge to reach the branch, effectively killing it. Trees with numerous cankers show strikingly reduced yield. Since peach trees are trimmed to hold 3 to 4 main scaffold limbs, the death of even one of the main limbs causes a 25 to 50% loss of fruit production.[1]
## References[edit]
1. ^ a b c d e f "Leucostoma canker of stone fruits".
2. ^ Jensen, Carolyn J. P.; Adams, Gerard C. (1 January 1995). "Nitrogen Metabolism of Leucostoma persoonii and L. cincta in Virulent and Hypovirulent Isolates". Mycologia. 87 (6): 864–875. doi:10.2307/3760862. JSTOR 3760862.
3. ^ a b c Biggs, Alan R. "Leucostoma Canker of Stone Fruits". Archived from the original on 2013-10-20. Retrieved 2013-10-20.
4. ^ Wensley, R. N. (1 March 1971). "The microflora of peach bark and its possible relation to perennial canker (Leucostoma cincta (Fr.) v. Hohnel (Valsa cincta))". Can. J. Microbiol. 17 (3): 333–337. doi:10.1139/m71-056. PMID 5551316.
5. ^ Leucostoma facts
6. ^ "Search".
7. ^ a b http://www.plantpath.iastate.edu/files/SUL11.pdf
8. ^ "MG6 Fruit Production - University of Missouri Extension".
9. ^ Puterka, G. J.; Scorza, R.; Brown, M. W. (1 November 1993). "Reduced Incidence of Lesser Peachtree Borer and Leucostoma Canker in Peach-Almond Hybrids". J. Am. Soc. Hort. Sci. 118 (6): 864–867. doi:10.21273/JASHS.118.6.864.
10. ^ Adams, Gerard C.; Surve-Iyer, Rupa S.; Iezzoni, Amy F. (1 January 2002). "Ribosomal DNA Sequence Divergence and Group I Introns within the Leucostoma Species L. cinctum, L. persoonii, and L. parapersoonii sp. nov., Ascomycetes That Cause Cytospora Canker of Fruit Trees". Mycologia. 94 (6): 947–967. doi:10.2307/3761863. JSTOR 3761863. PMID 21156569.
*[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-hydroxybutyric 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
|
Leucostoma canker
|
None
| 25,737 |
wikipedia
|
https://en.wikipedia.org/wiki/Leucostoma_canker
| 2021-01-18T18:31:12 |
{"wikidata": ["Q16984500"]}
|
Auditory agnosia is a form of agnosia that manifests itself primarily in the inability to recognize or differentiate between sounds. It is not a defect of the ear or "hearing", but rather a neurological inability of the brain to process sound meaning. It is caused by bilateral damage to the anterior superior temporal gyrus, which is part of the auditory pathway responsible for sound recognition, the auditory "what" pathway.[1]
Persons with auditory agnosia can physically hear the sounds and describe them using unrelated terms, but are unable to recognize them. They might describe the sound of some environmental sounds, such as a motor starting, as resembling a lion roaring, but would not be able to associate the sound with "car" or "engine", nor would they say that it was a lion creating the noise.[2] All auditory agnosia patients read lips in order to enhance the speech comprehension.[3]
It is yet unclear whether auditory agnosia (also called general auditory agnosia) is a combination of milder disorders, such auditory verbal agnosia (pure word deafness), non-verbal auditory agnosia, amusia and word-meaning deafness, or a mild case of the more severe disorder, cerebral deafness. As of 2014[update], 203 patients with auditory perceptual deficits due to CNS damage were reported in the medical literature, of which 183 diagnosed with general auditory agnosia or word deafness, 34 with cerebral deafness, 51 with non-verbal auditory agnosia-amusia and 8 word meaning deafness (for a list of patients see[4]).
## Contents
* 1 History
* 2 Related disorders
* 2.1 Cerebral deafness
* 2.2 Pure word deafness
* 2.3 Non-verbal auditory agnosia
* 2.4 Amusia
* 2.5 Word meaning deafness / associative auditory agnosia
* 3 Neurological mechanism
* 4 See also
* 5 References
* 6 Further reading
* 7 External links
## History[edit]
A relationship between hearing and the brain was first documented by Ambroise Paré, a 16th century battlefield doctor, who associated parietal lobe damage with acquired deafness (reported in Henschen, 1918[5]). Systematic research into the manner in which the brain processes sounds, however, only began toward the end of the 19th century. In 1874, Wernicke[6] was the first to ascribe to a brain region a role in auditory perception. Wernicke proposed that the impaired perception of language in his patients was due to losing the ability to register sound frequencies that are specific to spoken words (he also suggested that other aphasic symptoms, such as speaking, reading and writing errors occur because these speech specific frequencies are required for feedback). Wernicke localized the perception of spoken words to the posterior half of the left STG (superior temporal gyrus). Wernicke also distinguished between patients with auditory agnosia(which he labels as receptive aphasia) with patients who cannot detect sound at any frequency (which he labels as cortical deafness).[7]
In 1877, Kussamul was the first to report auditory agnosia in a patient with intact hearing, speaking, and reading-writing abilities. This case-study led Kussamul to propose of distinction between the word perception deficit and Wernicke's sensory aphasia. He coined the former disorder as "word deafness". Kussamul also localized this disorder to the left STG. Wernicke interpreted Kussamul's case as an incomplete variant of his sensory aphasia.[7]
In 1885,[8] Lichtheim also reported of an auditory agnosia patient. This patient, in addition to word deafness, was impaired at recognizing environmental sounds and melodies. Based on this case study, as well as other aphasic patients, Lichtheim proposed that the language reception center receives afferents from upstream auditory and visual word recognition centers, and that damage to these regions results in word deafness or word blindness (i.e., alexia), respectively. Because the lesion of Lichtheim's auditory agnosia patient was sub-cortical deep to the posterior STG (superior temporal gyrus), Lichtheim renamed auditory agnosia as "sub-cortical speech deafness".
The language model proposed by Wernicke and Lichtheim wasn't accepted at first. For example, in 1897 Bastian[9] argued that, because aphasic patients can repeat single words, their deficit is in the extraction of meaning from words. He attributed both aphasia and auditory agnosia to damage in Lichtheim's auditory word center. He hypothesized that aphasia is the outcome of partial damage to the left auditory word center, whereas auditory agnosia is the result of complete damage to the same area. Bastian localized the auditory word center to the posterior MTG (middle temporal gyrus).
Other opponents to the Wernicke-Lichtheim model were Sigmund Freud and Carl Freund. Freud[10] (1891) suspected that the auditory deficits in aphasic patients was due to a secondary lesion to cochlea. This assertion was confirmed by Freund[11] (1895), who reported two auditory agnosia patients with cochlear damage (although in a later autopsy, Freund reported also the presence of a tumor in the left STG in one of these patients). This argument, however, was refuted by Bonvicini[12] (1905), who measured the hearing of an auditory agnosia patient with tuning forks, and confirmed intact pure tone perception. Similarly, Barrett's aphasic patient,[13] who was incapable of comprehending speech, had intact hearing thresholds when examined with tuning forks and with a Galton whistle. The most adverse opponent to the model of Wernicke and Lichtheim was Marie[14] (1906), who argued that all aphasic symptoms manifest because of a single lesion to the language reception center, and that other symptoms such as auditory disturbances or paraphasia are expressed because the lesion encompasses also sub-cortical motor or sensory regions.
In the following years, increasing number of clinical reports validated the view that the right and left auditory cortices project to a language reception center located in the posterior half of the left STG, and thus established the Wernicke-Lichtheim model. This view was also consolidated by Geschwind[15] (1965) who reported that, in humans, the left planum temporale is larger in the left hemisphere than on the right. Geschwind interpreted this asymmetry as anatomical verification for the role of left posterior STG in the perception of language.
The Wernicke-Lichtheim-Geschwind model persisted throughout the 20th century. However, with the advent of MRI and its usage for lesion mapping, it was shown that this model is based on incorrect correlation between symptoms and lesions.[16][17][18] Although this model is considered outdated, it is still widely mentioned in Psychology and medical textbooks, and consequently in medical reports of auditory agnosia patients. As will be mentioned below, based on cumulative evidence the process of sound recognition was recently shifted to the left and right anterior auditory cortices, instead of the left posterior auditory cortex.
## Related disorders[edit]
After auditory agnosia was first discovered, subsequent patients were diagnosed with different types of hearing impairments. In some reports, the deficit was restricted to spoken words, environmental sounds or music. In one case study, each of the three sound types (music, environmental sounds, speech) was also shown to recover independently (Mendez and Geehan, 1988-case 2[19]). It is yet unclear whether general auditory agnosia is a combination of milder auditory disorders, or whether the source of this disorder is at an earlier auditory processing stage.
### Cerebral deafness[edit]
Cerebral deafness (also known as cortical deafness or central deafness) is a disorder characterized by complete deafness that is the result of damage to the central nervous system. The primary distinction between auditory agnosia and cerebral deafness is the ability to detect pure tones, as measured with pure tone audiometry. Using this test, auditory agnosia patients were often reported[20][21] capable of detecting pure tones almost as good as healthy individuals, whereas cerebral deafness patients found this task almost impossible or they required very loud presentations of sounds (above 100 dB). In all reported cases, cerebral deafness was associated with bilateral temporal lobe lesions. A study[21] that compared the lesions of two cerebral deafness patients to an auditory agnosia patient concluded that cerebral deafness is the result of complete de-afferentation of the auditory cortices, whereas in auditory agnosia some thalamo-cortical fibers are spared. In most cases the disorder is transient and the symptoms mitigate into auditory agnosia (although chronic cases were reported[22]). Similarly, a monkey study[23] that ablated both auditory cortices of monkeys reported of deafness that lasted 1 week in all cases, and that was gradually mitigated into auditory agnosia in a period of 3–7 weeks.
### Pure word deafness[edit]
Since the early days of aphasia research, the relationship between auditory agnosia and speech perception has been debated. Lichtheim[8] (1885) proposed that auditory agnosia is the result of damage to a brain area dedicated to the perception of spoken words, and consequently renamed this disorder from 'word deafness' to 'pure word deafness'. The description of word deafness as being exclusively for words was adopted by the scientific community despite the patient reported by Lichtheim's who also had more general auditory deficits. Some researchers who surveyed the literature, however, argued against labeling this disorder as pure word deafness on the account that all patients reported impaired at perceiving spoken words were also noted with other auditory deficits or aphasic symptoms.[24][3] In one review of the literature, Ulrich[25] (1978) presented evidence for separation of word deafness from more general auditory agnosia, and suggested naming this disorder "linguistic auditory agnosia" (this name was later rephrased into "verbal auditory agnosia"[26]). To contrast this disorder with auditory agnosia in which speech repetition is intact (word meaning deafness), the name "word sound deafness"[27] and "phonemic deafness"[28] (Kleist, 1962) were also proposed. Although some researchers argued against the purity of word deafness, some anecdotal cases with exclusive impaired perception of speech were documented.[29][30][31][32][33][34][35][36][37] On several occasions, patients were reported to gradually transition from pure word deafness to general auditory agnosia/cerebral deafness[38][39][40] or recovery from general auditory agnosia/cerebral deafness to pure word deafness.[41][42]
In a review of the auditory agnosia literature, Phillips and Farmer[43] showed that patients with word deafness are impaired in their ability to discriminate gaps between click sounds as long as 15-50 milliseconds, which is consistent with the duration of phonemes. They also showed that patients with general auditory agnosia are impaired in their ability to discriminate gaps between click sounds as long as 100–300 milliseconds. The authors further showed that word deafness patients liken their auditory experience to hearing foreign language, whereas general auditory agnosia described speech as incomprehensible noise. Based on these findings, and because both word deafness and general auditory agnosia patients were reported to have very similar neuroanatomical damage (bilateral damage to the auditory cortices), the authors concluded that word deafness and general auditory agnosia is the same disorder, but with a different degree of severity.
Pinard et al[40] also suggested that pure word deafness and general auditory agnosia represent different degrees of the same disorder. They suggested that environmental sounds are spared in the mild cases because they are easier to perceive than speech parts. They argued that environmental sounds are more distinct than speech sounds because they are more varied in their duration and loudness. They also proposed that environmental sounds are easier to perceive because they are composed of a repetitive pattern (e.g., the bark of a dog or the siren of the ambulance).
Auerbach et al[44] considered word deafness and general auditory agnosia as two separate disorders, and labelled general auditory agnosia as pre-phonemic auditory agnosia and word deafness as post-phonemic auditory agnosia. They suggested that pre-phonemic auditory agnosia manifests because of general damage to the auditory cortex of both hemispheres, and that post-phonemic auditory agnosia manifests because of damage to a spoken word recognition center in the left hemisphere. Recent evidence, possibly verified Auerbach hypothesis, since an epileptic patient who undergone electro-stimulation to the anterior superior temporal gyrus was demonstrated a transient loss of speech comprehension, but with intact perception of environmental sounds and music.[45]
### Non-verbal auditory agnosia[edit]
The term auditory agnosia was originally coined by Freud[10] (1891) to describe patients with selective impairment of environmental sounds. In a review of the auditory agnosia literature, Ulrich[25] re-named this disorder as non-verbal auditory agnosia (although sound auditory agnosia and environmental sound auditory agnosia are also commonly used). This disorder is very rare and only 18 cases have been documented.[4] In contradiction to pure word deafness and general auditory agnosia, this disorder is likely under-diagnosed because patients are often not aware of their disorder, and thus don't seek medical intervention.[46][47][48]
Throughout the 20th century, all reported non-verbal auditory agnosia patients had bilateral or right temporal lobe damage. For this reason, the right hemisphere was traditionally attributed with the perception of environmental sounds. However, Tanaka et al[49] reported 8 patients with non-verbal auditory agnosia, 4 with right hemisphere lesions and 4 with left hemisphere lesions. Saygin[46] et al also reported a patient with damage to the left auditory cortex.
The underlying deficit in non-verbal auditory agnosia appears to be varied. Several patients were characterized by impaired discrimination of pitch[50][51][52] whereas others reported with impaired discrimination of timbre and rhythm[53][54][55] (discrimination of pitch was relatively preserved in one of these cases[53]). In contrast, to patients with pure word deafness and general auditory agnosia, patients with non-verbal auditory agnosia were reported impaired at discriminating long gaps between click sounds, but impaired at short gaps.[56][57] A possible neuroanatomical structure that relays longer sound duration was suggested by Tanaka et al.[21] By comparing the lesions of two cortically deaf patients with the lesion of a word deafness patient, they proposed the existence of two thalamocortical pathways that inter-connect the MGN with the auditory cortex. They suggested that spoken words are relayed via a direct thalamocortical pathway that passes underneath the putamen, and that environmental sounds are relayed via a separate thalamocortical pathway that passes above the putamen near the parietal white matter.
### Amusia[edit]
Auditory agnosia patients are often impaired in the discrimination of all sounds, including music. However, in two such patients music perception was spared[56][58] and in one patient music perception was enhanced.[59] The medical literature reports of 33 patients diagnosed with an exclusive deficit for the discrimination and recognition of musical segments[4] (i.e., amusia). The damage in all these cases was localized to the right hemisphere or was bilateral. (with the exception of one case.[60]) The damage in these cases tended to focus around the temporal pole. Consistently, removal of the anterior temporal lobe was also associated with loss of music perception,[61] and recordings directly from the anterior auditory cortex revealed that in both hemispheres, music is perceived medially to speech.[62] These findings therefore imply that the loss of music perception in auditory agnosia is because of damage to the medial anterior STG. In contrast to the association of amusia specific to recognition of melodies (amelodia) with the temporal pole, posterior STG damage was associated with loss of rhythm perception (arryhthmia).[63][64][65] Conversely, in two patients rhythm perception was intact, while recognition/discrimination of musical segments was impaired.[66][67] Amusia also dissociates in regard to enjoyment from music. In two reports,[68][69] amusic patients, who weren't able to distinguish musical instruments, reported that they still enjoy listening to music. On the other hand, a patient with left hemispheric damage in the amygdala was reported to perceive, but not enjoy, music.[70]
### Word meaning deafness / associative auditory agnosia[edit]
In 1928, Kleist[28] suggested that the etiology of word deafness could be due either to impaired perception of the sound (apperceptive auditory agnosia), or to impaired extraction of meaning from a sound (associative auditory agnosia). This hypothesis was first tested by Vignolo et al[71] (1969), who examined unilateral stroke patients. They reported that patients with left hemisphere damage were impaired in matching environmental sounds with their corresponding pictures, whereas patients with right hemisphere damage were impaired in the discrimination of meaningless noise segments. The researchers then concluded that left hemispheric damage results in associative auditory agnosia, and right hemisphere damage results in apperceptive auditory agnosia. Although the conclusion reached by this study could be considered over-reaching, associative auditory agnosia could correspond with the disorder word meaning deafness.
Patients with word meaning deafness are characterized by impaired speech recognition but intact repetition of speech and left hemisphere damage.[72][73][74][75][76][28][77][78] These patients often repeat words in an attempt to extract its meaning (e.g., "Jar....Jar....what is a jar?"[72]). In the first documented case,[73] Bramwell (1897 - translated by Ellis, 1984) reported a patient, who in order to comprehend speech wrote what she heard and then read her own handwriting. Kohn and Friedman,[77] and Symonds[78] also reported word meaning deafness patients who are able to write to dictation. In at least 12 cases, patients with symptoms that correspond with word meaning deafness were diagnosed as auditory agnosia.[4] Unlike most auditory agnosia patients, word meaning deafness patients are not impaired at discriminating gaps of click sounds.[79][80][81] It is yet unclear whether word meaning deafness is also synonymous with the disorder deep dysphasia, in which patients cannot repeat nonsense words and produce semantic paraphasia during repetition of real words.[82][83] Word meaning deafness is also often confused with transcortical sensory aphasia, but such patients differ from the latter by their ability to express themselves appropriately orally or in writing.
## Neurological mechanism[edit]
Auditory agnosia (with the exception of non-verbal auditory agnosia and amusia) is strongly dependent on damage to both hemispheres.[4] The order of hemispheric damage is irrelevant to manifestation of symptoms, and years could take between the damage of the first hemisphere and the second hemisphere (after which the symptoms suddenly emerge).[3][25] A study[84] that compared lesion locations, reported that in all cases with bilateral hemispheric damage, at least in one side the lesion included Heschl's gyrus or its underlying white matter. A rare insight into the etiology of this disorder was reported in a study of an auditory agnosia patient with damage to the brainstem, instead of cortex.[1] fMRI scanning of the patient revealed weak activation of the anterior Heschl's gyrus (area R) and anterior superior temporal gyrus. These brain areas are part of the auditory 'what' pathway, and are known from both human and monkey research to participate in the recognition of sounds.[85]
## See also[edit]
* Amusia
* Aphasia
* Apraxia
* Auditory verbal agnosia
## References[edit]
1. ^ a b Poliva O, Bestelmeyer PE, Hall M, Bultitude JH, Koller K, Rafal RD (September 2015). "Functional Mapping of the Human Auditory Cortex: fMRI Investigation of a Patient with Auditory Agnosia from Trauma to the Inferior Colliculus" (PDF). Cognitive and Behavioral Neurology. 28 (3): 160–80. doi:10.1097/WNN.0000000000000072. PMID 26413744. S2CID 913296.
2. ^ Martin GN (2006). Human neuropsychology. Harlow, England; New York: Pearson/Prentice Hall. ISBN 978-0-13-197452-4. OCLC 61692682.
3. ^ a b c Buchman AS, Garron DC, Trost-Cardamone JE, Wichter MD, Schwartz M (May 1986). "Word deafness: one hundred years later". Journal of Neurology, Neurosurgery, and Psychiatry. 49 (5): 489–99. doi:10.1136/jnnp.49.5.489. PMC 1028802. PMID 2423648.
4. ^ a b c d e Poliva O (2014). Neuroanatomical and perceptual deficits in auditory agnosia: a study of an auditory agnosia patient with inferior colliculus damage (Ph.D. thesis). Prifysgol Bangor University. pp. 67–74.
5. ^ Henschen SE (January 1918). "On the hearing Sphere". Acta Oto-Laryngologica. 1 (1): 423–485. doi:10.3109/00016481809122009. ISSN 0001-6489.
6. ^ Wernicke C (1974). "Der aphasische Symptomenkomplex". Springer Berlin Heidelberg. pp. 1–70. doi:10.1007/978-3-642-65950-8_1. ISBN 978-3-540-06905-8. Missing or empty `|title=` (help)
7. ^ a b Wernicke C, Friedlander C (1883). "Ein Fall von Taubheit in folge von doppelseiteger Laesion des Schläfenlappens". Fortschr. Med. 1: 177–185.
8. ^ a b Lichteim L (January 1885). "On Aphasia". Brain. 7 (4): 433–484. doi:10.1093/brain/7.4.433.
9. ^ Bastian HC (April 1897). "The Lumleian Lectures on some problems in connection with aphasia and other speech defects: Lecture 1". The Lancet. 149 (3843): 1131–1137. doi:10.1016/s0140-6736(01)95713-7. ISSN 0140-6736.
10. ^ a b Freud S (1891). Zur Auffassung der Aphasien. Vienna: Franz Deuticke.
11. ^ Freund CS (1895). Labyrinthtaubheit und Sprachtaubheit. Wiesbaden: Bergmann.
12. ^ Bonvicini G (1905). "Über subcorticale sensorische Aphasie". Jahrbücher für Psychiatrie. 26: 126–229.
13. ^ Barrett AM (February 1910). "A case of pure word-deafness with autopsy". The Journal of Nervous and Mental Disease. 37 (2): 73–92. doi:10.1097/00005053-191002000-00001. S2CID 148432237.
14. ^ Marie P (1906). "What to think about subcortical aphasias (pure aphasias)". In Cole MR, Cole M (eds.). Pierre Marie's Papers on Speech Disorders. Semaine Medicale 26. New York: Hafner. pp. 493–500.
15. ^ Geschwind N (June 1965). "Disconnexion syndromes in animals and man. I". Brain. 88 (2): 237–94. doi:10.1093/brain/88.2.237. PMID 5318481.
16. ^ DeWitt I, Rauschecker JP (February 2012). "Phoneme and word recognition in the auditory ventral stream". Proceedings of the National Academy of Sciences of the United States of America. 109 (8): E505–14. Bibcode:2012PNAS..109E.505D. doi:10.1073/pnas.1113427109. PMC 3286918. PMID 22308358.
17. ^ Mesulam MM, Thompson CK, Weintraub S, Rogalski EJ (August 2015). "The Wernicke conundrum and the anatomy of language comprehension in primary progressive aphasia". Brain. 138 (Pt 8): 2423–37. doi:10.1093/brain/awv154. PMC 4805066. PMID 26112340.
18. ^ Poeppel D, Emmorey K, Hickok G, Pylkkänen L (October 2012). "Towards a new neurobiology of language". The Journal of Neuroscience. 32 (41): 14125–31. doi:10.1523/jneurosci.3244-12.2012. PMC 3495005. PMID 23055482.
19. ^ Mendez MF, Geehan GR (January 1988). "Cortical auditory disorders: clinical and psychoacoustic features". Journal of Neurology, Neurosurgery, and Psychiatry. 51 (1): 1–9. doi:10.1136/jnnp.51.1.1. PMC 1032706. PMID 2450968.
20. ^ Vignolo LA (2017-07-12), "Auditory Agnosia: A Review and Report of Recent Evidence", Brain & Behavior, Routledge, pp. 172–208, doi:10.4324/9781315082035-8, ISBN 978-1-315-08203-5
21. ^ a b c Tanaka Y, Kamo T, Yoshida M, Yamadori A (December 1991). "'So-called' cortical deafness. Clinical, neurophysiological and radiological observations". Brain. 114 ( Pt 6) (6): 2385–401. doi:10.1093/brain/114.6.2385. PMID 1782522.
22. ^ Polster MR, Rose SB (February 1998). "Disorders of auditory processing: evidence for modularity in audition". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 34 (1): 47–65. doi:10.1016/s0010-9452(08)70736-6. PMID 9533993. S2CID 2717085.
23. ^ Heffner HE, Heffner RS (July 1990). "Effect of bilateral auditory cortex lesions on absolute thresholds in Japanese macaques". Journal of Neurophysiology. 64 (1): 191–205. doi:10.1152/jn.1990.64.1.191. PMID 2388065.
24. ^ Head H (1920). "Aphasia and kindred disorders of speech". Brain. 43 (2): 87–165. doi:10.1093/brain/43.2.87. hdl:11858/00-001M-0000-002B-9E28-0.
25. ^ a b c Ulrich G (May 1978). "Interhemispheric functional relationships in auditory agnosia. An analysis of the preconditions and a conceptual model". Brain and Language. 5 (3): 286–300. doi:10.1016/0093-934x(78)90027-5. PMID 656899. S2CID 33841186.
26. ^ Wang E, Peach RK, Xu Y, Schneck M, Manry C (July 2000). "Perception of dynamic acoustic patterns by an individual with unilateral verbal auditory agnosia". Brain and Language. 73 (3): 442–55. doi:10.1006/brln.2000.2319. PMID 10860565. S2CID 18865116.
27. ^ Kohn SE, Friedman RB (August 1986). "Word-meaning deafness: A phonological-semantic dissociation". Cognitive Neuropsychology. 3 (3): 291–308. doi:10.1080/02643298608253361.
28. ^ a b c Kleist K (1962). "Phonemic Deafness (So-Called Pure Word Deafness).". Sensory Aphasia and Amusia. New York: Pergamon Press. pp. 28–41.
29. ^ Mills CK (1891). "On the localisation of the auditory centre". Brain. 14 (4): 465–472. doi:10.1093/brain/14.4.465. ISSN 0006-8950.
30. ^ Ziehl F (March 1896). "Ueber einen Fall von Worttaubheit und das Lichtheim'sche Krankheitsbild der subcorticalen sensorischen Aphasie". Deutsche Zeitschrift für Nervenheilkunde. 8–8 (3–4): 259–307. doi:10.1007/bf01666315. ISSN 0340-5354. S2CID 37283541.
31. ^ Hemphill RE, Stengel E (July 1940). "a study on pure word-deafness". Journal of Neurology and Psychiatry. 3 (3): 251–62. doi:10.1136/jnnp.3.3.251. PMC 1088185. PMID 21610977.
32. ^ Klein R, Harper J (January 1956). "The problem of agnosia in the light of a case of pure word deafness". The Journal of Mental Science. 102 (426): 112–20. doi:10.1192/bjp.102.426.112. PMID 13307190.
33. ^ Saffran EM, Marin OS, Yeni-Komshian GH (April 1976). "An analysis of speech perception in word deafness". Brain and Language. 3 (2): 209–28. doi:10.1016/0093-934x(76)90018-3. PMID 938928. S2CID 12334367.
34. ^ Yaqub BA, Gascon GG, Al-Nosha M, Whitaker H (April 1988). "Pure word deafness (acquired verbal auditory agnosia) in an Arabic speaking patient". Brain. 111 ( Pt 2) (2): 457–66. doi:10.1093/brain/111.2.457. PMID 3378145.
35. ^ Takahashi N, Kawamura M, Shinotou H, Hirayama K, Kaga K, Shindo M (June 1992). "Pure word deafness due to left hemisphere damage". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 28 (2): 295–303. doi:10.1016/s0010-9452(13)80056-1. PMID 1499314. S2CID 4488260.
36. ^ Tanaka Y, Yamadori A, Mori E (April 1987). "Pure word deafness following bilateral lesions. A psychophysical analysis". Brain. 110 ( Pt 2) (2): 381–403. doi:10.1093/brain/110.2.381. PMID 3567528.
37. ^ Wolmetz M, Poeppel D, Rapp B (March 2011). "What does the right hemisphere know about phoneme categories?". Journal of Cognitive Neuroscience. 23 (3): 552–69. doi:10.1162/jocn.2010.21495. PMC 4471482. PMID 20350179.
38. ^ Iizuka O, Suzuki K, Endo K, Fujii T, Mori E (April 2007). "Pure word deafness and pure anarthria in a patient with frontotemporal dementia". European Journal of Neurology. 14 (4): 473–5. doi:10.1111/j.1468-1331.2007.01671.x. PMID 17389003. S2CID 45767094.
39. ^ Szirmai I, Farsang M, Csüri M (May 2003). "Cortical auditory disorder caused by bilateral strategic cerebral bleedings. Analysis of two cases". Brain and Language. 85 (2): 159–65. doi:10.1016/s0093-934x(02)00597-7. PMID 12735933. S2CID 42467221.
40. ^ a b Pinard M, Chertkow H, Black S, Peretz I (February 2002). "A case study of pure word deafness: modularity in auditory processing?". Neurocase. 8 (1–2): 40–55. doi:10.1093/neucas/8.1.40. PMID 11997484. S2CID 38623636.
41. ^ Goldstein MN, Brown M, Hollander J (July 1975). "Auditory agnosia and cortical deafness: analysis of a case with three-year followup". Brain and Language. 2 (3): 324–32. doi:10.1016/s0093-934x(75)80073-3. PMID 1182499. S2CID 1337350.
42. ^ Zhu RJ, Lv ZS, Shan CL, Xu MW, Luo BY (November 2010). "Pure word deafness associated with extrapontine myelinolysis". Journal of Zhejiang University Science B. 11 (11): 842–7. doi:10.1631/jzus.b1000200. PMC 2970893. PMID 21043052.
43. ^ Phillips DP, Farmer ME (November 1990). "Acquired word deafness, and the temporal grain of sound representation in the primary auditory cortex". Behavioural Brain Research. 40 (2): 85–94. doi:10.1016/0166-4328(90)90001-u. PMID 2285476. S2CID 9626294.
44. ^ Auerbach SH, Allard T, Naeser M, Alexander MP, Albert ML (June 1982). "Pure word deafness: analysis of a case with bilateral lesions and a defect at the prephonemic level". Brain. 105 (2): 271–300. doi:10.1093/brain/105.2.271. PMID 7082991.
45. ^ Matsumoto R, Imamura H, Inouchi M, Nakagawa T, Yokoyama Y, Matsuhashi M, Mikuni N, Miyamoto S, Fukuyama H, Takahashi R, Ikeda A (April 2011). "Left anterior temporal cortex actively engages in speech perception: A direct cortical stimulation study". Neuropsychologia. 49 (5): 1350–1354. doi:10.1016/j.neuropsychologia.2011.01.023. hdl:2433/141342. PMID 21251921. S2CID 1831334.
46. ^ a b Saygin AP, Leech R, Dick F (January 2010). "Nonverbal auditory agnosia with lesion to Wernicke's area". Neuropsychologia. 48 (1): 107–13. doi:10.1016/j.neuropsychologia.2009.08.015. PMC 2794980. PMID 19698727.
47. ^ Vignolo LA (November 2003). "Music agnosia and auditory agnosia. Dissociations in stroke patients". Annals of the New York Academy of Sciences. 999 (1): 50–7. Bibcode:2003NYASA.999...50V. doi:10.1196/annals.1284.005. PMID 14681117. S2CID 145136859.
48. ^ Yamamoto T, Kikuchi T, Nagae J, Ogata K, Ogawa M, Kawai M (January 2004). "[Dysprosody associated with environmental auditory sound agnosia in right temporal lobe hypoperfusion—a case report]". Rinsho Shinkeigaku = Clinical Neurology (in Japanese). 44 (1): 28–33. PMID 15199735.
49. ^ Tanaka Y, Nakano I, Obayashi T (February 2002). "Environmental sound recognition after unilateral subcortical lesions". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 38 (1): 69–76. doi:10.1016/s0010-9452(08)70639-7. PMID 11999335. S2CID 4478056.
50. ^ Johannes S, Jöbges ME, Dengler R, Münte TF (1998). "Cortical auditory disorders: a case of non-verbal disturbances assessed with event-related brain potentials". Behavioural Neurology. 11 (1): 55–73. doi:10.1155/1998/190715. PMID 11568403.
51. ^ Habib M, Daquin G, Milandre L, Royere ML, Rey M, Lanteri A, Salamon G, Khalil R (March 1995). "Mutism and auditory agnosia due to bilateral insular damage--role of the insula in human communication". Neuropsychologia. 33 (3): 327–39. doi:10.1016/0028-3932(94)00108-2. PMID 7791999. S2CID 12592266.
52. ^ Spreen O, Benton AL, Fincham RW (July 1965). "Auditory Agnosia Without Aphasia". Archives of Neurology. 13 (1): 84–92. doi:10.1001/archneur.1965.00470010088012. PMID 14314279.
53. ^ a b Fujii T, Fukatsu R, Watabe S, Ohnuma A, Teramura K, Kimura I, Saso S, Kogure K (June 1990). "Auditory sound agnosia without aphasia following a right temporal lobe lesion". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 26 (2): 263–8. doi:10.1016/s0010-9452(13)80355-3. PMID 2082956. S2CID 4478913.
54. ^ Mazzucchi A, Marchini C, Budai R, Parma M (July 1982). "A case of receptive amusia with prominent timbre perception defect". Journal of Neurology, Neurosurgery, and Psychiatry. 45 (7): 644–7. doi:10.1136/jnnp.45.7.644. PMC 491481. PMID 7119832.
55. ^ Eustache F, Lechevalier B, Viader F, Lambert J (January 1990). "Identification and discrimination disorders in auditory perception: a report on two cases". Neuropsychologia. 28 (3): 257–70. doi:10.1016/0028-3932(90)90019-k. PMID 2325838. S2CID 20121045.
56. ^ a b Motomura N, Yamadori A, Mori E, Tamaru F (June 1986). "Auditory agnosia. Analysis of a case with bilateral subcortical lesions". Brain. 109 ( Pt 3) (3): 379–91. doi:10.1093/brain/109.3.379. PMID 3719283.
57. ^ Lambert J, Eustache F, Lechevalier B, Rossa Y, Viader F (March 1989). "Auditory agnosia with relative sparing of speech perception". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 25 (1): 71–82. doi:10.1016/s0010-9452(89)80007-3. PMID 2707006. S2CID 4484014.
58. ^ Godefroy O, Leys D, Furby A, De Reuck J, Daems C, Rondepierre P, Debachy B, Deleume JF, Desaulty A (March 1995). "Psychoacoustical deficits related to bilateral subcortical hemorrhages. A case with apperceptive auditory agnosia". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 31 (1): 149–59. doi:10.1016/s0010-9452(13)80113-x. PMID 7781312. S2CID 4481214.
59. ^ Mendez MF (February 2001). "Generalized auditory agnosia with spared music recognition in a left-hander. Analysis of a case with a right temporal stroke". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 37 (1): 139–50. doi:10.1016/s0010-9452(08)70563-x. PMID 11292159. S2CID 14398211.
60. ^ Piccirilli M, Sciarma T, Luzzi S (October 2000). "Modularity of music: evidence from a case of pure amusia". Journal of Neurology, Neurosurgery, and Psychiatry. 69 (4): 541–5. doi:10.1136/jnnp.69.4.541. PMC 1737150. PMID 10990522.
61. ^ Liégeois-Chauvel C, Peretz I, Babaï M, Laguitton V, Chauvel P (October 1998). "Contribution of different cortical areas in the temporal lobes to music processing". Brain. 121 ( Pt 10) (10): 1853–67. doi:10.1093/brain/121.10.1853. PMID 9798742.
62. ^ Lachaux JP, Jerbi K, Bertrand O, Minotti L, Hoffmann D, Schoendorff B, Kahane P (October 2007). "A blueprint for real-time functional mapping via human intracranial recordings". PLOS ONE. 2 (10): e1094. Bibcode:2007PLoSO...2.1094L. doi:10.1371/journal.pone.0001094. PMC 2040217. PMID 17971857.
63. ^ Di Pietro M, Laganaro M, Leemann B, Schnider A (January 2004). "Receptive amusia: temporal auditory processing deficit in a professional musician following a left temporo-parietal lesion". Neuropsychologia. 42 (7): 868–77. doi:10.1016/j.neuropsychologia.2003.12.004. PMID 14998702. S2CID 18348937.
64. ^ Griffiths TD, Rees A, Witton C, Cross PM, Shakir RA, Green GG (May 1997). "Spatial and temporal auditory processing deficits following right hemisphere infarction. A psychophysical study". Brain. 120 ( Pt 5) (5): 785–94. doi:10.1093/brain/120.5.785. PMID 9183249.
65. ^ Mavlov L (August 1980). "Amusia due to rhythm agnosia in a musician with left hemisphere damage: a non-auditory supramodal defect". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 16 (2): 331–8. doi:10.1016/s0010-9452(80)80070-0. PMID 7471774. S2CID 4487375.
66. ^ Fries W, Swihart AA (January 1990). "Disturbance of rhythm sense following right hemisphere damage". Neuropsychologia. 28 (12): 1317–23. doi:10.1016/0028-3932(90)90047-r. PMID 2280838. S2CID 28075918.
67. ^ Murayama J, Kashiwagi T, Kashiwagi A, Mimura M (October 2004). "Impaired pitch production and preserved rhythm production in a right brain-damaged patient with amusia". Brain and Cognition. 56 (1): 36–42. doi:10.1016/j.bandc.2004.05.004. PMID 15380874. S2CID 33074495.
68. ^ Lechevalier B (February 2017). "La querelle de l'aphasie". Revue Neurologique. 173: S10–1. doi:10.1016/j.neurol.2016.12.011.
69. ^ Zhang Q, Kaga K, Hayashi A (July 2011). "Auditory agnosia due to long-term severe hydrocephalus caused by spina bifida - specific auditory pathway versus nonspecific auditory pathway". Acta Oto-Laryngologica. 131 (7): 787–92. doi:10.3109/00016489.2011.553631. PMID 21413843. S2CID 28225991.
70. ^ Griffiths TD, Warren JD, Dean JL, Howard D (February 2004). ""When the feeling's gone": a selective loss of musical emotion". Journal of Neurology, Neurosurgery, and Psychiatry. 75 (2): 344–5. doi:10.1136/jnnp.2003.015586 (inactive 2021-01-10). PMC 1738902. PMID 14742630.CS1 maint: DOI inactive as of January 2021 (link)
71. ^ Vignolo LA (2017-07-12). "Auditory Agnosia: A Review and Report of Recent Evidence". Brain & Behavior. Routledge. pp. 172–208. doi:10.4324/9781315082035-8. ISBN 978-1-315-08203-5.
72. ^ a b Bormann T, Weiller C (March 2012). ""Are there lexicons?" A study of lexical and semantic processing in word-meaning deafness suggests "yes"". Cortex. 48 (3): 294–307. doi:10.1016/j.cortex.2011.06.003. PMID 21752361. S2CID 24076165.
73. ^ a b Ellis AW (April 1984). "Introduction to Byrom Bramwell's (1897) case of word meaning deafness". Cognitive Neuropsychology. 1 (3): 245–258. doi:10.1080/02643298408252025.
74. ^ Franklin S, Howard D, Patterson K (February 1994). "Abstract word meaning deafness". Cognitive Neuropsychology. 11 (1): 1–34. doi:10.1080/02643299408251964.
75. ^ Franklin S, Turner J, Ralph MA, Morris J, Bailey PJ (December 1996). "A distinctive case of word meaning deafness?". Cognitive Neuropsychology. 13 (8): 1139–62. doi:10.1080/026432996381683.
76. ^ Hall DA, Riddoch MJ (December 1997). "Word meaning deafness: Spelling words that are not understood". Cognitive Neuropsychology. 14 (8): 1131–64. doi:10.1080/026432997381295.
77. ^ a b Kohn SE, Friedman RB (August 1986). "Word-meaning deafness: A phonological-semantic dissociation". Cognitive Neuropsychology. 3 (3): 291–308. doi:10.1080/02643298608253361.
78. ^ a b Symonds SC (1953-02-01). "APHASIA". Journal of Neurology, Neurosurgery & Psychiatry. 16 (1): 1–6. doi:10.1136/jnnp.16.1.1. PMC 503107. PMID 13023433.
79. ^ Best W, Howard D (May 1994). "Word sound deafness resolved?". Aphasiology. 8 (3): 223–56. doi:10.1080/02687039408248655.
80. ^ Slevc LR, Martin RC, Hamilton AC, Joanisse MF (January 2011). "Speech perception, rapid temporal processing, and the left hemisphere: a case study of unilateral pure word deafness". Neuropsychologia. 49 (2): 216–30. doi:10.1016/j.neuropsychologia.2010.11.009. PMC 3031136. PMID 21093464.
81. ^ Nakakoshi S, Kashino M, Mizobuchi A, Fukada Y, Katori H (February 2001). "Disorder in sequential speech perception: a case study on pure word deafness". Brain and Language. 76 (2): 119–29. doi:10.1006/brln.2000.2417. PMID 11254253. S2CID 28958236.
82. ^ Michel F, Andreewsky E (March 1983). "Deep dysphasia: an analog of deep dyslexia in the auditory modality". Brain and Language. 18 (2): 212–23. doi:10.1016/0093-934x(83)90016-0. PMID 6188511. S2CID 41300060.
83. ^ Duhamel JR, Poncet M (January 1986). "Deep dysphasia in a case of phonemic deafness: role of the right hemisphere in auditory language comprehension". Neuropsychologia. 24 (6): 769–79. doi:10.1016/0028-3932(86)90076-x. PMID 3808285. S2CID 25905211.
84. ^ Griffiths TD, Johnsrude I, Dean JL, Green GG (December 1999). "A common neural substrate for the analysis of pitch and duration pattern in segmented sound?". NeuroReport. 10 (18): 3825–30. doi:10.1097/00001756-199912160-00019. PMID 10716217.
85. ^ Poliva O (2017-09-20). "From where to what: a neuroanatomically based evolutionary model of the emergence of speech in humans". F1000Research. 4: 67. doi:10.12688/f1000research.6175.3. PMC 5600004. PMID 28928931.
## Further reading[edit]
* Polster MR, Rose SB (February 1998). "Disorders of auditory processing: evidence for modularity in audition" (PDF). Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 34 (1): 47–65. doi:10.1016/S0010-9452(08)70736-6. PMID 9533993. S2CID 2717085.
## External links[edit]
* Psychnet Definition
*[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-hydroxybutyric 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
|
Auditory agnosia
|
c0234501
| 25,738 |
wikipedia
|
https://en.wikipedia.org/wiki/Auditory_agnosia
| 2021-01-18T18:57:00 |
{"mesh": ["D000377"], "wikidata": ["Q1511436"]}
|
Tick-borne encephalitis is caused by an arbovirus of the Flaviviridae family (tick-borne encephalitis virus, TBEV), transmitted principally by the bite of the Ixodes ricinus tick. The symptomology is biphasic, with the initial phase being associated with a flu-like illness and the second phase (occurring in less than 10% of patients) with symptoms of meningitis or, more rarely, meningoencephalitis.
## Epidemiology
Endemic zones (natural foci) include most European countries. In these natural foci, less than 1% of ticks carry the TBEV.
## Management and treatment
Treatment is symptomatic. Vaccination of individuals at increased risk of infection (forests of Central Europe) and early administration of immunoglobulin may prevent development of the disease.
## Prognosis
Mortality is between 1 and 2%. Sequelae (such as headaches, paralysis, vertigo or sensorial problems) may persist for several months.
*[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-hydroxybutyric 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
|
Tick-borne encephalitis
|
c0014061
| 25,739 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=297
| 2021-01-23T17:54:43 |
{"gard": ["5216"], "mesh": ["D004675"], "umls": ["C0014061"], "icd-10": ["A84.0", "A84.1", "A84.8", "A84.9"], "synonyms": ["TBE"]}
|
A rare, congenital, mitral valve malformation characterized by hypoplastic annulus which usually appears within a complete mitral valve hypoplasia, causing mitral valve stenosis. Association with other cardiac malformation is common, including coarctation of the aorta, aortic valve stenosis, Shone complex and hypoplastic left heart syndrome.
*[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-hydroxybutyric 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
|
Hypoplasia of the mitral valve annulus
|
c3165203
| 25,740 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99058
| 2021-01-23T17:12:38 |
{"umls": ["C3165203"], "icd-10": ["Q23.2"]}
|
An extremely rare genetic congenital heart disease characterized by the presence of atrial septal defect, mostly of the ostium secundum type, associated with conduction anomalies like atrioventricular block, atrial fibrillation or right bundle branch block.
*[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-hydroxybutyric 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
|
Atrial septal defect-atrioventricular conduction defects syndrome
|
c3502353
| 25,741 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1479
| 2021-01-23T17:11:55 |
{"mesh": ["C566238"], "omim": ["108900"], "umls": ["C3502353"], "icd-10": ["Q21.1"]}
|
A rare hyperthyroidism characterized by mild to severe hyperthyroidism, presence of goiter, absence of features of autoimmunity, frequent relapses while on treatment and a positive family history.
*[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-hydroxybutyric 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
|
Familial hyperthyroidism due to mutations in TSH receptor
|
c1836706
| 25,742 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=424
| 2021-01-23T18:52:27 |
{"gard": ["2858"], "mesh": ["C563786"], "omim": ["609152"], "icd-10": ["E05.8"], "synonyms": ["Familial non-immune hyperthyroidism", "Resistance to thyroid stimulating hormone"]}
|
Trisomy 18 is a chromosome disorder characterized by having 3 copies of chromosome 18 instead of the usual 2 copies. Signs and symptoms include severe intellectual disability; low birth weight; a small, abnormally shaped head; a small jaw and mouth; clenched fists with overlapping fingers; congenital heart defects; and various abnormalities of other organs. Trisomy 18 is a life-threatening condition; many affected people die before birth or within the first month of life. Some children have survived to their teenage years, but with serious medical and developmental problems. Most cases are not inherited and occur sporadically (by chance).
*[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-hydroxybutyric 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
|
Trisomy 18
|
c0152096
| 25,743 |
gard
|
https://rarediseases.info.nih.gov/diseases/6321/trisomy-18
| 2021-01-18T17:57:17 |
{"mesh": ["D000073842"], "umls": ["C0152096"], "orphanet": ["3380"], "synonyms": ["Chromosome 18 trisomy", "18 trisomy", "Edwards syndrome", "Trisomy 16-18 (formerly)", "Trisomy E (formerly)"]}
|
This syndrome is characterised by the association of Pierre Robin sequence (retrognathia, cleft palate and glossoptosis) with facial dysmorphism (high forehead with frontal bossing) and digital anomalies (tapering fingers, hyperconvex nails, clinodactyly of the fifth fingers and short distal phalanges, finger-like thumbs and easily subluxated first metacarpophalangeal joints).Growth and mental development were normal.
## Epidemiology
It has been described in two half brothers born to the same mother.
## Genetic counseling
Transmission appears to be X-linked recessive.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Pierre Robin syndrome-faciodigital anomaly syndrome
|
c2931064
| 25,744 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2888
| 2021-01-23T18:01:13 |
{"gard": ["1274"], "mesh": ["C564078"], "omim": ["311895"], "umls": ["C2931064"], "icd-10": ["Q87.8"], "synonyms": ["Chitayat-Meunier-Hodgkinson syndrome", "Pierre Robin sequence-faciodigital anomaly syndrome"]}
|
A rare, genetic, otorhinolaryngological malformation characterized by congenital impatency of the nasolacrimal draingage system in various members of a family. Presentation is not specific and may include a uni- or bilateral medial canthal mass, dacryocystitis, nasal obstruction, periorbital cellulitis, and epiphora. Dacryocystocele and lacrimal puncta agenesis may be associated.
*[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-hydroxybutyric 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
|
Familial congenital nasolacrimal duct obstruction
|
c1835612
| 25,745 |
orphanet
|
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{"omim": ["149700"], "icd-10": ["Q10.5"]}
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Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery.[1] Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth.[2] Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being.[1] The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy.[1] The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%.[3] If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease.[1] Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards.This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.[4]
## Contents
* 1 The thyroid in pregnancy
* 2 Hypothyroidism
* 2.1 Clinical evaluation
* 2.2 Risks of hypothyroidism on fetal and maternal well-being
* 2.3 Management of hypothyroidism in pregnancy
* 3 Hyperthyroidism
* 3.1 Clinical evaluation
* 3.2 Risks of hyperthyroidism on fetal and maternal well-being
* 3.3 Management of hyperthyroidism in pregnancy
* 4 Postpartum thyroiditis
* 5 References
## The thyroid in pregnancy[edit]
Fetal thyroxine is wholly obtained from maternal sources in early pregnancy since the fetal thyroid gland only becomes functional in the second trimester of gestation. As thyroxine is essential for fetal neurodevelopment it is critical that maternal delivery of thyroxine to the fetus is ensured early in gestation.[5] In pregnancy, iodide losses through the urine and the feto-placental unit contribute to a state of relative iodine deficiency.[6] Thus, pregnant women require additional iodine intake. A daily iodine intake of 250 µg is recommended in pregnancy but this is not always achieved even in iodine sufficient parts of the world.[7]
Thyroid hormone concentrations in blood are increased in pregnancy, partly due to the high levels of estrogen and due to the weak thyroid stimulating effects of human chorionic gonadotropin (hCG) that acts like TSH. Thyroxine (T4) levels rise from about 6–12 weeks, and peak by mid-gestation; reverse changes are seen with TSH. Gestation specific reference ranges for thyroid function tests are not widely in use although many centres are now preparing them.[citation needed]
## Hypothyroidism[edit]
### Clinical evaluation[edit]
Hypothyroidism is common in pregnancy with an estimated prevalence of 2-3% and 0.3-0.5% for subclinical and overt hypothyroidism respectively.[8] Endemic iodine deficiency accounts for most hypothyroidism in pregnant women worldwide while chronic autoimmune thyroiditis is the most common cause of hypothyroidism in iodine sufficient parts of the world.[9][10] The presentation of hypothyroidism in pregnancy is not always classical and may sometimes be difficult to distinguish from the symptoms of normal pregnancy. A high index of suspicion is therefore required especially in women at risk of thyroid disease e.g. women with a personal or family history of thyroid disease, goitre, or co-existing primary autoimmune disorder like type 1 diabetes.[citation needed]
### Risks of hypothyroidism on fetal and maternal well-being[edit]
Hypothyroidism is diagnosed by noting a high TSH associated with a subnormal T4 concentration. Subclinical hypothyroidism (SCH) is present when the TSH is high but the T4 level is in the normal range but usually low normal. SCH is the commonest form of hypothyroidism in pregnancy and is usually due to progressive thyroid destruction due to autoimmune thyroid disease.[citation needed]
Several studies, mostly retrospective, have shown an association between overt hypothyroidism and adverse fetal and obstetric outcomes (e.g. Glinoer 1991).[11] Maternal complications such as miscarriages, anaemia in pregnancy, pre-eclampsia, abruptio placenta and postpartum haemorrhage can occur in pregnant women with overt hypothyroidism.[12][13] Also, the offspring of these mothers can have complications such as premature birth, low birth weight and increased neonatal respiratory distress.[14] Similar complications have been reported in mothers with subclinical hypothyroidism. A three-fold risk of placental abruption and a two-fold risk of pre-term delivery were reported in mothers with subclinical hypothyroidism.[15] Another study showed a higher prevalence of subclinical hypothyroidism in women with pre-term delivery (before 32 weeks) compared to matched controls delivering at term.[16] An association with adverse obstetrics outcome has also been demonstrated in pregnant women with thyroid autoimmunity independent of thyroid function. Treatment of hypothyroidism reduces the risks of these adverse obstetric and fetal outcomes; a retrospective study of 150 pregnancies showed that treatment of hypothyroidism led to reduced rates of abortion and premature delivery. Also, a prospective intervention trial study showed that treatment of euthyroid antibody positive pregnant women led to fewer rates of miscarriage than non treated controls.[17]
It has long been known that cretinism (i.e. gross reduction in IQ) occurs in areas of severe iodine deficiency due to the fact that the mother is unable to make T4 for transport to the fetus particularly in the first trimester. This neurointellectual impairment (on a more modest scale) has now been shown in an iodine sufficient area (USA) where a study showed that the IQ scores of 7- to 9-year-old children, born to mothers with undiagnosed and untreated hypothyroidism in pregnancy, were seven points lower than those of children of matched control women with normal thyroid function in pregnancy.[18] Another study showed that persistent hypothyroxinaemia at 12 weeks gestation was associated with an 8-10 point deficit in mental and motor function scores in infant offspring compared to children of mothers with normal thyroid function.[19] Even maternal thyroid peroxidase antibodies were shown to be associated with impaired intellectual development in the offspring of mothers with normal thyroid function.[20] It has been shown that it is only the maternal FT4 levels that are associated with child IQ and brain morphological outcomes, as opposed to maternal TSH levels.[5]
### Management of hypothyroidism in pregnancy[edit]
Medications to treat hypothyroidism have been found to be safe during pregnancy.[21] Levothyroxine is the treatment of choice for hypothyroidism in pregnancy. Thyroid function should be normalised prior to conception in women with pre-existing thyroid disease. Once pregnancy is confirmed the thyroxine dose should be increased by about 30-50% and subsequent titrations should be guided by thyroid function tests (FT4 and TSH) that should be monitored 4-6 weekly until euthyroidism is achieved. It is recommended that TSH levels are maintained below 2.5 mU/l in the first trimester of pregnancy and below 3 mU/l in later pregnancy.[22] The recommended maintenance dose of thyroxine in pregnancy is about 2.0-2.4 µg/kg daily. Thyroxine requirements may increase in late gestation and return to pre-pregnancy levels in the majority of women on delivery. Pregnant patients with subclinical hypothyroidism (normal FT4 and elevated TSH) should be treated as well, since supplementation with levothyroxine in such cases results in significantly higher delivery rate, with a pooled relative chance of 2.76.[23]
## Hyperthyroidism[edit]
### Clinical evaluation[edit]
Hyperthyroidism occurs in about 0.2-0.4% of all pregnancies. Most cases are due to Graves’ disease although less common causes (e.g. toxic nodules and thyroiditis) may be seen.[24] Clinical assessment alone may occasionally be inadequate in differentiating hyperthyroidism from the hyperdynamic state of pregnancy. Distinctive clinical features of Graves’ disease include the presence of ophthalmopathy, diffuse goitre and pretibial myxoedema. Also, hyperthyroidism must be distinguished from gestational transient thyrotoxicosis, a self-limiting hyperthyroid state due to the thyroid stimulatory effects of beta-hCG . This distinction is important since the latter condition is typically mild and will not usually require specific antithyroid treatment. Red cell zinc may also be useful in differentiating the two.[25] Hyperthyroidism due to Graves’ disease may worsen in the first trimester of pregnancy, remit in later pregnancy, and subsequently relapse in the postpartum.[citation needed]
### Risks of hyperthyroidism on fetal and maternal well-being[edit]
Uncontrolled hyperthyroidism in pregnancy is associated with an increased risk of severe pre-eclampsia and up to a four-fold increased risk of low birth weight deliveries. Some of these unfavourable outcomes are more marked in women who are diagnosed for the first time in pregnancy. A recent study has also shown that already high normal maternal FT4 levels are associated with a decrease in child IQ and gray matter and cortex volumes, similar to the effects of hypothyroidism.[5]
Uncontrolled and inadequately treated maternal hyperthyroidism may also result in fetal and neonatal hyperthyroidism[26] due to the transplacental transfer of stimulatory TSH receptor antibodies (TRAbs).[27] Clinical neonatal hyperthyroidism occurs in about 1% of infants born to mothers with Graves’ disease. Rarely neonatal hypothyroidism may also be observed in the infants of mothers with Graves’ hyperthyroidism. This may result from transplacental transfer of circulating maternal anti-thyroid drugs, pituitary-thyroid axis suppression from transfer of maternal thyroxine.[citation needed]
### Management of hyperthyroidism in pregnancy[edit]
Ideally a woman who is known to have hyperthyroidism should seek pre-pregnancy advice, although as yet there is no evidence for its benefit. Appropriate education should allay fears that are commonly present in these women. She should be referred for specialist care for frequent checking of her thyroid status, thyroid antibody evaluation and close monitoring of her medication needs. Medical therapy with anti-thyroid medications is the treatment of choice for hyperthyroidism in pregnancy.[28][29]Methimazole and propylthiouracil (PTU) are effective in preventing pregnancy complications by hyperthyroidism.[30] Surgery is considered for patients who suffer severe adverse reactions to anti-thyroid drugs and this is best performed in the second trimester of pregnancy. Radioactive iodine is absolutely contraindicated in pregnancy and the puerperium. If a woman is already receiving carbimazole, a change to propylthiouracil (PTU) is recommended but this should be changed back to carbimazole after the first trimester. This is because carbimazole can rarely be associated with skin and also mid line defects in the fetus but PTU long term also can cause liver side effects in the adult. Carbimazole and PTU are both secreted in breast milk but evidence suggests that antithyroid drugs are safe during lactation.[31] There are no adverse effects on IQ or psychomotor development in children whose mothers have received antithyroid drugs in pregnancy.Current guidelines suggest that a pregnant patient should be on PTU during the first trimester of pregnancy due to lower tetragenic effect and then be switched to methimazole during the second and third trimester due to lower liver dysfunction side effects.[citation needed]
## Postpartum thyroiditis[edit]
Main article: Postpartum thyroiditis
Postpartum thyroid dysfunction (PPTD) is a syndrome of thyroid dysfunction occurring within the first 12 months of delivery as a consequence of the postpartum immunological rebound that follows the immune tolerant state of pregnancy. PPTD is a destructive thyroiditis with similar pathogenetic features to Hashimoto's thyroiditis.[32]
The disease is very common with a prevalence of 5-9% of unselected postpartum women. Typically there is a transient hyperthyroid phase that is followed by a phase of hypothyroidism. Permanent hypothyroidism occurs in as much as 30% of cases after 3 years, and in 50% at 7–10 years. The hyperthyroid phase will not usually require treatment but, rarely, propanolol may be used for symptom control in severe cases. The hypothyroid phase should be treated with thyroxine if patients are symptomatic, planning to get pregnant, or if TSH levels are above 10 mU/L. Long-term follow up is necessary due to the risk of permanent hypothyroidism.[citation needed]
Nearly all the women with PPTD have positive TPO antibodies. This marker can be a useful screening test in early pregnancy as 50% of women with antibodies will develop thyroid dysfunction postpartum. In addition some but not all studies have shown an association between PPTD and depression so that thyroid function should be checked postpartum in women with mood changes.[citation needed]
## References[edit]
1. ^ a b c d Korevaar, Tim I. M.; Medici, Marco; Visser, Theo J.; Peeters, Robin P. (2017-08-04). "Thyroid disease in pregnancy: new insights in diagnosis and clinical management". Nature Reviews. Endocrinology. 13 (10): 610–622. doi:10.1038/nrendo.2017.93. ISSN 1759-5037. PMID 28776582. S2CID 24810888.
2. ^ Okosieme, OE; Marx, H; Lazarus, JH (Sep 2008). "Medical management of thyroid dysfunction in pregnancy and the postpartum". Expert Opinion on Pharmacotherapy. 9 (13): 2281–93. doi:10.1517/14656566.9.13.2281. PMID 18710353. S2CID 71280624.
3. ^ Korevaar, Tim I. M.; de Rijke, Yolanda B.; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W. V.; Steegers, Eric A. P.; Visser, Theo J.; Peeters, Robin P. (March 2017). "Stimulation of Thyroid Function by Human Chorionic Gonadotropin During Pregnancy: A Risk Factor for Thyroid Disease and a Mechanism for Known Risk Factors". Thyroid. 27 (3): 440–450. doi:10.1089/thy.2016.0527. ISSN 1557-9077. PMID 28049387.
4. ^ Spencer, Laura; Bubner, Tanya; Bain, Emily; Middleton, Philippa (2015-09-21). "Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health". The Cochrane Database of Systematic Reviews (9): CD011263. doi:10.1002/14651858.cd011263.pub2. PMID 26387772.
5. ^ a b c Korevaar, Tim I M; Muetzel, Ryan; Medici, Marco; Chaker, Layal; Jaddoe, Vincent W V; de Rijke, Yolanda B; Steegers, Eric A P; Visser, Theo J; White, Tonya; Tiemeier, Henning; Peeters, Robin P (September 2015). "Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study". The Lancet Diabetes & Endocrinology. 4 (1): 35–43. doi:10.1016/s2213-8587(15)00327-7. PMID 26497402.
6. ^ Smyth, PP; Hetherton, AM; Smith, DF; Radcliff, M; O'Herlihy, C (Sep 1997). "Maternal iodine status and thyroid volume during pregnancy: correlation with neonatal iodine intake". The Journal of Clinical Endocrinology and Metabolism. 82 (9): 2840–3. doi:10.1210/jcem.82.9.4203. PMID 9284707.
7. ^ WHO S, Andersson M, de Benoist B, Delange F, Zupan J (Dec 2007). "Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation". Public Health Nutrition. 10 (12A): 1606–11. doi:10.1017/S1368980007361004. PMID 18053287.
8. ^ Klein, RZ; Haddow, JE; Faix, JD; Brown, RS; Hermos, RJ; Pulkkinen, A; Mitchell, ML (Jul 1991). "Prevalence of thyroid deficiency in pregnant women". Clinical Endocrinology. 35 (1): 41–6. doi:10.1111/j.1365-2265.1991.tb03494.x. PMID 1889138.
9. ^ Mandel SJ. "Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal aspects." Best Pract Res Clin Endocrinol Metab. 2004; 18: 213-24.
10. ^ Mandel, SJ (Jun 2004). "Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal aspects". Best Practice & Research. Clinical Endocrinology & Metabolism. 18 (2): 213–24. doi:10.1016/j.beem.2004.03.006. PMID 15157837.
11. ^ Glinoer, D; Soto, MF; Bourdoux, P; Lejeune, B; Delange, F; Lemone, M; Kinthaert, J; Robijn, C; Grun, JP; de Nayer, P (Aug 1991). "Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions". The Journal of Clinical Endocrinology and Metabolism. 73 (2): 421–7. doi:10.1210/jcem-73-2-421. PMID 1906897.
12. ^ "Thyroid Disease & Pregnancy". Office on Women’s Health, U.S. Department of Health and Human Services. 1 February 2017. Archived from the original on 12 July 2017. Retrieved 9 December 2017. This article incorporates text from this source, which is in the public domain.
13. ^ "Postpartum Thyroiditis" (PDF). American Thyroid Association. 2014. Retrieved 9 December 2017.
14. ^ Davis, LE; Leveno, KJ; Cunningham, FG (Jul 1988). "Hypothyroidism complicating pregnancy". Obstetrics and Gynecology. 72 (1): 108–12. PMID 3380497.
15. ^ Casey, BM; Dashe, JS; Wells, CE; McIntire, DD; Byrd, W; Leveno, KJ; Cunningham, FG (Feb 2005). "Subclinical hypothyroidism and pregnancy outcomes". Obstetrics and Gynecology. 105 (2): 239–45. doi:10.1097/01.AOG.0000152345.99421.22. PMID 15684146. S2CID 11231790.
16. ^ Stagnaro-Green, A; Chen, X; Bogden, JD; Davies, TF; Scholl, TO (Apr 2005). "The thyroid and pregnancy: a novel risk factor for very preterm delivery". Thyroid. 15 (4): 351–7. doi:10.1089/thy.2005.15.351. PMID 15876159.
17. ^ Negro, R; Formoso, G; Mangieri, T; Pezzarossa, A; Dazzi, D; Hassan, H (Jul 2006). "Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications". The Journal of Clinical Endocrinology and Metabolism. 91 (7): 2587–91. doi:10.1210/jc.2005-1603. PMID 16621910.
18. ^ Haddow, JE; Palomaki, GE; Allan, WC; Williams, JR; Knight, GJ; Gagnon, J; O'Heir, CE; Mitchell, ML; Hermos, RJ; Waisbren, SE; Faix, JD; Klein, RZ (Aug 19, 1999). "Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child". The New England Journal of Medicine. 341 (8): 549–55. doi:10.1056/NEJM199908193410801. PMID 10451459. S2CID 4654832.
19. ^ Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ (Sep 2003). "Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study". Clinical Endocrinology. 59 (3): 282–8. doi:10.1046/j.1365-2265.2003.01822.x. PMID 12919150. S2CID 12993173.
20. ^ Pop VJ, de Vries E, van Baar AL, Waelkens JJ, de Rooy HA, Horsten M, Donkers MM, Komproe IH, van Son MM, Vader HL (Dec 1995). "Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development?". The Journal of Clinical Endocrinology and Metabolism. 80 (12): 3561–6. doi:10.1210/jcem.80.12.8530599. PMID 8530599.
21. ^ "Hypothyroidism". National Institute of Diabetes and Digestive and Kidney Diseases. March 2013. Archived from the original on 5 March 2016. Retrieved 9 December 2017.
22. ^ Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, Mandel SJ, Stagnaro-Green A (Aug 2007). "Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 92 (8 Suppl): S1–47. doi:10.1210/jc.2007-0141. PMID 17948378.
23. ^ Velkeniers B, Van Meerhaeghe A, Poppe K, Unuane D, Tournaye H, Haentjens P (May–Jun 2013). "Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: systematic review and meta-analysis of RCTs". Human Reproduction Update. 19 (3): 251–8. doi:10.1093/humupd/dms052. PMID 23327883.
24. ^ Marx, H; Amin, P; Lazarus, JH (Mar 22, 2008). "Hyperthyroidism and pregnancy". BMJ (Clinical Research Ed.). 336 (7645): 663–7. doi:10.1136/bmj.39462.709005.AE. PMC 2270981. PMID 18356235.
25. ^ Swaminathan, R. (2000-07-01). "Thyroid Function during Pregnancy". Clinical Chemistry. 46 (7): 1016–1017. doi:10.1093/clinchem/46.7.1016. ISSN 0009-9147. PMID 10894853.
26. ^ Zimmerman D (1999). "Fetal and neonatal hyperthyroidism". Thyroid. 9 (7): 727–33. doi:10.1089/thy.1999.9.727. PMID 10447021.
27. ^ Polak M, Le Gac I, Vuillard E, et al. (2004). "Fetal and neonatal thyroid function in relation to maternal Graves' disease". Best Pract Res Clin Endocrinol Metab. 18 (2): 289–302. doi:10.1016/s1521-690x(04)00019-3. PMID 15157841.
28. ^ Mestman JH (2004). "Hyperthyroidism in pregnancy". Best Pract Res Clin Endocrinol Metab. 18 (2): 267–88. doi:10.1016/j.beem.2004.03.005. PMID 15157840.
29. ^ Fumarola, A; Di Fiore, A; Dainelli, M; Grani, G; Carbotta, G; Calvanese, A (June 2011). "Therapy of hyperthyroidism in pregnancy and breastfeeding". Obstetrical & Gynecological Survey. 66 (6): 378–85. doi:10.1097/ogx.0b013e31822c6388. PMID 21851752. S2CID 28728514.
30. ^ Vissenberg, R.; Van Den Boogaard, E.; Van Wely, M.; Van Der Post, J. A.; Fliers, E.; Bisschop, P. H.; Goddijn, M. (2012). "Treatment of thyroid disorders before conception and in early pregnancy: A systematic review". Human Reproduction Update. 18 (4): 360–73. doi:10.1093/humupd/dms007. PMID 22431565.
31. ^ Mandel, SJ; Cooper, DS (Jun 2001). "The use of antithyroid drugs in pregnancy and lactation". The Journal of Clinical Endocrinology and Metabolism. 86 (6): 2354–9. doi:10.1210/jcem.86.6.7573. PMID 11397822.
32. ^ Muller, AF; Drexhage, HA; Berghout, A (Oct 2001). "Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care". Endocrine Reviews. 22 (5): 605–30. doi:10.1210/er.22.5.605. PMID 11588143.
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*[NI]: Northern Ireland
*[%DV]: Percentage of Daily Value
*[NSW DCR]: New South Wales District Court Reports
|
Thyroid disease in pregnancy
|
c0558372
| 25,746 |
wikipedia
|
https://en.wikipedia.org/wiki/Thyroid_disease_in_pregnancy
| 2021-01-18T18:42:37 |
{"wikidata": ["Q7799747"]}
|
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 19q13.11. One patient carried a deletion (chr19:31,765,881-31,812,396, GRCh37) which spanned only the TSHZ3 gene (614119).
See also distal chromosome 19q13.11 deletion syndrome (613026), which shows some phenotypic overlap.
Description
Proximal chromosome 19q13.11 deletion syndrome is an autosomal dominant neurodevelopmental disorder characterized by delayed development, intellectual disability with poor speech, feeding difficulties, and autistic features. Some patients may have additional features, including renal tract anomalies (summary by Caubit et al., 2016).
Clinical Features
Chowdhury et al. (2014) reported 3 unrelated patients (patients 3, 4, and 5) with a neurodevelopmental disorder associated with de novo heterozygous deletions involving chromosome 19q12-q31.1. The patients had feeding difficulties, postnatal growth retardation, delayed development, and other distinct features: congenital hydroureter, clubfoot, and hip dysplasia in patient 3, anemia in patient 4, hypotonia in patients 4 and 5, and pyloric stenosis and autism in patient 5. Two patients had dysmorphic facial features.
Caubit et al. (2016) reported 7 patients from 6 unrelated families with a neurodevelopmental disorder associated with heterozygous deletion of 19q12-q13.11. Six of the patients had autism or autism-like behaviors. Three patients had renal abnormalities, including pyelocalyceal dilatation, nephrolithiasis, and vesicoureteral reflux. Other common features included feeding difficulties, growth retardation, speech delay, and cognitive impairment. The phenotype could be distinguished from that observed in distal chromosome 19q13.11 deletion syndrome.
Cytogenetics
Chowdhury et al. (2014) reported 3 unrelated patients with de novo heterozygous deletions involving chromosome 19q12-q31.1 that were proximal to the smallest region of overlap described for chromosome 19q13.11 deletion syndrome. The deletions, which were found by array CGH testing, were 6.25, 3.91, and 4.61 Mb, respectively.
Caubit et al. (2016) reported 7 patients from 6 unrelated families with a neurodevelopmental disorder associated with heterozygous deletion of 19q12-q13.11. The mutations in 6 patients ranged from 0.46 to 4.02 Mb. The deletions occurred de novo in 3 patients and were inherited from an unaffected parent in 3 cases, suggesting incomplete penetrance in some patients. The seventh patient had a 50-kb intragenic microdeletion that deleted the second exon and part of the intron of the TSHZ3 gene. This deletion was not detected in the unaffected mother, but DNA from the father was unavailable. The smallest region of overlap of all deletions included only the TSHZ3 gene, suggesting to the authors that this gene is responsible for the phenotype.
Animal Model
Caubit et al. (2008) found that Tshz3-null mutant mice developed congenital hydronephrosis without anatomic obstruction. Tshz3 was demonstrated to be required for differentiation of smooth muscle cells in the proximal ureter. The authors concluded that this mouse model of functional urinary obstruction resembles congenital pelviureteric junction obstruction in humans.
Caubit et al. (2016) noted that homozygous Tshz3-null mice die at birth from respiratory failure due to poor survival of neurons in the hindbrain that control breathing, and that heterozygous Tshz3 +/- mutant mice have decreased neonatal viability, even up to 100% lethality, depending on the genetic background. In the mouse cortex, Caubit et al. (2016) found that homozygous and heterozygous deletion of the Tshz3 gene altered the expression of genes involved in pathways related to neurotransmitter/neuropeptide signaling and neuronal and axon development, projection, and differentiation. The changes in gene expression showed spatial caudal-rostral variation and layer specificity. For example, there was increased expression of Fezf2 (607414) and decreased expression of Ngfr (162010). These findings suggested that the TSHZ3 gene is a nexus in a brain developmental gene network. The brains of these mice did not show defects in cortical layering, neuronal density, or axonal pathfinding compared to controls. However, detailed study of heterozygous Tshz3 mutant mice showed alterations in synaptic transmission with increased probability of action potential-dependent glutamate release from cortical projection neurons compared to wildtype. Corticostriatal long-term potentiation was also enhanced in heterozygous mice, indicating altered plasticity. Heterozygous mice showed behavioral abnormalities consistent with autistic behaviors, including impaired social interaction, increased repetitive behaviors, and increased anxiety.
INHERITANCE \- Autosomal dominant GROWTH Other \- Postnatal growth retardation HEAD & NECK Face \- Dysmorphic features, nonspecific (in some patients) ABDOMEN Gastrointestinal \- Feeding difficulties \- Pyloric stenosis GENITOURINARY Kidneys \- Renal tract abnormalities, variable \- Pyelocalyceal dilatation \- Nephrolithiasis Ureters \- Hydroureter Bladder \- Vesicoureteral reflux SKELETAL Pelvis \- Hip dysplasia Hands \- Tapered fingers \- Fifth finger clinodactyly Feet \- Clubfoot MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed development \- Intellectual disability \- Poor or absent speech \- Seizures (rare) Behavioral Psychiatric Manifestations \- Autistic features LABORATORY ABNORMALITIES \- Minimal overlapping critical region for deletion 19:31,765,881-31,812,396 (Hg19)found in 1 patient MISCELLANEOUS \- Contiguous gene deletion syndrome \- Most deletions occur de novo \- Incomplete penetrance (some deletions inherited from unaffected parent) \- Variable features MOLECULAR BASIS \- Contiguous gene syndrome caused by 50-kb deletion of proximal 19q13.11 ▲ 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-hydroxybutyric 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
|
CHROMOSOME 19q13.11 DELETION SYNDROME, PROXIMAL
|
c4311046
| 25,747 |
omim
|
https://www.omim.org/entry/617219
| 2019-09-22T15:46:26 |
{"omim": ["617219"]}
|
Type of aphasia involving noun selection difficulty
Jargon aphasia is a type of fluent aphasia in which an individual's speech is incomprehensible, but appears to make sense to the individual. Persons experiencing this condition will either replace a desired word with another that sounds or looks like the original one, or has some other connection to it, or they will replace it with random sounds. Accordingly, persons with jargon aphasia often use neologisms, and may perseverate if they try to replace the words they can not find with sounds.
## Contents
* 1 Causes
* 2 Diagnosis
* 3 Treatments
* 4 History
* 5 Other meanings and types
* 6 Contradictions and different viewpoints
* 7 References
* 8 Further reading
## Causes[edit]
People affected by jargon aphasia usually are elderly and/or people who have damage to the neural pathways of certain parts of the brain. This is usually the result of the following conditions:[1]
* Stroke
* Traumatic brain injury
* Epilepsy
* Migraine
* Brain tumor
* Alzheimer's disease
* Parkinson's disease
Since jargon is associated with fluent (Wernicke's) aphasia, it is usually caused by damage to the temporal lobe, and more specifically, Wernicke's area. After the condition is diagnosed, a CT or MRI scan is typically used to determine the location and severity of the brain damage that has caused the aphasia.[1]
There have been cases in which aphasia has developed after damage to only the right hemisphere of the brain. These cases are few and far between, and usually involve unique circumstances for the individual. Most commonly, these results can stem from brain organization that is different than the general population, or a heavier than normal reliance on the right hemisphere of the brain.[2]
## Diagnosis[edit]
Someone with jargon aphasia may exhibit the following behaviors:[3]
* intermixing real words and nonsensical words while speaking or writing
* failing to recognize mistakes being made while speaking or writing
* using real words in incorrect situations
* frequent, repetitive uttering of low frequency words
* the inability to say or write a specific word or phrase
Some of the specific types of language errors that occur are:[4]
lexical (real word)
semantic
Real word that was semantically related to target. ("dog" instead of "cat")
formal
Real word that shared either the initial phoneme or at least 50% of phonemes with target. ("dog" instead of "desk" or "dog" instead of "frog")
mixed
Real word that was both semantically and phonologically related to target. ("bicycle" instead of "motorcycle")
visual
Real word of an item similar in visual form to the target. ("ball" instead of "orange")
unrelated
Real word that was not related to the target in any obvious way. ("dog" instead of "apple")
non-lexical (nonword)
phonological
Nonword that shared either the initial phoneme or at least 50% of phonemes with target. ("deg" instead of "dog")
neologistic
Nonword not reaching the criterion for phonological relatedness (i.e., sharing less than 50% of phonemes with the target and with a different initial phoneme). Nonwords that are pseudo-compound words. ("kib" instead of "dog")
other errors
Don't know
Indication that response was unknown or item was not responded to at all. ("I don’t know" or silence)
description
Attempts to describe as opposed to name item. (Multiple word responses)
Jargon aphasia must be diagnosed through a series of tests. Since the number of individuals that have aphasia after suffering a stroke is high, a test is usually carried out soon after the stroke occurs. There is a list of basic exercises to help assess a person's language skills, such as:
* naming objects that begin with a certain letter
* reading or writing
* holding a conversation
* understanding directions and commands
There is also a common test used, called the Boston Diagnostic Aphasia Examination test, which incorporates exercises that extensively review the person's language skills.[1]
## Treatments[edit]
The only way to treat aphasia is with a speech-language pathologist (SLP). It will not completely restore the person's prior level of communication, but SLP can lead to a massive improvement of jargon aphasia. Recipients of this treatment typically achieve better use of residual language abilities, improved language skills, and the ability to communicate in a different way by making up for missing words in their speech.[1]
One specific method that has shown to lead to improvements with certain symptoms is phonological component analysis, or PCA for short. Participants in PCA therapy tend to improve in the ability to name specific items that they are test on, as well as the decrease in use of nonwords to describe said items. Seeing promising results from this type of therapy has led to much optimism in hopes of developing more treatment methods for jargon aphasia.[5]
## History[edit]
Hughlings Jackson is believed to have been the person who initially contributed the term "jargon" to aphasiology. He used this term not to distinguish a separate type of aphasia, but to describe the language output of certain people that was meaningless and incomprehensible to the listener, although it appeared to have some meaning for the speaker.[3]
## Other meanings and types[edit]
There are many different meanings when people refer to jargon aphasia. Since Hughling Jackson's time, it has covered a broad range of similar verbal behaviors and has been used to describe a multitude of different aphiastic disturbances. Some of the behaviors are described as the person having speaking in a "confused, unintelligible language", "a strange, outlandish, or barbarous dialect", "a hybrid language", and can be referred to as a pretentious language marked by circumlocutions and long words. Observation of these behaviors has led to a branching of different types of jargon.
* Neologistic jargon is the production of language containing non-existent words that are not related to what the person is attempting to convey.
* Phonemic jargon is the production of language containing inappropriate words that are phonemically related to what the person is attempting to convey.
* Semantic jargon is the production of language which is devoid of content and consists of real words that are inappropriate given the context of the situation.
All of these types of jargon are seen in fluent aphasia, which can more commonly be addressed as Wernicke's aphasia.[4][6]
## Contradictions and different viewpoints[edit]
Weinstein
Weinstein's viewpoint of jargon illustrates just the basic rambling and incoherent but structurally intact speech. It does not include details about neologisms and paraphasias. He and his coworkers view jargon as a positive symptom of aphasia, and as an adaptive behavior and form of denial, or anosognosia, in the presence of language deficit.
Schuell
Shuell views jargon as the result of severe impairment in the recall of learned auditory patterns and imperfect auditory feedback processes. The lack of control of verbal output is related to reduced auditory input.
Cohn and Neumann
Their viewpoint is that jargon results from the disruption of the sequential ordering of speech.
Alajouanine
Alajouanine came up with the most unusual viewpoint of all. He pointed out that the reason for jargon cannot be found in the breakdown of the intrinsic speech structure itself. He stressed that incomprehensibility and lack of meaning, rather than articulatory abnormality or lack of proper grammatical sequencing were the essence of jargon. He often spoke of a "suppression of the semantic values of language" in jargon.[6]
## References[edit]
1. ^ a b c d Paddock, M. (2014). "What is aphasia? What causes aphasia?". Medical News Today. Retrieved 2015-05-01.
2. ^ Coppens, Patrick; Hungerford, Suzanne; Yamaguchi, Satoshi; Yamadori, Atsushi (December 2002). "Crossed aphasia: an analysis of the symptoms, their frequency, and a comparison with left-hemisphere aphasia symptomatology". Brain & Language. 83 (3): 425–463. doi:10.1016/s0093-934x(02)00510-2. PMID 12468397.
3. ^ a b Marshall, Jane (2006-05-01). "Jargon aphasia: What have we learned?". Aphasiology. 20 (5): 387–410. doi:10.1080/02687030500489946.
4. ^ a b Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D. (2009-02-15). "Neologistic jargon aphasia and agraphia in primary progressive aphasia". Journal of the Neurological Sciences. 277 (1–2): 155–159. doi:10.1016/j.jns.2008.10.014. PMC 2633035. PMID 19033077.
5. ^ Bose, Arpita (2013-09-21). "Phonological therapy in jargon aphasia: effects on naming and neologisms". International Journal of Language and Communication Disorders. 48 (5).
6. ^ a b Rau, Marie T. Jargon Aphasia: A confusing state of affairs (PDF).
## Further reading[edit]
* Deramecourt V, Lebert F, Debachy B, et al. (2010-01-05). "Prediction of pathology in primary progressive language and speech disorders". Neurology. 74 (1): 42–49. doi:10.1212/WNL.0b013e3181c7198e. PMID 19940270.
* Sampson, Monica; Faroqi-Shah, Yasmeen (2011). "Investigation of self-monitoring in fluent aphasia with jargon". Aphasiology. 25 (4): 505–528. doi:10.1080/02687038.2010.523471. ISSN 0268-7038.
case histories
* Butterworth, Brian (1979). "Hesitation and the production of verbal paraphasias and neologisms in jargon aphasia". Brain & Language. 8 (2): 133–161. doi:10.1016/0093-934X(79)90046-4. ISSN 0093-934X. PMID 487066.
* Ostberg P, Bogdanovic N, Fernaeus SE, Wahlund LO (November 2001). "Jargonagraphia in a case of frontotemporal dementia". Brain and Language. 79 (2): 333–339. doi:10.1006/brln.2001.2491. PMID 11712852.
* Zeman A, Carson A, Rivers C, Nath U (September 2006). "A case of evolving post-ictal language disturbance secondary to a left temporal arteriovenous malformation: jargon aphasia or formal thought disorder?". Cognitive Neuropsychiatry. 11 (5): 465–479. doi:10.1080/13546800544000019. PMID 17354082.
*[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-hydroxybutyric 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
|
Jargon aphasia
|
c0234473
| 25,748 |
wikipedia
|
https://en.wikipedia.org/wiki/Jargon_aphasia
| 2021-01-18T18:29:37 |
{"mesh": ["D001041"], "wikidata": ["Q6160183"]}
|
## Clinical Features
Beals (1969) observed multiple cases of vertebral hypoplasia leading to kyphosis in the upper lumbar area in multiple generations of a family, with male-to-male transmission. The familial cases reported by van Assen (1930) and by Bauer (1933) may have been the same condition.
Inheritance
The transmission pattern of vertebral hypoplasia with lumbar kyphosis in the family reported by Beals (1969) was consistent with autosomal dominant inheritance.
Spine \- Lumbar kyphosis Radiology \- Lumbar vertebral hypoplasia Inheritance \- Autosomal dominant ▲ 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-hydroxybutyric 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
|
VERTEBRAL HYPOPLASIA WITH LUMBAR KYPHOSIS
|
c1860463
| 25,749 |
omim
|
https://www.omim.org/entry/192900
| 2019-09-22T16:32:00 |
{"mesh": ["C566002"], "omim": ["192900"]}
|
Male accessory gland infection
Other namesMale accessory gland inflammation[1]
Prostate with seminal vesicles and seminal ducts, viewed from in front and above
SpecialtyUrology
Male accessory gland infection (MAGI) is a condition with signs of inflammation involving one or more sites in the male genital tract. Diagnosis is made according to parameters defined by the World Health Organization, and it is particularly made in relation to infectious or inflammatory causes of male infertility.
Although it is usually caused by infection spreading from the urethra, non-infectious causes also exist.
## Contents
* 1 Definition
* 2 Diagnosis
* 2.1 WHO criteria
* 2.2 Biomarkers
* 3 Causes
* 4 Complications
* 5 References
* 6 External links
## Definition[edit]
MAGI includes infections (bacterial, viral, fungal etc.) involving one or more of the following male genital organs or tracts:[2]
* seminal vesicles (seminal vesiculitis)
* prostate gland (prostatitis)
* vas deferens
* epididymis (epididymitis)
* testicles (orchitis)
* urethra (urethritis)
* Cowper's glands
## Diagnosis[edit]
As infection has a negative impact on the secretory function of the accessory glands, findings that could indicate the presence of MAGI include:[3]
* signs of inflammation in a semen analysis (leukocytes ≥ 1x106/mL and/or elastase ≥ 230 ng/mL)
* low semen volume
* elevated semen pH
* low levels of alpha-glucosidase, fructose and zinc
### WHO criteria[edit]
MAGI can be diagnosed when there are two or more factors present that meet criteria defined by the World Health Organization (WHO):[1][4]
Factors Description For positive diagnosis
A History of:
* urinary tract infection
* epididymitis
* sexually transmitted infection
Physical signs:
* thickened or tender epididymis
* tender vas deferens
* abnormal digital rectal examination (DRE)
(i) Any one Factor A feature
plus
(ii) one feature from either Factor B or Factor C
B Prostatic fluid:
* abnormal expressed prostatic secretion (EPS)
* abnormal voided urine after prostate massage (VB3)
(i) Either one of the Factor B features
plus
(ii) one feature from either Factor A or Factor C
C Semen:
* leukocytes ≥ 1x106/mL
* semen culture with significant growth of pathogenic bacteria
* abnormal semen appearance
* increased semen viscosity (hyperviscosity)
* increased pH
* abnormal biochemistry of the seminal plasma
Any two Factor C features
or
(i) any one Factor C feature
plus
(ii) one feature from either Factor A or Factor B
### Biomarkers[edit]
One study has proposed that elevated levels of soluble urokinase-type plasminogen activator receptor (SuPAR) in seminal plasma might be useful as a marker for MAGI.[5]
## Causes[edit]
The main infectious agents are Enterobacteriaceae (such as Escherichia coli and Klebsiella), Neisseria gonorrhoeae, and Chlamydia trachomatis.[2]
One study has shown that men with MAGI who have lower serum levels of total testosterone tend to have a more complicated form of MAGI, such as involving more than one site, than those with normal levels.[6]
## Complications[edit]
Potential complications include:[2][3][7]
* obstruction of the epididymis
* impairment of spermatogenesis
* impairmentment of sperm function
* induction of sperm auto-antibodies
* dysfunctions of the male accessory glands
These complications can result in sexual dysfunction[7] and male subfertility.[4][8]
## References[edit]
1. ^ a b Rosita A Condorelli; Enzo Vicari; Aldo E Calogero; Sandro La Vignera (25 April 2014). "Male accessory gland inflammation prevalence in type 2 diabetic patients with symptoms possibly reflecting autonomic neuropathy". Asian Journal of Andrology. 16 (5): 761–766. doi:10.4103/1008-682X.125911. PMC 4215658. PMID 24799635.
2. ^ a b c Walter K.H. Krause (April 2008). "Male accessory gland infection". Andrologia. 40 (2): 113–116. doi:10.1111/j.1439-0272.2007.00822.x. PMID 18336461.
3. ^ a b Marcelo Marconi; Adrian Pilatz; Florian Wagenlehner; Thorsten Diemer; Wolfgang Weidner (May–June 2009). "Impact of infection on the secretory capacity of the male accessory glands". International Brazilian Journal of Urology. 35 (3): 299–308. doi:10.1016/S0022-5347(09)60344-X. PMID 19538765.
4. ^ a b Sandro La Vignera; Enzo Vicari; Rosita A Condorelli; R D'Agata; Aldo E Calogero (November 2011). "Hypertrophic-congestive and fibro-sclerotic ultrasound variants of male accessory gland infection have different sperm output". Journal of Endocrinological Investigation. 34 (10): e330–e335. doi:10.1007/bf03346729. PMID 22234181.
5. ^ C. Autilio; R. Morelli; D. Milardi; G. Grande; R. Marana; A. Pontecorvi; C. Zuppi; S. Baroni (September 2015). "Soluble urokinase-type plasminogen activator receptor as a putative marker of male accessory gland inflammation". Andrology. 3 (6): 1054–61. doi:10.1111/andr.12084. PMID 26384478.
6. ^ R. A. Condorelli; A. E. Calogero; E. Vicari; V. Favilla; S. Cimino; G. I. Russo; G. Morgia; S. La Vignera (8 September 2014). "Male Accessory Gland Infection: Relevance of Serum Total Testosterone Levels". International Journal of Endocrinology. 2014 (915752): 915752. doi:10.1155/2014/915752. PMC 4172872. PMID 25276133.
7. ^ a b Sandro La Vignera; Rosita A Condorelli; Enzo Vicari; R D'Agata; Aldo E Calogero (May 2012). "High frequency of sexual dysfunction in patients with male accessory gland infections". Andrologia. 44 (Supplement s1): 438–446. doi:10.1111/j.1439-0272.2011.01202.x. PMID 21793867.
8. ^ Sandro La Vignera; Rosita A Condorelli; R D'Agata; Enzo Vicari; Aldo E Calogero (February 2012). "Semen alterations and flow-citometry evaluation in patients with male accessory gland infections". Journal of Endocrinological Investigation. 35 (2): 219–223. doi:10.3275/7924. PMID 21946047.
## External links[edit]
Classification
D
* ICD-10: N49.8
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Male accessory gland infection
|
c0403693
| 25,750 |
wikipedia
|
https://en.wikipedia.org/wiki/Male_accessory_gland_infection
| 2021-01-18T18:41:46 |
{"umls": ["C0403693"], "wikidata": ["Q25091279"]}
|
COG4-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the single reported case to date by seizures, some dysmorphic features, axial hyponia, slight peripheral hypertonia and hyperreflexia.
*[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-hydroxybutyric 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
|
COG4-CDG
|
c3150736
| 25,751 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=263501
| 2021-01-23T18:53:01 |
{"gard": ["12412"], "omim": ["613489"], "icd-10": ["E77.8"], "synonyms": ["CDG syndrome type IIj", "CDG-IIj", "CDG2J", "Carbohydrate deficient glycoprotein syndrome type IIj", "Congenital disorder of glycosylation type 2j", "Congenital disorder of glycosylation type IIj"]}
|
A rare, congenital, heart malformation characterized by anomalous origin of one branch of the pulmonary arteries directly from the aorta and a normal origin of the other pulmonary artery from the main pulmonary artery coming from the right ventricular outflow tract. Patients present respiratory distress, congestive heart failure and failure to thrive within the first days/months of life.
## Epidemiology
The incidence is estimated at 0.1% of all congenital cardiac anomalies.
## Clinical description
Abnormal origin of right or left pulmonary artery from aorta usually occurs in infants or in the newborns where it manifests by respiratory distress, recurrent respiratory infection, moderate to severe pulmonary hypertension, congestive heart failure, and failure to thrive within the first months of life. Infants are usually cyanotic and may present chest pain and dyspnea on exertion. Two forms may be distinguished: anomalous origin of the left pulmonary artery from the aorta (AOLPA; about 25% of cases) and anomalous origin of the right pulmonary artery from the aorta (AORPA; about 75% of cases). Abnormal origin of right or left pulmonary artery from aorta frequently occurs as an isolated form with or without patent arterial duct. However, AOLPA may be associated with Tetralogy of Fallot, Right aortic arch, aortopulmonary window and anomalous subclavian arteries. On the contrary, patent ductus arteriosus and aortic coarctation or interruption (type A) may be associated with AORPA. Atrial and ventricular septal defects may be also present.
## Etiology
The pathogenesis still remains unknown, although an association has been reported with 22q11.2 deletion syndrome in children with AOLPA, usually associated with Right aortic arch, Tetralogy of Fallot and Absent pulmonary valve. Indeed, deletions 22q11.2 may impair the second heart field causing anomalies of development of the pharyngeal pouch derivate, aortic arches and conotruncal part of the heart.
## Diagnostic methods
Initial diagnosis is made with 2D-echocardiography which allows the definition of morphology and the detection of systemic or supra-systemic pressures in the right ventricle. Diagnosis is confirmed by catheterization, angiocardiography, MRI and CT angiography.
## Differential diagnosis
Occasionally, one pulmonary artery (more frequently the left one) can origin via a patent ductus arteriosus coming from the aorta, however this morphological anomaly should be differentiated from Abnormal origin of right or left pulmonary artery from aorta.
## Genetic counseling
Abnormal origin of right or left pulmonary artery from aorta is usually non-syndromic and sporadic. However, association with the 22q11.2 deletion syndrome is described in patients with AOLPA. Familial recurrence has also been reported.
## Management and treatment
Early diagnosis and surgical treatment are mandatory in order to prevent cardiac failure and pulmonary hypertension. Treatment involves different techniques to implant the anomalous pulmonary artery branch to the main pulmonary artery. This includes direct implantation, end-to-end anastomosis with a synthetic graft, homograft patch, and an "aortic-ring" flap. In cases with AOLPA, the direct implantation technique is the strategy of choice, while for AORPA, different technique employing autologous tissues for increasing the length of the pulmonary artery branch may be used. Postoperative restenosis across the anastomotic site is frequently observed. Postoperative echocardiographic study is thus recommended to detect presence of stenosis.
## Prognosis
Patients treated early in life have good short and long-term outcome. If left untreated, the disease may lead to congestive cardiac failure and pulmonary hypertension, with 30% of infants dying within 3 months. Palliative treatment such as pulmonary artery banding, ligation of the associated ductus arteriosus and aortopulmonary shunt, increases mortality substantially.
*[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-hydroxybutyric 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
|
Abnormal origin of right or left pulmonary artery from the aorta
|
None
| 25,752 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99050
| 2021-01-23T18:59:59 |
{"gard": ["4586"], "icd-10": ["Q25.7"], "synonyms": ["Hemitruncus arteriosus", "Pulmonary artery coming from the aorta"]}
|
Achondroplasia is a form of short-limbed dwarfism. The word achondroplasia literally means "without cartilage formation." Cartilage is a tough but flexible tissue that makes up much of the skeleton during early development. However, in achondroplasia the problem is not in forming cartilage but in converting it to bone (a process called ossification), particularly in the long bones of the arms and legs. Achondroplasia is similar to another skeletal disorder called hypochondroplasia, but the features of achondroplasia tend to be more severe.
All people with achondroplasia have short stature. The average height of an adult male with achondroplasia is 131 centimeters (4 feet, 4 inches), and the average height for adult females is 124 centimeters (4 feet, 1 inch). Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence.
Health problems commonly associated with achondroplasia include episodes in which breathing slows or stops for short periods (apnea), obesity, and recurrent ear infections. In childhood, individuals with the condition usually develop a pronounced and permanent sway of the lower back (lordosis) and bowed legs. Some affected people also develop abnormal front-to-back curvature of the spine (kyphosis) and back pain. A potentially serious complication of achondroplasia is spinal stenosis, which is a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord. Spinal stenosis is associated with pain, tingling, and weakness in the legs that can cause difficulty with walking. Another uncommon but serious complication of achondroplasia is hydrocephalus, which is a buildup of fluid in the brain in affected children that can lead to increased head size and related brain abnormalities.
## Frequency
Achondroplasia is the most common type of short-limbed dwarfism. The condition occurs in 1 in 15,000 to 40,000 newborns.
## Causes
Mutations in the FGFR3 gene cause achondroplasia. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia. Researchers believe that these mutations cause the FGFR3 protein to be overly active, which interferes with skeletal development and leads to the disturbances in bone growth seen with this disorder.
### Learn more about the gene associated with Achondroplasia
* FGFR3
## Inheritance Pattern
Achondroplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 80 percent of people with achondroplasia have average-size parents; these cases result from new mutations in the FGFR3 gene. In the remaining cases, people with achondroplasia have inherited an altered FGFR3 gene from one or two affected parents. Individuals who inherit two altered copies of this gene typically have a severe form of achondroplasia that causes extreme shortening of the bones and an underdeveloped rib cage. These individuals are usually stillborn or die shortly after birth from respiratory failure.
*[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-hydroxybutyric 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
|
Achondroplasia
|
c0001080
| 25,753 |
medlineplus
|
https://medlineplus.gov/genetics/condition/achondroplasia/
| 2021-01-27T08:24:47 |
{"gard": ["8173"], "mesh": ["D000130"], "omim": ["100800"], "synonyms": []}
|
Relative incidences of gastric polyps (with fundic gland polyp at upper right).[1]
A fundic gland polyp is a type of polyp, found in the fundus of the stomach. Fundic gland polyps are found in 0.8 to 1.9% of patients who undergo esophagogastroduodenoscopy, and are more common in middle-aged women.[2]
The risk of malignancy is very low or none, when sporadic.[3]
Fundic gland polyposis is a medical syndrome with multiple fundic gland polyps. The condition has been described both in patients with familial adenomatous polyposis (FAP) and attenuated variants (AFAP), and in patients in whom it occurs sporadically.[4]
* On histopathology, a fundic gland polyp displays cystically dilated glands.[5]
* The glands are lined by chief cells and parietal cells, and possibly also mucinous foveolar cells.[5]
## References[edit]
1. ^ García-Alonso, Francisco Javier; Martín-Mateos, Rosa María; González-Martín, Juan Ángel; Foruny, José Ramón; Vázquez-Sequeiros, Enrique; Boixeda de Miquel, Daniel (2011). "Gastric polyps: analysis of endoscopic and histological features in our center". Revista Española de Enfermedades Digestivas. 103 (8): 416–420. doi:10.4321/S1130-01082011000800005. ISSN 1130-0108.
2. ^ Weston, BR; Helper, DJ; Rex, DK (2003). "Positive predictive value of endoscopic features deemed typical of gastric fundic gland polyps". Journal of Clinical Gastroenterology. 36 (5): 399–402. doi:10.1097/00004836-200305000-00007. PMID 12702980. S2CID 7220827.
3. ^ Varocha Mahachai, MDDavid Y Graham, MDRobert D Odze, MD, FRCPC. "Gastric polyps". UpToDate.CS1 maint: multiple names: authors list (link) Literature review current through: Sep 2020. | This topic last updated: Feb 14, 2019.
4. ^ Declich, P; Tavani, E; Ferrara, A; Caruso, S; Bellone, S (2005). "Sporadic fundic gland polyps: clinico-pathologic features and associated diseases". Polish Journal of Pathology. 56 (3): 131–7. PMID 16334981.
5. ^ a b Naziheh Assarzadegan, M.D., Raul S. Gonzalez, M.D. "Stomach Polyps - Fundic gland polyp". PathologyOutlines.CS1 maint: multiple names: authors list (link) Topic Completed: 1 November 2017. Minor changes: 11 December 2019
*[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-hydroxybutyric 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
|
Fundic gland polyp
|
c0920184
| 25,754 |
wikipedia
|
https://en.wikipedia.org/wiki/Fundic_gland_polyp
| 2021-01-18T18:34:33 |
{"umls": ["C0920184"], "wikidata": ["Q104631351"]}
|
## Description
Platelet prostaglandin-endoperoxidase synthase-1 deficiency is a hematologic disorder characterized by mildly increased bleeding due to a platelet defect. The PTGS1 gene (176805) encodes prostaglandin-endoperoxidase synthase-1, also known as COX1 or PGHS1, which catalyzes the formation of prostaglandin G2 (PGG2) and prostaglandin H2 from arachidonic acid, and the downstream formation of thromboxane A2 (TXA2) and prostacyclin. Thromboxane A2 is important for platelet aggregation (summary by Matijevic-Aleksic et al., 1996).
Clinical Features
Malmsten et al. (1975) studied a 30-year-old man with a tendency to easy bruising and retinal bleeding at age 19. An uncle had excessive bleeding twice during surgery. Laboratory studies showed impaired platelet aggregation due to a deficiency of platelet cyclooxygenase that catalyzes formation of PGG2. Normal platelet aggregation and release reaction were restored with added PGG2.
In a study on the Aland Islands, Nyman et al. (1979) identified a family with mild bleeding due to defective platelet function in 7 members of 3 generations, suggesting autosomal dominant inheritance. Only platelet aggregation with arachidonate was deficient; response to other inducers of platelet aggregation was normal. Cyclooxygenase deficiency was suggested. Lagarde et al. (1978) studied 2 patients with impaired TXA2 synthesis from arachidonic acid. Pareti et al. (1980) reported a woman with a bleeding disorder characterized by a mildly prolonged bleeding time and defective platelet-release reaction due to congenital deficiency of cyclooxgenase.
Horellou et al. (1983) reported a mother and her 2 children with a bleeding disorder due to platelet cyclooxygenase deficiency. Clinical features included spontaneous hematomas, menorrhagia, epistaxis, and hemarthroses. Biochemical studies showed impaired platelet aggregation and lack of TXA2 formation.
Matijevic-Aleksic et al. (1996) reported 3 unrelated adult women with a history of a bleeding disorder, including recurrent spontaneous bruising, epistaxis, postsurgical bleeding, recurrent gastrointestinal bleeding, and menorrhagia. Laboratory studies showed that all had a functional platelet defect, with defective second-wave aggregation and defective TXA2 synthesis. Further biochemical studies indicated normal TXAS1 (TBXAS1; 274180) activity, but decreased PGHS1 activity. Treatment of patient platelets with prostaglandin H2 resulted in normal thromboxane levels. One patient had a normal amount of platelet PGHS1 protein, but the other 2 patients had undetectable protein levels. Matijevic-Aleksic et al. (1996) concluded that the 3 patients represented 2 types of PGHS1 deficiency. Type 1 manifested as complete loss of platelet PGHS1 protein and was postulated to result from a transcriptional defect or posttranslational modification resulting in rapid protein degradation. Type 2 manifested as normal levels of a dysfunctional protein that was postulated to result from inhibitory extrinsic factors or a mutation in the active site of the enzyme. Matijevic-Aleksic et al. (1996) noted that the deficiency appeared to be restricted to platelets, although PGHS1 is constitutively expressed in most cells.
Fuse et al. (1996) reported a 41-year-old Japanese woman with a lifelong history of mild bleeding. Laboratory studies showed prolonged bleeding time and inability of the patient's platelets to transform arachidonic acid to prostaglandin G2, indicating a deficiency in PGHS1. However, the PGHS1 defect was not observed in vascular endothelial cells or bone marrow fibroblasts. Oral administration of aspirin, which inhibits PGHS1, resulted in a marked prolongation of the bleeding time. These findings suggested that TXA2 released from vessel walls plays an important role in maintaining hemostasis.
Dube et al. (2001) studied an 18-year-old woman with a lifelong bleeding disorder, moderate thrombocytopenia, and a prolonged bleeding time. Her platelets aggregated in the presence of both prostaglandin H2 (PGH2) and a stable TXA2 analog, but did not aggregate in the presence of arachidonic acid. The activity of PGHS1 in platelets was reduced to 13% of the activity measured in control subjects. The PGHS1 protein level was reduced in B lymphocytes. However, PGHS1 mRNA was detected as a 2.8-kb band in both the patient and control, with similar intensity of the band; this suggested a normal transcriptional rate of PGHS1. Dube et al. (2001) concluded that the defect responsible for the reduced levels of PGHS1 protein was probably posttranscriptional, and not due to a mutation in the PGHS1 gene.
INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Epistaxis ABDOMEN Gastrointestinal \- Gastrointestinal bleeding GENITOURINARY Internal Genitalia (Female) \- Menorrhagia SKELETAL Limbs \- Hemarthroses SKIN, NAILS, & HAIR Skin \- Easy bruising HEMATOLOGY \- Increased bleeding (menorrhagia, gastrointestinal bleeding, hemarthroses) \- Post-surgical bleeding \- Platelet aggregation defect \- Prostaglandin-endoperoxide synthase 1 (PTGS1, 176805 ) deficiency in platelets \- Platelets cannot synthesize thromboxane A2 from arachidonic acid MISCELLANEOUS \- Congenital onset ▲ 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-hydroxybutyric 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
|
BLEEDING DISORDER, PLATELET-TYPE, 12
|
c2751535
| 25,755 |
omim
|
https://www.omim.org/entry/605735
| 2019-09-22T16:11:05 |
{"mesh": ["C567786"], "omim": ["605735"], "synonyms": ["Alternative titles", "PROSTAGLANDIN-ENDOPEROXIDE SYNTHASE 1 DEFICIENCY, PLATELET", "PGHS1 DEFICIENCY", "PLATELET CYCLOOXYGENASE 1 DEFICIENCY", "PLATELET COX1 DEFICIENCY"]}
|
Hydrocephalus-blue sclera-nephropathy syndrome is a rare, genetic, renal or urinary tract malformation syndrome characterized by nephrotic syndrome with focal segmental sclerosis associated with hydrocephalus, thin skin and blue sclerae. There have been no further descriptions in the literature since 1978.
*[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-hydroxybutyric 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
|
Hydrocephalus-blue sclerae-nephropathy syndrome
|
c2931014
| 25,756 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2186
| 2021-01-23T19:03:38 |
{"gard": ["236"], "mesh": ["C535768"], "umls": ["C2931014"], "icd-10": ["Q87.8"], "synonyms": ["Daentl-Townsend-Siegel syndrome"]}
|
A rare superficial pemphigus disease characterized by multiple, pruritic, scaly, crusted cutaneous erosions, with flaky circumscribed patches, localized mostly on the face, scalp, trunk and extremities, often presenting an erythematous base. Mucosal involvement is rarely 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-hydroxybutyric 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
|
Pemphigus foliaceus
|
c0263313
| 25,757 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79481
| 2021-01-23T17:17:56 |
{"gard": ["7354"], "mesh": ["D010392"], "umls": ["C0263313"], "icd-10": ["L10.2"]}
|
## Description
Zur Stadt et al. (2005) summarized the clinical features of hemophagocytic lymphohistiocytosis (HLH), a rare autosomal recessive disorder characterized by massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently central nervous system involvement. In FHL, the familial form of the disease, first episodes occur mostly during infancy, with a rapidly fatal outcome if untreated. Diagnostic criteria also include low fibrinogen and high triglyceride and ferritin levels. Chemoimmunotherapy based on corticosteroids, epipodophyllotoxins, and cyclosporin succeeds in controlling the disease in the majority of patients, although remission is rarely obtained (Henter et al., 2002). Most patients suffer an early death unless they are treated by hematopoietic stem cell transplantation (Durken et al., 1999).
### Genetic Heterogeneity of Familial Hemophagocytic Lymphohistiocytosis
Familial hemophagocytic lymphohistiocytosis exhibits genetic heterogeneity. In some families, familial hemophagocytic lymphohistiocytosis has been found to be linked to chromosome 9q (HPLH1, FHL1). FHL2 (603553) is caused by mutation in the PRF1 gene (170280) on chromosome 10q22; FHL3 (608898) is caused by mutation in the UNC13D gene (608897) on chromosome 17q25; FHL4 (603552) is caused by mutation in the syntaxin-11 gene (STX11; 605014) on chromosome 6q24; and FHL5 (613101) is caused by mutation in the syntaxin-binding protein-2 (STXBP2; 601717), which is an interaction partner of STX11, on chromosome 19p13.
Furthermore, before the identification of mutations in the RAG1 (179615) and RAG2 (179616) genes, both of which map to 11p, Omenn syndrome (familial reticuloendotheliosis with eosinophilia; 603554) was not thought to be clearly distinct from other reported cases of hemophagocytic lymphohistiocytosis.
Mutation in the HAVCR2 gene (606652) on chromosome 5q23 causes an inflammatory disorder sometimes associated with HLH (SPTCL; 618398).
Clinical Features
Anemia, granulocytopenia, and thrombocytopenia are produced in part by phagocytosis of blood cells, and in part by replacement of the marrow by histiocytic infiltration. Families have been reported by Marrian and Sanerkin (1963) and by Farquhar and Claireaux (1952) and Farquhar et al. (1958). In the latter family 4 sibs were affected. The father showed autoantibody and shortened red cell life span. Farquhar et al. (1958) concluded that the minor changes observed in the father and one sib represented the heterozygous state. They were not concerned about the lack of changes in the mother since expression in the heterozygote is often variable. Miller (1966) described 5 sisters--a complete sibship, including a pair of twins--with clinical features of failure to thrive, recurrent infections, lymphadenopathy, hepatosplenomegaly, pulmonary infiltration, and terminal pancytopenia and hypergammaglobulinemia. Death occurred between ages 20 months and 57 months. Autopsy showed diffuse reticulum cell infiltration of most organs including the central nervous system, obliteration of architecture of lymph glands and marked plasmacytosis. The family reported by Farquhar and Claireaux (1952) and Farquhar et al. (1958) was Scottish. Another Scottish family, with 3 affected sibs, was reported by Goodall et al. (1965). Bell et al. (1968) described affected brothers born 11 years apart. Meningoencephalitis during infancy was a feature in each. Hemophagocytosis in bone marrow preparations made the diagnosis.
Donohue (1968) had autopsy information on 6 cases that occurred in an inbred Mennonite group in Ontario. De Veber (1974) provided further information on these cases, which he considered to be in the general group of histiocytoses. (These cases are also discussed in entry 246400.) A major difference from other reported families was raised platelet counts. Cutbush et al. (1974) identified 22 cases in an inbred Mennonite kindred. Six of them were still living. The disease presented at about 3 months of age with hepatomegaly and variable lymphadenopathy, and untreated cases died rapidly with high fever, hemolytic anemia, and a picture resembling acute leukemia. Some cases responded to prednisone. Others died despite prednisone and cytotoxic agents. Healthy relatives may have high platelet counts.
The familial histiocytoses are nosologically confused. Even the terminology, based on histopathology, is confusing: lymphohistiocytic, erythrophagocytic, lymphoreticular, etc. The confused group of histiocytoses includes monocytic leukemia, histiocytic lymphoma, Letterer-Siwe disease, malignant histiocytosis, Hand-Schuller-Christian disease, eosinophilic granuloma, histiocytosis X, reticuloendotheliosis, histiocytic reticulosis, disseminated lipogranulomatosis, and familial hemophagocytic reticulosis. Newton and Hamoudi (1973) gave a useful review, but a convincing classification has not been achieved. Confusion is compounded by failure to distinguish infectious diseases such as histoplasmosis and graft-versus-host reaction such as occurs in infants with severe combined immunodeficiency transfused with fresh whole blood or receiving maternal blood transplacentally. Some authors have suggested that familial erythrophagocytic lymphohistiocytosis, familial reticuloendotheliosis with eosinophilia, and Letterer-Siwe disease (246400) can be lumped together, whereas other authors have considered them to be separate entities. Nelson et al. (1961) claimed that the disorder they described was quite different from Letterer-Siwe disease and presumably also from the disorder described here.
Mozziconacci et al. (1965) described 2 brothers, aged 6 and 8, with this fatal disease characterized by a high and irregular fever, hepatosplenomegaly, purpura, and, later, jaundice, polyneuritis, meningeal reaction, choked disks, moderate anemia, and severe granulocytopenia. A possible relationship to ceroid storage disease (214200) is only speculative. Price et al. (1971) described 4 of 12 sibs with a progressive neurologic disease characterized by diffuse lymphohistiocytic infiltrations of the central nervous system in association with multiple foci of parenchymal destruction. The range of age at death was 15 months to 12 years. The spinal fluid showed pleocytosis and increased protein. Histologically the disorder resembled familial hemophagocytic reticulosis or familial erythrophagocytic lymphohistiocytosis but unlike these conditions the process was largely confined to CNS. Since lymphocytic and histiocytic infiltration of viscera was present in some of the patients and leukopenia with hypocellular bone marrow was described, most would consider this the same as familial histiocytic reticulosis.
Nemoto and Ohnishi (1987) reported histologic studies of the spleen, liver, and mesenteric lymph nodes from a patient in whom splenectomy and biopsy of the other tissues were performed. They described lymphoid cells of various sizes, with atypical features including mitotic figures and convoluted nuclei; these were suspected to be T cells on the basis of immunohistochemical findings. The authors suggested that this may be a special type of lymphoproliferative disease accompanied by severe proliferation of erythrophagocytic histiocytes rather than being a true histiocytic disease.
Ladisch et al. (1978) demonstrated abnormal lipid metabolism and defects in both humoral and cellular immunity, together with a plasma inhibitor of in vitro lymphocyte blastogenesis. Because a component of the immunodeficiency is plasma-mediated inhibition of lymphocyte proliferation, Ladisch et al. (1982) tested whether repeated plasma or blood exchange would help in FEL. Clinical improvement was complete in 2 and partial in 1 of 3 patients studied. Laboratory values also improved. Relapse, which was ultimately fatal, was accompanied by recurrence of the immune defects.
Stark et al. (1984) studied 11 patients in 4 Jewish families of Iranian and Iraqi origin. Parental consanguinity was found in 3. The age of onset varied from 6 weeks to 36 months. All had fever, wasting, and hepatosplenomegaly. Lymph node enlargement and neurologic abnormalities were common. Pancytopenia, atypical lymphomonocytoid cells in the peripheral blood, abnormal liver function tests, and increased CSF protein were the most consistent laboratory findings. In 9 patients death occurred in 2 weeks to 3 months after presentation. The longest survival was 2 years after presentation.
Janka (1983) reviewed 121 cases, and Henter and Elinder (1991) provided a clinical review based on the findings in 7 children.
The excessive immune activation that occurs in FHL is characterized by uncontrolled T lymphocyte and macrophage activation (Henter et al., 1991; Hirst et al., 1994). Infiltration of the liver, spleen, bone marrow, and central nervous system by activated T cells and macrophages results in a multisystem disorder with onset in early infancy, which, in the absence of treatment with epipodophyllotoxins, immunosuppressive agents, or bone marrow transplantation, progresses rapidly, with a median survival of 2 months. In Sweden, Henter et al. (1991) studied the incidence of hemophagocytic lymphohistiocytosis in children during a 16-year period, 1971-1986; the incidence was 1.2 per 1 million children per year. One child per 50,000 live births developed the disorder during this period. The sex ratio was approximately 1:1. Prominent early clinical signs were fever, splenomegaly, hepatomegaly, rash, and lymph node enlargement. Neurologic symptoms, which developed in 47%, could totally dominate the clinical picture and develop before other symptoms and signs. In only 11 of 32 children was the diagnosis made during their lifetime.
Henter et al. (1991) demonstrated elevated levels of circulating interferon-gamma (147570), tumor necrosis factor (191160), and interleukin-6 (147620) in children during active phases of FHL. Soluble CD8 was also increased in all of 7 children tested. Henter et al. (1991) suggested that a genetic defect in cytokine regulation underlies this disorder.
The entity described here should not be confused with Langerhans cell histiocytosis, which has little or no tendency to familial aggregation; see 604856 for evidence to the contrary. The Langerhans cell, a dendritic cell of the epidermis, was described by medical student Paul Langerhans, who thought that it was part of the nervous system (Langerhans, 1868). Birbeck et al. (1961) found that the Langerhans cell displays a unique electron-microscopic morphology. The discoveries that these cells are not confined to skin and that they make up a sizable portion of the cellular infiltrate in histiocytosis X, along with other evidence, suggest that they play an immunologic role in protecting against environmental antigens. Egeler and D'Angio (1995) presented a classification of histiocytosis syndromes in children: class I, Langerhans cell histiocytosis; class II, histiocytosis of mononuclear macrophages other than Langerhans cells, including familial hemophagocytic lymphohistiocytosis; and class III, malignant histiocytic disorders, including histiocytic lymphoma.
Henter and Elinder (1995) pointed out that hemophagocytic lymphohistiocytosis can be divided into 2 categories, a primary and a secondary form. The primary form is hereditary, whereas the secondary form is a reactive condition, commonly associated with immunosuppressive therapy, malignancies and/or infections, which often are of viral origin. Henter et al. (1991) published diagnostic guidelines for hemophagocytic lymphohistiocytoses. Henter and Elinder (1995) pointed out that a viral infection may elicit a bout of familial hemophagocytic lymphohistiocytosis in a genetically predisposed child.
Dufourcq-Lagelouse et al. (1999) pointed out that other causes of inherited hemophagocytic lymphohistiocytosis include Chediak-Higashi syndrome (214500) and Griscelli syndrome (214450), both associated with partial albinism, and X-linked lymphoproliferative syndrome (308240). Acquired forms of lymphohistiocytosis, such as Letterer-Siwe disease (246400), usually occur later in childhood. The diagnosis of hemophagocytic lymphohistiocytosis depends on both positive and negative criteria, including the early occurrence and severity of the hemophagocytic syndrome, the occurrence of relapse, evidence of autosomal recessive inheritance, and the absence of associated albinism.
Diagnosis
Janka and Schneider (2004) summarized revised diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH).
Henter et al. (2007) reviewed the diagnostic and therapeutic guidelines for HLH and stated that the 5 criteria from the 1991 guidelines remained valid: fever, splenomegaly, cytopenia affecting at least 2 of the 3 cell lineages in the peripheral blood, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis in bone marrow, spleen, or lymph nodes. In addition, 3 more criteria had been introduced: low or absent natural killer cell activity, hyperferritinemia, and high levels of soluble IL2RA (147730). Henter et al. (2007) noted that 5 of the 8 criteria must be fulfilled, but that patients with a molecular diagnosis consistent with HLH do not necessarily need to fulfill the diagnostic criteria.
Clinical Management
The review of Henter and Elinder (1991) indicated successful results with chemotherapy.
Bergholz et al. (1978) reviewed the evidence that 'congenital allogeneity' with graft-versus-host reaction might be involved. Nespoli et al. (1991) treated 3 patients, aged 6 to 20 months, with allogeneic bone marrow transplantation (BMT). They concluded that when an HLA-identical family donor exists, the BMT followed by intensive chemotherapy can produce a stable remission.
Mache et al. (1994) reported 2 sibs who were thought to have disseminated T-cell lymphoma at the time of diagnosis of familial hemophagocytic lymphohistiocytosis. DNA hybridization studies provided evidence of a monoclonal T-cell receptor beta-chain gene rearrangement. One sib received an allogeneic bone marrow transplant from a related healthy donor.
Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in patients with familial hemophagocytic lymphohistiocytosis. However, fewer than 20% of patients have a disease-free HLA-identical sib. Jabado et al. (1997) described BMTs from 13 HLA-nonidentical related donors and from a matched unrelated donor that were performed in 2 centers and 14 consecutive cases of this disorder. Remission of disease was achieved before BMT in 10 patients. Marrow was T-cell-depleted to minimize graft-versus-host disease (GVHD; see 614395). In addition to a conditioning regimen of cytotoxic drugs or antithymocyte globulin (ATG), antiadhesion antibodies specific for the alpha chain of the leukocyte function-associated antigen-1 (ITGAL; 153370) and CD2 (186990) were infused pre-BMT and post-BMT to help prevent graft rejection. Acute GVHD greater than stage 1 was not observed, and 1 patient had mild cutaneous chronic GVHD that resolved. Sustained engraftment was obtained in 11 of 17 transplants (3 patients had 2 transplants), and disease-free survival in 9 patients, with a follow-up period of 8 to 69 months (mean, 33), was observed.
Mapping
By homozygosity mapping in 4 inbred families of Pakistani descent, Ohadi et al. (1999) demonstrated linkage of familial hemophagocytic lymphohistiocytosis to markers in the 9q21.3-q22 region (FHL1). In an additional kindred of Arab origin, linkage to this interval could not be demonstrated; the maximum multipoint lod score was -0.12. All affected children in the 5 kindreds exhibited typical features of FHL, which included fever, liver and spleen enlargement, bi- or pancytopenia, hypertriglyceridemia, and hypofibrinogenemia. Hemophagocytosis was identified on examination of bone marrow and, in 2 cases, cerebrospinal fluid. All patients received treatment with etoposide and cortical steroids alone or in combination with cyclosporin A. One individual subsequently underwent successful allogeneic bone marrow transplantation from an HLA-identical sib donor and remained disease free 54 months after diagnosis. One patient survived in partial remission with continuing therapy for 15 months. The remaining 3 patients died 9 to 17 months after diagnosis because of disease progression despite treatment.
Dufourcq-Lagelouse et al. (1999) likewise found evidence for genetic heterogeneity in familial hemophagocytic lymphohistiocytosis. In studies of 17 families with FHL, they found that 10 showed no recombination with 3 tightly linked markers in the proximal region of 10q (see 603553). The maximum multipoint lod score was 11.22 at D10S1650. They established D10S206 and D10S1665 as the telomeric and the centromeric flanking markers, respectively. In the other 7 families, FHL was not linked to 10q21-q22.
Further genetic heterogeneity in familial hemophagocytic lymphohistiocytosis was suggested by a study in which FHL in 2 unrelated Canadian families with affected first cousins was not linked to 9q21.3-q22 or 10q21-q22 (Graham et al., 2000).
Molecular Genetics
Although the genes encoding granulysin (188855) and granzyme B (123910) had been considered reasonable candidates for the site of mutations causing FHL, Ericson et al. (2003) found no mutations in either gene in 16 well-defined FHL families.
Zur Stadt et al. (2006) performed mutation analysis of the STX11 (605014), PRF1 (170280), and UNC13D (608897) genes in 63 unrelated patients with FHL of different geographic origins: Turkey, 32; Germany, 23; others, 8. They identified mutations in 38 of 63 samples: 20 in PRF1, 12 in UNC13D, and 6 in STX11. Of the 32 patients from Turkey, 14 had mutations in PRF1, 6 had mutations in UNC13D, and 6 had mutations in STX11. The mutation trp374 to ter in PRF1 (170280.0002) was found in 12 patients from Turkey and was associated with a very early onset of the disease, below the age of 3 months in all cases. In contrast, 3 of the 23 and 4 of the 23 patients from Germany, and 3 of 8 and 2 of 8 from other origins, showed mutations in PRF1 and UNC13D, respectively, but none in STX11. Thus, FHL2, and FHL3, and FHL4 account for 80% of the hemophagocytic lymphohistiocytosis cases of Turkish origin, and for 30% of German patients.
Zur Stadt et al. (2006) identified mutations in RAB27A (603868) in 3 patients with Griscelli syndrome type 2 (607624), the presentation of which can include typical signs of FHL. In functional studies using a mammalian 2-hybrid system, they found that the ala87-to-pro mutation in RAB27A (603868.0010) and leu403 to pro in UNC13D (608897.0007) each prevented the formation of a stable UNC13D/RAB27A complex in vitro. The findings of Zur Stadt et al. (2006) demonstrated extensive genetic and allelic heterogeneity in FHL and delineated an approach for functionally characterizing missense mutations in RAB27A and UNC13D.
Genotype/Phenotype Correlations
Among 76 FHL patients from 65 unrelated families, Horne et al. (2008) found that 13 (18%) of 74 had PRF1 mutations, 6 (10%) of 61 had UNC13D mutations, and 14 (20%) of 70 had STX11 mutations. No molecular diagnosis was found in 27 (45%) of 60 patients. STX11 mutations were most common in Turkish families (7 of 28, 25%), whereas PRF1 mutations were most common in Middle East families (6 of 13, 46%). No biallelic mutations were identified in most families of Nordic origin (13 of 14, 93%). Patients carrying PRF1 mutations had higher risk of early onset before age 6 months compared to patients carrying STX11 mutations. Patients without identified mutations had increased risk of pathologic cerebrospinal fluid at diagnosis compared to patients with STX11 mutations. The results revealed some genotype/phenotype correlations among FHL patients with different disease-causing mutations.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Head \- Bulging fontanelle ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly SKIN, NAILS, & HAIR Skin \- Purpuric rashes \- Jaundice MUSCLE, SOFT TISSUES \- Generalized edema NEUROLOGIC Central Nervous System \- Meningitis \- Encephalitis \- Irritability \- Hypotonia \- Hypertonia \- Seizures \- Ataxia \- Hemiplegia \- Tetraplegia \- Coma \- Increased intracranial pressure \- Delayed psychomotor development HEMATOLOGY \- Anemia \- Leukopenia \- Thrombocytopenia IMMUNOLOGY \- Lymphadenopathy \- Overproduction by T lymphocytes and macrophages of cytokines, particularly interferon gamma and tumor necrosis factor alpha \- Activated HLA DR+ T cells in peripheral blood \- Reduced Natural Killer cell cytotoxicity \- Reduced T cell cytotoxicity \- Hemophagocytosis in bone marrow, lymph nodes, spleen, liver, and central nervous system \- Non-malignant mixed lymphohistiocytic infiltration of the reticuloendothelial system LABORATORY ABNORMALITIES \- Hypertriglyceridemia \- Increased VLDL \- Increased LDL \- Decreased HDL \- Hypofibrinogenemia \- Increased alanine aminotransferase \- Increased total bilirubin \- Hyponatremia \- Hypoproteinemia \- Hypoalbuminemia \- Prolonged prothrombin time \- Increased serum ferritin level \- CSF pleocytosis, particularly of lymphocytes \- Increased protein in CSF ▲ 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-hydroxybutyric 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
|
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 1
|
c0272199
| 25,758 |
omim
|
https://www.omim.org/entry/267700
| 2019-09-22T16:22:45 |
{"doid": ["0110921"], "mesh": ["D051359"], "omim": ["267700"], "icd-10": ["D76.1"], "orphanet": ["540"], "synonyms": ["Alternative titles", "HPLH1", "HLH1", "HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL", "RETICULOSIS, FAMILIAL HISTIOCYTIC", "HEMOPHAGOCYTIC RETICULOSIS, FAMILIAL", "ERYTHROPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL"], "genereviews": ["NBK1444"]}
|
Budd-Chiari syndrome is a rare disorder characterized by obstruction of the veins of the liver that carry the blood flow from the liver. When the blood flow out of the liver is impeded, blood backs up in the liver, causing it to enlarge (hepatomegaly). The spleen may also enlarge (splenomegaly). This backup of blood increases blood pressure in the portal vein, which carries blood to the liver from the intestines (portal hypertension), and result in dilated, twisted veins in the esophagus (esophageal varices). Portal hypertension, leads to fluid accumulating in the abdomen (called ascites). The clot may extend to also block the inferior vena cava (the large vein that carries blood from the lower parts of the body to the heart). Varicose veins in the abdomen near the skin’s surface may develop and become visible. In some cases, scarring of the liver (cirrhosis) occurs. Other symptoms may include fatigue, abdominal pain, nausea, jaundice and bleeding in the esophagus. The severity of the disorder varies from case to case, depending on the site and number of affected veins. It most often occurs in patients which have a disorder that makes blood more likely to clot, such as those who are pregnant or who have a tumor, a chronic inflammatory disease, a clotting disorder, an infection, or a myeloproliferative disorder. In about one third of the cases, the cause of Budd-Chiari syndrome is unknown. Drugs or surgical interventions may be used to dissolve or decrease the size of the obstruction (if it is a clot). In some cases liver transplantation is needed.
Budd-Chiari syndrome should be considered separate from veno-occlusive disease (VOD).
*[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-hydroxybutyric 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
|
Budd-Chiari syndrome
|
c0019154
| 25,759 |
gard
|
https://rarediseases.info.nih.gov/diseases/5968/budd-chiari-syndrome
| 2021-01-18T18:01:41 |
{"mesh": ["D006502"], "omim": ["600880"], "orphanet": ["131"], "synonyms": ["Membranous obstruction of the inferior vena cava"]}
|
Niemann-Pick disease type A is a very severe subtype of Niemann-Pick disease, an autosomal recessive lysosomal disease, and is characterized clinically by onset in infancy or early childhood with failure to thrive, hepatosplenomegaly, and rapidly progressive neurodegenerative 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-hydroxybutyric 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
|
Niemann-Pick disease type A
|
c0268242
| 25,760 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=77292
| 2021-01-23T17:57:34 |
{"gard": ["7206"], "mesh": ["D052536"], "omim": ["257200"], "umls": ["C0268242"], "icd-10": ["E75.2"]}
|
Lynch and Bushby (1997) reported an 8-year-old boy with obesity, mental retardation, downslanting palpebral fissures, large ears, sensorineural deafness, cryptorchidism, and a penoscrotal web. He had congenital emphysema, and the upper lobe of his left lung was removed. He was born to healthy, unrelated parents and had a normal karyotype. Lynch and Bushby (1997) excluded Prader-Willi syndrome (176270). They suggested that this association may be a previously unreported syndrome of multiple congenital abnormalities.
*[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-hydroxybutyric 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
|
EMPHYSEMA, CONGENITAL, WITH DEAFNESS, PENOSCROTAL WEB, AND MENTAL RETARDATION
|
c1865180
| 25,761 |
omim
|
https://www.omim.org/entry/602564
| 2019-09-22T16:13:33 |
{"mesh": ["C566519"], "omim": ["602564"]}
|
2q37 deletion syndrome is a condition that can affect many parts of the body. Most babies with 2q37 deletion syndrome are born with weak muscle tone (hypotonia), which usually improves with age. Other neurological abnormalities that are common in affected individuals include mild to severe intellectual disability; delayed development of motor skills, such as sitting and walking; and behavioral problems. About 25 percent of people with this condition have autism spectrum disorder, a developmental condition that affects communication and social interaction.
Unusual physical features are also common in people with 2q37 deletion syndrome. About half of affected individuals have unusually short fingers and toes (brachydactyly), often with abnormally short fourth toes that may overlap the other toes. Additional features of this condition may include short stature, obesity, or sparse hair. Many people with 2q37 deletion syndrome have characteristic facial features that can include a prominent forehead, a low frontal hairline, thin eyelids, skin folds covering the inner corner of the eyes (epicanthal folds), outside corners of the eyes that point upward (upslanting palpebral fissures), a small nose, a small mouth with thin lips, a smooth space between the upper lip and nose (smooth philtrum), prominent cheekbones, a large chin, and minor ear abnormalities.
Other features of 2q37 deletion syndrome can include seizures and an inflammatory skin disorder called eczema. Some affected individuals have malformations of the brain, heart, gastrointestinal system, kidneys, or genitalia. A few people with 2q37 deletion syndrome develop a rare form of kidney cancer called Wilms tumor.
## Frequency
2q37 deletion syndrome appears to be a rare condition, although its exact prevalence is unknown. At least 115 cases have been reported worldwide.
## Causes
2q37 deletion syndrome is caused by deletions of genetic material from a specific region in the long (q) arm of chromosome 2. The deletions occur near the end of the chromosome at a location designated 2q37. The size of the deletion varies among affected individuals, with most affected people missing 2 million to 9 million DNA building blocks (also written as 2 Mb to 9 Mb).
Researchers are working to identify all of the genes whose loss contributes to the features of 2q37 deletion syndrome. Many of these genes have not been well characterized. However, genes in this region appear to be critical for the normal development of many parts of the body.
Researchers have determined that loss of a particular gene on chromosome 2, called HDAC4, is likely to account for many of the syndrome's characteristic signs (such as intellectual disability and skeletal abnormalities). While the deleted segment in 2q37 deletion syndrome varies in size, it always contains the HDAC4 gene. Additionally, a few people with mutations in only the HDAC4 gene have many of the features of 2q37 deletion syndrome. It is unclear what role the other genes on 2q37 play in this disorder.
### Learn more about the gene and chromosome associated with 2q37 deletion syndrome
* HDAC4
* chromosome 2
## Inheritance Pattern
Most cases of 2q37 deletion syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.
Rarely, an affected individual inherits a copy of chromosome 2 with a deleted segment from an affected parent. In these cases, the parent is usually less severely affected than the child, for reasons that are unknown. When an affected child inherits a chromosomal deletion from a parent, it is inherited in an autosomal dominant pattern, which means one copy of the altered chromosome in each cell is sufficient to cause the 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-hydroxybutyric 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
|
2q37 deletion syndrome
|
c2931817
| 25,762 |
medlineplus
|
https://medlineplus.gov/genetics/condition/2q37-deletion-syndrome/
| 2021-01-27T08:25:39 |
{"gard": ["10202"], "mesh": ["C538317"], "omim": ["600430"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that dyschromatosis universalis hereditaria-1 (DUH1) is caused by heterozygous mutation in the SASH1 gene (607955) on chromosome 6q24.
Homozygous mutation in the SASH1 gene results in cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma (CAPOK; 618373).
Description
Dyschromatosis universalis hereditaria (DUH) is a rare autosomal dominant genodermatosis characterized by irregularly shaped, asymptomatic hyper- and hypopigmented macules that appear in infancy or early childhood and occur in a generalized distribution over the trunk, limbs, and sometimes the face. Involvement of the palms or soles is unusual. Abnormalities of hair and nails have been reported, and DUH may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications (summary by Zhang et al., 2013).
The autosomal dominant SASH1-associated DUH1 phenotype is characterized by generalized lentigines accompanied by mottled hyper- and hypopigmentation (Zhang et al., 2017).
DUH is distinct from dyschromatosis symmetrica hereditaria (DSH; 127400), which also occurs particularly in Japanese and Korean individuals, but shows a characteristic mixture of hyper- and hypopigmented macules limited largely to the dorsal aspects of the hands and feet (Suenaga, 1952). Gao et al. (2005) noted that lesions associated with DUH appear within the first year of life predominantly on the trunk, whereas the age of onset of DSH is approximately 6 years and lesions appear predominantly on the extremities.
### Genetic Heterogeneity of Dyschromatosis Universalis Hereditaria
Dyschromatosis universalis hereditaria-2 (DUH2; 612715) maps to chromosome 12q21-q23. DUH3 (615402) is caused by mutation in the ABCB6 gene (605452) on chromosome 2q35.
Clinical Features
Pacheco et al. (2002) studied a large 6-generation Hispanic family with multiple lentigines. Affected family members presented multiple small 1- to 5-millimeter hyperpigmented macules over the entire body, sparing the palmoplantar surfaces. Histopathologic analysis of biopsies of select lesions revealed increased numbers of melanocytes along the dermal-epidermal junction. Three family members had undefined learning disabilities, but the authors stated that there was no evidence of other features of LEOPARD syndrome (see 151100) in the observed affected family members.
Shellman et al. (2015) restudied the family described by Pacheco et al. (2002) and noted that the lentigines were most prominent in sun-exposed areas. In some patients, the lentigines covered the face, trunk, and extremities, whereas other affected individuals showed lesions primarily over the face and distal extremities. Analysis of patient skin biopsies showed an approximately 2-fold increase in the number of melanocytes per millimeter of skin in both hyperpigmented lesional skin and nonlesional skin; however, only lesional skin showed a dramatic increase in melanin. In addition, there were approximately 2-fold more proliferating cells in both lesional and nonlesional patient skin compared to control skin.
Xing et al. (2003) reported 2 large families from the Henan and Yunnan provinces of China segregating autosomal dominant cutaneous dyschromatosis: a 5-generation pedigree (family A) and a 3-generation pedigree (family B). The authors provided photographs showing a mixture of hypopigmented and hyperpigmented macules of various sizes on the trunks and arms of the affected individuals. One patient, shown in their Figure 2A, had a mixture of hypo- and hyperpigmented macules of various sizes on the entire trunk and on the arms, as well as on the neck and face. Biopsies of hypo- and hyperpigmented macules from the dorsa of the feet revealed basal melanosis and hypomelanosis, similar to previous reports in Japanese patients who also showed an increased number of melanocytes with high metabolic activity; however, none of the affected members in either Chinese family was found to have skin cancer. Although Xing et al. (2003) designated the disorder as DSH, Miyamura et al. (2003) suggested that these patients, who exhibited dyschromatosis over almost their entire bodies, in fact had DUH.
In a family with DUH reported by Nuber et al. (2004), the male proband presented with randomly distributed hyper- and hypopigmented skin lesions of variable shape and size with a mottled appearance. Light and electron microscopy showed normal numbers of active melanocytes, but different amounts of fully melanized melanosomes in hyper- and hypopigmented macules. The findings were interpreted as indicating that DUH is not a disorder of melanocyte number.
Zhang et al. (2016) studied 2 Chinese boys with multiple lentigines. Hypopigmented spots were intermixed with the lentigines, and there was mild dyschromatosis at the elbows and on the dorsa of the hands and feet. Histologic analysis of affected skin was consistent with features of typical lentigines.
Wang et al. (2017) reported a Chinese mother and son with multiple lentigines. The son had multiple 'freckles' on his forehead beginning at age 18 months; the lesions gradually increased and spread to his entire body by age 10 years. Neither patient had facial malformations, cardiac defects, or mental abnormalities.
Zhong et al. (2019) described the probands from 2 unrelated Chinese families with DUH. The proband from the first family was a 25-year-old woman born with normal skin pigmentation, who developed freckle-like macules at 3 years of age that appeared initially on her trunk, then extended to her face, neck, and limbs, with accentuation on sun-exposed areas. Hypopigmented patches were also noted on these areas, intermingled with hyperpigmentation. Her mother and deceased maternal grandfather exhibited similar lesions. The proband from the second family was a 42-year-old man with a similar clinical history but with earlier onset of skin lesions, at 7 months of age. The dyschromatosis progressed with age and involved nearly his entire body by age 7 years, with sparing of the palmoplantar and mucosal areas. There were 12 similarly affected members over 4 generations in the second family.
Inheritance
In a family with DUH reported by Suenaga (1952), a consanguineous marriage occurred in each of 4 successive generations, suggesting autosomal recessive inheritance.
Nuber et al. (2004) described a familial case of DUH compatible with autosomal dominant inheritance; in 2 instances there was father-to-son transmission.
Mapping
In 2 Chinese families from the Henan and Yunnan provinces with DUH, Xing et al. (2003) found evidence of linkage to chromosome 6q24.2-q25.2, with a maximum multipoint lod score of 10.64. Haplotype analysis placed the locus within an interval of 10.2 Mb. The 2 families showed no haplotype identity within the defined region, suggesting that these 2 families were different in origin.
In a large Hispanic family with nonsyndromic multiple lentigines, previously studied by Pacheco et al. (2002), Pacheco et al. (2004) performed pairwise linkage analysis and obtained a maximum lod score of 4.129 at marker D6S1654 on chromosome 6q, in the 10-cM region between markers D6S308 and D6S411.
### Exclusion Studies
In a large 7-generation Hispanic family with multiple lentigines, Pacheco et al. (2002) excluded linkage to chromosomes 2, 10, 12, 17, and 19. In addition, lod scores for genetic markers flanking the PTEN (601728), NF1 (162200), STK11/LKB1 (602216), PRKAR1A (188830), and PTPN11 (176876) genes, as well as 'Carney locus 1' on chromosome 2p16 and 'Peutz-Jeghers locus 2' on chromosome 19p13.4, were less than 3.
Molecular Genetics
By screening 50 candidate genes within a 10-Mb DUH-associated region on chromosome 6q24.2-q25.2, Zhou et al. (2013, 2017) identified heterozygous missense mutations in the SASH1 gene (Y551D, 607955.0001; L515P, 607955.0002; and E509K, 607955.0003) in affected individuals from 3 nonconsanguineous families with dyschromatosis, including 2 Chinese families from the Henan and Yunnan provinces (families I and II) and 1 American family (family III). The mutations segregated fully with disease in each family, respectively, and were not found in 500 controls or in public variant databases.
In 17 affected members of a large Hispanic family with nonsyndromic multiple lentigines mapping to a 10-Mb interval on chromosome 6q24.2-q25.2, previously studied by Pacheco et al. (2002, 2004), Shellman et al. (2015) screened candidate genes and identified heterozygosity for a SASH1 missense mutation (S519N; 607955.0005) that segregated fully with disease and was not found in 150 ethnically matched controls or in public variant databases.
In 2 Chinese boys with multiple lentigines, Zhang et al. (2016) screened 4 candidate genes and identified heterozygous SASH1 mutations in both: a missense mutation (S513R; 607955.0006) in patient 1, and a frameshift mutation (607955.0007) in patient 2. The mutations segregated with disease in the respective families and were not found in 100 controls.
In a Chinese mother and son with multiple lentigines, Wang et al. (2017) identified heterozygosity for a SASH1 missense mutation (S507A; 607955.0008) that had arisen de novo in the mother. The authors stated that their findings further verified SASH1 as a causal gene of lentiginous phenotypes with or without dyschromatosis.
In 2 Chinese families with DUH, Zhong et al. (2019) screened 3 dyschromatosis-associated genes and identified heterozygous missense mutations in SASH1 in affected members of both families: Y551H (607955.0009) and M595T (607955.0010), respectively.
INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Hyperpigmented/hypopigmented macules (trunk, extremities, occasionally face) MISCELLANEOUS \- Onset in infancy/early childhood \- New skin lesions stop appearing before adolescence \- Majority of cases in Japan ▲ 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-hydroxybutyric 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
|
DYSCHROMATOSIS UNIVERSALIS HEREDITARIA 1
|
c1306229
| 25,763 |
omim
|
https://www.omim.org/entry/127500
| 2019-09-22T16:42:06 |
{"doid": ["0060304"], "omim": ["127500"], "orphanet": ["241"]}
|
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-32 (EIEE32) is caused by heterozygous mutation in the KCNA2 gene (176262) on chromosome 1p13.
For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Clinical Features
Syrbe et al. (2015) reported 7 unrelated patients with severe epilepsy and residual neurologic deficits. All patients had normal early development until the onset of seizures between 5 and 17 months of age. Seizure types included febrile, hemiclonic, myoclonic, myoclonic-atonic, focal dyscognitive, generalized tonic-clonic, and absence. EEG findings were variable, and included multifocal sharp waves, sharp slow waves, polyspikes, and generalized spike waves. The seizures remitted in 4 patients between 4 and 15 years, and were significantly decreased by medication in the 2 more severely affected patients as young adults. Despite the decrease in frequency or full remission, all patients had residual neurologic deficits, including intellectual disability, delayed speech, ataxia, tremor, and myoclonus.
Molecular Genetics
By exome sequencing in a 7-year-old boy who presented in infancy with an encephalopathy characterized by ataxia and myoclonic epilepsy, Pena and Coimbra (2015) identified a heterozygous de novo mutation in the KCNA2 gene (R297Q; 176262.0004).
In 7 unrelated patients with EIEE32, Syrbe et al. (2015) identified 4 different de novo heterozygous missense mutations in the KCNA2 gene (176262.0001-176262.0004). The mutations were found by targeted next-generation sequencing or whole-exome sequencing from several different cohorts of patients with a similar phenotype, and accounted for about 1.7% of the total cases. In vitro functional expression studies in Xenopus oocytes showed that 2 mutations (P405L, 176262.0001 and I263T, 176262.0002) resulted in a loss of function with a dominant-negative effect, whereas the other 2 mutations (L298F, 176262.0003 and R297Q, 176262.0004) resulted in a significant gain of function and permanently opened channels, also with a dominant effect. The 2 patients with dominant gain-of-function mutations had a more severe phenotype, suggesting a possible genotype/phenotype correlation.
Animal Model
Xie et al. (2010) identified a mouse mutant, termed 'Pingu' (Pgu), carrying an I402T mutation in the S6 segment of the voltage-gated potassium channel Kcna2. Mutant mice showed chronic motor incoordination, with abnormal gait and splayed hindlimbs, consistent with ataxia. Other features included shorter latency on the rotarod test, tremors, and myoclonic jerks. Homozygous mice were more severely affected than heterozygous mice. The phenotype was ameliorated by treatment with acetazolamide. Voltage-clamp recordings in cerebellar slices showed that mutant mice had increased frequency and amplitude of spontaneous GABAergic inhibitory postsynaptic currents and reduced action potential firing frequency in Purkinje cells. Expression of Kcna2 channels was significantly reduced in the basket cell terminals of Pgu mice, consistent with an absence of the Kv1.2-mediated current from basket cells to Purkinje cells. Transfection studies in CHO cells showed that the mutation reduced the number of functional channels.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Normal early development \- Epileptic encephalopathy \- Seizures, refractory \- Intellectual disability, mild to profound \- Poor or absent speech \- Ataxia \- Myoclonus \- Tremor \- Multifocal or generalized spike waves seen on EEG \- Sharp slow wave activity MISCELLANEOUS \- Onset in infancy \- Normal development before onset of seizures \- Seizures may remit later in childhood MOLECULAR BASIS \- Caused by mutation in the potassium channel, voltage-gated, shaker-related subfamily, member 2 gene (KCNA2, 176262.0001 ) ▲ 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-hydroxybutyric 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
|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 32
|
c4225350
| 25,764 |
omim
|
https://www.omim.org/entry/616366
| 2019-09-22T15:49:07 |
{"doid": ["0080416"], "omim": ["616366"], "orphanet": ["442835"], "synonyms": ["Undetermined EOEE"]}
|
Myxoid liposarcoma is a subtype of liposarcoma, tumors that arise in the body’s fat tissue. Other categories of liposarcoma include well-differentiated; dedifferentiated; round cell; and pleomorphic.[1] Round cell and myxoid liposarcomas are sometimes grouped together into one category known as myxoid/round cell liposarcoma (MRCLS).[2] In adults, liposarcomas are the most common type of soft tissue sarcoma. The cause of liposarcomas is not well-established but trauma has been implicated in some cases. Myxoid liposarcomas generally arise in the lower extremities. Symptoms may vary depending on the location of the tumor but may include swelling; decreased range of motion; numbness; fatigue; abdominal pain; weight loss; nausea; and vomiting. Many patients with liposarcoma have no symptoms until the tumor is large and interferes with neighboring structures. When possible, surgical removal is the preferred treatment. In some cases, additional therapy may be indicated.[1] The prognosis is generally favorable for those with a low grade myxoid liposarcoma with a small percentage of round cells. A significant round cell component is associated with a poorer prognosis.[1][2] Although these tumors rarely spread, they can recur if not completely removed.[1]
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Myxoid liposarcoma
|
c0206634
| 25,765 |
gard
|
https://rarediseases.info.nih.gov/diseases/7157/myxoid-liposarcoma
| 2021-01-18T17:58:48 |
{"mesh": ["D018208"], "omim": ["613488"], "umls": ["C0206634"], "orphanet": ["99967"], "synonyms": ["MRCLS", "Myxoid/round cell liposarcoma", "Myxoliposarcoma"]}
|
Laryngomalacia
Omega shaped epiglottis, seen in laryngomalacia
SpecialtyMedical genetics
Laryngomalacia (literally, "soft larynx") is the most common cause of chronic stridor in infancy, in which the soft, immature cartilage of the upper larynx collapses inward during inhalation, causing airway obstruction. It can also be seen in older patients, especially those with neuromuscular conditions resulting in weakness of the muscles of the throat. However, the infantile form is much more common. Laryngomalacia is one of the most common laryngeal congenital disease in infancy and public education about the signs and symptoms of the disease is lacking.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
In infantile laryngomalacia, the supraglottic larynx (the part above the vocal cords) is tightly curled, with a short band holding the cartilage shield in the front (the epiglottis) tightly to the mobile cartilage in the back of the larynx (the arytenoids). These bands are known as the aryepiglottic folds. The shortened aryepiglottic folds cause the epiglottis to be curled on itself. This is the well known "omega shaped" epiglottis in laryngomalacia. Another common finding of laryngomalacia involves the posterior or back part of the larynx, where the arytenoid cartilages or the mucosa/tissue over the arytenoid cartilages can collapse into the airway and cause airway obstruction.[citation needed]
Laryngomalacia results in partial airway obstruction, most commonly causing a characteristic high-pitched squeaking noise on inhalation (inspiratory stridor). Some infants have feeding difficulties related to this problem. Rarely, children will have significant life-threatening airway obstruction. The vast majority, however, will only have stridor without other more serious symptoms such as dyspnea (difficulty breathing).[citation needed]
## Causes[edit]
Although laryngomalacia is not associated with a specific gene, there is evidence that some cases may be inherited.[1][2] Relaxation or a lack of muscle tone in the upper airway may be a factor. It is often worse when the infant is on his or her back, because the floppy tissues can fall over the airway opening more easily in this position.[3]
## Diagnosis[edit]
The physician will ask some questions about the baby's health problems and may recommend a flexible laryngoscopy to further evaluate the infant's condition.[3] Additional testing can be done to confirm the diagnoses including; flexible fiberoptic laryngoscopy, airway fluoroscopy, direct laryngoscopy and bronchoscopy.[4]
## Treatment[edit]
Time is the only treatment necessary in more than 90% of infant cases.[5] In other cases, surgery may be necessary.[6][7][8] Most commonly, this involves cutting the aryepiglottic folds to let the supraglottic airway spring open. Trimming of the arytenoid cartilages or the mucosa/ tissue over the arytenoid cartilages can also be performed as part of the supraglottoplasty. Supraglottoplasty can be performed bilaterally (on both the left and right sides at the same time), or be staged where only one side is operated on at a time.[9]
Treatment of gastroesophageal reflux disease can also help in the treatment of laryngomalacia, since gastric contents can cause the back part of the larynx to swell and collapse even further into the airway.In some cases, a temporary tracheostomy may be necessary.[citation needed]
## Prognosis[edit]
Laryngomalacia becomes symptomatic after the first few months of life (2–3 months), and the stridor may get louder over the first year, as the child moves air more vigorously. Most of the cases resolve spontaneously and fewer than 15% of the cases will need surgical intervention. Parents need to be supported and educated about the condition.[citation needed]
## Epidemiology[edit]
Although this is a congenital lesion, airway sounds typically begin at age 4–6 weeks. Until that age, inspiratory flow rates may not be high enough to generate the sounds. Symptoms typically peak at age 6–8 months and remit by age 2 years.
Late-onset laryngomalacia may be a distinct entity, which can present after age of 2 years.
## References[edit]
1. ^ Shulman JB, Hollister DW, Thibeault DW, Krugman ME (1976). "Familial laryngomalacia: a case report". Laryngoscope. 86 (1): 84–91. doi:10.1288/00005537-197601000-00018. PMID 1256207.
2. ^ Shohat M, Sivan Y, Taub E, Davidson S (1992). "Autosomal dominant congenital laryngomalacia". Am. J. Med. Genet. 42 (6): 813–4. doi:10.1002/ajmg.1320420613. PMID 1554019.
3. ^ a b "Laryngomalacia – The Children's Hospital of Philadelphia". The Children's hospital of Philadelphia. Retrieved 31 August 2012.
4. ^ "laryngomalacia". rarediseases. genetic and rare diseases information center. Retrieved 17 April 2018.
5. ^ Bye Michael R MD (September 13, 2007). "Laryngomalacia: Treatment & Medication". eMedicine from WebMD. Cite journal requires `|journal=` (help)
6. ^ Holinger LD, Konior RJ (1989). "Surgical management of severe laryngomalacia". Laryngoscope. 99 (2): 136–42. doi:10.1288/00005537-198902000-00004. PMID 2913424.
7. ^ Zalzal GH (1989). "Stridor and airway compromise". Pediatr. Clin. North Am. 36 (6): 1389–402. doi:10.1016/S0031-3955(16)36795-5. PMID 2685719.
8. ^ Solomons NB, Prescott CA (1987). "Laryngomalacia. A review and the surgical management for severe cases". Int. J. Pediatr. Otorhinolaryngol. 13 (1): 31–9. doi:10.1016/0165-5876(87)90005-X. PMID 3305399.
9. ^ Walner, D.L. (2015). "Supraglottoplasty in Infants: A Staged Approach". Annals of Otology, Rhinology, and Laryngology. 124 (10): 803–7. doi:10.1177/0003489415585869. PMID 25944597.
## External links[edit]
Classification
D
* ICD-10: Q31.5
* ICD-9-CM: 748.3
* OMIM: 150280
* MeSH: D055092
* DiseasesDB: 29421
External resources
* eMedicine: ped/1280
* v
* t
* e
Congenital malformations and deformations of respiratory system
Upper RT
Nose
* Choanal atresia
* Arrhinia
Larynx
* Laryngeal cyst
* Laryngocele
* Laryngomalacia
Lower RT
Trachea and bronchus
* Tracheomalacia
* Tracheal stenosis
* Bronchomalacia
* Tracheobronchomegaly
Lung
* Bronchiectasis
* Pulmonary hypoplasia
* Pulmonary sequestration
* Congenital cystic adenomatoid malformation
* v
* t
* e
Diseases of the respiratory system
Upper RT
(including URTIs,
common cold)
Head
sinuses
Sinusitis
nose
Rhinitis
Vasomotor rhinitis
Atrophic rhinitis
Hay fever
Nasal polyp
Rhinorrhea
nasal septum
Nasal septum deviation
Nasal septum perforation
Nasal septal hematoma
tonsil
Tonsillitis
Adenoid hypertrophy
Peritonsillar abscess
Neck
pharynx
Pharyngitis
Strep throat
Laryngopharyngeal reflux (LPR)
Retropharyngeal abscess
larynx
Croup
Laryngomalacia
Laryngeal cyst
Laryngitis
Laryngopharyngeal reflux (LPR)
Laryngospasm
vocal cords
Laryngopharyngeal reflux (LPR)
Vocal fold nodule
Vocal fold paresis
Vocal cord dysfunction
epiglottis
Epiglottitis
trachea
Tracheitis
Laryngotracheal stenosis
Lower RT/lung disease
(including LRTIs)
Bronchial/
obstructive
acute
Acute bronchitis
chronic
COPD
Chronic bronchitis
Acute exacerbation of COPD)
Asthma (Status asthmaticus
Aspirin-induced
Exercise-induced
Bronchiectasis
Cystic fibrosis
unspecified
Bronchitis
Bronchiolitis
Bronchiolitis obliterans
Diffuse panbronchiolitis
Interstitial/
restrictive
(fibrosis)
External agents/
occupational
lung disease
Pneumoconiosis
Aluminosis
Asbestosis
Baritosis
Bauxite fibrosis
Berylliosis
Caplan's syndrome
Chalicosis
Coalworker's pneumoconiosis
Siderosis
Silicosis
Talcosis
Byssinosis
Hypersensitivity pneumonitis
Bagassosis
Bird fancier's lung
Farmer's lung
Lycoperdonosis
Other
* ARDS
* Combined pulmonary fibrosis and emphysema
* Pulmonary edema
* Löffler's syndrome/Eosinophilic pneumonia
* Respiratory hypersensitivity
* Allergic bronchopulmonary aspergillosis
* Hamman-Rich syndrome
* Idiopathic pulmonary fibrosis
* Sarcoidosis
* Vaping-associated pulmonary injury
Obstructive / Restrictive
Pneumonia/
pneumonitis
By pathogen
* Viral
* Bacterial
* Pneumococcal
* Klebsiella
* Atypical bacterial
* Mycoplasma
* Legionnaires' disease
* Chlamydiae
* Fungal
* Pneumocystis
* Parasitic
* noninfectious
* Chemical/Mendelson's syndrome
* Aspiration/Lipid
By vector/route
* Community-acquired
* Healthcare-associated
* Hospital-acquired
By distribution
* Broncho-
* Lobar
IIP
* UIP
* DIP
* BOOP-COP
* NSIP
* RB
Other
* Atelectasis
* circulatory
* Pulmonary hypertension
* Pulmonary embolism
* Lung abscess
Pleural cavity/
mediastinum
Pleural disease
* Pleuritis/pleurisy
* Pneumothorax/Hemopneumothorax
Pleural effusion
Hemothorax
Hydrothorax
Chylothorax
Empyema/pyothorax
Malignant
Fibrothorax
Mediastinal disease
* Mediastinitis
* Mediastinal emphysema
Other/general
* Respiratory failure
* Influenza
* Common cold
* SARS
* Coronavirus disease 2019
* Idiopathic pulmonary haemosiderosis
* Pulmonary alveolar proteinosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Laryngomalacia
|
c0345160
| 25,766 |
wikipedia
|
https://en.wikipedia.org/wiki/Laryngomalacia
| 2021-01-18T19:02:30 |
{"gard": ["6865"], "mesh": ["D055092"], "umls": ["C0345160"], "icd-9": ["748.3"], "icd-10": ["Q31.5"], "orphanet": ["2373"], "wikidata": ["Q598035"]}
|
"Blackhead" redirects here. For other uses, see Blackhead (disambiguation).
Comedo
Other namesPlural: comedones[1]
Illustration comparing a normal skin pore with a whitehead and a blackhead
SpecialtyDermatology
A comedo is a clogged hair follicle (pore) in the skin.[2] Keratin (skin debris) combines with oil to block the follicle.[3] A comedo can be open (blackhead) or closed by skin (whitehead) and occur with or without acne.[3] The word comedo comes from the Latin comedere, meaning 'to eat up', and was historically used to describe parasitic worms; in modern medical terminology, it is used to suggest the worm-like appearance of the expressed material.[1]
The chronic inflammatory condition that usually includes both comedones, inflamed papules and pustules (pimples), is called acne.[3][4] Infection causes inflammation and the development of pus.[2] Whether a skin condition classifies as acne depends on the amount of comedones and infection.[4] Comedones should not be confused with sebaceous filaments.
Comedo-type ductal carcinoma in situ (DCIS) is not related to the skin conditions discussed here. DCIS is a non-invasive form of breast cancer, but comedo-type DCIS may be more aggressive and so may be more likely to become invasive.[5]
## Contents
* 1 Causes
* 2 Pathophysiology
* 3 Management
* 4 Rare conditions
* 5 References
* 6 External links
## Causes[edit]
Oil production in the sebaceous glands increases during puberty, causing comedones and acne to be common in adolescents.[3][4] Acne is also found premenstrually and in women with polycystic ovarian syndrome.[3] Smoking may worsen acne.[3]
Oxidation rather than poor hygiene or dirt causes blackheads to be black.[2] Washing or scrubbing the skin too much could make it worse, by irritating the skin.[2] Touching and picking at comedones might cause irritation and spread infection.[2] It is not clear what effect shaving has on the development of comedones or acne.[2]
Some, but not all, skin products might increase comedones by blocking pores,[2] and greasy hair products (like pomades) can worsen acne.[3] Skin products that claim to not clog pores may be labeled noncomedogenic or non-acnegenic.[6] Make-up and skin products that are oil-free and water-based may be less likely to cause acne.[6] It is not known whether dietary factors or sun exposure make comedones better, worse or have no effect.[3]
A hair that does not emerge normally, an ingrown hair, can also block the pore and cause a bulge or lead to infection (causing inflammation and pus).[4]
Genes may play a role in the chances of developing acne.[3] Comedones may be more common in some ethnic groups.[3][7] People of Latino and recent African descent may experience more inflammation in comedones, more comedonal acne, and earlier onset of inflammation.[3][7]
## Pathophysiology[edit]
Multiple closed comedones at the nasolabial fold and the alar of the nose
Comedones are associated with the pilosebaceous unit, which includes a hair follicle and sebaceous gland. These units are mostly on the face, neck, upper chest, shoulders and back.[3] Excess keratin combined with sebum can plug the opening of the follicle.[3][8] This small plug is called a microcomedo.[8] Androgens increase sebum (oil) production.[3] If sebum continues to build up behind the plug, it can enlarge and form a visible comedo.[8]
A comedone may be open to the air ("blackhead") or closed by skin ("whitehead").[2] Being open to the air causes oxidation, which turns it black.[2] Cutibacterium acnes is the suspected infectious agent in acne.[3] It can proliferate in sebum and cause inflamed pustules (pimples) characteristic of acne.[3] Nodules are inflamed, painful deep bumps under the skin.[3]
Comedones that are 1 mm or larger are called macrocomedones.[9] They are closed comedones and are more frequent on the face than neck.[10]
Solar comedones (sometimes called senile comedones) are related to many years of exposure to the sun, usually on the cheeks, not to acne-related pathophysiology.[11]
## Management[edit]
Using non-oily cleansers and mild soap may not cause as much irritation to the skin as regular soap.[12][13] Blackheads can be removed across an area with commercially available pore-cleansing strips (which can still damage the skin by leaving the pores wide open and ripping excess skin) or the more aggressive cyanoacrylate method used by dermatologists.[14]
Squeezing blackheads and whiteheads can remove them, but it can also damage the skin.[2] Doing so increases the risk of causing or transmitting infection and scarring, as well as potentially pushing any infection deeper into the skin.[2] Comedo extractors are used with careful hygiene in beauty salons and by dermatologists, usually after using steam or warm water.[2]
Complementary medicine options for acne in general have not been shown to be effective in trials.[3] These include aloe vera, pyridoxine (vitamin B6), fruit-derived acids, kampo (Japanese herbal medicine), ayurvedic herbal treatments and acupuncture.[3]
Some acne treatments target infection specifically, but there are treatments that are aimed at the formation of comedones as well.[15] Others remove the dead layers of the skin and may help clear blocked pores.[2][3][4]
Dermatologists can often extract open comedones with minimal skin trauma, but closed comedones are more difficult.[3] Laser treatment for acne might reduce comedones,[16] but dermabrasion and laser therapy have also been known to cause scarring.[9]
Macrocomedones (1 mm or larger) can be removed by a dermatologist using surgical instruments or cauterized with a device that uses light.[9][10] The acne drug isotretinoin can cause severe flare-ups of macrocomedones, so dermatologists recommend removal before starting the drug and during treatment.[9][10]
Some research suggests that the common acne medications retinoids and azelaic acid are beneficial and do not cause increased pigmentation of the skin.[17] If using a retinoid, sunscreen is recommended.
## Rare conditions[edit]
Favre–Racouchot syndrome occurs in sun-damaged skin and includes open and closed comedones.[18]
Nevus comedonicus or comedo nevus is a benign hamartoma (birthmark) of the pilosebaceous unit around the oil-producing gland in the skin.[19] It has widened open hair follicles with dark keratin plugs that resemble comedones, but they are not actually comedones.[19][20]
Dowling-Degos disease is a genetic pigment disorder that includes comedo-like lesions and scars.[21][22]
Familial dyskeratotic comedones is a rare autosomal dominant genetic condition, with keratotic (tough) papules and comedo-like lesions.[23][24]
## References[edit]
1. ^ a b "Comedo". Oxford Dictionary. Oxford University Press. Retrieved 16 June 2013.
2. ^ a b c d e f g h i j k l m Informed Health Online. "Acne". Fact sheet. Institute for Quality and Efficiency in Health Care (IQWiG). Retrieved 9 June 2013.
3. ^ a b c d e f g h i j k l m n o p q r s t u Williams, HC; Dellavalle, RP; Garner, S (Jan 28, 2012). "Acne vulgaris". Lancet. 379 (9813): 361–72. doi:10.1016/S0140-6736(11)60321-8. PMID 21880356.
4. ^ a b c d e Purdy, Sarah; De Berker, David (2011). "Acne vulgaris". BMJ Clinical Evidence. 2011: 1714. PMC 3275168. PMID 21477388.
5. ^ National Cancer Institute. "Breast cancer treatment". Physician Desk Query. National Cancer Institute. Retrieved 13 June 2013.
6. ^ a b British Association of Dermatologists. "Acne". Patient information leaflet. British Association of Dermatologists. Archived from the original on 2013-10-04. Retrieved 12 June 2013.
7. ^ a b Davis, EC; Callender, VD (April 2010). "A review of acne in ethnic skin: pathogenesis, clinical manifestations, and management strategies". The Journal of Clinical and Aesthetic Dermatology. 3 (4): 24–38. PMC 2921746. PMID 20725545.
8. ^ a b c Burkhart, CG; Burkhart, CN (October 2007). "Expanding the microcomedone theory and acne therapeutics: Propionibacterium acnes biofilm produces biological glue that holds corneocytes together to form plug". Journal of the American Academy of Dermatology. 57 (4): 722–4. doi:10.1016/j.jaad.2007.05.013. PMID 17870436.
9. ^ a b c d Wise, EM; Graber, EM (November 2011). "Clinical pearl: comedone extraction for persistent macrocomedones while on isotretinoin therapy". The Journal of Clinical and Aesthetic Dermatology. 4 (11): 20–1. PMC 3225139. PMID 22132254.
10. ^ a b c Primary Care Dermatology Society. "Acne: macrocomedones". Clinical Guidance. Primary Care Dermatology Society. Retrieved 12 June 2013.
11. ^ DermNetNZ. "Solar comedones". New Zealand Dermatological Society. Retrieved 16 June 2013.
12. ^ Poli, F (Apr 15, 2002). "[Cosmetic treatments and acne]". La Revue du Praticien. 52 (8): 859–62. PMID 12053795.
13. ^ Korting, HC; Ponce-Pöschl, E; Klövekorn, W; Schmötzer, G; Arens-Corell, M; Braun-Falco, O (Mar–Apr 1995). "The influence of the regular use of a soap or an acidic syndet bar on pre-acne". Infection. 23 (2): 89–93. doi:10.1007/bf01833872. PMID 7622270.
14. ^ Pagnoni, A; Kligman, AM; Stoudemayer, T (1999). "Extraction of follicular horny impactions the face by polymers. Efficacy and safety of a cosmetic pore-cleansing strip (Bioré)". Journal of Dermatological Treatment. 10 (1): 47–52. doi:10.3109/09546639909055910.
15. ^ Gollnick, HP; Krautheim, A (2003). "Topical treatment in acne: current status and future aspects". Dermatology. 206 (1): 29–36. doi:10.1159/000067820. PMID 12566803.
16. ^ Orringer, JS; Kang, S; Hamilton, T; Schumacher, W; Cho, S; Hammerberg, C; Fisher, GJ; Karimipour, DJ; Johnson, TM; Voorhees, JJ (Jun 16, 2004). "Treatment of acne vulgaris with a pulsed dye laser: a randomized controlled trial". JAMA: The Journal of the American Medical Association. 291 (23): 2834–9. doi:10.1001/jama.291.23.2834. PMID 15199033.
17. ^ Woolery-Lloyd, HC; Keri, J; Doig, S (Apr 1, 2013). "Retinoids and azelaic Acid to treat acne and hyperpigmentation in skin of color". Journal of Drugs in Dermatology. 12 (4): 434–7. PMID 23652891.
18. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1847. ISBN 978-1-4160-2999-1.
19. ^ a b Zarkik, S; Bouhllab, J; Methqal, A; Afifi, Y; Senouci, K; Hassam, B (Jul 15, 2012). "Keratoacanthoma arising in nevus comedonicus". Dermatology Online Journal. 18 (7): 4. PMID 22863626.
20. ^ DermNetNZ. "Comedo Naevus". New Zealand Dermatological Society. Retrieved 16 June 2013.
21. ^ Bhagwat, PV; Tophakhane, RS; Shashikumar, BM; Noronha, TM; Naidu, V (Jul–Aug 2009). "Three cases of Dowling Degos disease in two families" (PDF). Indian Journal of Dermatology, Venereology and Leprology. 75 (4): 398–400. doi:10.4103/0378-6323.53139. PMID 19584468.
22. ^ Khaddar, RK; Mahjoub, WK; Zaraa, I; Sassi, MB; Osman, AB; Debbiche, AC; Mokni, M (January 2012). "[Extensive Dowling-Degos disease following long term PUVA therapy]". Annales de Dermatologie et de Vénéréologie. 139 (1): 54–7. doi:10.1016/j.annder.2011.10.403. PMID 22225744.
23. ^ Hallermann, C; Bertsch, HP (Jul–Aug 2004). "Two sisters with familial dyskeratotic comedones". European Journal of Dermatology. 14 (4): 214–5. PMID 15319152.
24. ^ OMIM. "Comedones, familial dyskeratotic". OMIM database. OMIM. Archived from the original on 15 June 2013. Retrieved 13 June 2013.
## External links[edit]
Classification
D
* ICD-9-CM: 706.1
* Rines, George Edwin, ed. (1920). "Comedones" . Encyclopedia Americana.
* 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
* What causes blackheads, Treatment and Prevention
*[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-hydroxybutyric 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
|
Comedo
|
c0221228
| 25,767 |
wikipedia
|
https://en.wikipedia.org/wiki/Comedo
| 2021-01-18T19:07:26 |
{"umls": ["C0221228"], "icd-9": ["706.1"], "wikidata": ["Q1146379"]}
|
Pityriasis rotunda is a rare skin disease characterized by round, scaly, pigmented patches that mainly occur on the trunk, arms and legs. There are two types of pityriasis rotunda. Type 1 is seen mainly in East/Southeast Asian and South African individuals older than 60 years, and is often associated with internal disease or malignancy (cancer). Type 2 occurs in lighter skinned individuals younger than 40 years, and often in several members of the same family. Type 2 pityriasis rotunda is not associated with internal disease or malignancy. The cause of pityriasis rotunda is unknown, but it may be a variant of ichthyosis vulgaris. Type 1 most often occurs with liver and stomach cancer.
*[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-hydroxybutyric 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
|
Pityriasis rotunda
|
c0343060
| 25,768 |
gard
|
https://rarediseases.info.nih.gov/diseases/10904/pityriasis-rotunda
| 2021-01-18T17:58:17 |
{"synonyms": []}
|
A number sign (#) is used with this entry because somatic mutations in several genes have been identified in malignant mesothelioma. These genes include WT1 (607102) on chromosome 11p13, BCL10 (603517) on chromosome 1p22, CDKN2A (600160) on chromosome 9p21, NF2 (607379) on chromosome 22q12, and BAP1 (603089) on chromosome 3p21.
Description
Malignant mesothelioma is an aggressive neoplasm of the serosal lining of the chest etiologically linked to asbestos. It is diagnosed in approximately 2,000 to 3,000 individuals annually in the United States, most of whom die within 2 years of diagnosis (summary by Bott et al., 2011).
See also 614327 for a tumor predisposition syndrome that may contribute to the development of malignant mesothelioma upon asbestos exposure and is caused by germline mutation in the BAP1 gene (603089) on chromosome 3p21.
Inheritance
In connection with the etiology of mesothelioma, primary attention has appropriately been focused on environmental factors, particularly asbestos exposure. Li et al. (1978) reported pleural mesothelioma in the wife and daughter of a man who worked for about 25 years as a pipe insulator at a shipyard and who also developed pulmonary asbestosis and lung cancer. The wife and daughter had no asbestos exposure other than that from the man's clothing.
Risberg et al. (1980) described a family in Sweden in which the father, 3 brothers and a sister died of malignant mesothelioma. Four of the 5 probably had had asbestos exposure in the building industry. All were smokers. The area showed low incidence of malignant mesothelioma. There were 8 other sibs who were unaffected at the time of report (2 had died of other causes). The authors suggested that, in addition to smoking and asbestos, genetic factors may be involved in the pathogenesis.
Martensson et al. (1984) observed malignant mesothelioma in 2 pairs of sibs and raised a question of a hereditary predisposing factor.
Although common household or occupational exposure may be responsible for familial aggregation, Lynch et al. (1985) also raised the question of a host factor in the occurrence and/or the histologic characteristics of mesothelioma. They reported brothers who died of malignant pleural mesothelioma.
Hammar et al. (1989) reported 3 brothers who worked in the asbestos insulation business and developed mesothelioma. In a second family, a father, who was occupationally exposed to asbestos, died from a tubulopapillary peritoneal mesothelioma 11 years before his son died from a peritoneal mesothelioma of identical histologic type. Although it is possible that the son was secondarily exposed to asbestos from the father's work clothes, quantitative asbestos analysis of the son's lung tissue showed numbers of asbestos bodies well within the lower limits seen in the general urban population with no occupational exposure to asbestos. The simulation of mendelian dominant inheritance was indicated by the occurrence of familial mesothelioma contracted as an infant by a woman who died of this disorder at age 32.
A combination of asbestos exposure and host predisposition was suggested also by the report of pleural malignant mesothelioma in 3 sisters and a male cousin by Ascoli et al. (1998). The 3 women had worked in the same confectionary shop as pastry cooks and/or pastry shop assistants; the use of an asbestos-insulated oven was the putative source of exposure. The man had occupational exposure as a heating system insulation worker. Malignant cancers were reported in other relatives (larynx in a brother; pleura and lung in a mother; lung in an aunt and uncle; and lung in a cousin).
Erionite present in stones used to build the villages of Karain and Tuzkoy, Turkey, mined from nearby caves, is purported to cause mesothelioma in half of the villagers. Roushdy-Hammady et al. (2001) constructed genetic epidemiology maps to test whether some villagers were genetically predisposed to mesothelioma. Analysis of a 6-generation extended pedigree of 526 individuals showed that mesothelioma was genetically transmitted, probably in an autosomal dominant way. The incidence of malignant mesothelioma in immigrants from Karain and Tuzkoy living in Sweden and Germany was similar to or higher than that of the 2 Turkish villages, suggesting that erionite is only a cofactor in the cause of malignant mesothelioma in genetically predisposed individuals. This suggestion is supported by data showing an absence of mesothelioma cases in the towns of Karlik and other nearby villages, whose houses contain a similar amount of erionite.
Carbone and Testa (2001) claimed that genetic susceptibility to mesothelioma in the Cappadocian region of Turkey was conclusively demonstrated by the study of Roushdy-Hammady et al. (2001). Saracci and Simonato (2001) presented several reasons why the study did not prove genetic causation. One of the reasons was that before 1978, when endemic mesothelioma was recognized in this area by the study of Baris et al. (1978), mesothelioma was diagnosed as tuberculosis, lung cancer, metastatic cancers, or other disorders. Some members of the family in the reported pedigree must have died no later than 1960, long before local recognition of the disease. Dogan et al. (2001) defended the conclusion concerning a genetic factor for susceptibility to erionite carcinogenicity. Saracci and Simonato (2001) pointed out that the question has wide public health implications, given the weight that a genetic factor may carry when debating liability in asbestos-related mesotheliomas.
Cytogenetics
In 24 human malignant mesothelioma cell lines derived from untreated primary tumors, Balsara et al. (1999) performed comparative genomic hybridization analysis to identify chromosomal imbalances. Chromosomal losses accounted for the majority of genomic imbalances. The most frequent underrepresented segments were 22q (58%) and 15q11.1-q21 (54%). To map more precisely the region of 15q deletion, loss of heterozygosity analyses were performed with a panel of polymorphic microsatellite markers distributed along 15q, which defined a minimal region of chromosomal loss at 15q11.1-q15. Balsara et al. (1999) suggested that this region harbors a putative tumor suppressor gene whose loss or inactivation may contribute to the pathogenesis of many malignant mesotheliomas.
Musti et al. (2002) described a family in which 3 sisters were affected by malignant mesothelioma, 2 pleural and 1 peritoneal, and 1 brother was affected by pleural plaques. All family members had been subjected to previous asbestos exposure of environmental-residential type. For 13 years, from 1951 to 1964, their housing was provided by the father's employer, an asbestos cement factory; the factory warehouse was on the ground floor of the building in which they lived. DNA extracted from paraffin-embedded malignant mesothelioma samples was used to search for chromosomal alterations by comparative genomic hydridization (CGH). A loss at chromosome 9p, a frequent event in malignant mesothelioma, was the only change in 2 of the sisters, which suggested that this region may be the site of 1 or more oncosuppressor genes that play an important role in the development of the disease and in inducing greater genetic susceptibility to the carcinogenic effects of asbestos.
Molecular Genetics
By immunohistochemical analysis of archival paraffin specimens and tumor cell lines, Kratzke et al. (1995) found that p16(INK4) (CDKN2; 600160) was expressed in a nonsmall cell lung cancer cell line but not in 12 of 12 primary thoracic mesotheliomas and 15 of 15 mesothelioma cell lines. All tumor specimens and the tumor cell lines showed expression of wildtype RB1 protein (614041). In addition, transfection of CDKN2 suppressed the growth of 2 independent mesothelioma cell lines. The authors concluded that inactivation of the CDKN2 gene is an essential step in the etiology of malignant mesotheliomas.
Baser et al. (2002) reported a patient with neurofibromatosis type II (NF2; 101000) who developed malignant mesothelioma after a long occupational exposure to asbestos. Genetic analysis of the tumor tissue showed loss not only of chromosome 22, where the NF2 gene (607379) is located, but also of chromosomes 14 and 15, and gain of chromosome 7. Baser et al. (2002) suggested that an individual with a constitutional mutation of an NF2 allele is more susceptible to mesothelioma. Although mesothelioma is not a common feature in NF2, the authors cited the observation of Knudson (1995) that somatic mutations of a tumor suppressor gene, such as NF2, RB1, or p53 (191170), can be common in a tumor type that is not characteristic of the hereditary disorder, perhaps due to the proliferative timing of the cells involved.
By studying copy number alterations followed by candidate gene sequencing of 53 primary malignant pleural mesothelioma (MPM) samples, Bott et al. (2011) identified the BAP1 gene (603089) on chromosome 3p21.1 as a commonly somatically inactivated gene. Twelve (23%) of 53 tumors had nonsynonymous mutations, and 16 (30%) had at least single copy genomic loss of the BAP1 locus. Tumors with mutations showed loss of nuclear staining for BAP1. BAP1 losses were confirmed in an independent collection of MPM tumors. The somatic nature of the mutations was confirmed in all tumors that had matched normal tissue available. Knockdown of BAP1 in mesothelioma cell lines expressing wildtype BAP1 resulted in proliferation defects with an accumulation of cells in S phase and also downregulated E2F (see, e.g., 189971)-responsive genes. Given the known role of BAP1 in regulatory ubiquitination of histones, the findings suggested transcriptional deregulation as a pathogenic mechanism. Sequencing also confirmed frequent inactivating mutations in the NF2 gene (11 of 53; 21%) and identified previously undescribed missense mutations in the LATS2 gene (604861) (2 of 53; 3.8%) and the LATS1 gene (603473) (2 of 53; 3.8%).
INHERITANCE \- Somatic mutation RESPIRATORY Lung \- Mesothelioma, malignant NEOPLASIA \- Mesothelioma MISCELLANEOUS \- Etiologically linked to asbestos \- May be seen in conjunction with other cancer syndromes (e.g., TDPS 614327 ) MOLECULAR BASIS \- Susceptibility conferred by mutation in the B-cell leukemia/lymphoma 10 gene (BCL10, 603517.0001 ) \- Susceptibility conferred by mutation in the WT1 gene (WT1, 607102.0016 ) ▲ 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-hydroxybutyric 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
|
MESOTHELIOMA, MALIGNANT
|
c0025500
| 25,769 |
omim
|
https://www.omim.org/entry/156240
| 2019-09-22T16:38:17 |
{"doid": ["1790"], "mesh": ["D008654"], "omim": ["156240"], "orphanet": ["50251"]}
|
## Description
The features of frontofacionasal dysplasia include blepharophimosis, lower lid lagophthalmos, primary telecanthus, S-shaped palpebral fissues, facial hypoplasia, eyelid coloboma, widow's peak, cranium bifidum occultum, frontal lipoma, nasal hypoplasia, deformed nostrils, bifid nose, and cleft of lip, premaxilla, palate, and uvula (White et al., 1991). Also see frontonasal dysplasia (136760).
Clinical Features
Gollop (1981) suggested that a disorder observed in a brother and sister whose parents were first cousins once removed represented a 'new' autosomal recessive disorder, which he called frontofacionasal dysostosis. The girl showed brachycephaly, bilateral blepharophimosis and ptosis, S-shaped palpebral fissures, bilateral lower lid lagophthalmos ('hare eye'; inability to close the eye completely), limbic dermoid of the left eye, coloboma of the upper lid, bilateral cleft lip and palate, deformed nostrils, and severe midface hypoplasia. The brother had, in addition, prefrontal lipomata, cranium bifidum occultum, and ankyloblepharon filiforme on the right.
Gollop et al. (1984) reported a 2-month-old girl whose parents were first cousins. Features were encephalocele, hypertelorism, midface hypoplasia, hypoplasia of frontal bone on the left side, malformed left eye, absent inner eyelashes, irregular S-shaped palpebral fissures, deformed nostrils, hypoplastic right nasal wing and cleft lip, and clefts of premaxilla, palate, and uvula.
White et al. (1991) reported a fourth case of this disorder.
Reardon et al. (1994) described a child with a severe form of FFND whose features were similar to those in the 2 sibs reported by Gollop (1981).
Suthers et al. (1997) reported a male child with FFND, the offspring of healthy unrelated parents. The authors suggested that the key distinguishing features of the disorder are S-shaped palpebral fissures, eyelid coloboma, epibulbar dermoid, microphthalmia, and coloboma of iris or optic disc.
Ozkinay et al. (2000) reported 2 sisters, born of second-cousin parents, with typical features of FFND, including blepharophimosis, lagophthalmos, primary telecanthus, midface hypoplasia, nasal dysplasia, defect of alae nasi, bifid nose, microphthalmia, S-shaped palpebral fissures, brachycephaly, and cranium bifidum. In addition, both sisters had intracranial abnormalities, one had spina bifida, and the other had umbilical hernia.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Brachycephaly \- Encephalocele \- Prefrontal lipoma Face \- Midface hypoplasia Eyes \- Blepharophimosis \- Ptosis \- S-shaped palpebral fissures \- Lower lid lagophthalmos \- Hare eye \- Incomplete eye closure \- Limbic dermoid \- Eyelid coloboma \- Iris coloboma \- Ankyloblepharon filiforme \- Hypertelorism \- Telecanthus \- Malformed eye \- Absent inner eyelashes \- Cataract \- Microphthalmia \- Microcornea Nose \- Nasal hypoplasia \- Hypoplastic nasal wings \- Bifid nose Mouth \- Cleft lip/palate \- Cleft uvula ▲ 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-hydroxybutyric 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
|
FRONTOFACIONASAL DYSPLASIA
|
c2931720
| 25,770 |
omim
|
https://www.omim.org/entry/229400
| 2019-09-22T16:27:44 |
{"mesh": ["C538063"], "omim": ["229400"], "orphanet": ["1791"], "synonyms": ["Alternative titles", "FFND", "FRONTOFACIONASAL DYSOSTOSIS"]}
|
A number sign (#) is used with this entry because retinitis pigmentosa-4 (RP4) is caused by heterozygous, and rarely by homozygous, mutation in the RHO gene (180380) on chromosome 3q22.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical Features
Bradley et al. (1989, 1989) reported a large 5-generation Irish family segregating autosomal dominant early-onset retinitis pigmentosa. Affected status was determined by using titally extinguished electroretinogram (ERG) and/or symptoms characteristic of RP, including nyctolopia and peripheral visual field loss. In addition, all affected individuals exhibited funduscopic disturbances typical of RP: disc pallor, attenuation of retinal vessels, and classic bone-spicule pigmentary deposits in the retinal periphery. All of those affected reported difficulty with night vision before the age of 10 yeaqrs, and extinguished ERG patterns coupled with funduscopic disturbances were obtained in 4 children aged 6 to 10 years.
Of the 12 families with RP in which mutations in the RHO gene were identified by Inglehearn et al. (1992), 4 had the D type, 3 had the sectoral type, and the remainder were of uncertain classification. All families excluded from chromosome 3q by linkage had been classified R type. The sectoral type of RP affects only 1 or 2 quadrants of the retina, with the remaining retina left intact. The disease is nonprogressive or progresses very slowly. The D type causes 'diffuse' and severe loss of rod function with retention of cone function until much later in the disease process. ERG and psychophysical testing show that rod function is abnormal over the entire fundus. The R type causes 'regional' or patchy and equal loss of rod and cone function.
Mapping
In a large Irish kindred segregating retinitis pigmentosa in which the disorder was previously excluded from the short arm of chromosome 1 (Bradley et al. (1989, 1989)), McWilliam et al. (1989) localized the disorder to 3q by demonstration of tight linkage to D3S47; maximum lod score = 14.4 at theta = 0.00. The marker they used was placed approximately 36 cM distal to D3S1, which had been localized to 3q12 by Donis-Keller et al. (1987). Because of the coincidence of mapping of the RP gene in the Irish kindred and the rhodopsin gene to 3q, the mutation presumably resided in the rhodopsin gene, thus starting a search for mutations.
In a large Australian kindred with what was referred to as type II autosomal dominant RP, Olsson et al. (1990) found linkage to marker D3S47 located on 3q; maximum lod = 4.78 at theta = 0.08. The results in the 2 families, Irish (McWilliam et al., 1989) and Australian, gave confidence limits that were overlapping. However, Olsson et al. (1990) raised the possibility of the existence of 2 separate RP loci on 3q and pointed out that, in addition to rhodopsin, there are 2 other candidate genes, those for retinol binding proteins 1 and 2 (180260, 180280), located on 3q. By statistical analysis, Kumar-Singh et al. (1993) concluded that there is only one autosomal dominant RP locus on 3q. They performed an admixture test on 10 D3S47-linked retinitis pigmentosa pedigrees and also on all families with known rhodopsin mutations.
Molecular Genetics
In patients with autosomal dominant retinitis pigmentosa mapping to 3q, Dryja et al. (1990) identified a heterozygous pro23-to-his mutation (P23H; 180380.0001) in the RHO gene. The proline residue at position 23 in the NH2 portion of the rhodopsin gene is highly conserved. Dryja et al. (1990) reported 3 additional missense mutations (180380.0002-180380.0004) in the RHO gene in patients with RP4. They found that these 4 mutations accounted for 27 of 150 unrelated patients with ADRP (18%).
In the original family with autosomal dominant retinitis pigmentosa linked to 3q (McWilliam et al., 1989), Farrar et al. (1992) identified an arg207-to-met mutation (180380.0030) in the RHO gene.
On the basis of a complete screen for mutations in the RHO gene in patients with autosomal dominant retinitis pigmentosa, Inglehearn et al. (1992) concluded that approximately 30% of such families have 'rhodopsin rp,' whereas the remainder probably have a defect elsewhere in the genome. Specifically they found 9 different RHO mutations in a total of 12 out of 39 families screened.
In a 5-generation Chinese Bai family segregating autosomal dominant RP mapping to chromosome 3q, Guo et al. (2010) identified heterozygosity for the P347L mutation in the RHO gene (180380.0002). The authors stated that, although mutations in RHO account for approximately 7.7% of autosomal dominant RP in the Chinese Han population, this was the first RHO mutation reported in RP patients of the Chinese Bai nationality.
In affected members of 2 Indonesian families segregating autosomal recessive RP4, Kartasasmita et al. (2011) identified a homozygous nonsense mutation in the RHO gene (180380.0045). Haplotype analysis suggested that this is a founder mutation.
Genotype/Phenotype Correlations
Jacobson et al. (1991) studied rod and cone function in 20 patients from 6 families with autosomal dominant RP due to 5 different point mutations in the rhodopsin gene. In addition to traditional ocular examination methods and electroretinography, they performed dark- and light-adapted perimetry, dark adaptometry, and imaging fundus reflectometry. Jacobson et al. (1991) observed discernible differences in the pattern of retinal dysfunction between families with different mutations (see T58R, 180380.0004; T17M, 180380.0006; and Q344X, 180380.0015) and noted that 3 families with mutations at the same amino acid position, arg135 (see R135W, 180380.0012, and R135L, 180380.0011), showed a similar functional phenotype involving early, severe retinal dysfunction with no intrafamilial variability.
Andreasson et al. (1992) reported a 6-generation Swedish family segregating autosomal dominant retinitis pigmentosa in whom they identified an R135L mutation (180380.0011). They noted that affected members of this family had a history of night blindness from early childhood and visual field losses were always noted before age 20. Andreasson et al. (1992) concluded that the R135L mutation may cause a more rapidly progressive form of RP than other mutations.
Pannarale et al. (1996) studied a large Sicilian pedigree with autosomal dominant retinitis pigmentosa due to the R135W mutation (180380.0012) in the rhodopsin molecule. The rate of progression of disease was unusually high, with an average 50% loss per year of baseline ERG amplitude and visual field area. Later in the course of the disease, macular function was also severely compromised, leaving only residual central vision by the fourth decade of life. Pannarale et al. (1996) concluded that the phenotype associated with mutations in codon 135 of the rhodopsin molecule appears to have an unusually high progression rate and to yield an extremely poor prognosis.
Ponjavic et al. (1997) examined a 4-generation Swedish RP family with the R135W mutation, in whom they documented a severe form of RP similar to the phenotype observed by Andreasson et al. (1992) in a family with the R135L mutation. Ponjavic et al. (1997) noted that both mutations cause the substitution of hydrophobic amino acids at codon 135, and that point mutations in this specific region of the rhodopsin molecule seem to cause an aggressive form of retinitis pigmentosa.
Oh et al. (2000) reported the clinical characteristics of a family with autosomal dominant retinitis pigmentosa caused by a pro23-to-ala mutation (P23A; 180380.0043) in the rhodopsin gene, and compared this phenotype with that associated with the more common pro23-to-his mutation (P23H; 180380.0001). The rare P23A mutation caused a mild RP in presentation and course, with greater preservation of ERG amplitudes than that resulting from the more prevalent P23H mutation.
Sandberg et al. (2007) measured the rates of visual acuity, visual field, and electroretinogram (ERG) loss in 2 large cohorts, one of patients with XLRP (RP3; 300029) due to mutations in the RPGR gene (312610) and the other of patients with autosomal dominant RP due to mutations in the RHO gene. Patients with RPGR mutations lost Snellen visual acuity at more than twice the mean rate of patients with RHO mutations. The median age of legal blindness was 32 years younger in patients with RPGR mutation than in patients with RHO mutations. Legal blindness was due primarily to loss of visual acuity in RPGR patients and to loss of visual field in RHO patients.
Using longitudinal data, Sakami et al. (2011) found that the earliest expression of retinal disease in ADRP patients with the P23H opsin mutation involved abnormal thinning of the outer nuclear layer and shortening of the rod outer segment. These changes were followed by shortening of the cone outer segment. With more extensive disease, there was further abnormality of inner and outer segments, followed by loss of all remaining photoreceptors.
Clinical Management
In a randomized, controlled, double-masked trial, Berson et al. (1993) concluded that oral vitamin A supplementation slowed, on average, the rate of retinal degeneration in adult patients with the common forms of retinitis pigmentosa. The conclusion was based on measuring the rate of electroretinogram (ERG) amplitude decline. Li et al. (1998) monitored the course of photoreceptor degeneration in 2 murine models of retinitis pigmentosa fed a diet containing either a normal or a higher amount of vitamin A. As the murine model of RP, they chose transgenic mice with the thr17-to-met (T17M) mutation (180380.0006) and mice with the pro347-to-ser (P347S; 180380.0003) mutation of the rhodopsin gene. The P347S mutation was chosen to be representative of class I mutant opsins, which are indistinguishable from wildtype opsin in all in vitro assays, including formation of photo pigment and efficient transport to the plasma membrane. The T17M mutation was selected as an example of class II mutant opsins, which are defective in thermal stability/folding, lack full regenerability with the chromophore 11-cis-retinal, and fail to reach the plasma membrane. In vivo, the P347S mutation appeared to cause aberrant transport of rhodopsin, possibly by disrupting a signal sequence that normally directs the vectorial transport of rhodopsin to the outer segments. Li et al. (1998) hypothesized that class II rhodopsin mutants are more likely to respond to vitamin A supplementation than are class I mutants. One putative mechanism through which vitamin A supplementation may slow photoreceptor degeneration is by increasing the availability of the chromophore, 11-cis-retinal. Chromophore binding increases the thermal stability of wildtype opsin and might stabilize the class II mutant rhodopsin. Li et al. (1998) found that a high vitamin A diet significantly reduced the rate of decline of a-wave and b-wave amplitudes in mice carrying a T17M rhodopsin mutation (class II) but had no significant effect on the decline of ERG amplitude in P347S (class I) mice. Correspondingly, histologic evaluation showed that the treatment was associated with significantly longer photoreceptor inner and outer segments and a thicker outer nuclear layer in the T17M mice but had no effect on photoreceptor morphology in the P347S mice. In a separate series of experiments, Li et al. (1998) found that the instability defect of the T17M mutant opsin expressed in vitro was partially alleviated by inclusion of 11-cis-retinal in the culture media. These results suggested that vitamin A supplementation can confer therapeutic benefit in the case of class II rhodopsin mutations by stabilizing mutant opsins through increased availability of the chromophore.
O'Reilly et al. (2007) noted that mutational heterogeneity represents a significant barrier to development of therapies for many dominantly inherited diseases. For example, more than 100 mutations in the rhodopsin gene have been identified in patients with retinitis pigmentosa. The development of therapies for dominant disorders that correct the primary genetic lesion and overcome mutational heterogeneity is challenging. Hence, therapeutics comprising 2 elements--gene suppression in conjunction with gene replacement--had been investigated. Suppression is targeted to a site independent of the mutation; therefore, both mutant and wildtype alleles are suppressed. In parallel with suppression, a codon-modified replacement gene refractory to suppression is provided. O'Reilly et al. (2007) undertook both in vitro and in vivo validation of suppression and replacement of RHO-associated retinitis pigmentosa. RNA interference (RNAi) was used to achieve approximately 90% in vivo suppression of RHO in photoreceptors, with use of adeno-associated virus (AAV) for delivery. Demonstration that codon-modified RHO genes express functional wildtype protein was explored transgenically, together with in vivo expression of AAV-delivered RHO-replacement genes in the presence of targeting RNAi molecules. Observation of potential therapeutic benefit from AAV-delivered suppression and replacement therapies was obtained in mice with the pro23-to-his mutation (180380.0001). Results provided the first in vivo indication that suppression and replacement can provide a therapeutic solution for dominantly inherited disorders such as RHO-associated RP and can be employed to circumvent mutational heterogeneity.
Hernan et al. (2011) investigated the cellular expression of cis-acting splicing mutations in the RHO gene that lead to autosomal dominant or recessive RP and the role of nonsense-mediated mRNA decay (NMD) in its pathogenic mechanisms, hoping to design a potential therapeutic RNAi-based suppression strategy for cis-acting adRP splicing mutants. Two RHO cis-acting splicing mutations causing adRP (531-2A-G and 937-1G-T) induced cryptic splicing. In contrast, a 936+1G-T mutation, causing arRP, resulted in exon skipping. Although the 531-2A-G and 745G-T RHO sequences predicted a premature termination codon (PTC) that should be a target for NMD, these mutant proteins were detected in transfected cells. The siRNAs designed to interfere with adRP mutants silence the corresponding mRNA with varying efficiency. Thus, different levels of mutant protein might be necessary to trigger the RP phenotype. Hernan et al. (2011) concluded that their findings demonstrate the potential use of siRNA to interfere with cis-acting splicing RHO transcripts, but noted that limitations in the mutation sequence and incomplete mutant transcript elimination should be considered in a therapeutic approach for adRP.
Animal Model
To investigate the mechanism by which the presence of both mutated rhodopsin and normal rhodopsin leads to the slow degeneration of the photoreceptor cells, Naash et al. (1993) established a transgenic mouse line that carried a mutated mouse opsin gene in addition to the endogenous opsin gene. The alterations consisted of 3 amino acid substitutions near the N terminus of which 1 was the P23H mutation. During early postnatal development, mice heterozygous for the mutated opsin gene appeared to develop normal photoreceptors, but their light-sensitive outer segments never reached normal length. With advancing age, both rod and cone photoreceptors were reduced progressively in number. The slow degeneration of the transgenic retina was associated with a gradual decrease of light-evoked electroretinogram responses.
Lem et al. (1999) stated that mutations in the RHO gene account for approximately 15% of all inherited human retinal degenerations. Investigations into the pathophysiologic and molecular events underlying these disease processes have included studies of transgenic mice expressing opsin genes containing defined mutations. A caveat of this approach is that even the overexpression of normal opsin levels leads to photoreceptor cell degeneration (Olsson et al., 1992). To overcome this problem, Lem et al. (1999) reduced or eliminated endogenous rhodopsin by targeted gene disruption. Retinas in mice lacking both opsin alleles initially developed normally, except that rod outer segments failed to form. Within months of birth, photoreceptor cells degenerated completely. Retinas from mice with a single copy of the opsin gene developed normally, and rods elaborated outer segments of normal size but with half the normal complement of rhodopsin. Photoreceptor cells in these retinas also degenerated but did so over a much slower time course. Physiologic and biochemical experiments showed that rods from mice with a single opsin gene were approximately 50% less sensitive to light, had accelerated flash-response kinetics, and contained approximately 50% more phosducin (171490) than wildtype controls.
To understand better the functional and structural role of rhodopsin in normal retina and the pathogenesis of retinal disease, Humphries et al. (1997) generated mice carrying a targeted disruption of the Rho gene. Rho -/- mice did not elaborate rod outer segments and lost their photoreceptors over 3 months. There was no rod ERG response in 8-week-old animals. Heterozygous animals retained most of their photoreceptors, although the inner and outer segments of these cells displayed some structural disorganization, the outer segments becoming shorter in older mice. Humphries et al. (1997) commented that these animals should provide a useful genetic background on which to express other mutant opsin transgenes, as well as a model to assess therapeutic potential of reintroducing functional rhodopsin genes into degenerating retinal tissues.
Kijas et al. (2002) identified English Mastiff dogs with a naturally occurring autosomal dominant retinal degeneration and determined the cause to be a thr4-to-arg mutation in the Rho gene. Dogs with this mutant allele manifested a retinal phenotype that closely mimicked that in humans with RHO mutations. The phenotypic features shared by dog and man included a dramatically slowed time course of recovery of rod photoreceptor function after light exposure and a distinctive topographic pattern of the retinal degeneration. The Rho mutant dog should be useful in preclinical trials of therapies.
Organisciak et al. (2003) found that light-induced retinal damage in transgenic rats depended on the time of day of exposure to light, prior light-or-dark-rearing environment, and the relative level of rhodopsin-transgene expression. Retinal light damage led to apoptotic photoreceptor cell loss and appeared to result from oxidative stress. The authors concluded that reduced environmental lighting and/or antioxidant treatment may delay retinal degenerations arising from rhodopsin mutations.
Jacobson and McInnes (2002) commented on the demonstration of the different pathways, a bright-light pathway and a low-light-dependent pathway. Although both pathways are initiated by excessive activation of the photopigment rhodopsin, they differ in that only the bright-light pathway is AP-1-dependent and only the low-light pathway is dependent on phototransduction.
White et al. (2007) found that expression of a human T17M mutant rhodopsin transgene in mice was associated with photoreceptor apoptosis in response to moderate exposure to light. This phenotype was not observed in nontransgenic littermates or in mice expressing a human P28H mutant rhodopsin transgene. White et al. (2007) noted that the T17M mutation abolishes glycosylation at the asn15 site of rhodopsin. They suggested that elimination of glycosylation at this site is associated with increased sensitivity to light-induced damage.
Congenital night blindness affects retinal rod photoreceptor cells and is expressed as an inability to see under dim light conditions. The disease appears to be caused by inappropriate stimulation, and consequent desensitization, of rod cells, and 2 models have been proposed for the source of the stimulatory signal. Model I suggests that the signal comes from constitutively active mutant apoprotein, or opsin, generated by thermal dissociation of 11-cis-retinal. Model II suggests that desensitization is caused by metarhodopsin II, an intermediate formed from increased thermal isomerization of the 11-cis-retinal chromophore in the mutant rhodopsins. Using a transgenic Xenopus model with disease-causing mutations, Jin et al. (2003) showed that incubation with exogenously added 11-cis-retinal resulted in recovery of wildtype sensitivity, findings that argue against the thermal isomerization theory of model II. The authors concluded that constitutively active mutant opsin cause the desensitization of the congenital night blindness photoreceptor cells, consistent with model I.
Galy et al. (2005) reported that P37H-transgenic flies, which correspond to the human P23H mutation (180380.0001), exhibited dominant photoreceptor degeneration, mimicking human age-, light-dependent and progressive ADRP. Most of mutant protein accumulated in endoplasmic reticulum, and expression of mislocalized mutant Rho led to cytotoxicity via activation of 2 stress-specific MAPKs, p38 (MAPK14; 600289) and JNK (MAPK8; 601158), which are known to control stress-induced apoptosis. In P37H-mutant flies, visual loss and degeneration were accompanied by apoptotic features and were prevented by expression of the baculovirus p35 apoptosis inhibitor.
Fernandez-Sanchez et al. (2011) evaluated the preventive effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa. TUDCA treatment was capable of preserving cone and rod structure and function, together with their contacts with their postsynaptic neurons. The amplitude of the electroretinogram a- and b-waves was significantly higher in TUDCA-treated animals under both scotopic and photopic conditions than in controls. TUDCA-treated P23H rats showed 3-fold more photoreceptors than control animals and photoreceptor morphology was preserved. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in TUDCA-treated P23H rats. Fernandez-Sanchez et al. (2011) concluded that the neuroprotective effects of TUDCA made the compound potentially useful for delaying retinal degeneration in RP.
History
A second locus for autosomal dominant RP, independent of the rhodopsin locus and called RP5, had been postulated by Olsson et al. (1990), McInnes and Bascom (1992), and Inglehearn et al. (1992). McInnes and Bascom (1992) commented that ironically no mutation in the rhodopsin gene had been found in the large Irish kindred studied by McWilliam et al. (1989) in which linkage of RP to 3q first stimulated search for rhodopsin mutations. They argued that although a mutation in a regulatory element had not been entirely excluded, the failure of 2 null alleles to result in abnormalities in obligate heterozygotes (Rosenfeld et al. (1992, 1992)) made it unlikely that a carrier of a regulatory domain mutation that reduced even to nothing the synthesis of a normal rhodopsin molecule would show photoreceptor degeneration in the heterozygous state. However, Inglehearn et al. (1993) later reported that mutations in the rhodopsin gene had been found in all 3 families with the presumably RHO-unlinked chromosome 3q form of RP: the Irish family of McWilliam et al. (1989) was found to have a met207-to-arg mutation (180380.0030); the family reported by Lester et al. (1990) was found to have a tyr178-to-cys mutation (180380.0013); and the family reported by Olsson et al. (1990) was found to have a thr58-to-arg mutation (180380.0004).
INHERITANCE \- Autosomal dominant \- Autosomal recessive HEAD & NECK Eyes \- Retinitis pigmentosa \- Pigmentary retinopathy \- Abnormal electroretinograms in heterozygotes \- Inferior and inferonasal retinal pigmentation (e.g. 180380.0004 and 180380.0025 ) \- Superior hemisphere field impairment (e.g. 180380.0004 and 180380.0025 ) \- Early onset night blindness and abnormal fundus (e.g. 180380.0013 ) \- Cataracts (e.g. 180380.0016 ) MISCELLANEOUS \- Mild asymmetric regional disease (e.g. 180380.0029 ) \- Onset in first decade (e.g. 180380.0028 ) MOLECULAR BASIS \- Caused by mutation in the rhodopsin gene (RHO, 180380.0001 ) ▲ 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-hydroxybutyric 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
|
RETINITIS PIGMENTOSA 4
|
c0035334
| 25,771 |
omim
|
https://www.omim.org/entry/613731
| 2019-09-22T15:57:39 |
{"doid": ["0110372"], "mesh": ["D012174"], "omim": ["613731"], "orphanet": ["791"], "synonyms": ["Alternative titles", "RETINITIS PIGMENTOSA, RHODOPSIN-RELATED"], "genereviews": ["NBK1417"]}
|
A number sign (#) is used with this entry because of evidence that Emery-Dreifuss muscular dystrophy-7 (EDMD7) is caused by heterozygous mutation in the TMEM43 gene (612048) on chromosome 3p25.
Description
Emery-Dreifuss muscular dystrophy is a genetically heterogeneous muscular disease that presents with muscular dystrophy, joint contractures, and cardiomyopathy with conduction defects (summary by Liang et al., 2011).
For a discussion of genetic heterogeneity of EDMD, see 310300.
Clinical Features
Liang et al. (2011) reported 2 unrelated Japanese patients with adult-onset Emery-Dreifuss muscular dystrophy. The first patient was a 40-year-old man who was diagnosed with typical clinical EDMD with limb-girdle type muscular dystrophy with cardiac conduction defects and muscle biopsy that showed marked fiber size variation with scattered internal nuclei. He died soon after, and no other medical records were available. He reportedly had an affected son, suggesting autosomal dominant inheritance, but the son was lost to follow-up. The second patient was a 68-year-old woman who had slowly progressive muscle weakness at atrophy involving the proximal muscles. These features were noted at age 64 when she had a pacemaker implanted for atrial fibrillation with bradycardia. Muscle biopsy showed a necrotic and regenerating process. There was no family history of a similar disorder.
Inheritance
Emery-Dreifuss muscular dystrophy-7 is inherited as an autosomal dominant trait (Liang et al., 2011).
Molecular Genetics
Based on the putative role for TMEM43 in the nuclear envelope, Liang et al. (2011) analyzed the TMEM43 gene in 41 patients with Emery-Dreifuss muscular dystrophy who were negative for mutations in known EDMD-related genes and identified different heterozygous missense mutations in 2 unrelated individuals (612048.0002 and 612048.0003).
INHERITANCE \- Autosomal dominant HEAD & NECK Neck \- Neck muscle weakness CARDIOVASCULAR Heart \- Arrhythmia \- Atrial fibrillation \- Cardiac conduction defects \- Bradycardia MUSCLE, SOFT TISSUES \- Muscle weakness, proximal \- Muscle atrophy, proximal \- Muscle biopsy shows dystrophic changes MISCELLANEOUS \- Adult onset \- Slowly progressive \- Two Japanese patients have been reported (last curated March 2013) MOLECULAR BASIS \- Caused by mutation in the transmembrane 43 gene (TMEM43, 612048.0002 ) ▲ 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-hydroxybutyric 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
|
EMERY-DREIFUSS MUSCULAR DYSTROPHY 7, AUTOSOMAL DOMINANT
|
c0410190
| 25,772 |
omim
|
https://www.omim.org/entry/614302
| 2019-09-22T15:55:45 |
{"doid": ["0070252"], "mesh": ["D020389"], "omim": ["614302"], "orphanet": ["98853", "261"]}
|
## Summary
### Clinical characteristics.
Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia despite normal glomerular filtration rate (GFR) and frequently by hypertension. Other associated findings in both children and adults include hyperchloremia, metabolic acidosis, and suppressed plasma renin levels. Aldosterone levels are variable, but are relatively low given the degree of hyperkalemia (elevated serum potassium is a potent stimulus for aldosterone secretion). Hypercalciuria is well described.
### Diagnosis/testing.
The diagnosis of PHAII is established in a proband:
* With hyperkalemia (in the setting of normal glomerular filtration), hypertension, metabolic acidosis, hyperchloremia, and suppressed plasma renin levels;
AND/OR
* By the identification of a heterozygous pathogenic variant in CUL3, WNK1, or WNK4 or a heterozygous pathogenic variant or biallelic pathogenic variants in KLHL3.
### Management.
Treatment of manifestations: Electrolyte and blood pressure abnormalities of PHAII in children and adults are often corrected with thiazide diuretics.
Prevention of secondary complications: Control of blood pressure is important to reduce the risk of cardiovascular and renal disease and stroke.
Surveillance: Routine electrolyte and blood pressure measurements.
Agents/circumstances to avoid: Untreated individuals with PHAII should avoid excessive intake of foods high in salt and potassium as these may exacerbate hypertension and hyperkalemia.
Evaluation of relatives at risk: Measurement of serum potassium concentration and blood pressure or identification of the known familial CUL3, KLHL3, WNK1, and WNK4 pathogenic variant(s) in first-degree relatives of individuals with PHAII allows for early diagnosis and treatment .
Pregnancy management: Affected pregnant women should undergo routine monitoring of electrolytes and blood pressure, with adjustments to antihypertensive medication dosage as needed. Some antihypertensive medications, including thiazide diuretics, have been associated with adverse fetal outcome, especially when taken during the first trimester of pregnancy; referral to an obstetrics group with expertise in high-risk pregnancies should be considered.
### Genetic counseling.
PHAII is frequently inherited in an autosomal dominant manner; PHAIID (caused by pathogenic variants in KLHL3) may also be inherited in an autosomal recessive manner. Many pathogenic variants in CUL3 arise de novo and are not inherited from a parent. Each child of an individual with autosomal dominant PHAII has a 50% chance of inheriting the pathogenic variant. Prenatal testing for a pregnancy at increased risk is possible if the pathogenic variant(s) in the family are known.
## Diagnosis
No formal diagnostic criteria for PHAII have been published.
### Suggestive Findings
Pseudohypoaldosteronism type II (PHAII) should be suspected in individuals with the following clinical features, supportive laboratory findings, and family history.
Clinical features. Hypertension (blood pressure >140/90 mm Hg) generally manifesting in adolescence or adulthood but also reported in children. Note: The absence of frank hypertension does not preclude the diagnosis.
Supportive laboratory findings
* Hyperkalemia in the absence of impaired glomerular filtration
* Serum concentration of potassium ranges from mildly (serum K ~5.0-6.0 mmol/L) to severely elevated (>8.0 mmol/L) (normal range: ~3.5-5.1 mmol/L).
* This finding is nearly universal in affected individuals at all ages.
* Metabolic acidosis: serum concentration of bicarbonate ranging from 14 to 24 mmol/L (normal range: ~22-29 mmol/L)
* Hyperchloremia: serum concentration of chloride ranging from 105 to 117 mmol/L (normal range: ~99-108 mmol/L)
* Suppressed plasma renin levels
* Variable serum aldosterone levels that tend to be relatively suppressed in the context of hyperkalemia
* Serum calcium and parathyroid hormone levels that are normal. However, hypercalciuria is noted in at least a subset of individuals.
Family history. A first-degree relative with similar findings. Note: Absence of a family history of a first-degree relative with similar findings does not preclude the diagnosis.
### Establishing the Diagnosis
The diagnosis of PHAII is established in a proband with hyperkalemia (in the setting of normal glomerular filtration) often accompanied by hypertension, metabolic acidosis, hyperchloremia, and suppressed plasma renin levels and/or by the identification of a heterozygous pathogenic variant in CUL3, KLHL3, WNK1, or WNK4 or biallelic pathogenic variants in KLHL3 (see Table 1). Note: PHAII is sometimes referred to by a subtype designation based on the associated gene; see Nomenclature.
Molecular genetic testing approaches can include serial single-gene testing and use of a multigene panel.
Serial single-gene testing
* It is reasonable to perform sequence analysis for pathogenic variants in CUL3 and/or KLHL3 first.
* If only one pathogenic variant in KLHL3 is identified in an individual in whom autosomal recessive inheritance is suspected, gene-targeted deletion/duplication analysis of KLHL3 should be considered.
* Sequence analysis of WNK4 may be performed next.
* If no pathogenic variant is identified through sequencing of WNK4, gene-targeted deletion/duplication analysis of WNK1 may be considered next.
* If no disease-causing deletion or duplication is found in WNK1, consider sequencing of WNK1.
A multigene panel that includes CUL3, KLHL3, WNK1, and WNK4 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included and the sensitivity of multigene panels 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.
### Table 1.
Molecular Genetic Testing Used in Pseudohypoaldosteronism Type II
View in own window
Gene 1Proportion of PHAII Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detectable by Method
Sequence analysis 3Gene-targeted deletion / duplication analysis 4
CUL325/86 families reportedAll reported cases to dateNone reported
KLHL341/86 families reported 5AD: 29/86
AR: 12/86Unknown 6
WNK18/86 families reportedSee footnote 7.2/2 8
WNK48/86 families reportedAll reported cases to dateNone reported
Unknown 94/52 10NA
AD = autosomal dominant; AR = autosomal recessive
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
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.
5\.
Both heterozygous (autosomal dominant) and biallelic (autosomal recessive) pathogenic variants in KLHL3 cause PHAII [Mayan et al 2004, Boyden et al 2012, Picard et al 2015a, Mitani et al 2016].
6\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
7\.
Recently, six kindreds (9 individuals) were reported in preliminary results to have pathogenic missense variants in WNK1 (detailed in Molecular Genetics).
8\.
Two large deletions have been reported (see Molecular Genetics) [Wilson et al 2001].
9\.
An additional locus on 1q31-q42 has been identified as harboring a gene associated with PHAII [Mansfield et al 1997]. The identity of this gene is unknown. PHAII has been reported in at least ten families that lack identifiable pathogenic variants in CUL3, KLHL3, WNK1, and WNK4 [Boyden et al 2012, Glover et al 2014].
10\.
Denominator is from the only report to document the number of PHAII individuals who did not have variants in CUL3, KLHL3, WNK1, or WNK4 [Boyden et al 2012].
## Clinical Characteristics
### Clinical Description
Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia despite normal glomerular filtration rate (GFR) and frequently by hypertension. More than 180 individuals and families with PHAII have been reported.
The clinical presentation of PHAII is heterogeneous. The most consistent clinical feature in both children and young adults is hyperkalemia [Gordon 1986]. As with essential hypertension, blood pressure is usually normal in young persons, with hypertension developing later in life. Untreated individuals with elevated blood pressure are at risk of developing complications of hypertension including cardiac disease, renal impairment, and stroke.
Other associated findings in both children and adults include hyperchloremia, metabolic acidosis, and suppressed plasma renin levels. Aldosterone levels are variable, but are relatively low given the degree of hyperkalemia (elevated serum potassium is a potent stimulus for aldosterone secretion). Hypercalciuria is also well described in PHAII [Mayan et al 2004].
Other features reported in a subset of individuals with PHAII include short stature, myalgias, periodic paralysis, and dental abnormalities [Gordon 1986]. It has been suggested that these findings may be more prevalent in individuals with severe hyperkalemia and metabolic acidosis; however, exceptions have been reported [Gordon 1986, Farfel et al 2011].
### Phenotype Correlations by Gene
Individuals with a heterozygous CUL3 pathogenic variant tend to have more severe hyperkalemia and metabolic acidosis, earlier development of hypertension, and greater likelihood of growth impairment compared to those harboring KLHL3, WNK1, or WNK4 alterations [Boyden et al 2012].
In general, clinical manifestations of PHAII appear to be milder in individuals with a heterozygous WNK1 or WNK4 pathogenic variant compared to those with a heterozygous CUL3 or a heterozygous or biallelic KLHL3 pathogenic variant(s) [Boyden et al 2012].
Individuals with biallelic KLHL3 pathogenic variants may have a more severe phenotype than individuals with a heterozygous pathogenic variant in KLHL3 [Boyden et al 2012, Louis-Dit-Picard et al 2012].
### Nomenclature
The term "pseudohypoaldosteronism" has historically been used to describe the finding of persistent hyperkalemia despite the presence of normal or elevated serum levels of aldosterone [Schambelan et al 1981]. The term was initially used to describe persons with an inherited disorder characterized by hyperkalemia, elevated serum aldosterone, and volume depletion (now referred to as pseudohypoaldosteronism type I).
Therefore, the term "pseudohypoaldosteronism" is a misnomer in the context of PHAII, as affected individuals have hyperkalemia with hypertension (instead of volume depletion). Some authorities prefer the descriptive name familial hyperkalemic hypertension (FHHt) for this reason.
PHAII is sometimes referred to by a subtype designation based on the associated gene, as follows:
* PHA type IIA (PHA2A): Unknown genetic cause (see Table 1, footnotes 9 and 10)
* PHA type IIB (PHA2B): WNK4
* PHA type IIC (PHA2C): WNK1
* PHA type IIE (PHA2E): CUL3
* PHA type IID (PHA2D): KLHL3
### Prevalence
The prevalence of the disorder is unknown. To date more than 180 individuals and families with PHAII have been reported.
## Differential Diagnosis
Other causes of hyperkalemia. Hyperkalemia resulting from the following can generally be distinguished from hyperkalemia caused by PHAII on the basis of plasma renin levels, which are increased in the following conditions and suppressed in PHAII:
* Chronic kidney disease, especially when secondary to diabetes, is the most commonly identified cause of hyperkalemia.
* When renal function is normal, consider the following:
* Hypoaldosteronism or acquired renal tubular acidosis (type 4), particularly in the setting of marked volume depletion
* Medication effects. Examples include potassium-sparing diuretics (e.g., spironolactone), nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin inhibitors, trimethoprim, and cyclosporine.
* Primary adrenal insufficiency or deficiency of an adrenal synthetic enzyme
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs of an individual diagnosed with pseudohypoaldosteronism type II (PHAII), the following evaluations (if not performed as part of the diagnostic evaluation) are recommended:
* Serum electrolyte analysis
* Noninvasive blood pressure measurement
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Electrolyte and blood pressure abnormalities of PHAII are often corrected with thiazide diuretics. Metabolic abnormalities and hypertension generally improve within one week.
Different thiazide diuretics exist, with different dosing regimens. In general dosing is titrated to normalization of blood pressure. It is possible that dosing will need to be increased over time or that additional anti-hypertensives will be required to adequately control blood pressure.
There are no established guidelines regarding age at which treatment should begin for individuals with PHAII, but affected children who have hypertension are generally treated.
### Prevention of Primary Manifestations
See Treatment of Manifestations.
### Prevention of Secondary Complications
Control of blood pressure is important to reduce the risk for cardiovascular and renal disease and stroke.
### Surveillance
Appropriate surveillance includes routine electrolyte and blood pressure measurements, monitored in the same manner as for any person treated with a thiazide diuretic.
### Agents/Circumstances to Avoid
Untreated individuals with PHAII should avoid excessive intake of foods high in salt and potassium as these may exacerbate hypertension and hyperkalemia.
### Evaluation of Relatives at Risk
It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment. Evaluations can include:
* Measurement of serum potassium concentration and blood pressure;
* Molecular genetic testing if the pathogenic variant(s) in the family are known.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
During the pregnancy of a woman with PHAII, electrolytes and blood pressure should be monitored regularly and blood pressure medication adjusted as needed.
Some antihypertensive medications (including thiazide diuretics) have been associated with adverse fetal outcome, especially when taken during the first trimester of pregnancy. The best time to discuss the risk to the fetus associated with a maternal medication is prior to conception. Women with PHAII who become pregnant should be referred to an obstetrics group with expertise in high-risk pregnancies.
See MotherToBaby for further information on medication use during pregnancy.
### 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-hydroxybutyric 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
|
Pseudohypoaldosteronism Type II
|
c1449844
| 25,773 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK65707/
| 2021-01-18T21:01:22 |
{"mesh": ["D011546"], "synonyms": ["Familial Hyperkalemic Hypertension", "Gordon's Syndrome", "PHAII"]}
|
A number sign (#) is used with this entry because of evidence that Alazami-Yuan syndrome (ALYUS) is caused by homozygous mutation in the TAF6 gene (602955) on chromosome 7q22.
Clinical Features
Alazami et al. (2015) reported an 11-year-old boy, born of consanguineous Saudi Arabian parents, with intellectual disability and dysmorphic features. He had hypotonia and poor feeding soon after birth, and later showed delayed psychomotor development with poor speech acquisition. Dysmorphic features included strabismus, low hairline, synophrys, curved eyebrows, prominent nasal bridge, short columella, hypoplastic nasal wings, and high-arched palate with crowded teeth. He also had widely spaced nipples and cryptorchidism. Brain imaging was normal.
Yuan et al. (2015) reported a 4-year-old boy, born of consanguineous Turkish parents, with ALYUS. He had delayed psychomotor development with intellectual disability. Physical features included short stature, microcephaly, narrow shoulders, single transverse palmar crease on the right hand, unilateral cryptorchidism, hirsutism, and a dysmorphic facial appearance, including arched eyebrows with synophrys, long curly eyelashes, long philtrum, prominent nose, microstomia, and thin upper lip. These features were reminiscent of Cornelia de Lange syndrome (see, e.g., CDLS1, 122470). Family history revealed 2 deceased infant sibs with similar features. Yuan et al. (2015) also independently reported 3 sibs from the consanguineous Saudi family reported by Alazami et al. (2015) who had a similar disorder with milder dysmorphic facial features.
Inheritance
The transmission pattern of ALYUS in the families reported by Yuan et al. (2015) was consistent with autosomal recessive inheritance.
Molecular Genetics
In an 11-year-old boy with intellectual disability and dysmorphic features, Alazami et al. (2015) identified a homozygous missense mutation in the TAF6 gene (I71T; 602955.0001). The family was part of a large cohort of 143 multiplex consanguineous families with various neurodevelopmental disorders who underwent whole-exome sequencing. Functional studies of the variant and studies of patient cells were not performed.
In a Turkish boy, born of consanguineous parents, with ALYUS, Yuan et al. (2015) identified a homozygous missense mutation in the TAF6 gene (R46C; 602955.0002). The patient was part of a cohort of 32 Turkish patients with a clinical diagnosis of CDLS who underwent genome sequencing. In addition, 3 sibs from the consanguineous Saudi family with a similar disorder identified by Alazami et al. (2015) were found to be homozygous for the I71T mutation. The mutations segregated with the disorder in both families. In vitro functional expression studies in a Drosophila cell line showed that both mutations reduced the binding interaction with other components of the transcription factor IID complex (TFIID; see 313650), with the I71T variant showing a more deleterious effect than R45C. Transfection of the mutations into yeast resulted in a slight, but not obvious, growth reduction. The findings were consistent with a loss of function and suggested that the phenotype resulted from changes in transcriptional regulation pathways.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly Face \- Long philtrum Eyes \- Long eyelashes \- Arched eyebrows \- Thick eyebrows \- Synophrys Nose \- Prominent nose \- Prominent nasal bridge \- Hypoplastic nasal wings \- Long columella Mouth \- Microstomia \- Thin upper lip \- High-arched palate Teeth \- Crowded teeth GENITOURINARY External Genitalia (Male) \- Cryptorchidism SKELETAL Hands \- Palmar crease Feet \- Broad great toes SKIN, NAILS, & HAIR Hair \- Long eyelashes \- Arched eyebrows \- Thick eyebrows \- Synophrys \- Low frontal hairline \- Hirsutism MUSCLE, SOFT TISSUES \- Hypotonia, neonatal NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Poor speech Behavioral Psychiatric Manifestations \- Hyperactivity MISCELLANEOUS \- Variable features \- Five patients from 3 consanguineous families have been reported (last curated September 2016) MOLECULAR BASIS \- Caused by mutation in the TAF6 RNA polymerase II, TATA box-binding protein-associated factor, 80-kD gene (TAF6, 602955.0001 ) ▲ 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-hydroxybutyric 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
|
ALAZAMI-YUAN SYNDROME
|
c4310702
| 25,774 |
omim
|
https://www.omim.org/entry/617126
| 2019-09-22T15:46:52 |
{"omim": ["617126"]}
|
A number sign (#) is used with this entry because of evidence that proteasome-associated autoinflammatory syndrome-3 (PRAAS3) is caused by homozygous mutation in the PSMB4 gene (602177) on chromosome 1q21. One such patient has been reported.
One unrelated family with a similar phenotype was found to have a digenic form of PRAAS3 due to a heterozygous mutation in the PSMB4 gene and a heterozygous mutation in the PSMB9 gene (177045) on chromosome 6p21.
Description
Proteasome-associated autoinflammatory syndrome-3 is an autosomal recessive syndrome with onset in early infancy. Affected individuals present with nodular dermatitis, recurrent fever, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and dysregulation of the immune response, particularly associated with abnormal type I interferon-induced gene expression patterns. Additional features are highly variable, but may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications (summary by Brehm et al., 2015).
For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).
Clinical Features
Liu et al. (2012) reported a 5.5-year-old Caucasian boy of American descent (patient 6) with onset of an autoinflammatory disease in the first 2 weeks of life. He presented with a rash, periorbital erythema with violaceous eyelids, and swelling of the foot. He had recurrent fevers associated with increased acute-phase reactants (erythrocyte sedimentation rate and C-reactive protein), lymphadenopathy, finger swelling, annular plaques, hepatosplenomegaly, and failure to thrive with poor overall growth. Additional features included arthritis, prominent abdomen with lipodystrophy, recurrent otitis and sinusitis, and bronchiolitis obliterans organizing pneumonia (BOOP) of the lungs, consistent with inflammation. Laboratory studies showed hypochromic anemia, intermittently elevated liver function tests, and mildly increased triglycerides. He was treated with multiple antiinflammatory medications, including steroids and methotrexate, without success. Brehm et al. (2015) reported follow-up of this patient (patient 1) at age 8 years. He was also noted to have myositis, joint contractures, hypergammaglobulinemia, antinuclear autoantibodies, thrombocytopenia, lymphopenia, and metabolic syndrome.
### Digenic Inheritance
Brehm et al. (2015) reported 2 sibs of Jamaican descent (family 4) with digenic PRAAS (see MOLECULAR GENETICS). The patients presented in the first week of life with skin lesions, fever, and swallowing difficulties. They had annular plaques, violaceous eyelids, conjunctivitis, keratitis, hyperpigmented macules, and scarring. Additional features included poor overall growth, lymphadenopathy, myositis, arthritis/arthralgias, joint contractures, and lipodystrophy. Most had recurrent infections. Laboratory studies showed elevated acute phase reactants, microcytic anemia, thrombocytopenia, lymphopenia, hypercholesterolemia, and variable hypergammaglobulinemia. One patient had autoantibodies. More variable features included metabolic syndrome and peripheral calcinosis.
Inheritance
The transmission pattern of PRAAS3 in a family (family 1) reported by Brehm et al. (2015) was consistent with autosomal recessive inheritance.
The transmission pattern in a family with PRAAS3 (family 4) reported by Brehm et al. (2015) was consistent with digenic inheritance.
Molecular Genetics
In an 8-year-old Caucasian boy of American descent (patient 1) with PRAAS3, Brehm et al. (2015) identified compound heterozygous mutations in the PSMB4 gene (602177.0001 and 602177.0002). The mutations, which were found by a combination of whole-exome sequencing and sequencing of proteasome candidate genes and confirmed by Sanger sequencing, segregated with the disorder in the families. Detailed functional studies, including in vitro studies of patient cells, expression of the mutations into HeLa cells, and siRNA-mediated knockdown of the proteasomal genes, demonstrated that the mutations resulted in variable defects in proteasome 20S and 26S assembly and maturation, with accumulation of proteasome precursor complexes, as well as impaired proteolytic activity. The defects were associated with induction of a type I interferon response with strong expression of IFN-inducible genes and an increase in the secretion of chemokines and cytokines. Patient skin biopsies showed increased ubiquitin-positive keratinocytes and impaired proteasomal assembly due to impaired incorporation of subunits. Brehm et al. (2015) concluded that mutations in proteasomal subunit genes adversely affect proteasomal function, leading to cell stress and the triggering of a type I IFN gene response, causing a vicious cycle of uncontrolled inflammation in both hematopoietic and nonhematopoietic cells.
### Digenic Inheritance
Brehm et al. (2015) reported 2 sibs of Jamaican descent (family 4) with digenic PRAAS. A combination of whole-exome sequencing and sequencing of proteasome candidate genes showed that the patients had a heterozygous mutation in the PSMB4 gene (602177.0003) on 1 allele and a heterozygous mutation in the PSMB9 gene (177045.0001) on the other allele. The mutations were confirmed by Sanger sequencing and segregated with the disorder in the family.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive \- Poor overall growth HEAD & NECK Head \- Sinusitis Face \- Facial edema Ears \- Otitis Eyes \- Periorbital swelling \- Periorbital erythema \- Violaceous eyelids \- Conjunctivitis ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly SKELETAL \- Arthralgia \- Arthritis \- Joint contractures Hands \- Finger swelling Feet \- Toe swelling SKIN, NAILS, & HAIR Skin \- Skin rash \- Skin lesions \- Annular plaques \- Acanthosis nigricans \- Neutrophilic dermatosis MUSCLE, SOFT TISSUES \- Lipodystrophy \- Intraabdominal fat \- Myositis \- Panniculitis \- Peripheral calcinosis NEUROLOGIC Central Nervous System \- Aseptic meningitis METABOLIC FEATURES \- Fever, recurrent \- Metabolic syndrome HEMATOLOGY \- Anemia \- Thrombocytopenia \- Lymphopenia IMMUNOLOGY \- Hypergammaglobulinemia \- Autoantibodies \- Autoinflammation, chronic \- Lymphadenopathy \- Lymphopenia \- Recurrent infections LABORATORY ABNORMALITIES \- Increased acute phase reactants \- Increased erythrocyte sedimentation rate \- Increased C-reactive protein \- Increased triglycerides \- High LDL \- Low HDL \- Elevated liver enzymes MISCELLANEOUS \- Onset in early infancy \- One patient with only PSMB4 mutations has been reported (last curated July 2018) \- Digenic inheritance (mutation in PSMB4 and PSMB9) has been reported in 1 family (last curated July 2018) MOLECULAR BASIS \- Caused by mutation in the proteasome subunit, beta-type, 4 gene (PSMB4, 602177.0001 ) ▲ 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-hydroxybutyric 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
|
PROTEASOME-ASSOCIATED AUTOINFLAMMATORY SYNDROME 3
|
None
| 25,775 |
omim
|
https://www.omim.org/entry/617591
| 2019-09-22T15:45:29 |
{"omim": ["617591"]}
|
Inflammation of the gums
Gingivitis
A severe case of gingivitis.
SpecialtyDentistry
Gingivitis is a non-destructive disease that causes inflammation of the gums.[1] The most common form of gingivitis, and the most common form of periodontal disease overall, is in response to bacterial biofilms (also called plaque) that is attached to tooth surfaces, termed plaque-induced gingivitis. Most forms of gingivitis are plaque-induced.[2]
While some cases of gingivitis never progress to periodontitis,[3] periodontitis is always preceded by gingivitis.[4]
Gingivitis is reversible with good oral hygiene; however, without treatment, gingivitis can progress to periodontitis, in which the inflammation of the gums results in tissue destruction and bone resorption around the teeth. Periodontitis can ultimately lead to tooth loss.[5]
## Contents
* 1 Signs and symptoms
* 1.1 Complications
* 1.1.1 Alzheimer's and dementia
* 2 Cause
* 2.1 Risk factors
* 3 Diagnosis
* 3.1 Classification
* 3.1.1 1999 Classification
* 3.1.2 2017 Classification
* 4 Prevention
* 5 Treatment
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Gingivitis
The symptoms of gingivitis are somewhat non-specific and manifest in the gum tissue as the classic signs of inflammation:
* Swollen gums
* Bright red or purple gums
* Gums that are tender or painful to the touch
* Bleeding gums or bleeding after brushing and/or flossing
* Bad breath (halitosis)
Additionally, the stippling that normally exists in the gum tissue of some individuals will often disappear and the gums may appear shiny when the gum tissue becomes swollen and stretched over the inflamed underlying connective tissue. The accumulation may also emit an unpleasant odor. When the gingiva are swollen, the epithelial lining of the gingival crevice becomes ulcerated and the gums will bleed more easily with even gentle brushing, and especially when flossing.
### Complications[edit]
* Recurrence of gingivitis
* Periodontitis
* Infection or abscess of the gingiva or the jaw bones
* Trench mouth (bacterial infection and ulceration of the gums)
* Swollen lymph nodes
* Associated with premature birth and low birth weight[6]
#### Alzheimer's and dementia[edit]
A new study from 2018 found compelling evidence that gingivitis bacteria may be linked to Alzheimer's disease. Scientists agree that more research is needed to prove a cause and effect link.[7] "Studies have also found that the bacteria P. gingivalis – which are responsible for many forms of gum disease – can migrate from the mouth to the brain in mice. And on entry to the brain, P. gingivalis can reproduce all of the characteristic features of Alzheimer’s disease."
## Cause[edit]
Because plaque-induced gingivitis is by far the most common form of gingival diseases, the following sections will deal primarily with this condition.
The cause of plaque-induced gingivitis is bacterial plaque, which acts to initiate the body's host response. This, in turn, can lead to destruction of the gingival tissues, which may progress to destruction of the periodontal attachment apparatus.[8] The plaque accumulates in the small gaps between teeth, in the gingival grooves and in areas known as plaque traps: locations that serve to accumulate and maintain plaque. Examples of plaque traps include bulky and overhanging restorative margins, clasps of removable partial dentures and calculus (tartar) that forms on teeth. Although these accumulations may be tiny, the bacteria in them produce chemicals, such as degradative enzymes, and toxins, such as lipopolysaccharide (LPS, otherwise known as endotoxin) or lipoteichoic acid (LTA), that promote an inflammatory response in the gum tissue. This inflammation can cause an enlargement of the gingiva and subsequent formation. Early plaque in health consists of a relatively simple bacterial community dominated by Gram-positive cocci and rods. As plaque matures and gingivitis develops, the communities become increasingly complex with higher proportions of Gram-negative rods, fusiforms, filaments, spirilla and spirochetes. Later experimental gingivitis studies, using culture, provided more information regarding the specific bacterial species present in plaque. Taxa associated with gingivitis included Fusobacterium nucleatum subspecies polymorphum, Lachnospiraceae [G-2] species HOT100, Lautropia species HOTA94, and Prevotella oulorum (a species of Prevotella bacterium), whilst Rothia dentocariosa was associated with periodontal health.[9] Further study of these taxa is warranted and may lead to new therapeutic approaches to prevent periodontal disease.
### Risk factors[edit]
Risk factors associated with gingivitis include the following:
* age
* osteoporosis
* low dental care utilization
* poor oral hygiene
* overly aggressive oral hygiene such as brushing with stiff bristles
* Mouth breathing during sleep
* medications and conditions that dry the mouth
* cigarette smoking
* genetic factors
* stress
* mental health issues such as depression
* pre-existing conditions such as diabetes
## Diagnosis[edit]
Gingivitis is a category of periodontal disease in which there is no loss of bone but inflammation and bleeding are present.
Each tooth is divided into four gingival units (mesial, distal, buccal, and lingual) and given a score from 0–3 based on the gingival index. The four scores are then averaged to give each tooth a single score.
The diagnosis of the periodontal disease gingivitis is done by a dentist. The diagnosis is based on clinical assessment data acquired during a comprehensive periodontal exam. Either a registered dental hygienist or a dentist may perform the comprehensive periodontal exam but the data interpretation and diagnosis are done by the dentist. The comprehensive periodontal exam consists of a visual exam, a series of radiographs, probing of the gingiva, determining the extent of current or past damage to the periodontium and a comprehensive review of the medical and dental histories.
Current research shows that activity levels of the following enzymes in saliva samples are associated with periodontal destruction: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and acid phosphatase (ACP). Therefore, these enzyme biomarkers may be used to aid in the diagnosis and treatment of gingivitis and periodontitis.
A dental hygienist or dentist will check for the symptoms of gingivitis, and may also examine the amount of plaque in the oral cavity. A dental hygienist or dentist will also look for signs of periodontitis using X-rays or periodontal probing as well as other methods.
If gingivitis is not responsive to treatment, referral to a periodontist (a specialist in diseases of the gingiva and bone around teeth and dental implants) for further treatment may be necessary.
### Classification[edit]
#### 1999 Classification[edit]
As defined by the 1999 World Workshop in Clinical Periodontics, there are two primary categories of gingival diseases, each with numerous subgroups:[10]
1. Dental plaque-induced gingival diseases.
1. Gingivitis associated with plaque only
2. Gingival diseases modified by systemic factors
3. Gingival diseases modified by medications
4. Gingival diseases modified by malnutrition
2. Non-plaque-induced gingival lesions
1. Gingival diseases of specific bacterial origin
2. Gingival diseases of viral origin
3. Gingival diseases of fungal origin
4. Gingival diseases of genetic origin
5. Gingival manifestations of systemic conditions
6. Traumatic lesions
7. Foreign body reactions
8. Not otherwise specified
#### 2017 Classification[edit]
As defined by the 2017 World Workshop, periodontal health, gingival diseases/ conditions have been categorised into the following:[11]
1. Periodontal health and gingival health
1. Clinical gingival health on an intact periodontium
2. Clinical gingival health on a reduced periodontium
1. Stable periodontitis patient
2. Non-periodontitis patient
2. Gingivitis – dental biofilm-induced
1. Associated with dental biofilm alone
2. Mediated by systemic or local risk factors
3. Drug-influenced gingival enlargement
3. Gingival diseases – non-dental biofilm induced
1. Genetic/ developmental disorders
2. Specific infections
3. Inflammatory and immune conditions
4. Reactive processes
5. Neoplasms
6. Endocrine, nutritional & metabolic diseases
7. Traumatic lesions
8. Gingival pigmentation
## Prevention[edit]
Gingivitis can be prevented through regular oral hygiene that includes daily brushing and flossing.[12] Hydrogen peroxide, saline, alcohol or chlorhexidine mouth washes may also be employed. In a 2004 clinical study, the beneficial effect of hydrogen peroxide on gingivitis has been highlighted.[13] The use of oscillation type brushes might reduce the risk of gingivitis compared to manual brushing.[14]
Rigorous plaque control programs along with periodontal scaling and curettage also have proved to be helpful, although according to the American Dental Association, periodontal scaling and root planing are considered as a treatment for periodontal disease, not as a preventive treatment for periodontal disease.[15] In a 1997 review of effectiveness data, the U.S. Food and Drug Administration (FDA) found clear evidence showing that toothpaste containing triclosan was effective in preventing gingivitis.[16]
## Treatment[edit]
Gingivitis before (top) and after (bottom) a thorough mechanical debridement of the teeth
Analgesic and antiseptic gum paint with applicator buds used in treatment of gingivitis
The focus of treatment is to remove plaque. Therapy is aimed at the reduction of oral bacteria and may take the form of regular periodic visits to a dental professional together with adequate oral hygiene home care. Thus, several of the methods used in the prevention of gingivitis can also be used for the treatment of manifest gingivitis, such as scaling, root planing, curettage, mouth washes containing chlorhexidine or hydrogen peroxide, and flossing. Interdental brushes also help remove any causative agents.
Powered toothbrushes work better than manual toothbrushes in reducing the disease.[17]
The active ingredients that "reduce plaque and demonstrate effective reduction of gingival inflammation over a period of time" are triclosan, chlorhexidine digluconate, and a combination of thymol, menthol, eucalyptol, and methyl salicylate. These ingredients are found in toothpaste and mouthwash. Hydrogen peroxide was long considered a suitable over-the-counter agent to treat gingivitis. There has been evidence to show the positive effect on controlling gingivitis in short-term use. A study indicates the fluoridated hydrogen peroxide-based mouth rinse can remove teeth stain and reduce gingivitis.[13]
Based on a limited evidence, mouthwashes with essential oils may also be useful, as they contain ingredients with anti-inflammatory properties, such as thymol, menthol and eucalyptol.[18]
The bacteria that causes gingivitis can be controlled by using an oral irrigator daily with a mouthwash containing an antibiotic. Either amoxicillin, cephalexin, or minocycline in 500 grams of a non-alcoholic fluoride mouthwash is an effective mixture.[19]
Overall, intensive oral hygiene care has been shown to improve gingival health in individuals with well-controlled type 2 diabetes. Periodontal destruction is also slowed due to the extensive oral care. Intensive oral hygiene care (oral health education plus supra-gingival scaling) without any periodontal therapy improves gingival health, and may prevent progression of gingivitis in well-controlled diabetes.
## See also[edit]
* Medicine portal
* Periodontitis
* Pericoronitis
* "Full width gingivitis" of orofacial granulomatosis
* Desquamative gingivitis
## References[edit]
1. ^ The American Academy of Periodontology. Proceedings of the World Workshop in Clinical Periodontics. Chicago:The American Academy of Periodontology; 1989:I/23-I/24.
2. ^ Dental Hygiene - E-Book: Theory and Practice, by Michele Leonardi Darby, Margaret Walsh, page 318
3. ^ Ammons, WF; Schectman, LR; Page, RC (1972). "Host tissue response in chronic periodontal disease. 1. The normal periodontium and clinical manifestations of dental and periodontal disease in the marmoset". Journal of Periodontal Research. 7 (2): 131–43. doi:10.1111/j.1600-0765.1972.tb00638.x. PMID 4272039.
4. ^ Page, RC; Schroeder, HE (1976). "Pathogenesis of inflammatory periodontal disease. A summary of current work". Laboratory Investigation. 34 (3): 235–49. PMID 765622.
5. ^ "Parameter on Plaque-Induced Gingivitis". Journal of Periodontology. 71 (5 Suppl): 851–2. 2000. doi:10.1902/jop.2000.71.5-S.851. PMID 10875689.
6. ^ Saini, Rajiv; Saini, Santosh; Saini, Sugandha R. (2010-01-01). "Periodontitis: A risk for delivery of premature labor and low-birth-weight infants". Journal of Natural Science, Biology, and Medicine. 1 (1): 40–42. doi:10.4103/0976-9668.71672. ISSN 0976-9668. PMC 3217279. PMID 22096335.
7. ^ Sim K. Singhrao (January 30, 2019). "Alzheimer's is linked to gum disease – but bad oral health is not the only culprit". theconversation.com.
8. ^ Research, Science and Therapy Committee of the American Academy of Periodontology (2001). "Treatment of Plaque-Induced Gingivitis, Chronic Periodontitis, and Other Clinical Conditions". Journal of Periodontology. 72 (12): 1790–1800. doi:10.1902/jop.2001.72.12.1790. PMID 11811516.
9. ^ Kistler, James O.; Booth, Veronica; Bradshaw, David J.; Wade, William G.; Glogauer, Michael (14 August 2013). "Bacterial Community Development in Experimental Gingivitis". PLOS ONE. 8 (8): e71227. Bibcode:2013PLoSO...871227K. doi:10.1371/journal.pone.0071227. PMC 3743832. PMID 23967169.
10. ^ Armitage, Gary C. (1999). "Development of a Classification System for Periodontal Diseases and Conditions" (PDF). Annals of Periodontology. 4 (1): 1–6. doi:10.1902/annals.1999.4.1.1. PMID 10863370. Archived from the original (PDF) on 2010-06-12. Retrieved 2010-05-12.
11. ^ Caton, Jack G.; Armitage, Gary; Berglundh, Tord; Chapple, Iain L. C.; Jepsen, Søren; Kornman, Kenneth S.; Mealey, Brian L.; Papapanou, Panos N.; Sanz, Mariano; Tonetti, Maurizio S. (2018). "A new classification scheme for periodontal and peri-implant diseases and conditions – Introduction and key changes from the 1999 classification". Journal of Clinical Periodontology. 45 (S20): S1–S8. doi:10.1111/jcpe.12935. ISSN 1600-051X. PMID 29926489.
12. ^ Sambunjak, D.; Nickerson, J. W.; Poklepovic, T.; Johnson, T. M.; Imai, P.; Tugwell, P.; Worthington, H. V. (2011). Johnson, Trevor M (ed.). "Flossing for the management of periodontal diseases and dental caries in adults". The Cochrane Database of Systematic Reviews (12): CD008829. doi:10.1002/14651858.CD008829.pub2. PMID 22161438.
13. ^ a b Hasturk, Hatice; Nunn, Martha; Warbington, Martha; Van Dyke, Thomas E. (2004). "Efficacy of a Fluoridated Hydrogen Peroxide-Based Mouthrinse for the Treatment of Gingivitis: A Randomized Clinical Trial". Journal of Periodontology. 75 (1): 57–65. doi:10.1902/jop.2004.75.1.57. PMID 15025217.
14. ^ Deacon, Scott A; Glenny, Anne-Marie; Deery, Chris; Robinson, Peter G; Heanue, Mike; Walmsley, A Damien; Shaw, William C (2010-12-08). "Cochrane Database of Systematic Reviews". The Cochrane Database of Systematic Reviews (12): CD004971. doi:10.1002/14651858.cd004971.pub2. PMID 21154357.
15. ^ American Dental Hygienists’ Association Position Paper on the Oral Prophylaxis Archived 2012-06-26 at the Wayback Machine, Approved by the ADHA Board of Trustees April 29, 1998
16. ^ FDA Triclosan: What Consumers Should Know Accessed 2010-08-12
17. ^ Yaacob, M; Worthington, HV; Deacon, SA; Deery, C; Walmsley, AD; Robinson, PG; Glenny, AM (17 June 2014). "Powered versus manual toothbrushing for oral health". The Cochrane Database of Systematic Reviews. 6 (6): CD002281. doi:10.1002/14651858.CD002281.pub3. PMC 7133541. PMID 24934383.
18. ^ Stoeken, Judith E.; Paraskevas, Spiros; Van Der Weijden, Godefridus A. (2007). "The Long-Term Effect of a Mouthrinse Containing Essential Oils on Dental Plaque and Gingivitis: A Systematic Review". Journal of Periodontology. 78 (7): 1218–28. doi:10.1902/jop.2007.060269. PMID 17608576.
19. ^ WebMD Treatments for Gum Disease
## External links[edit]
Classification
D
* ICD-10: K05.0-K05.1
* ICD-9-CM: 523.0-523.1
* MeSH: D005891
* DiseasesDB: 34517
* SNOMED CT: 66383009
External resources
* MedlinePlus: 001056
* eMedicine: article/763801
* v
* t
* e
Dentistry involving supporting structures of teeth (Periodontology)
Anatomy
* Periodontium
* Alveolar bone
* Biologic width
* Bundle bone
* Cementum
* Free gingival margin
* Gingiva
* Gingival fibers
* Gingival sulcus
* Junctional epithelium
* Mucogingival junction
* Periodontal ligament
* Sulcular epithelium
* Stippling
Disease
Diagnoses
* Chronic periodontitis
* Localized aggressive periodontitis
* Generalized aggressive periodontitis
* Periodontitis as a manifestation of systemic disease
* Periodontosis
* Necrotizing periodontal diseases
* Abscesses of the periodontium
* Combined periodontic-endodontic lesions
Infection
* A. actinomycetemcomitans
* Capnocytophaga sp.
* F. nucleatum
* P. gingivalis
* P. intermedia
* T. forsythia
* T. denticola
* Red complex
* Entamoeba gingivalis (amoebic)
* Trichomonas tenax
Other
* Calculus
* Clinical attachment loss
* Edentulism
* Fremitus
* Furcation defect
* Gingival enlargement
* Gingival pocket
* Gingival recession
* Gingivitis
* Horizontal bony defect
* Linear gingival erythema
* Occlusal trauma
* Periodontal pocket
* Periodontal disease
* Periodontitis
* Plaque
* Vertical bony defect
Treatment and prevention
* Periodontal examination
* Ante's law
* Brushing
* Bleeding on probing
* Chlorhexidine gluconate
* Flossing
* Hydrogen peroxide
* Mouthwash
* Oral hygiene
* Tetracycline
* Triclosan
* Host modulatory therapy
Treatment
Conventional therapy
* Debridement
* Scaling and root planing
* Full mouth disinfection
* Full mouth ultrasonic debridement
Surgery
* Apically positioned flap
* Bone graft
* Coronally positioned flap
* Crown lengthening
* Free gingival graft
* Gingival grafting
* Gingivectomy
* Guided bone regeneration
* Guided tissue regeneration
* Enamel matrix derivative
* Implant placement
* Lateral pedicle graft
* Open flap debridement
* Pocket reduction surgery
* Socket preservation
* Sinus lift
* Subepithelial connective tissue graft
* Tools
* Curette
* Membrane
* Probe
* Scaler
Important personalities
* Tomas Albrektsson
* Frank Beube
* Per-Ingvar Brånemark
* Robert Gottsegen
* Gary Greenstein
* Jan Lindhe
* Brian Mealey
* Preston D. Miller
* Willoughby D. Miller
* Carl E. Misch
* John Mankey Riggs
* Jay Seibert
* Jørgen Slots
* Paul Roscoe Stillman
* Dennis P. Tarnow
* Hom-Lay Wang
* James Leon Williams
* W. J. Younger
Other specialties
* Endodontology
* Orthodontology
* Prosthodontology
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
* Microcheilia
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* Sun poisoning
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Tongue
* Ankyloglossia
* Black hairy tongue
* Caviar tongue
* Crenated tongue
* Cunnilingus tongue
* Fissured tongue
* Foliate papillitis
* Glossitis
* Geographic tongue
* Median rhomboid glossitis
* Transient lingual papillitis
* Glossoptosis
* Hypoglossia
* Lingual thyroid
* Macroglossia
* Microglossia
* Rhabdomyoma
Palate
* Bednar's aphthae
* Cleft palate
* High-arched palate
* Palatal cysts of the newborn
* Inflammatory papillary hyperplasia
* Stomatitis nicotina
* Torus palatinus
Oral mucosa – Lining of mouth
* Amalgam tattoo
* Angina bullosa haemorrhagica
* Behçet's disease
* Bohn's nodules
* Burning mouth syndrome
* Candidiasis
* Condyloma acuminatum
* Darier's disease
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* Erythema multiforme
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* Fibroma
* Giant-cell
* Focal epithelial hyperplasia
* Fordyce spots
* Hairy leukoplakia
* Hand, foot and mouth disease
* Hereditary benign intraepithelial dyskeratosis
* Herpangina
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* Leukoedema
* Leukoplakia
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* Lupus erythematosus
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* Molluscum contagiosum
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* Benign: Squamous cell papilloma
* Keratoacanthoma
* Malignant: Adenosquamous carcinoma
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* Ulceration
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* Verruca vulgaris
* Verruciform xanthoma
* White sponge nevus
Teeth (pulp, dentin, enamel)
* Amelogenesis imperfecta
* Ankylosis
* Anodontia
* Caries
* Early childhood caries
* Concrescence
* Failure of eruption of teeth
* Dens evaginatus
* Talon cusp
* Dentin dysplasia
* Dentin hypersensitivity
* Dentinogenesis imperfecta
* Dilaceration
* Discoloration
* Ectopic enamel
* Enamel hypocalcification
* Enamel hypoplasia
* Turner's hypoplasia
* Enamel pearl
* Fluorosis
* Fusion
* Gemination
* Hyperdontia
* Hypodontia
* Maxillary lateral incisor agenesis
* Impaction
* Wisdom tooth impaction
* Macrodontia
* Meth mouth
* Microdontia
* Odontogenic tumors
* Keratocystic odontogenic tumour
* Odontoma
* Dens in dente
* Open contact
* Premature eruption
* Neonatal teeth
* Pulp calcification
* Pulp stone
* Pulp canal obliteration
* Pulp necrosis
* Pulp polyp
* Pulpitis
* Regional odontodysplasia
* Resorption
* Shovel-shaped incisors
* Supernumerary root
* Taurodontism
* Trauma
* Avulsion
* Cracked tooth syndrome
* Vertical root fracture
* Occlusal
* Tooth loss
* Edentulism
* Tooth wear
* Abrasion
* Abfraction
* Acid erosion
* Attrition
Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures
* Cementicle
* Cementoblastoma
* Gigantiform
* Cementoma
* Eruption cyst
* Epulis
* Pyogenic granuloma
* Congenital epulis
* Gingival enlargement
* Gingival cyst of the adult
* Gingival cyst of the newborn
* Gingivitis
* Desquamative
* Granulomatous
* Plasma cell
* Hereditary gingival fibromatosis
* Hypercementosis
* Hypocementosis
* Linear gingival erythema
* Necrotizing periodontal diseases
* Acute necrotizing ulcerative gingivitis
* Pericoronitis
* Peri-implantitis
* Periodontal abscess
* Periodontal trauma
* Periodontitis
* Aggressive
* As a manifestation of systemic disease
* Chronic
* Perio-endo lesion
* Teething
Periapical, mandibular and maxillary hard tissues – Bones of jaws
* Agnathia
* Alveolar osteitis
* Buccal exostosis
* Cherubism
* Idiopathic osteosclerosis
* Mandibular fracture
* Microgenia
* Micrognathia
* Intraosseous cysts
* Odontogenic: periapical
* Dentigerous
* Buccal bifurcation
* Lateral periodontal
* Globulomaxillary
* Calcifying odontogenic
* Glandular odontogenic
* Non-odontogenic: Nasopalatine duct
* Median mandibular
* Median palatal
* Traumatic bone
* Osteoma
* Osteomyelitis
* Osteonecrosis
* Bisphosphonate-associated
* Neuralgia-inducing cavitational osteonecrosis
* Osteoradionecrosis
* Osteoporotic bone marrow defect
* Paget's disease of bone
* Periapical abscess
* Phoenix abscess
* Periapical periodontitis
* Stafne defect
* Torus mandibularis
Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities
* Bruxism
* Condylar resorption
* Mandibular dislocation
* Malocclusion
* Crossbite
* Open bite
* Overbite
* Overeruption
* Overjet
* Prognathia
* Retrognathia
* Scissor bite
* Maxillary hypoplasia
* Temporomandibular joint dysfunction
Salivary glands
* Benign lymphoepithelial lesion
* Ectopic salivary gland tissue
* Frey's syndrome
* HIV salivary gland disease
* Necrotizing sialometaplasia
* Mucocele
* Ranula
* Pneumoparotitis
* Salivary duct stricture
* Salivary gland aplasia
* Salivary gland atresia
* Salivary gland diverticulum
* Salivary gland fistula
* Salivary gland hyperplasia
* Salivary gland hypoplasia
* Salivary gland neoplasms
* Benign: Basal cell adenoma
* Canalicular adenoma
* Ductal papilloma
* Monomorphic adenoma
* Myoepithelioma
* Oncocytoma
* Papillary cystadenoma lymphomatosum
* Pleomorphic adenoma
* Sebaceous adenoma
* Malignant: Acinic cell carcinoma
* Adenocarcinoma
* Adenoid cystic carcinoma
* Carcinoma ex pleomorphic adenoma
* Lymphoma
* Mucoepidermoid carcinoma
* Sclerosing polycystic adenosis
* Sialadenitis
* Parotitis
* Chronic sclerosing sialadenitis
* Sialectasis
* Sialocele
* Sialodochitis
* Sialosis
* Sialolithiasis
* Sjögren's syndrome
Orofacial soft tissues – Soft tissues around the mouth
* Actinomycosis
* Angioedema
* Basal cell carcinoma
* Cutaneous sinus of dental origin
* Cystic hygroma
* Gnathophyma
* Ludwig's angina
* Macrostomia
* Melkersson–Rosenthal syndrome
* Microstomia
* Noma
* Oral Crohn's disease
* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Gingivitis
|
c0017574
| 25,776 |
wikipedia
|
https://en.wikipedia.org/wiki/Gingivitis
| 2021-01-18T19:00:18 |
{"mesh": ["D005891"], "umls": ["C0017574", "C0155937", "C0008684"], "wikidata": ["Q673083"]}
|
## Clinical Features
Tsukahara and Sugio (1998) reported 3 Japanese brothers, aged 6, 3, and 2 years, with an apparently hitherto undescribed combination of microcephaly, facial abnormalities, micromelia, and mild mental retardation. The facial abnormalities included a forehead with bitemporal constriction, upslanting palpebral fissures, synophrys, short nose with anteverted nostrils, short columella, cupid bow-shaped, thin vermilion border of the upper lip, and micrognathia. The mother had similar clinical manifestations but was of normal intelligence. The parents of the mother were both 36 years old at the time of her birth. The mother was 146 cm tall and had a head circumference of 52 cm. She had a narrow bifrontal diameter with a facial appearance similar to that of her sons. Synophrys, short nose with anteverted nostrils and a short columella, and thin vermilion border of the upper lip were also present. She had small hands with short 5th fingers. She had graduated from a 4-year college and had above average intelligence.
Inheritance
Tsukahara and Sugio (1998) suggested that this disorder is inherited in an autosomal or X-linked dominant manner.
*[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-hydroxybutyric 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
|
MICROCEPHALY, FACIAL ABNORMALITIES, MICROMELIA, AND MENTAL RETARDATION
|
c1863702
| 25,777 |
omim
|
https://www.omim.org/entry/603572
| 2019-09-22T16:12:50 |
{"mesh": ["C566361"], "omim": ["603572"]}
|
Familial hypocalciuric hypercalcemia
SpecialtyEndocrinology, medical genetics
Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Pathogenesis
* 3.1 Functions of the calcium-sensing receptor
* 4 Diagnosis
* 5 Treatment
* 6 References
* 7 External links
## Signs and symptoms[edit]
Most cases of familial hypocalciuric hypercalcemia are asymptomatic. Laboratory signs of FHH include:
* High blood levels of calcium (hypercalcemia)
* A low amount of calcium excreted in the urine ( Ca excretion rate < 0.02 mmol/L)
* High blood levels of magnesium (hypermagnesemia)
* High normal to mildly elevated parathyroid hormone
## Causes[edit]
Types include:
Name OMIM Locus Gene
HHC1 145980 3q13.3-q21 CaSR
HHC2 145981 19p13.3 ?
HHC3 600740 19q13[1] ?
## Pathogenesis[edit]
Most cases of FHH are associated with loss of function mutations in the calcium-sensing receptor (CaSR) gene,[2] expressed in parathyroid and kidney tissue. These mutations decrease the receptor's sensitivity to calcium, resulting in reduced receptor stimulation at normal serum calcium levels. As a result, inhibition of parathyroid hormone release does not occur until higher serum calcium levels are attained, creating a new equilibrium. This is the opposite of what happens with the CaSR sensitizer, cinacalcet. Functionally, parathyroid hormone (PTH) increases calcium resorption from the bone and increases phosphate excretion from the kidney which increases serum calcium and decreases serum phosphate. Individuals with FHH, however, typically have normal PTH levels, as normal calcium homeostasis is maintained, albeit at a higher equilibrium set point. As a consequence, these individuals are not at increased risk of the complications of hyperparathyroidism.
Another form has been associated with chromosome 3q.[3]
### Functions of the calcium-sensing receptor[edit]
* Parathyroid gland: mediates negative feedback mechanisms relating to PTH secretion. In normal individuals, PTH secretion decreases with increasing blood calcium levels. Loss of function abnormalities in the CaSR here cause hypercalcemia.
* Kidneys: mediates negative feedback mechanisms relating to calcium reabsorption from the tubular system. In normal individuals, reabsorption of calcium and other electrolytes decreases with increasing blood calcium level. Loss of function abnormalities in the CaSR here contribute to both hypercalcemia and hypocalciuria.
## Diagnosis[edit]
As most cases of FHH are asymptomatic and benign, the diagnosis of FHH is less likely to be made. Typically, diagnosis is made in the pursuit of uncovering the etiology of hypercalcemia. Calcium levels are often in the high normal range or slightly elevated. Commonly, the parathyroid hormone level is checked and may be slightly elevated or also on the high normal end. Normally, high calcium should cause low PTH and so this level of PTH is inappropriately high due to the decreased sensitivity of the parathyroid to calcium. This may be mistaken for primary hyperparathyroidism. However, evaluation of urine calcium level will reveal a low level of urine calcium. This too is inappropriate as high serum calcium should result in high urine calcium. If urine calcium is not checked, this may lead to parathyroidectomy for presumed primary hyperparathyroidism.
Additionally as the name implies, there may be a family history of benign hypercalcemia.
Ultimately, diagnosis of familial hypocalciuric hypercalcemia is made — as the name implies — by the combination of low urine calcium and high serum calcium.
## Treatment[edit]
No treatment is generally required, as bone demineralisation and kidney stones are relatively uncommon in the condition.[4]
## References[edit]
1. ^ Lloyd SE, Pannett AA, Dixon PH, Whyte MP, Thakker RV (January 1999). "Localization of familial benign hypercalcemia, Oklahoma variant (FBHOk), to chromosome 19q13". Am. J. Hum. Genet. 64 (1): 189–95. doi:10.1086/302202. PMC 1377717. PMID 9915958.
2. ^ Schade, David S.; Carroll, Mary F. (May 2003). "A Practical Approach to Hypercalcemia - May 1, 2003 - American Family Physician". American Family Physician. 67 (9): 1959–1966. Retrieved 2009-03-29.
3. ^ Chou YH, Brown EM, Levi T, et al. (July 1992). "The gene responsible for familial hypocalciuric hypercalcemia maps to chromosome 3q in four unrelated families". Nat. Genet. 1 (4): 295–300. doi:10.1038/ng0792-295. PMID 1302026.
4. ^ "Familial Hypouricemic Hypercalcemia". Archived from the original on 2009-02-24. Retrieved 2009-06-07.
## External links[edit]
Classification
D
* ICD-10: E83.5
* OMIM: 145980 145981 600740
* MeSH: D006934
* DiseasesDB: 1326
External resources
* Orphanet: 405
* v
* t
* e
Electrolyte imbalances
Sodium
* High
* Salt poisoning
* Low
* Hypotonic
* Isotonic
* Cerebral salt-wasting syndrome
Potassium
* High
* Low
Chloride
* High
* Low
Calcium
* High
* Low
* Symptoms and signs
* Chvostek sign
* Trousseau sign
* Milk-alkali syndrome
* Disorders of calcium metabolism
* Calcinosis (Calciphylaxis, Calcinosis cutis)
* Calcification (Metastatic calcification, Dystrophic calcification)
* Familial hypocalciuric hypercalcemia
Phosphate
* High
* Low
Magnesium
* High
* Low
* v
* t
* e
Cell surface receptor deficiencies
G protein-coupled receptor
(including hormone)
Class A
* TSHR (Congenital hypothyroidism 1)
* LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty)
* FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis)
* GnRHR (Gonadotropin-releasing hormone insensitivity)
* EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
* AVPR2 (Nephrogenic diabetes insipidus 1)
* PTGER2 (Aspirin-induced asthma)
Class B
* PTH1R (Jansen's metaphyseal chondrodysplasia)
Class C
* CASR (Familial hypocalciuric hypercalcemia)
Class F
* FZD4 (Familial exudative vitreoretinopathy 1)
Enzyme-linked receptor
(including
growth factor)
RTK
* ROR2 (Robinow syndrome)
* FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
* FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome)
* FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
* INSR (Donohue syndrome
* Rabson–Mendenhall syndrome)
* NTRK1 (Congenital insensitivity to pain with anhidrosis)
* KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
STPK
* AMHR2 (Persistent Müllerian duct syndrome II)
* TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
* TGFBR1/TGFBR2 (Loeys–Dietz syndrome)
GC
* GUCY2D (Leber's congenital amaurosis 1)
JAK-STAT
* Type I cytokine receptor: GH (Laron syndrome)
* CSF2RA (Surfactant metabolism dysfunction 4)
* MPL (Congenital amegakaryocytic thrombocytopenia)
TNF receptor
* TNFRSF1A (TNF receptor associated periodic syndrome)
* TNFRSF13B (Selective immunoglobulin A deficiency 2)
* TNFRSF5 (Hyper-IgM syndrome type 3)
* TNFRSF13C (CVID4)
* TNFRSF13B (CVID2)
* TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
Lipid receptor
* LRP: LRP2 (Donnai–Barrow syndrome)
* LRP4 (Cenani–Lenz syndactylism)
* LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
* LDLR (LDLR Familial hypercholesterolemia)
Other/ungrouped
* Immunoglobulin superfamily: AGM3, 6
* Integrin: LAD1
* Glanzmann's thrombasthenia
* Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR hypohidrotic ectodermal dysplasia)
* PTCH1 (Nevoid basal-cell carcinoma syndrome)
* BMPR1A (BMPR1A juvenile polyposis syndrome)
* IL2RG (X-linked severe combined immunodeficiency)
See also
cell surface receptors
* v
* t
* e
Congenital endocrine disorders
Pituitary
* Congenital hypopituitarism
Thyroid
* Thyroid disease
* Persistent thyroglossal duct
* Thyroglossal cyst
* Congenital hypothyroidism
* Thyroid dysgenesis
* Thyroid dyshormonogenesis
* Pendred syndrome
Parathyroid
* Congenital absence of parathyroid
Adrenal
* Absent adrenal gland
*[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-hydroxybutyric 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
|
Familial hypocalciuric hypercalcemia
|
c1809471
| 25,778 |
wikipedia
|
https://en.wikipedia.org/wiki/Familial_hypocalciuric_hypercalcemia
| 2021-01-18T18:58:04 |
{"gard": ["10828"], "umls": ["C1809471"], "orphanet": ["405"], "wikidata": ["Q1395332"]}
|
Familial amyloidosis, Finnish type, or gelsolin amyloidosis, is a condition characterized by abnormal deposits of amyloid protein that mainly affect the eyes, nerves and skin. The 3 main features are amyloid deposits in the cornea (corneal lattice dystrophy), bilateral facial paralysis, and cutis laxa ("sagging" skin). Symptoms generally worsen with age. This condition is inherited in an autosomal dominant manner and is caused by mutations in the GSN gene. Treatment generally focuses on specific signs and symptoms. Plastic surgery may relieve problems caused by facial paralysis and cutis laxa.
*[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-hydroxybutyric 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
|
Familial amyloidosis, Finnish type
|
c0936273
| 25,779 |
gard
|
https://rarediseases.info.nih.gov/diseases/2339/familial-amyloidosis-finnish-type
| 2021-01-18T18:00:36 |
{"mesh": ["D028227"], "omim": ["105120"], "orphanet": ["85448"], "synonyms": ["Amyloidosis due to mutant gelsolin", " Amyloidosis, Meretoja type", "Amyloid cranial neuropathy with lattice corneal dystrophy", "Amyloidosis V", "Amyloidosis 5", "Lattice corneal dystrophy type II Finnish", "Familial amyloid polyneuropathy type IV", "Hereditary gelsolin amyloidosis", "AGel amyloidosis"]}
|
Thyroid hormone (T3) acts to stimulate the transcription of several genes and to decrease the transcription of others. The thyroid hormone receptor (190160) binds with high affinity to a thyroid hormone response element (TRE) in each gene and alters the rate of transcription. Binding of in vitro synthesized thyroid hormone receptor to thyroid hormone response elements is enhanced by the addition of nuclear extracts from several different cell types, suggesting that binding is partially dependent on a T3 receptor auxiliary protein (TRAP). Beebe et al. (1991) presented experiments prompting them to propose that TRAP forms heterodimers with thyroid hormone receptor on the TRE sequences.
*[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-hydroxybutyric 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
|
TRIIODOTHYRONINE RECEPTOR AUXILIARY PROTEIN
|
None
| 25,780 |
omim
|
https://www.omim.org/entry/190445
| 2019-09-22T16:32:17 |
{"omim": ["190445"]}
|
A number sign (#) is used with this entry because of evidence that osteopathia striata with cranial sclerosis (OSCS) is caused by mutation in the WTX gene (AMER1; 300647) on chromosome Xq11.
Description
Osteopathia striata with cranial sclerosis is an X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae (Jenkins et al., 2009). In males, the disorder is usually associated with fetal or neonatal lethality. Occasional surviving males have, in addition to hyperostosis, cardiac, intestinal, and genitourinary malformations. Osteosclerosis in the cranial and facial bones leads to disfigurement and to disability due to pressure on cranial nerves, e.g., deafness. Osteopathia striata is a frequent feature of focal dermal hypoplasia (FDH; 305600).
Although early reports of familial cases of this disorder appeared to suggest autosomal dominant inheritance (see, e.g., Horan and Beighton, 1978 and Konig et al., 1996), reappraisal of the literature (Behninger and Rott, 2000; Rott et al., 2003) and the finding of a molecular basis for the disorder by Jenkins et al. (2009) confirms that the inheritance pattern is X-linked dominant. Affected males who survive have a more severe phenotype than affected females, and sporadic male cases may result from somatic mosaicism (Behninger and Rott, 2000).
Clinical Features
Fairbank (1951) was one of the first to describe the clinical combination of osteopathia stria and cranial sclerosis. Walker (1969) and Jones and Mulcahy (1968) reported affected females.
Winter et al. (1980) observed osteopathia striata with cranial sclerosis in 4 persons spanning 3 generations of a family. The proband was a 29-year-old woman with large head, broad nasal bridge, wide-set eyes, cranial sclerosis, and spina bifida occulta. Osteopathia striata was present since childhood. She also had conductive hearing loss. Her first pregnancy ended in spontaneous abortion; her second pregnancy resulted in a severely affected son who died at 6 days of age. Her third pregnancy resulted in an affected daughter who also had cleft palate. The proband's 60-year-old father was possibly affected, as he had a large head and thickening of the cranial vault. Cleft palate occurred in 1 of 3 unrelated patients seen by McKusick (1986). This patient also had a small ventricular septal defect and right clubfoot. The fingers were unusually long and thin with clinodactyly of distal phalanges 3 to 5. Dental problems were occasioned by the sclerosis of the mandible and maxilla.
Whyte and Murphy (1980) observed osteopathia striata in a woman and her 2 daughters, consistent with X-linked dominant inheritance. All 3 also had a macular, hyperpigmented dermopathy, which included white forelock. Sequential x-rays in 1 daughter showed that bone lesions developed in early childhood.
Konig et al. (1996) described a 4-generation pedigree containing 6 affected individuals, including 5 females, with osteopathia striata with cranial sclerosis. Although the authors suggested autosomal dominant inheritance, the pedigree was also consistent with X-linked dominant inheritance. All the females had a characteristic facial appearance, with macrocephaly, frontal bossing, flat face, hypertelorism, and broad nasal bridge. One had an atrial septal defect and transient facial palsy, and another had cleft palate and mixed hearing loss. The 1 male was the most severely affected, with marked macrocephaly, Pierre Robin sequence (261800) with cleft palate and tracheomalacia. He had severe hypotonia, failure to thrive, and retarded psychomotor development. His facial features included prominent broad forehead, hypertelorism, broad nasal bridge, open mouth, thick lips, malpositioned teeth, microretrognathia, and low-set posteriorly angulated ears. Other features included flexed contraction of the index fingers and several toes. In a follow-up of the family reported by Konig et al. (1996), Perdu et al. (2010) noted that the affected male was alive at age 20 years; moreover, he had a 2-year-old affected brother. Affected family members were found to carry a mutation in the WTX gene (Q271X; 300647.0008).
Pellegrino et al. (1997) described 4 brothers with characteristics of OSCS, 3 of whom died from serious complications. The mother of these children, and her only daughter, had the mildest phenotype, with the typical linear striations in the long bones and macrocephaly. Pellegrino et al. (1997) raised the possibility of X-linked inheritance with mild expression in female relatives. In addition, they recognized absent fibulas, malrotation of abdominal organs, and omphalocele as new manifestations, as well as congenital heart disease.
Bueno et al. (1998) likewise reported a family in which an affected male was stillborn with multiple congenital anomalies, whereas a sister and the mother and maternal grandfather had mild features. They again suggested that this was an example of X-linked OSCS. They reviewed 11 previously reported pedigrees and pointed out that there was no instance of well-confirmed OSCS in a father and son.
Keymolen et al. (1997) described a family with at least 3 affected members. The proposita was 50 years old when first seen for manifestations of multiple sclerosis (126200). She had had extra fingers removed and showed macrocephaly, large forehead, hypertelorism, and left ptosis. X-rays showed basal sclerosis of the skull, a thickened calvaria, and fine linear striations in the long bones. Otosclerosis of the right ear was demonstrated. The concurrence of OSCS and multiple sclerosis in the proposita was considered coincidental. Her daughter had otosclerosis for which bilateral stapedectomy was performed at the age of 21 years. She had a permanent bilateral hearing deficit, irregular, malpositioned upper incisors, macrocephaly, flat nasal bridge, frontal bossing, and hypertelorism. A maternal male cousin was born prematurely with a cleft palate, macrocephaly, dental anomalies, impaired hearing, and delayed speech. He showed frontal bossing, hypertelorism, and bilateral epicanthal folds. X-rays showed a thickened calvaria, increased density of the cranial base, and waveform striations in the body of the mandible but no linear striations in the metaphyses of the femur. The family pattern was consistent with X-linked dominant inheritance. In a follow-up of the family reported by Keymolen et al. (1997), Perdu et al. (2010) noted that the affected male was alive at age 41 years. Affected family members were found to carry a mutation in the WTX gene (300647.0007).
Savarirayan et al. (1997) reported a 4-generation family with 5 affected individuals, all females, that extended the phenotype and lent further support for X-linked dominant inheritance. The proband had multiple congenital abnormalities, including cleft palate, anterior ectopic anus, cutaneous syndactyly of right middle and ring fingers, congenital cardiac defects, and left hydronephrosis with a small right kidney. Skull base sclerosis was present at birth, while metaphyseal striations were only evident on a skeletal survey performed at 2 years of age. Proximal fibular osteolysis was also noted at this time. The child's mother, maternal grandmother, and maternal great-grandmother were also affected, but much less severely so. The mother had a subsequent pregnancy; the fetus was found to have alobar holoprosencephaly, cleft lip and palate, and partial absence of the nose. The pregnancy was terminated, and radiographs showed abnormal sclerosis of the maxilla, mandible, and orbital roofs. The authors suggested that this fetus was also affected, and that holoprosencephaly is a manifestation of OSCS. In affected members of the family reported by Savarirayan et al. (1997), Perdu et al. (2010) found deletion of the WTX gene (300647.0003).
Nakamura et al. (1998) described a 33-year-old Japanese man who had had 5 fractures of the humerus, tibia, and femur as a result of mild traumatic incidents that occurred between the ages of 18 and 33 years, and also had the residual of rib fractures without apparent trauma, demonstrable on radiographs. He had short stature (-2.2 SD), and radiographic evaluation showed cranial sclerosis, longitudinal striations in the metaphyses of the femur and tibia, fan-like striation in the ileum, metaphyseal widening in the femur and tibia, and sclerosis of the ribs. Blood chemical findings, including serum calcium, phosphorus, and alkaline phosphatase, were normal. Biopsy from the ileum showed thick trabeculae composed of woven bone. The authors stated that the coexistence of osteopathia striata, cranial sclerosis, metaphyseal undermodeling, and bone fragility had not been recognized previously, but the disorder may be the same as osteopathia striata with cranial sclerosis, or hyperostosis generalisata with striations. There was no family history of a similar disorder.
Lazar et al. (1999) described a 27-year-old man with OSCS. He had multiple congenital abnormalities including cleft palate, cleft lip, hypertelorism, flat nasal bridge, and clubfeet. He also had mild intellectual impairment. The head was enlarged with prominent occipital bony protrusion. He had micrognathia and was unable to open his mouth fully because of ankylosis of the temporomandibular joints. Hearing was decreased bilaterally.
Particularly convincing evidence for X-linked dominant inheritance was provided by Viot et al. (2002) who reported 10 new cases of OSCS, including 2 sporadic cases and 3 families, with an excess of affected females (9F/1M). Phenotypic variability was observed, as well as several unusual findings. Hirschsprung disease, Pierre Robin sequence, coronal craniostenosis, and laryngotracheomalacia were associated with a poor prognosis. The X-inactivation pattern of peripheral blood lymphocytes in a mildly affected mother and her severely affected son demonstrated nonrandom X inactivation in the mother. This finding, in combination with a sex ratio in favor of females and an increased morbidity and mortality in males, was highly suggestive of X-linked dominant inheritance.
Rott et al. (2003) reported on an affected family with typical OSCS in the mother, a maternal aunt, and the grandmother, and multiple severe malformations in the son. He was affected by cranial sclerosis with frontal bossing, conductive hearing impairment, cleft palate, thoracic dysplasia, mesenterium commune with nonrotation of the gut, anal atresia, bilateral cutaneous syndactyly of third and fourth fingers, duplication of the distal phalanx of the second and third fingers on the right, bilateral fibular aplasia with clubfeet, developmental retardation, epileptic seizures, hypothyroidism, and hypertrophic pyloric stenosis. In one informative carrier woman, the X-inactivation pattern in peripheral leukocytes was random.
Ward et al. (2004) provided a comprehensive description of a skeletal phenotype in a French Canadian girl with a moderate to severe form of sporadic OSCS. Multiple medical problems, including anal stenosis and the Pierre-Robin sequence, were evident in the first few years of life. At 14 years, she was fully mobile with normal intellect and stature. She suffered chronic lower extremity pain in the absence of fractures, as well as severe headaches, unilateral facial paralysis, and bilateral mixed hearing loss. The radiologic and bone histologic findings were described.
Perdu et al. (2011) reported a boy and his mother with osteopathia striata with cranial sclerosis confirmed by genetic analysis (C143X; 300647.0006). The mother, who was heterozygous for the mutation, had macrocephaly, a long face, a long philtrum, thin lips, narrow palate, mild scoliosis, and a mild asymmetry of the legs. Radiographic studies showed cranial sclerosis and striations of the tubular bones. Her 17-year-old son had a severe phenotype, but had survived. He had severe mental retardation, seizures, mixed hearing loss, severe cranial sclerosis with dolichocephaly, atrial septal defect, patent ductus arteriosus, and intestinal malrotation. Dysmorphic facial features included high forehead, hypertelorism, downslanting palpebral fissures, broad nasal tip, cleft lip and palate, dysplastic low-set ears, dysplastic teeth, and short neck. Brain imaging showed ventricular dilatation and hypoplasia of the corpus callosum. Radiographs showed short, broad clavicles, proximal fibular hypoplasia, and scoliosis, but no clear metaphyseal striations of the tubular bones. Perdu et al. (2011) also reported an unrelated family in which a 21-week-old male fetus had severe hypoplastic left heart and bilateral fibula aplasia. Postmortem examination showed upturned nasal tip, long philtrum, micro- and retrognathia, low-set ears, and intestinal malrotation. His mother had a large forehead, hypertelorism, flat face, high-arched palate, broad nasal bridge, hearing deficits, learning disabilities, cranial sclerosis, and metaphyseal striations of the long bones. In a review of the literature, Perdu et al. (2011) noted the unpredictability of male survival in this disorder, and concluded that affected males rarely have striations of the long bones.
Holman et al. (2011) reviewed the features of 6 males with severe OSCS, 4 of whom had previously been reported, and 4 males with mild OSCS, 2 of whom had previously been reported. The patients with the mild form were alive at ages 17 to 26 years. All patients had a characteristic facial appearance with macrocephaly, broad forehead with frontal bossing, broad depressed nasal bridge, hypertelorism, and low-set ears. There was a high prevalence of palatal abnormalities. Sclerosis of the peripheral skeleton was more marked than that in females, but affected males had no metaphyseal striations, except in those with a mosaic mutation, where striations are presumably the result of differential lyonization. Patients with severe OSCS tended to have bilateral absence of the fibulae, duplication of phalanges, omphalocele, kidney malformations, and cardiac defects. Two patients had nephrogenic rests, which may be a precursor of Wilms tumor. Patients with milder OSCS had short stature, lumbar lordosis, and contractures; 1 had a progressive proximal myopathy reminiscent of nemaline myopathy.
Other Features
Kornreich et al. (1988) reported a 21-month-old female first evaluated because of right facial nerve palsy of 2 days' duration. At the age of 12 months she had suffered similar facial palsy, which had gradually subsided over the following 5-month period. The patient was an isolated case in the family, but the parents were 'third-grade' cousins.
Clementi et al. (1993) observed reduction in the visual fields related apparently to narrowing of optic foramina in a girl with fully expressed osteopathia striata with cranial sclerosis.
Inheritance
In an evaluation of the literature on osteopathia striata with cranial sclerosis, Behninger and Rott (2000) concluded that the pattern of inheritance was most consistent with X-linked dominant, and not autosomal dominant, as had been suggested. The authors noted that more affected females had been reported, that affected males have a more severe phenotype with associated mortality, that there has been no proven father-to-son transmission, and that osteopathia striata is a feature of focal dermal hypoplasia (FDH; 305600), which is an X-linked disorder.
Rott et al. (2003) reviewed the multiple malformations that occur in hemizygous males who are offspring of mothers with osteopathia striata (19 sons of 13 mothers). They concluded that there was no reason to assume the existence of an autosomal dominant variant of this disorder that is clearly X-linked in most cases. One instance of father-son transmission in 1 family had been assumed by Horan and Beighton (1978), but was not documented by x-ray examination.
Mapping
Rott et al. (2003) stated that preliminary linkage studies suggested that the OSCS locus maps to Xp11.4-p11.22.
Molecular Genetics
Jenkins et al. (2009) identified a female proband with severe hyperostosis of the skull and appendicular skeleton, marked developmental delay, and seizures. The skeletal phenotype was consistent with OSCS. DNA analysis revealed a de novo deletion greater than 2.1 Mb on chromosome Xq11.1. Of the 4 annotated genes within the deleted region, Jenkins et al. (2009) considered WTX as a potential monogenic contributor to the skeletal phenotype because of its role as a repressor of canonical WNT signaling. Jenkins et al. (2009) studied 19 probands with OSCS and their affected relatives. Of the 5 males, 3 were midgestation fetuses with multiple malformations (omphalocele, limb patterning defects, cardiac and genitourinary anomalies) incompatible with survival beyond the neonatal period. Two surviving males (aged 17 years and 23 years) had, in addition to sclerosing skeletal dysplasia, learning disability, cardiomyopathy, skeletal myopathy, and central nervous system malformations. Sequencing of WTX revealed mutations in 18 of 19 unrelated families. All mutations either deleted the entire gene or were nonsense or frameshift mutations. Mutations segregated with the phenotype in all familial cases. At least 10 mutations arose de novo. Three recurrent mutations (R353X, 300647.0004; R358X, 300647.0005; and whole-gene deletions) were identified and these had been observed as somatic mutations in Wilms tumors (see 194070). All point mutations identified clustered in the 5-prime region of WTX; mutations leading to lethality in males were located more 5-prime than those associated with survival.
In affected members of the families reported by Savarirayan et al. (1997), Keymolen et al. (1997), and Konig et al. (1996), Perdu et al. (2010) identified a deletion of the WTX gene and 2 mutations in the WTX gene, respectively (300647.0003; 300647.0007; 300647.0008). In addition, 4 unrelated females with the disorder were found to carry the recurrent R358X mutation (300647.0005).
In a 17-year-old boy with osteopathia striata with cranial sclerosis, Perdu et al. (2011) identified a hemizygous truncating mutation in the 5-prime end of the gene (C143X; 300647.0006). The mutation was predicted to result in a very short truncated form of the WTXS1 isoform and most likely complete absence of a functional protein. Perdu et al. (2011) noted that although this mutation occurred in the 5-prime region of the gene, which Jenkins et al. (2009) postulated would be correlated with reduced survival, the patient had unusually long survival. The report indicated that this genotype/phenotype correlation is not absolute.
Genotype/Phenotype Correlations
Jenkins et al. (2009) suggested a putative genotype/phenotype correlation for OSCS: mutations producing a WTXS1 isoform with an intact phosphatidylinositol (4,5)-bisphosphate binding domain and APC-binding domain-1 resulted in survival of males, whereas mutations causing truncation of WTXS1 5-prime to these domains resulted in male lethality. The presence of intact WTXS2 was not protective against the disease, most likely because the WTXS2 isoform is not localized to the plasma membrane. However, Perdu et al. (2010) and Perdu et al. (2011) reported at least 2 surviving males with mutations in the 5-prime region of the gene, indicating that the hypothesis presented by Jenkins et al. (2009) is not absolute.
Holman et al. (2011) found that 5 male patients with severe OSCS had truncating WTX mutations 5-prime to the beta-catenin binding domain; the sixth patient had a whole gene deletion. In contrast, 4 male patients with a milder form of OSCS and survival into the second or third decade had mutations 3-prime to the beta-catenin binding domain.
History
Horan and Beighton (1978) concluded that the disorder is autosomal dominant. However, several studies provided compelling evidence for X-linked dominant inheritance.
Rucker and Alfidi (1964) described a man with sclerotic bone disease which had the additional feature of striations. His father and grandfather were said to have the same disorder; the father died of severe aortic stenosis.
INHERITANCE \- X-linked dominant GROWTH Height \- Short stature (in males) Other \- Failure to thrive (in males) HEAD & NECK Head \- Macrocephaly \- Large fontanelle \- Widened sutures \- Delayed closure of anterior fontanelle Face \- Frontal bossing \- Bitemporal narrowing \- Micrognathia \- Facial palsy Ears \- Low-set ears \- Posteriorly rotated ears \- Small ears \- Overfolded ears \- Hearing loss, conductive Eyes \- Hypertelorism \- Epicanthal folds Nose \- Broad nasal bridge Mouth \- Cleft palate \- Cleft lip \- bifid uvula \- Pierre Robin sequence (in males) \- Thick lips (in males) \- High-arched palate (15%) Teeth \- Natal teeth \- Malocclusion \- Crowded teeth Neck \- Webbed neck CARDIOVASCULAR Heart \- Ventricular septal defect \- Atrial septal defect Vascular \- Patent ductus arteriosus RESPIRATORY \- Apnea Nasopharynx \- Paranasal sinus hypoplasia \- Tracheomalacia Larynx \- Laryngeal web CHEST Ribs Sternum Clavicles & Scapulae \- Broad, flat ribs \- Pectus excavatum \- Long, straight clavicles \- Broad medial and lateral clavicles Breasts \- Widely spaced nipples ABDOMEN External Features \- Omphalocele (rare, in males) Gastrointestinal \- Intestinal malrotation (rare, in males) \- Anal stenosis (rare, in males) \- Anal atresia (rare, in males) \- Gastroesophageal reflux GENITOURINARY Kidneys \- Multicystic kidney (rare, in males) \- Nephrogenic rests (rare, in males) SKELETAL \- Osteopathia striata (linear striations of long bone diametaphyses, only in females) \- Increased trabecular thickness seen on iliac bone biopsy \- Joint contractures Skull \- Sclerotic cranial base \- Sclerotic mastoids (31%) \- Occipital bossing \- Cranial sclerosis \- Thickened calvaria \- Trapezoidal shaped skull Spine \- Thoracolumbar gibbus \- Scoliosis (23%) \- Spina bifida occulta Limbs \- Absent fibulae \- Short fibulae Hands \- Fifth finger clinodactyly \- Long, slender fingers \- Finger contractures \- Camptodactyly \- Duplicate phalanges \- Spatulate distal phalanges Feet \- Club feet (in males) \- Toe contractures MUSCLE, SOFT TISSUES \- Nemaline myopathy (in 1 reported male) NEUROLOGIC Central Nervous System \- Hydrocephalus \- Headaches \- Speech delay (10%) \- Transitional facial palsy (15%) \- Hypotonia (in males) \- Seizures (rare, in males) \- Mental retardation, mild-moderate (28%, usually in males) \- Partial agenesis of corpus callosum (rare, in males) VOICE \- Nasal speech PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios \- Polyhydramnios MISCELLANEOUS \- Increased morbidity/mortality in affected males \- One-third of cases are sporadic \- Onset of linear striations between 5 months and 6 years (only in affected females) MOLECULAR BASIS \- Caused by mutation in the family with sequence similarity 123, member B gene (FAM123B, 300647.0001 ) ▲ 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-hydroxybutyric 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
|
OSTEOPATHIA STRIATA WITH CRANIAL SCLEROSIS
|
c0432268
| 25,781 |
omim
|
https://www.omim.org/entry/300373
| 2019-09-22T16:20:25 |
{"doid": ["0060886"], "mesh": ["C536053"], "omim": ["300373"], "orphanet": ["2780"], "synonyms": ["Alternative titles", "HYPEROSTOSIS GENERALISATA WITH STRIATIONS"]}
|
A number sign (#) is used with this entry because of evidence that this form of cerebral amyloid angiopathy (CAA) is caused by mutation in the gene encoding cystatin C (CST3; 604312) on chromosome 20p11.2.
For a discussion of genetic heterogeneity of CAA, see 605714.
Description
Cerebral amyloid angiopathy (CAA), defined by the deposition of congophilic material in the vessels of the cortex and leptomeninges, is a major cause of intracerebral hemorrhage in the elderly (Vinters, 1987, Greenberg, 1998). Palsdottir et al. (1988) referred to the disorder in Icelandic patients as hereditary cystatin C amyloid angiopathy (HCCAA).
Clinical Features
Arnason (1935) described 10 Icelandic families with a high incidence of cerebral hemorrhage and concluded that a hereditary form of the disease was present in these families. Also in Iceland, Gudmundsson et al. (1972) studied a kindred in which 18 persons in 3 generations had cerebral hemorrhage, some of them at a young age. Cerebral arteries showed thickening of the walls with deposition of material with the characteristics of amyloid. Amyloid was not found in other arteries except in a case of long-standing tuberculosis. Male-to-male transmission was observed, consistent with autosomal dominant inheritance.
Mandybur and Bates (1978) reported a 58-year-old normotensive woman who died 24 hours after a stroke. Two months earlier, she had a transient neurologic episode consistent with cerebrovascular insufficiency. Postmortem examination showed a massive recent hemorrhage in the right occipital lobe associated with severe cerebral amyloid angiopathy. The cerebral cortex showed interstitial and perivascular neuritic plaques but no tangles. There was no family history. A literature review indicated that massive intracerebral hemorrhage seemed to be more common in patients with familial Icelandic forms of cerebral amyloid angiopathy. The authors thus recognized cerebral amyloid angiopathy as a cause of sporadic intracerebral hemorrhage.
Cohen et al. (1983) stated that 75 cases of hereditary cerebral hemorrhage with amyloidosis (HCHWA) had been identified in the Icelandic population. Characteristically, nonhypertensive, previously healthy persons suffer sudden catastrophic, often multifocal cerebral hemorrhages from intraparenchymal and/or meningeal vessels extensively infiltrated with amyloid.
By 1986, the Icelandic experience included 128 affected members in 8 families originating from the same geographic area of Iceland (Jensson et al., 1986). Over 80% of those who died from this disease were less than 40 years of age. Abnormally low cystatin C in the cerebrospinal fluid was a characteristic that could be used in identifying asymptomatic affected persons.
Biochemical Features
Cohen et al. (1983) analyzed the amyloid proteins deposited in the cerebral arteries of 3 young Icelandic patients who died of cerebral hemorrhage. Amino-terminal sequencing showed the proteins to be similar to a human protein called gamma-trace, or cystatin C. The amyloid deposits in all 3 patients stained with rabbit anti-gamma-trace antiserum.
Grubb et al. (1984) found low levels of gamma-trace in 9 patients with the cerebrovascular form of amyloidosis. The CSF concentration of beta-2-microglobulin, a microprotein of about the same size as gamma-trace, did not differ from the normal. No structural abnormality of gamma-trace in the CSF of patients could be demonstrated. Grubb et al. (1984) concluded that the basic defect in this disease is an abnormality in the catabolic processing of gamma-trace. The findings provided a diagnostic index of high sensitivity and specificity.
Lofberg et al. (1987) found that amyloid angiopathy characterized by an immunoreactivity of cystatin C was present in a submandibular lymph node in addition to small arteries in the cerebrum, cerebellum, and leptomeninges. All 9 persons investigated showed low CSF cystatin C. The cystatin C in the CSF of these patients had an isoelectric point identical to that of normal persons. Fibroblasts and glial cells secrete cystatin C into tissue culture fluids (Palsdottir et al., 1988).
Diagnosis
### Differential Diagnosis
The forms of HCHWA in Iceland and in the Netherlands (605714) represent fundamentally separate diseases (van Duinen et al., 1987). Differences that have been noted between the 2 forms include the following: Icelandic patients suffer the first stroke at a mean age of 27 years, whereas the Dutch patients are approximately 25 years older; the level of cystatin C in the cerebrospinal fluid of Icelandic patients is lower than that in Dutch patients or in healthy persons; and, immunohistochemically, intense staining for cystatin C is found in diseased Icelandic brain vessels, whereas in the Dutch material only weak or dubious staining is found. There is no evidence of genealogic connection between the Dutch and Icelandic families. A critical piece of evidence indicating a difference between the 2 diseases is the finding by van Duinen et al. (1987) that in the Dutch form of the disease the vascular amyloid deposits have immunohistochemical characteristics of Alzheimer disease-related beta-protein (APP; 104760).
Molecular Genetics
In Icelandic patients with hereditary cerebral hemorrhage with amyloidosis, Abrahamson et al. (1987) identified a heterozygous mutation in the CST3 gene (L68Q; 604312.0001). Palsdottir et al. (1988) identified this mutation in affected members of 8 families, establishing incontrovertibly that the mutation is the cause of this disorder.
Abrahamson et al. (1992) described a rapid and simple method of diagnosis of the Icelandic form of amyloidosis based on oligonucleotide-directed enzymatic amplification of a 275-bp genomic DNA segment containing exon 2 of the cystatin C gene from a blood sample, followed by digestion of the amplification product with AluI. This process could identify the common L68Q mutation.
Graffagnino et al. (1994) failed to find the Icelandic cystatin C mutation in any of 48 consecutive patients with intracerebral hemorrhage admitted to Duke University Hospital. No pathology was reported on these cases.
Population Genetics
Jensson et al. (1989) reviewed the history of the Icelandic variety in an article appropriately called 'The saga of the cystatin C mutation causing amyloid angiopathy and brain hemorrhage.' They pointed out that the patients show cystatin C amyloid as a regular histopathologic finding in lymphoid tissue, spleen, salivary glands, and seminal vesicles. A biopsy of these tissues can be used in confirmation of the diagnosis. Geographic distribution of the cases demonstrated 2 clusters in Iceland. Jensson et al. (1989) also gave a listing of autosomal dominant, autosomal recessive, and X-linked disorders that have been identified and studied in Iceland.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Premature stroke \- Intracranial hemorrhage \- Dementia LABORATORY ABNORMALITIES \- Generalized amyloid deposition \- Abnormally low cerebrospinal fluid cystatin C MISCELLANEOUS \- Onset 3rd to 4th decade of life \- Death before age 40 \- Icelandic families MOLECULAR BASIS \- Caused by mutations in the cystatin C gene (CST3, 604312.0001 ) ▲ 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-hydroxybutyric 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
|
CEREBRAL AMYLOID ANGIOPATHY, CST3-RELATED
|
c1510489
| 25,782 |
omim
|
https://www.omim.org/entry/105150
| 2019-09-22T16:45:13 |
{"doid": ["0070027"], "mesh": ["D028243"], "omim": ["105150"], "orphanet": ["85458", "100008"], "synonyms": ["Alternative titles", "AMYLOIDOSIS, CEREBROARTERIAL, ICELANDIC TYPE", "AMYLOIDOSIS VI", "HEREDITARY CEREBRAL HEMORRHAGE WITH AMYLOIDOSIS", "CEREBRAL HEMORRHAGE, HEREDITARY, WITH AMYLOIDOSIS"]}
|
A number sign (#) is used with this entry because of evidence that type III TRPS is caused by heterozygous mutation in the TRPS1 gene (604386) on chromosome 8q23. Mutation in the same gene has been found to cause type I TRPS (190350).
Clinical Features
Sugio and Kajii (1984) described a kindred in which 9 persons in 4 generations showed a syndrome of sparse hair, beaked nose, long upper lip, and severe metacarpophalangeal shortening. They reported the condition as an example of Ruvalcaba syndrome (180870); however, as pointed out by Hunter (1985), the disorder could be differentiated from Ruvalcaba syndrome by the absence of mental retardation and microcephaly and the presence of other changes resembling those of trichorhinophalangeal syndrome I (190350). The abnormalities of the hands and feet present in the patients of Sugio and Kajii (1984) were more severe, however, than those of TRPS1 patients. Niikawa and Kamei (1986) reported on a sporadic case who had similar manifestations and proposed that the condition should be recognized as a new syndrome known as TRPS type III, or Sugio-Kajii syndrome. Nagai et al. (1994) added another family in which 4 persons in 3 generations were affected with 1 instance of male-to-male transmission. The sparse hair, 'pear-shaped nose' clearly demonstrated in the figures, and cone-shaped epiphyses were features like those of TRPS types I and II (TRPS2; 190350), but the presence of severe generalized shortening of all phalanges and metacarpals differentiated the condition from TRPS1 and the absence of mental deficiency and exostoses from TRPS2.
Vilain et al. (1999) reported a case of TRPS III in a patient of European descent. The patient had typical features of TRPS I as well as severe brachydactyly. The case was sporadic, consistent with a new mutation. The authors believed this to be the first reported case of TRPS III in a western European patient.
Molecular Genetics
To investigate whether TRPS III is caused by mutations in the TRPS1 gene and to establish a genotype-phenotype correlation in TRPS, Ludecke et al. (2001) performed extensive mutation analysis and evaluated height and degree of brachydactyly in patients with TRPS I or TRPS III. They found 35 different mutations in TRPS1 in 44 of 51 unrelated patients with TRPS I or TRPS III. The detection rate (86%) indicated that TRPS1 is the major locus for both type I and type III TRPS. They found no mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the 5 missense mutations altered the GATA DNA-binding zinc finger, and 6 of the 7 unrelated patients with these mutations could be classified as having TRPS III because they had severe brachydactyly, due to generalized shortness of all phalanges and metacarpals, and severe short stature. The data indicated that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature \- Normal birth length Weight \- Normal birth weight HEAD & NECK Face \- Long, flat philtrum Ears \- Protruding ears Eyes \- Laterally sparse eyebrows Nose \- Pear-shaped nose \- Hypoplastic alae nasi Mouth \- Thin upper lip Teeth \- Crowded teeth \- Supernumerary teeth SKELETAL \- Mild osteopenia \- Delayed bone age before puberty \- Accelerated bone age after puberty Spine \- Scoliosis Pelvis \- Coxa plana \- Coxa magna Limbs \- Absence of exostoses Hands \- Short hands \- Cone-shaped epiphyses (middle phalanges) \- Severe brachydactyly \- Short metacarpals \- Short phalanges Feet \- Short feet \- Short metatarsals SKIN, NAILS, & HAIR Hair \- Sparse hair \- Laterally sparse eyebrow NEUROLOGIC Central Nervous System \- Normal intelligence MISCELLANEOUS \- Cone-shaped epiphyses usually not present before age 2 years \- Allelic to TRP1 ( 190350 ) \- TRP2 (Langer-Giedion syndrome, 150230 ) is a microdeletion syndrome involving deletions of both the TRPS1 ( 604386 ) and EXT1 ( 608177 ) genes MOLECULAR BASIS \- Caused by mutations in the zinc finger transcription factor TRPS1 gene (TRPS1, 604386.0007 ) ▲ 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-hydroxybutyric 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
|
TRICHORHINOPHALANGEAL SYNDROME, TYPE III
|
c1860823
| 25,783 |
omim
|
https://www.omim.org/entry/190351
| 2019-09-22T16:32:30 |
{"doid": ["0080376"], "mesh": ["C566033"], "omim": ["190351"], "orphanet": ["77258"], "synonyms": ["Alternative titles", "SUGIO-KAJII SYNDROME"]}
|
Bernard Soulier syndrome (BSS) is an inherited platelet disorder characterized by mild to severe bleeding tendency , macrothrombocytopenia and absent ristocetin-induced platelet agglutination.
*[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-hydroxybutyric 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
|
Bernard-Soulier syndrome
|
c0005129
| 25,784 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=274
| 2021-01-23T18:57:11 |
{"gard": ["2470"], "mesh": ["D001606"], "omim": ["153670", "231200"], "umls": ["C0005129"], "icd-10": ["D69.1"], "synonyms": ["Giant platelet syndrome", "Hemorrhagiparous thrombocytic dystrophy"]}
|
Inguinal hernia
Diagram of an indirect, scrotal inguinal hernia (median view from the left).
Pronunciation
* /ˈɪŋɡwɪnəl ˈhɜːrniə/
SpecialtyGeneral surgery
SymptomsPain, bulging in the groin[1]
ComplicationsStrangulation[1]
Usual onset< 1 year old, > 50 years old[2]
Risk factorsFamily history, smoking, chronic obstructive pulmonary disease, obesity, pregnancy, peritoneal dialysis, collagen vascular disease, connective tissue disease, previous open appendectomy[1][2][3]
Diagnostic methodBased on symptoms, medical imaging[1]
TreatmentConservative, surgery[1]
Frequency27% (males), 3% (females)[1]
Deaths59,800 (2015)[4]
An inguinal hernia is a protrusion of abdominal-cavity contents through the inguinal canal.[1] Symptoms are present in about 66% of affected people.[1] This may include pain or discomfort especially with coughing, exercise, or bowel movements.[1] Often it gets worse throughout the day and improves when lying down.[1] A bulging area may occur that becomes larger when bearing down.[1] Inguinal hernias occur more often on the right than left side.[1] The main concern is strangulation, where the blood supply to part of the intestine is blocked.[1] This usually produces severe pain and tenderness of the area.[1]
Risk factors for the development of a hernia include: smoking, chronic obstructive pulmonary disease, obesity, pregnancy, peritoneal dialysis, collagen vascular disease, and previous open appendectomy, among others.[1][2] Predisposition to hernias is genetic[5] and they occur more often in certain families.[6][7][8][1] Deleterious mutations causing predisposition to hernias seem to have dominant inheritance (especially for men). It is unclear if inguinal hernias are associated with heavy lifting.[1] Hernias can often be diagnosed based on signs and symptoms.[1] Occasionally medical imaging is used to confirm the diagnosis or rule out other possible causes.[1]
Groin hernias that do not cause symptoms in males do not need to be repaired.[1] Repair, however, is generally recommended in females due to the higher rate of femoral hernias which have more complications.[1] If strangulation occurs immediate surgery is required.[1] Repair may be done by open surgery or by laparoscopic surgery.[1] Open surgery has the benefit of possibly being done under local anesthesia rather than general anesthesia.[1] Laparoscopic surgery generally has less pain following the procedure.[1][9]
In 2015 inguinal, femoral and abdominal hernias affected about 18.5 million people.[10] About 27% of males and 3% of females develop a groin hernia at some time in their life.[1] Groin hernias occur most often before the age of one and after the age of fifty.[2] Globally, inguinal, femoral and abdominal hernias resulted in 60,000 deaths in 2015 and 55,000 in 1990.[4][11]
## Contents
* 1 Signs and symptoms
* 2 Pathophysiology
* 3 Diagnosis
* 3.1 Direct inguinal hernia
* 3.2 Indirect inguinal hernia
* 3.3 Medical imaging
* 3.4 Differential diagnosis
* 4 Management
* 4.1 Conservative
* 4.2 Surgical
* 5 Epidemiology
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Frontal view of an inguinal hernia (right).
Hernias usually present as bulges in the groin area that can become more prominent when coughing, straining, or standing up. The bulge commonly disappears on lying down. Mild discomfort can develop over time. The inability to "reduce", or place the bulge back into the abdomen usually means the hernia is 'incarcerated' which requires emergency surgery.
As the hernia progresses, contents of the abdominal cavity, such as the intestines, can descend into the hernia and run the risk of being pinched within the hernia, causing an intestinal obstruction. Significant pain at the hernia site is suggestive of a more severe course, such as incarceration (the hernia cannot be reduced back into the abdomen) and subsequent ischemia and strangulation (when the hernia becomes deprived of blood supply).[12] If the blood supply of the portion of the intestine caught in the hernia is compromised, the hernia is deemed "strangulated" and gut ischemia and gangrene can result, with potentially fatal consequences. The timing of complications is not predictable.
## Pathophysiology[edit]
In males, indirect hernias follow the same route as the descending testes, which migrate from the abdomen into the scrotum during the development of the urinary and reproductive organs. The larger size of their inguinal canal, which transmitted the testicle and accommodates the structures of the spermatic cord, might be one reason why men are 25 times more likely to have an inguinal hernia than women. Although several mechanisms such as strength of the posterior wall of the inguinal canal and shutter mechanisms compensating for raised intra-abdominal pressure prevent hernia formation in normal individuals, the exact importance of each factor is still under debate. The physiological school of thought thinks that the risk of hernia is due to a physiological difference between patients who suffer hernia and those who do not, namely the presence of aponeurotic extensions from the transversus abdominis aponeurotic arch.[13]
Inguinal hernias mostly contain the omentum or a part of the small intestines, however, some unusual contents may be an appendicitis, diverticulitis, colon cancer, urinary bladder, ovaries, and rarely malignant lesions.[14]
* Illustration of an inguinal hernia.
* Different types of inguinal hernias.
* Inguinal fossae
## Diagnosis[edit]
An incarcerated inguinal hernia as seen on cross sectional CT scan
A frontal view of an incarcerated inguinal hernia (on the patient's left side) with dilated loops of bowel above.
An inguinal hernia which contains part of the bladder. Bladder cancer also present.
There are two types of inguinal hernia, direct and indirect, which are defined by their relationship to the inferior epigastric vessels. Direct inguinal hernias occur medial to the inferior epigastric vessels when abdominal contents herniate through a weak spot in the fascia of the posterior wall of the inguinal canal, which is formed by the transversalis fascia. Indirect inguinal hernias occur when abdominal contents protrude through the deep inguinal ring, lateral to the inferior epigastric vessels; this may be caused by failure of embryonic closure of the processus vaginalis.
In the case of the female, the opening of the superficial inguinal ring is smaller than that of the male. As a result, the possibility for hernias through the inguinal canal in males is much greater because they have a larger opening and therefore a much weaker wall through which the intestines may protrude.
Type Description Relationship to inferior epigastric vessels Covered by internal spermatic fascia? Usual onset
indirect inguinal hernia protrudes through the inguinal ring and is ultimately the result of the failure of embryonic closure of the processus vaginalis after the testicle passes through it Lateral Yes Congenital / Adult
direct inguinal hernia enters through a weak point in the fascia of the abdominal wall (Hesselbach triangle) Medial No Adult
Inguinal hernias, in turn, belong to groin hernias, which also includes femoral hernias. A femoral hernia is not via the inguinal canal, but via the femoral canal, which normally allows passage of the common femoral artery and vein from the pelvis to the leg.
In Amyand's hernia, the content of the hernial sac is the vermiform appendix.
Ultrasound image of inguinal hernia. Moving intestines in inguinal canal with respiration.
In Littre's hernia, the content of the hernial sac contains a Meckel's diverticulum.
Clinical classification of hernia is also important according to which hernia is classified into
1. Reducible hernia: is one which can be pushed back into the abdomen by putting manual pressure to it.
2. Irreducible/Incarcerated hernia: is one which cannot be pushed back into the abdomen by applying manual pressure.
Irreducible hernias are further classified into
1. Obstructed hernia: is one in which the lumen of the herniated part of intestine is obstructed.
2. Strangulated hernia: is one in which the blood supply of the hernia contents is cut off, thus, leading to ischemia. The lumen of the intestine may be patent or not.
### Direct inguinal hernia[edit]
The direct inguinal hernia enters through a weak point in the fascia of the abdominal wall, and its sac is noted to be medial to the inferior epigastric vessels. Direct inguinal hernias may occur in males or females, but males are ten times more likely to get a direct inguinal hernia.[15]
A direct inguinal hernia protrudes through a weakened area in the transversalis fascia near the medial inguinal fossa within an anatomic region known as the inguinal or Hesselbach's triangle, an area defined by the edge of the rectus abdominis muscle, the inguinal ligament and the inferior epigastric artery. These hernias are capable of exiting via the superficial inguinal ring and are unable to extend into the scrotum.
When a patient suffers a simultaneous direct and indirect hernia on the same side, the result is called a "pantaloon" hernia (because it looks like a pair of pants, with the epigastric vessels in the crotch), and the defects can be repaired separately or together.
Since the abdominal walls weaken with age, direct hernias tend to occur in the middle-aged and elderly. This is in contrast to indirect hernias which can occur at any age including the young, since their etiology includes a congenital component where the inguinal canal is left more patent (compared to individuals less susceptible to indirect hernias).[16][17] Additional risk factors include chronic constipation, overweight/obesity, chronic cough, family history and prior episodes of direct inguinal hernias.[15]
### Indirect inguinal hernia[edit]
Ultrasound of an indirect hernia containing fat, with testicle seen at right.
T2 weighted MRI of the same case (done for another purpose), also demonstrating fat content.
Play media
Ultrasound showing an indirect inguinal hernia[18]
Play media
Incarcerated inguinal hernia[19]
An indirect inguinal hernia results from the failure of embryonic closure of the deep inguinal ring after the testicle has passed through it. It is the most common cause of groin hernia.
In the male fetus, the peritoneum gives a coat to the testicle as it passes through this ring, forming a temporary connection called the processus vaginalis. In normal development, the processus is obliterated once the testicle is completely descended. The permanent coat of peritoneum that remains around the testicle is called the tunica vaginalis. The testicle remains connected to its blood vessels and the vas deferens, which make up the spermatic cord and descend through the inguinal canal to the scrotum.
The deep inguinal ring, which is the beginning of the inguinal canal, remains as an opening in the fascia transversalis, which forms the fascial inner wall of the spermatic cord. When the opening is larger than necessary for passage of the spermatic cord, the stage is set for an indirect inguinal hernia. The protrusion of peritoneum through the internal inguinal ring can be considered an incomplete obliteration of the processus.
In an indirect inguinal hernia, the protrusion passes through the deep inguinal ring and is located lateral to the inferior epigastric artery. Hence, the conjoint tendon is not weakened.
There are three main types
* Bubonocele: in this case the hernia is limited in inguinal canal.
* Funicular: here the processus vaginalis is closed at its lower end just above the epididymis. The content of the hernial sac can be felt separately from the testis which lies below the hernia.
* Complete (or scrotal): here the processus vaginalis is patent throughout. The hernial sac is continuous with the tunica vaginalis of the testis. The hernia descends down to the bottom of the scrotum and it is difficult to differentiate the testis from hernia.
In the female, groin hernias are only 4% as common as in males. Indirect inguinal hernia is still the most common groin hernia for females. If a woman has an indirect inguinal hernia, her internal inguinal ring is patent, which is abnormal for females. The protrusion of peritoneum is not called "processus vaginalis" in women, as this structure is related to the migration of the testicle to the scrotum. It is simply a hernia sac. The eventual destination of the hernia contents for a woman is the labium majus on the same side, and hernias can enlarge one labium dramatically if they are allowed to progress.
### Medical imaging[edit]
A physician may diagnose an inguinal hernia, as well as the type, from medical history and physical examination.[20] For confirmation or in uncertain cases, medical ultrasonography is the first choice of imaging, because it can both detect the hernia and evaluate its changes with for example pressure, standing and Valsalva maneuver.[21]
When assessed by ultrasound or cross sectional imaging with CT or MRI, the major differential in diagnosing indirect inguinal hernias is differentiation from spermatic cord lipomas, as both can contain only fat and extend along the inguinal canal into the scrotum.[22]
On axial CT, lipomas originate posterolateral to the cord, and are located inside the cremaster muscle, while inguinal hernias lie anteromedial to the cord and are not intramuscular. Large lipomas may appear nearly indistinguishable as the fat engulfs anatomic boundaries, but they do not change position with coughing or straining.[22]
### Differential diagnosis[edit]
Differential diagnosis of the symptoms of inguinal hernia mainly includes the following potential conditions:[23]
* Femoral hernia
* Epididymitis
* Testicular torsion
* Lipomas
* Inguinal adenopathy (Lymph node Swelling)
* Groin abscess
* Saphenous vein dilation, called Saphena varix
* Vascular aneurysm or pseudoaneurysm
* Hydrocele
* Varicocele
* Cryptorchidism (Undescended testes)
## Management[edit]
### Conservative[edit]
There is currently no medical recommendation about how to manage an inguinal hernia condition in adults, due to the fact that, until recently,[24][25] elective surgery used to be recommended. The hernia truss is intended to contain a reducible inguinal hernia within the abdomen. It is not considered to provide a cure, and if the pads are hard and intrude into the hernia aperture they may cause scarring and enlargement of the aperture. In addition, most trusses with older designs are not able effectively to contain the hernia at all times, because their pads do not remain permanently in contact with the hernia. The more modern variety of truss is made with non-intrusive flat pads and comes with a guarantee to hold the hernia securely during all activities. Although there is as yet no proof that such devices can prevent an inguinal hernia from progressing, they have been described by users as providing greater confidence and comfort when carrying out physically demanding tasks.[citation needed] A truss also increases the probability of complications, which include strangulation of the hernia, atrophy of the spermatic cord, and atrophy of the fascial margins. This allows the defect to enlarge and makes subsequent repair more difficult.[26] Their popularity is likely to increase, as many individuals with small, painless hernias are now delaying hernia surgery due to the risk of post-herniorrhaphy pain syndrome.[27] The elasticised pants used by athletes also provide useful support for the smaller hernia.
### Surgical[edit]
Main article: Inguinal hernia surgery
Surgical incision in groin after inguinal hernia operation
Surgical correction of inguinal hernias is called a hernia repair. It is not recommended in minimally symptomatic hernias, for which watchful waiting is advised, due to the risk of post herniorraphy pain syndrome. Surgery is commonly performed as outpatient surgery. There are various surgical strategies which may be considered in the planning of inguinal hernia repair. These include the consideration of mesh use (e.g. synthetic or biologic), open repair, use of laparoscopy, type of anesthesia (general or local), appropriateness of bilateral repair, etc. Laparoscopy is most commonly used for non-emergency cases, however, a minimally invasive open repair may have a lower incidence of post-operative nausea and mesh associated pain. During surgery conducted under local anaesthesia, the patient will be asked to cough and strain during the procedure to help in demonstrating that the repair is without tension and sound.[28]
Constipation after hernia repair results in strain to evacuate the bowel causing pain, and fear that the sutures may rupture. Opioid analgesia makes constipation worse. Promoting an easy bowel motion is important post-operatively.
Surgical correction is always recommended for inguinal hernias in children.[29]
Emergency surgery for incarceration and strangulation carry much higher risk than planned, "elective" procedures. However, the risk of incarceration is low, evaluated at 0.2% per year.[30] On the other hand, surgery has a risk of inguinodynia (10-12%), and this is why males with minimal symptoms are advised to watchful waiting.[30][31] However, if they experience discomfort while doing physical activities or they routinely avoid them for fear of pain, they should seek surgical evaluation.[32] For female patients, surgery is recommended even for asymptomatic patients.[33]
## Epidemiology[edit]
A direct inguinal hernia is less common (~25–30% of inguinal hernias) and usually occurs in men over 40 years of age.
Men have an 8 times higher incidence of inguinal hernia than women.[34]
## See also[edit]
* Birkett hernia
## 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 Fitzgibbons RJ, Jr; Forse, RA (19 February 2015). "Clinical practice. Groin hernias in adults". The New England Journal of Medicine. 372 (8): 756–63. doi:10.1056/NEJMcp1404068. PMID 25693015.
2. ^ a b c d Domino, Frank J. (2014). The 5-minute clinical consult 2014 (22nd ed.). Philadelphia, Pa.: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 562. ISBN 9781451188509.
3. ^ Burcharth J, Pommergaard HC, Rosenberg J (2013). "The inheritance of groin hernia: a systematic review". Hernia. 17 (2): 183–9. doi:10.1007/s10029-013-1060-4. PMID 23423330.
4. ^ a b GBD 2015 Mortality and Causes of Death, Collaborators. (8 October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/S0140-6736(16)31012-1. PMC 5388903. PMID 27733281.
5. ^ "Etiology of Inguinal Hernias: A Comprehensive Review".
6. ^ "Whole-exome Sequencing Identifies a Potential TTN Mutation in a Multiplex Family With Inguinal Hernia - PubMed".
7. ^ "Association of Collagen Type I Alpha 1 Gene Polymorphism With Inguinal Hernia - PubMed".
8. ^ "Genetic Study of Indirect Inguinal Hernia - PubMed".
9. ^ Simons MP, Aufenacker T, Bay-Nielsen M, et al. (August 2009). "European Hernia Society guidelines on the treatment of inguinal hernia in adult patients". Hernia. 13 (4): 343–403. doi:10.1007/s10029-009-0529-7. PMC 2719730. PMID 19636493.
10. ^ GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. (8 October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
11. ^ GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442.
12. ^ Neutra, Raymond; Velez, Adolfo; Ferrada, Ricardo; Galan, Ricardo (January 1981). "Risk of incarceration of inguinal hernia in Cali, Colombia". Journal of Chronic Diseases. 34 (11): 561–564. doi:10.1016/0021-9681(81)90018-7. PMID 7287860.
13. ^ Desarda, Mohan P (16 April 2003). "Surgical physiology of inguinal hernia repair - a study of 200 cases". BMC Surgery. 3 (1): 2. doi:10.1186/1471-2482-3-2. PMC 155644. PMID 12697071.
14. ^ Yoell, John H. (September 1959). "SURPRISES IN HERNIAL SACS—Diagnosis of Tumors by Microscopic Examination". California Medicine. 91 (3): 146–148. ISSN 0008-1264. PMC 1577810. PMID 13846556.
15. ^ a b "Direct Inguinal Hernia". University of Connecticut. Archived from the original on April 27, 2012. Retrieved May 6, 2012.
16. ^ James Harmon M.D. Lecture 13. Human Gross Anatomy. University of Minnesota. September 4, 2008.
17. ^ http://www.emedicinehealth.com/hernia/article_em.htm
18. ^ "UOTW #16 - Ultrasound of the Week". Ultrasound of the Week. 2 September 2014. Retrieved 27 May 2017.
19. ^ "UOTW #40 - Ultrasound of the Week". Ultrasound of the Week. 9 March 2015.
20. ^ LeBlanc, Kim Edward; LeBlanc, Leanne L; LeBlanc, Karl A (15 June 2013). "Inguinal hernias: diagnosis and management". American Family Physician. 87 (12): 844–8. PMID 23939566.
21. ^ Stavros, A. Thomas; Rapp, Cindy (September 2010). "Dynamic Ultrasound of Hernias of the Groin and Anterior Abdominal Wall". Ultrasound Quarterly. 26 (3): 135–169. doi:10.1097/RUQ.0b013e3181f0b23f. PMID 20823750.
22. ^ a b Burkhardt, Joan Hu; Arshanskiy, Yevgeniy; Munson, J. Lawrence; Scholz, Francis J. (March 2011). "Diagnosis of Inguinal Region Hernias with Axial CT: The Lateral Crescent Sign and Other Key Findings". RadioGraphics. 31 (2): E1–E12. doi:10.1148/rg.312105129. PMID 21415178.
23. ^ Klingensmith ME, Chen LE, Glasgow SC, Goers TA, Melby SJ (2008). The Washington manual of surgery. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-0-7817-7447-5.
24. ^ Simons MP, Aufenacker T, Bay-Nielsen M, Bouillot JL, Campanelli G, Conze J, et al. (August 2009). "European Hernia Society guidelines on the treatment of inguinal hernia in adult patients". Hernia. 13 (4): 343–403. doi:10.1007/s10029-009-0529-7. PMC 2719730. PMID 19636493.
25. ^ Rosenberg J, Bisgaard T, Kehlet H, Wara P, Asmussen T, Juul P, Strand L, Andersen FH, Bay-Nielsen M (February 2011). "Danish Hernia Database recommendations for the management of inguinal and femoral hernia in adults". Dan Med Bull. 58 (2): C4243. PMID 21299930.
26. ^ Purkayastha S, Chow A, Athanasiou T, Tekkis P, Darzi A (July 2008). "Inguinal hernia". BMJ Clin Evid. 2008. PMC 2908002. PMID 19445744.
27. ^ Aasvang E, Kehlet H (July 2005). "Chronic postoperative pain: the case of inguinal herniorrhaphy". Br J Anaesth. 95 (1): 69–76. doi:10.1093/bja/aei019. PMID 15531621.
28. ^ Inguinal Hernia Archived 2007-09-27 at the Wayback Machine
29. ^ "Inguinal Hernia". UCSF Pediatric Surgery.
30. ^ a b Fitzgibbons, Robert J.; Giobbie-Hurder, Anita; Gibbs, James O.; Dunlop, Dorothy D.; Reda, Domenic J.; McCarthy, Martin; Neumayer, Leigh A.; Barkun, Jeffrey S. T.; Hoehn, James L.; Murphy, Joseph T.; Sarosi, George A.; Syme, William C.; Thompson, Jon S.; Wang, Jia; Jonasson, Olga (18 January 2006). "Watchful Waiting vs Repair of Inguinal Hernia in Minimally Symptomatic Men". JAMA. 295 (3): 285–92. doi:10.1001/jama.295.3.285. PMID 16418463.
31. ^ Simons, MP; Aufenacker, TJ; Berrevoet, F; Bingener, J; Bisgaard, T; Bittner, R; Bonjer, HJ; Bury, K; Campanelli, G (2017). World guidelines for groin hernia management (PDF).
32. ^ Brooks, David. "Overview of treatment for inguinal and femoral hernia in adults". www.uptodate.com. Retrieved 2017-11-19.
33. ^ Rosenberg, Jacob; Bisgaard, Thue; Kehlet, Henrik; Wara, Pål; Asmussen, Torsten; Juul, Poul; Strand, Lasse; Andersen, Finn Heidmann; Bay-Nielsen, Morten (February 2011). "Danish Hernia Database recommendations for the management of inguinal and femoral hernia in adults". Danish Medical Bulletin. 58 (2): C4243. ISSN 1603-9629. PMID 21299930.
34. ^ "Inguinal hernia". Mayo Clinic. 2017-08-11.
## External links[edit]
Classification
D
* ICD-10: K40
* ICD-9-CM: 550
* MeSH: D006552
* DiseasesDB: 6806
External resources
* MedlinePlus: 000960
* eMedicine: med/2703 emerg/251 ped/2559
* Indirect Inguinal Hernia - University of Connecticut Health Center
* Media related to Inguinal hernia at Wikimedia Commons
* v
* t
* e
Diseases of the digestive system
Upper GI tract
Esophagus
* Esophagitis
* Candidal
* Eosinophilic
* Herpetiform
* Rupture
* Boerhaave syndrome
* Mallory–Weiss syndrome
* UES
* Zenker's diverticulum
* LES
* Barrett's esophagus
* Esophageal motility disorder
* Nutcracker esophagus
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* Diffuse esophageal spasm
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* Laryngopharyngeal reflux (LPR)
* Esophageal stricture
* Megaesophagus
* Esophageal intramural pseudodiverticulosis
Stomach
* Gastritis
* Atrophic
* Ménétrier's disease
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* Peptic (gastric) ulcer
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* Pyloric stenosis
* Achlorhydria
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Lower GI tract
Enteropathy
Small intestine
(Duodenum/Jejunum/Ileum)
* Enteritis
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Large intestine
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* Appendicitis
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* Acute liver failure
* Liver abscess
* Pyogenic
* Amoebic
* Hepatorenal syndrome
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* Metabolic disorders
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Gallbladder
* Cholecystitis
* Gallstone / Cholelithiasis
* Cholesterolosis
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* Postcholecystectomy syndrome
* Porcelain gallbladder
Bile duct/
Other biliary tree
* Cholangitis
* Primary sclerosing cholangitis
* Secondary sclerosing cholangitis
* Ascending
* Cholestasis/Mirizzi's syndrome
* Biliary fistula
* Haemobilia
* Common bile duct
* Choledocholithiasis
* Biliary dyskinesia
* Sphincter of Oddi dysfunction
Pancreatic
* Pancreatitis
* Acute
* Chronic
* Hereditary
* Pancreatic abscess
* Pancreatic pseudocyst
* Exocrine pancreatic insufficiency
* Pancreatic fistula
Other
Hernia
* Diaphragmatic
* Congenital
* Hiatus
* Inguinal
* Indirect
* Direct
* Umbilical
* Femoral
* Obturator
* Spigelian
* Lumbar
* Petit's
* Grynfeltt-Lesshaft
* Undefined location
* Incisional
* Internal hernia
* Richter's
Peritoneal
* Peritonitis
* Spontaneous bacterial peritonitis
* Hemoperitoneum
* Pneumoperitoneum
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Inguinal hernia
|
c0019294
| 25,785 |
wikipedia
|
https://en.wikipedia.org/wiki/Inguinal_hernia
| 2021-01-18T18:57:33 |
{"mesh": ["D006552"], "umls": ["C0019294", "C0019296", "C0019295"], "wikidata": ["Q1144039"]}
|
A number sign (#) is used with this entry because of evidence that nephrotic syndrome type 20 (NPHS20) is caused by hemizygous or heterozygous mutation in the TBC1D8B gene (301027) on chromosome Xq22.
Description
Nephrotic syndrome type 20 (NPHS20) is an X-linked renal disorder characterized by onset of steroid-resistant nephrotic syndrome and proteinuria in the first years of life in affected males. The disorder results in end-stage kidney disease and may cause death in childhood without renal transplantation. Carrier females may have a milder disorder with proteinuria or may be unaffected. Renal biopsy typically shows focal segmental glomerulosclerosis (FSGS) and effacement of podocyte foot processes (summary by Dorval et al., 2019).
For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Clinical Features
Dorval et al. (2019) reported 3 brothers, born of unrelated parents from Ecuador (family A), with congenital onset of steroid-resistant nephrotic syndrome. Two of the affected brothers died in the first years of life; the remaining brother reached end-stage kidney disease at age 2.8 years and underwent successful renal transplantation with no disease recurrence. The boys' mother and sister, who carried the same mutation in the TBC1D8B gene that had been identified in the living brother, had later onset of proteinuria without frank nephrotic syndrome: as an adult in the mother and at age 7 in the sister. In addition, the pregnancies were complicated by preeclampsia when carrying a male fetus. Renal biopsy of the male proband and his sister showed focal segmental glomerulosclerosis (FSGS) and effacement of podocyte foot processes. An unrelated European boy with the disease presented with steroid-resistant nephrotic syndrome at 2 years of age. Renal biopsy showed glomerulosclerosis and effacement of foot processes. He reached end-stage renal disease at age 9 and underwent successful renal transplant.
Inheritance
The transmission pattern of NPHS20 in the families reported by Dorval et al. (2019) was consistent with X-linked inheritance. In 1 family, female mutation carriers were mildly affected, whereas in the other family, the female carrier was unaffected.
Molecular Genetics
In a boy from a family from Ecuador (family A) with NPHS20, Dorval et al. (2019) identified a hemizygous missense mutation in the TBC1D8B gene (Q246H; 301027.0001). The patient's mother and sister, who had milder symptoms, were heterozygous for the mutation. The proband had 2 affected brothers who were deceased; their DNA was not available for study. Subsequently, an unrelated boy of European descent (family B) was found to carry a different hemizygous TBC1D8B missense mutation (F291S; 301027.0002) inherited from his unaffected mother. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, affected highly conserved residues in the GRAM domains and segregated with the disorder in the families. Podocytes from the second boy showed abnormalities in actin cytoskeletal organization associated with changes in adhesion and migration. Functional studies of patient podocytes or fibroblasts showed a delay in endocytosis, consistent with defects in vesicular recycling. Patient cells also showed mislocalization of Rab11b (604198) compared to controls. Expression of the human mutations only partially rescued the renal phenotype of zebrafish with knockdown of the tbc1d8b gene, suggesting that the mutations retained some residual function.
Animal Model
Dorval et al. (2019) found that knockdown or knockout of tbc1d8b in zebrafish caused a glomerular filtration barrier defect and proteinuria. Histologic and electron microscopic examination showed a retracted glomerulus in an enlarged Bowman capsule and significant foot process effacement and disappearance of slit diaphragms in kidney of tbc1d8b -/- zebrafish. Wildtype human TBC1D8B short isoform significantly rescued the phenotype in tbc1d8b -/- zebrafish, whereas human TBC1D8B with mutations associated with steroid-resistant nephrotic syndrome only partially rescued the phenotype.
INHERITANCE \- X-linked GENITOURINARY Kidneys \- Nephrotic syndrome \- End-stage renal disease (in affected males) \- Focal segmental glomerulosclerosis (FSGS) \- Effacement of foot processes PRENATAL MANIFESTATIONS Maternal \- Pre-eclampsia when carrying affected males LABORATORY ABNORMALITIES \- Proteinuria MISCELLANEOUS \- Males have onset at birth or in the first years of life \- Females may be unaffected or have proteinuria \- Two unrelated families have been reported (last curated July 2019) MOLECULAR BASIS \- Caused by mutation in the TBC1 domain family, member 8B gene (TBC1D8B, 301027.0001 ) ▲ 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-hydroxybutyric 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
|
NEPHROTIC SYNDROME, TYPE 20
|
None
| 25,786 |
omim
|
https://www.omim.org/entry/301028
| 2019-09-22T16:18:49 |
{"omim": ["301028"]}
|
A melanocytoma is a rare pigmented tumor that has been described as a variant of the melanocytic nevus[1] and is a derivative of the neural crest.[2] The term "melanocytoma" was introduced by Limas and Tio in 1972.[3][4]
## Contents
* 1 Histology
* 2 Optic melanocytoma
* 3 Meningeal melanocytoma
* 4 Differential diagnosis
* 5 Veterinary medicine
* 6 See also
* 7 References
## Histology[edit]
Histologically, the tumor is described by large, uniformly shaped polyhedral nevus cells that are pigmented and closely packed[5] Typically, it lacks signs of malignancy such as high mitotic rate, necroses or infiltrative growth.[6] Like the malignant melanoma, it shows an immunohistological profile with S-100 protein-, vimentin- and HMB-45-positive tumor cells.[6]
## Optic melanocytoma[edit]
Further information: Optic nerve tumor
Most commonly the melanocytoma is found on or adjacent to the optic nerve[7] as the optical melanocytoma. The lesion can be found at any age. Location and size could lead to clinical symptoms.While the melanocytoma is generally considered to be a benign tumor,[7] it has a potential for growth, recurrence, and transformation to a malignant melanoma.[5] Because malignant transformation is rare, optical melanocytomas can usually be observed.[1] Thus, in asymptomatic patients, regular observation by fundoscopy is indicated, perhaps supported by ocular ultrasonography.[8][9][10]
## Meningeal melanocytoma[edit]
The meningeal melanocytoma is found on the leptomeninges of the brain,[6][7] typically in the area of the base of the brain and brain stem,[2] or the spine.[4][11] Symptoms may be absent or related to growth and location. Like with the optic version, growth, recurrence, and malignant transformation are the main problems. Meningeal melanocytomas represent 0.06-0.1% of brain tumors.[12] In a 2003 review of 95 cases by Rahimi-Movaghar et al, 45 were intracranial (mostly supratentorial) and 50 spinal or along spinal roots.[13] The authors noted that the median age was 40 years for patients with intracranial and 49 for those with spinal tumors. Lesions were more common in women (57.9%). The review showed a recurrence rate of 26.3% and a death rate of 10.5% over 46 months.[13] A 2001 review by Rades et al concluded that complete resection is the best treatment.[14] If resection is incomplete, postoperative radiotherapy should be applied.
## Differential diagnosis[edit]
Pigmented tumors raise the possibility of a malignant melanoma, a condition that may present diagnostic and therapeutic dilemmas.[9] In the differential diagnosis, schwannoma and meningioma with pigmentation are to be considered as well.[11]
## Veterinary medicine[edit]
Melanocytomas have been described in animals, for instance, dogs and cats.[15][16]
## See also[edit]
* Dermal melanocytoma
* Melanocytic tumors of uncertain malignant potential
## References[edit]
1. ^ a b Shields, Jerry A.; Demirci, Hakan; Mashayekhi, Arman; Eagle, Ralph C.; Shields, Carol L. (2006). "Melanocytoma of the Optic Disk: A Review". Survey of Ophthalmology. 51 (2): 93–104. doi:10.1016/j.survophthal.2005.12.011. ISSN 0039-6257. PMID 16500211.
2. ^ a b Sethi, Divya; Duhan, Amrita; Sen, Rajeev; Goyal, Vandana; Modi, Shilpi (2011). "Spinal meningeal melanocytoma". Asian Journal of Neurosurgery. 6 (2): 110–2. doi:10.4103/1793-5482.92176. ISSN 1793-5482. PMC 3277064. PMID 22347335.
3. ^ Limas C, Tio FO (1972). "Meningeal melanocytoma ("melanotic meningioma"). Its melanocytic origin as revealed by electron microscopy". Cancer. 30 (5): 1286–94. doi:10.1002/1097-0142(197211)30:5<1286::aid-cncr2820300522>3.0.co;2-v. PMID 4343293.
4. ^ a b Shanthi, Vissa; Ramakrishna, BA; Bheemaraju, VydehiVenkata; Rao, NandamMohan; Athota, Venkata RamanaMurthy (2010). "Spinal meningeal melanocytoma: A rare meningeal tumor". Annals of Indian Academy of Neurology. 13 (4): 308–10. doi:10.4103/0972-2327.74192. ISSN 0972-2327. PMC 3021939. PMID 21264144.
5. ^ a b Mohmad, Zalilawati; Aik Kah, Tan; Chui Yong, Ku; Wan Abdul Halim, Wan Haslina; Kong Yong, Then (2011). "Melanocytoma of the optic nerve head - a diagnostic dilemma". Clinics and Practice. 1 (3): 60. doi:10.4081/cp.2011.e60. ISSN 2039-7283. PMC 3981369. PMID 24765321.
6. ^ a b c Schindler CU, Kuchelmeister K, Richter HP, Schachenmayr W (1998). "Das meningeale Melanozytom". Pathologe. 19 (4): 325–9. doi:10.1007/s002920050292. PMID 9746920.CS1 maint: multiple names: authors list (link)
7. ^ a b c Reidy, James J.; Apple, David J.; Steinmetz, Robert L.; Craythorn, Judy M.; Loftfield, Katherine; Gieser, Stephen C.; Brady, Steven E. (1985). "Melanocytoma: Nomenclature, pathogenesis, natural history and treatment". Survey of Ophthalmology. 29 (5): 319–327. doi:10.1016/0039-6257(85)90107-9. ISSN 0039-6257. PMID 3992470.
8. ^ P. M. Sharma u. a.: Malignant transformation of optic disc melanocytoma? A clinical dilemma at presentation with a review of the literature. In: Ophthalmologica 216, 2002, S. 292–295. PMID 12207136 (Review).
9. ^ a b Timothy Murray, Timothy G. (2010). "Clinical imaging and high-resolution ultrasonography in melanocytoma management". Clinical Ophthalmology: 855. doi:10.2147/OPTH.S11891. ISSN 1177-5483. PMID 20714362.
10. ^ Lisker-Cervantes, Andrés; Ancona-Lezama, David Arturo; Arroyo-Garza, Luis Javier; Martinez, Jaime D.; Barreiro, Roberta Gomez Diaz; Valdepeña-López-Velarde, Victor Daniel; Morales-Canton, Virgilio; Moragrega-Adame, Eduardo (2017). "Ocular ultrasound findings in optic disk melanocytoma". Revista Mexicana de Oftalmología. 91 (6): 316–320. doi:10.1016/j.mexoft.2017.03.003. ISSN 0187-4519.
11. ^ a b Wang, F.; Li, X.; Chen, L.; Pu, X. (2007). "Malignant transformation of spinal meningeal melanocytoma. Case report and review of the literature". Journal of Neurosurgery. Spine. 6 (5): 451–4. doi:10.3171/spi.2007.6.5.451. PMID 17542513.
12. ^ Elazim, AhmedAbd; Elbadry, Rasha; Mohamed, Kazim; Issa, Mamdouh; Ayyad, Ali (2018). "Primary meningeal melanocytoma of the cerebellopontine angle associated with ipsilateral nevus of Ota: A case report". Surgical Neurology International. 9 (1): 245. doi:10.4103/sni.sni_235_18. ISSN 2152-7806. PMC 6293867. PMID 30613434.
13. ^ a b Rahimi-Movaghar, Vafa; Karimi, Mehrbod (2003). "Meningeal melanocytoma of the brain and oculodermal melanocytosis (nevus of ota): case report and literature review". Surgical Neurology. 59 (3): 200–210. doi:10.1016/S0090-3019(02)01052-2. ISSN 0090-3019. PMID 12681556.
14. ^ Rades, Dirk; Heidenreich, Fedor; Tatagiba, Marcos; Brandis, Almuth; Karstens, Johann Hinrich (2001). "Therapeutic options for meningeal melanocytoma". Journal of Neurosurgery: Spine. 95 (2): 225–231. doi:10.3171/spi.2001.95.2.0225. ISSN 1547-5654. PMID 11599841.
15. ^ Martens, A. L. (2007). "Unusual presentation of an anterior uveal melanocytoma in a 3-year-old poodle". The Canadian Veterinary Journal. 48 (7): 748–50. PMC 1899854. PMID 17824163.
16. ^ Wilcock B, Dubielzig RR, Render JA. Histological Classification of Ocular and Otic Tumors of Domestic Animals. In: Schulman FY, editor. WHO International Histological Classification of Tumors of Domestic Animals. IX. Armed Forces Institute of Pathology; Washington, D.C: 2002.
*[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-hydroxybutyric 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
|
Melanocytoma
|
c0334431
| 25,787 |
wikipedia
|
https://en.wikipedia.org/wiki/Melanocytoma
| 2021-01-18T19:04:38 |
{"umls": ["C0334431"], "wikidata": ["Q1919036"]}
|
Keratosis pilaris atrophicans faciei
Other namesFolliculitis rubra, Keratosis pilaris rubra atrophicans faciei, Lichen pilare, Lichen pilaire ou xerodermie pilaire symetrique de la face, Ulerythema ophryogenes, and Xerodermie pilaire symetrique de la face
Keratosis pilaris atrophicans faciei begins in infancy as follicular papules with perifollicular erythema.[1]:762 Initially, the lesions are restricted to the lateral eyebrows, but with time spread to involve the cheeks and forehead, and may also be associated with keratosis pilaris on the extremities and buttocks.[1]:762[2]:714[3]
## See also[edit]
* Skin lesion
* Cicatricial alopecia
* Ulerythema
* List of cutaneous conditions
## References[edit]
1. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 522. ISBN 978-1-4160-2999-1.
## External links[edit]
Classification
D
* OMIM: 604093
This Genodermatoses 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-hydroxybutyric 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
|
Keratosis pilaris atrophicans faciei
|
c0263429
| 25,788 |
wikipedia
|
https://en.wikipedia.org/wiki/Keratosis_pilaris_atrophicans_faciei
| 2021-01-18T18:31:12 |
{"gard": ["5395", "1042"], "mesh": ["C537412"], "umls": ["C0263429"], "orphanet": ["3406"], "wikidata": ["Q3548166"]}
|
This article is about increased activity and resistance in muscles. For increased blood pressure, see Hypertension.
Not to be confused with muscular hypertrophy.
Hypertonia
SpecialtyNeurology
Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions.[1] Impaired ability of damaged motor neurons to regulate descending pathways gives rise to disordered spinal reflexes, increased excitability of muscle spindles, and decreased synaptic inhibition.[2] These consequences result in abnormally increased muscle tone of symptomatic muscles.[3] Some authors suggest that the current definition for spasticity, the velocity-dependent over-activity of the stretch reflex, is not sufficient as it fails to take into account patients exhibiting increased muscle tone in the absence of stretch reflex over-activity. They instead suggest that "reversible hypertonia" is more appropriate and represents a treatable condition that is responsive to various therapy modalities like drug and/or physical therapy.[4]
## Contents
* 1 Presentation
* 2 Pathophysiology
* 3 Management
* 3.1 Physical interventions
* 3.2 Pharmaceutical interventions
* 4 See also
* 5 References
* 6 External links
## Presentation[edit]
Symptoms associated with central nervous systems disorders are classified into positive and negative categories. Positive symptoms include those that increase muscle activity through hyper-excitability of the stretch reflex (i.e., rigidity and spasticity) where negative symptoms include those of insufficient muscle activity (i.e. weakness) and reduced motor function.[5] Often the two classifications are thought to be separate entities of a disorder; however, some authors propose that they may be closely related.[6]
## Pathophysiology[edit]
Hypertonia is caused by upper motor neuron lesions which may result from injury, disease, or conditions that involve damage to the central nervous system. The lack of or decrease in upper motor neuron function leads to loss of inhibition with resultant hyperactivity of lower motor neurons. Different patterns of muscle weakness or hyperactivity can occur based on the location of the lesion, causing a multitude of neurological symptoms, including spasticity, rigidity, or dystonia.[3]
Spastic hypertonia involves uncontrollable muscle spasms, stiffening or straightening out of muscles, shock-like contractions of all or part of a group of muscles, and abnormal muscle tone. It is seen in disorders such as cerebral palsy, stroke, and spinal cord injury. Rigidity is a severe state of hypertonia where muscle resistance occurs throughout the entire range of motion of the affected joint independent of velocity. It is frequently associated with lesions of the basal ganglia. Individuals with rigidity present with stiffness, decreased range of motion and loss of motor control. Dystonic hypertonia refers to muscle resistance to passive stretching (in which a therapist gently stretches the inactive contracted muscle to a comfortable length at very low speeds of movement) and a tendency of a limb to return to a fixed involuntary (and sometimes abnormal) posture following movement.[citation needed]
## Management[edit]
Therapeutic interventions are best individualized to particular patients.[citation needed]
Basic principles of treatment for hypertonia are to avoid noxious stimuli and provide frequent range of motion exercise.[citation needed]
### Physical interventions[edit]
Physiotherapy has been shown to be effective in controlling hypertonia through the use of stretching aimed to reduce motor neuron excitability.[7] The aim of a physical therapy session could be to inhibit excessive tone as far as possible, give the patient a sensation of normal position and movement, and to facilitate normal movement patterns. While static stretch has been the classical means to increase range of motion, PNF stretching has been used in many clinical settings to effectively reduce muscle spasticity.[8]
Icing and other topical anesthetics may decrease the reflexive activity for short period of time in order to facilitate motor function. Inhibitory pressure (applying firm pressure over muscle tendon) and promoting body heat retention and rhythmic rotation (slow repeated rotation of affected body part to stimulate relaxation)[9] have also been proposed as potential methods to decrease hypertonia. Aside from static stretch casting, splinting techniques are extremely valuable to extend joint range of motion lost to hypertonicity.[10] A more unconventional method for limiting tone is to deploy quick repeated passive movements to an involved joint in cyclical fashion; this has also been demonstrated to show results on persons without physical disabilities.[7] For a more permanent state of improvement, exercise and patient education is imperative.[9] Isokinetic,[11][12][13][14] aerobic,[15][16][17] and strength training[18][19][20][21] exercises should be performed as prescribed by a physiotherapist, and stressful situations that may cause increased tone should be minimized or avoided.[9]
### Pharmaceutical interventions[edit]
Baclofen, diazepam and dantrolene remain the three most commonly used pharmacologic agents in the treatment of spastic hypertonia. Baclofen is generally the drug of choice for spinal cord types of spasticity, while sodium dantrolene is the only agent which acts directly on muscle tissue. Tizanidine is also available. Phenytoin with chlorpromazine may be potentially useful if sedation does not limit their use. Ketazolam, not yet available in the United States, may be a significant addition to the pharmacologic set of options. Intrathecal administration of antispastic medications allows for high concentrations of drug near the site of action, which limits side effects.[10]
## See also[edit]
* Dystonia
* Hypotonia
* Spasticity
* Clasp-knife response
## References[edit]
1. ^ http://www.ninds.nih.gov/disorders/hypertonia/hmypertonia.htm[full citation needed]
2. ^ O'Sullivan, Susan (2007). Physical Rehabilitation. Philadelphia, PA: F.A Davis Company. p. 234.
3. ^ a b Sheean, Geoffrey; McGuire, John R. (2009). "Spastic Hypertonia and Movement Disorders: Pathophysiology, Clinical Presentation, and Quantification". PM&R. 1 (9): 827–33. doi:10.1016/j.pmrj.2009.08.002. PMID 19769916.
4. ^ Bakheit, AM; Fheodoroff, K; Molteni, F (2011). "Spasticity or reversible muscle hypertonia?". Journal of Rehabilitation Medicine. 43 (6): 556–7. doi:10.2340/16501977-0817. PMID 21491075.
5. ^ Sanger, T. D.; Chen, D.; Delgado, M. R.; Gaebler-Spira, D.; Hallett, M.; Mink, J. W. (2006). "Definition and Classification of Negative Motor Signs in Childhood". Pediatrics. 118 (5): 2159–67. doi:10.1542/peds.2005-3016. PMID 17079590. S2CID 1974796.
6. ^ Damiano, Diane L; Dodd, Karen (2002). "Should we be testing and training muscle strength in cerebral palsy?". Developmental Medicine & Child Neurology. 44 (1): 68–72. doi:10.1111/j.1469-8749.2002.tb00262.x. PMID 11811654.
7. ^ a b Chang, Ya-Ju; Fang, Chia-Ying; Hsu, Miao-Ju; Lien, Hen-Yu; Wong, Mei-Kwan (2007). "Decrease of hypertonia after continuous passive motion treatment in individuals with spinal cord injury". Clinical Rehabilitation. 21 (8): 712–8. doi:10.1177/0269215507079137. PMID 17846071. S2CID 12538385.
8. ^ Sharman, Melanie J; Cresswell, Andrew G; Riek, Stephan (2006). "Proprioceptive Neuromuscular Facilitation Stretching". Sports Medicine. 36 (11): 929–39. doi:10.2165/00007256-200636110-00002. PMID 17052131. S2CID 3123371.
9. ^ a b c O'Sullivan, Susan (2007). Physical Rehabilitation. Philadelphia, PA: F.A Davis Company. p. 497.
10. ^ a b Katz, Richard T. (1988). "Management of spasticity". American Journal of Physical Medicine & Rehabilitation. 67 (3): 108–16. doi:10.1097/00002060-198806000-00004. PMID 3288246. S2CID 45292155.
11. ^ Giuliani, Carol A. (1997). "The Relationship of Spasticity to Movement and Considerations for Therapeutic Interventions". Neurology Report. 21 (3): 78–84. doi:10.1097/01253086-199721030-00009.
12. ^ Light, K E; Giuliani, C A (1992). "Effect of Isokinetic Exercise Effort on the Arm Coordination of Spastic Hemiparetic Subjects". Neurology Report. 16 (4): 19. doi:10.1097/01253086-199216040-00016.
13. ^ Giuliani, C A; Light, K E; Rose, D K. (1993). "The Effect of an Isokinetic Exercise Program on Gait Patterns in Patients with Hemiparesis". Neurology Report. 17 (4): 23–4. doi:10.1097/01253086-199317040-00029.
14. ^ Brown, D. A.; Kautz, S. A. (1998). "Increased Workload Enhances Force Output During Pedaling Exercise in Persons With Poststroke Hemiplegia". Stroke. 29 (3): 598–606. CiteSeerX 10.1.1.568.9281. doi:10.1161/01.STR.29.3.598. PMID 9506599.
15. ^ Hunter, Marque; Tomberlin, JoAnn; Kirkikis, Carol; Kuna, Samuel T (1990). "Progressive exercise testing in closed head-injured subjects: comparison of exercise apparatus in assessment of a physical conditioning program". Physical Therapy. 70 (6): 363–71. doi:10.1093/ptj/70.6.363. PMID 2345780.
16. ^ Jankowski, LW; Sullivan, SJ (1990). "Aerobic and neuromuscular training: effect on the capacity, efficiency, and fatigability of patients with traumatic brain injuries". Archives of Physical Medicine and Rehabilitation. 71 (7): 500–4. PMID 2350220.
17. ^ Potempa, K.; Lopez, M.; Braun, L. T.; Szidon, J. P.; Fogg, L.; Tincknell, T. (1995). "Physiological Outcomes of Aerobic Exercise Training in Hemiparetic Stroke Patients". Stroke. 26 (1): 101–5. doi:10.1161/01.STR.26.1.101. PMID 7839377.
18. ^ Damiano, Diane L.; Abel, Mark F. (1998). "Functional outcomes of strength training in spastic cerebral palsy". Archives of Physical Medicine and Rehabilitation. 79 (2): 119–25. doi:10.1016/S0003-9993(98)90287-8. PMID 9473991.
19. ^ Damiano, Diane L.; Vaughan, Christopher L.; Abel, Mark E. (1995). "Muscle response to heavy resistance exercise in children with spastic cerebral palsy". Developmental Medicine and Child Neurology. 37 (8): 731–9. doi:10.1111/j.1469-8749.1995.tb15019.x. PMID 7672470. S2CID 33519087.
20. ^ Miller, G T; Light, K E; Kellog, R. (1996). "Comparison of Isometric-Force Control Measures in Spastic Muscle of Poststroke Individuals Before and After Graded Resistive Exercise". Neurology Report. 20 (2): 92–3. doi:10.1097/01253086-199620020-00041.
21. ^ Hall, C; Light, K (1990). "Heavy restrictive exercise effect on reciprocal movement coordination of closed-head injured subjects with spasticity". Neurology Report. 14: 19.
## External links[edit]
Classification
D
* ICD-10: P94.1
* ICD-9-CM: 358, 779.89
* MeSH: D009122
* DiseasesDB: 20872
* v
* t
* e
Diseases of muscle, neuromuscular junction, and neuromuscular disease
Neuromuscular-
junction disease
* autoimmune
* Myasthenia gravis
* Lambert–Eaton myasthenic syndrome
* Neuromyotonia
Myopathy
Muscular dystrophy
(DAPC)
AD
* Limb-girdle muscular dystrophy 1
* Oculopharyngeal
* Facioscapulohumeral
* Myotonic
* Distal (most)
AR
* Calpainopathy
* Limb-girdle muscular dystrophy 2
* Congenital
* Fukuyama
* Ullrich
* Walker–Warburg
XR
* dystrophin
* Becker's
* Duchenne
* Emery–Dreifuss
Other structural
* collagen disease
* Bethlem myopathy
* PTP disease
* X-linked MTM
* adaptor protein disease
* BIN1-linked centronuclear myopathy
* cytoskeleton disease
* Nemaline myopathy
* Zaspopathy
Channelopathy
Myotonia
* Myotonia congenita
* Thomsen disease
* Neuromyotonia/Isaacs syndrome
* Paramyotonia congenita
Periodic paralysis
* Hypokalemic
* Thyrotoxic
* Hyperkalemic
Other
* Central core disease
Mitochondrial myopathy
* MELAS
* MERRF
* KSS
* PEO
General
* Inflammatory myopathy
* Congenital myopathy
* 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
Authority control
* GND: 4026372-1
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Hypertonia
|
c0026826
| 25,789 |
wikipedia
|
https://en.wikipedia.org/wiki/Hypertonia
| 2021-01-18T19:01:22 |
{"mesh": ["D009122"], "umls": ["C0026826"], "icd-9": ["358", "779.89"], "icd-10": ["P94.1"], "wikidata": ["Q574942"]}
|
## Summary
### Clinical characteristics.
The disorder of congenital mirror movements (CMM) is characterized by early-onset, obvious mirror movements (involuntary movements of one side of the body that mirror intentional movements on the opposite side) in individuals who typically have no other clinical signs or symptoms. Although mirror movements vary in severity, most affected individuals have strong and sustained mirror movements of a lesser amplitude than the corresponding voluntary movements. Mirror movements usually persist throughout life, without deterioration or improvement, and are not usually associated with subsequent onset of additional neurologic manifestations. However, a subset of affected individuals with a heterozygous pathogenic variant in DCC may have CMM with abnormalities of the corpus callosum and concomitant cognitive and/or neuropsychiatric issues.
### Diagnosis/testing.
The diagnosis of CMM is established in a proband with suggestive clinical findings and occasionally by identification of a heterozygous pathogenic variant in DCC, NTN1, or RAD51.
### Management.
Treatment of manifestations: Adaptation of the school environment (e.g., allocation of extra time during examinations and limitation of the amount of handwriting) is recommended. Stigmatizing children and adolescents should be avoided to assure that educational opportunities are not lost as a result of mirror movements. Adolescents and young adults should be encouraged to consider a profession that does not require complex bimanual movements, repetitive or sustained hand movements, or extensive handwriting. Standard therapy for any neurocognitive issues is recommended.
Agents/circumstances to avoid: Complex bimanual movements or sustained/repetitive hand activity in order to reduce pain or discomfort in the upper limbs.
### Genetic counseling.
CMM is generally inherited in an autosomal dominant (AD) manner; (autosomal recessive inheritance has been suggested in one family). For AD inheritance: most individuals with CMM resulting from a pathogenic variant in DCC, NTN1, or RAD51 inherited the pathogenic variant from a parent who may be symptomatic or asymptomatic. If a parent of the proband is affected and/or has a DCC, NTN1, or RAD51 pathogenic variant, the risk to the sibs of inheriting the variant is 50%. Of note, the sibs of a proband who has clinically unaffected parents are still at increased risk for CMM because of the significant possibility of reduced penetrance in a heterozygous parent. Each child of an individual with AD CMM has a 50% chance of inheriting the causative variant; however, because of reduced penetrance, offspring who inherit the pathogenic variant may not manifest CMM. Once the CMM-causing pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
## Diagnosis
The diagnosis of the disorder of congenital mirror movements (CMM) is established by clinical findings and, in some instances, molecular genetic testing.
### Suggestive Findings
CMM should be suspected in individuals with the following clinical features, imaging findings, and family history.
Clinical features
* Onset of mirror movements (defined as involuntary movements of one side of the body that mirror intentional movements on the opposite side) in infancy or early childhood
* Predominant involvement of the upper limbs, with more severe distal involvement, especially in the muscles controlling the fingers and hands, which are always involved
* Persistence of mirror movements throughout adulthood and absence of the following:
* Evidence of other clinical findings that would suggest an underlying syndrome [Bonnet et al 2010] (See Differential Diagnosis.)
* Subsequent development of additional neurologic findings
Imaging findings. Normal brain MRI or partial or complete agenesis of the corpus callosum
Family history. Consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations). Absence of a known family history does not preclude the diagnosis.
### Establishing the Diagnosis
The diagnosis of CMM is established in a proband with suggestive clinical findings and occasionally by identification of a heterozygous pathogenic variant in DCC, NTN1, or RAD51 by molecular genetic testing (see Table 1).
Note: Identification of a heterozygous DCC, NTN1, or RAD51 variant of uncertain significance does not establish or rule out a diagnosis of CMM.
Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of CMM has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic findings suggest the diagnosis of CMM, molecular genetic testing approaches include use of a multigene panel.
A multigene panel that includes DCC, NTN1, and RAD51 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the diagnosis of CMM has not been considered because an individual has atypical phenotypic features, comprehensive genomic testing may be pursued.
Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.
If exome sequencing is not diagnostic – and particularly when evidence supports autosomal dominant inheritance – exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
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 Congenital Mirror Movements
View in own window
Gene 1Proportion of Probands with a Pathogenic Variant 2 Detectable by Method
Sequence analysis 3Gene-targeted deletion/duplication analysis 4
DCC24/25 51/25 6
NTN13/3 7None reported 7
RAD517/7 8None reported 8
Unknown 9NA
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
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.
5\.
Srour et al [2010], Depienne et al [2011], Djarmati-Westenberger et al [2011], Depienne et al [2012], Ahmed et al [2014], Méneret et al [2014a], Méneret et al [2014b], Franz et al [2015], Marsh et al [2017], Bierhals et al [2018], Sagi-Dain et al [2020]
6\.
Méneret et al [2014a]
7\.
Méneret et al [2017]
8\.
Srour et al [2010], Depienne et al [2011], Djarmati-Westenberger et al [2011], Depienne et al [2012], Ahmed et al [2014], Méneret et al [2014a], Méneret et al [2014b], Franz et al [2015], Trouillard et al [2016], Demirayak et al [2018]
9\.
Significant locus heterogeneity is hypothesized. Pathogenic variants in DNAL4 have been suggested, but not confirmed, as a cause of CMM [Ahmed et al 2014, Méneret et al 2014b].
## Clinical Characteristics
### Clinical Description
Physiologic mild mirror movements may be seen in young children, but their persistence after age seven years is pathologic [Galléa et al 2011]. The disorder of congenital mirror movements (CMM) is characterized by early-onset obvious mirror movements that persist throughout adulthood in individuals who typically have no other clinical disorders. In particular, the mirror movements are not usually associated with subsequent onset of additional neurologic manifestations. However, a subset of individuals with a heterozygous DCC pathogenic variant may have concomitant cognitive and/or neuropsychiatric issues, particularly if abnormalities of the corpus callosum are present (see Phenotype Correlations by Gene and Genetically Related Disorders). Mirror movements usually persist throughout life, without deterioration or improvement.
Mirror movements (MM) predominantly involve the upper limbs, with more severe distal involvement. The muscles that control the fingers and hands are always involved. Muscles involving the toes may be slightly involved, without interfering with ambulation.
Although mirror movements vary in severity, most affected individuals have strong and sustained mirror movements of a lesser amplitude than the corresponding voluntary movements.
The severity of the mirror movements is defined according to the Woods and Teuber scale [Woods & Teuber 1978] as follows:
1.
No MM
2.
Barely discernible but repetitive MM
3.
Slight but sustained MM or stronger but briefer MM
4.
Strong and sustained repetitive MM
5.
MM equal to that observed in the intended hand
Affected individuals have moderate difficulties with activities of daily living, including inability to perform pure unimanual movements, difficulty with tasks requiring skilled bimanual coordination, and occasional pain in the upper limbs during sustained manual activities [Galléa et al 2011, Méneret et al 2015].
Sensory issues. There are no sensory issues in CMM, but clinical examination in rare affected individuals may show sensory coupling, which is the perception of a sensation in the limb contralateral to the one being stimulated [Spencer-Smith et al 2020].
Neuroimaging. Brain MRI is normal in most cases but may show partial or complete agenesis of the corpus callosum (ACC) in some individuals with a heterozygous pathogenic DCC variant (see Phenotype-Correlations by Gene).
### Phenotype Correlations by Gene
DCC. Individuals with a heterozygous DCC pathogenic variant may have CMM with or without partial or complete agenesis of the corpus callosum. These individuals may also have specific neuropsychological deficits associated with variable cognitive outcomes [Marsh et al 2017, Brown & Paul 2019, Spencer-Smith et al 2020]. The possible occurrence of slight neuropsychological deficits has also been suggested in individuals with a heterozygous DCC pathogenic variant without ACC [Spencer-Smith et al 2020].
NTN1 and RAD51. So far, there have been no reports of individuals with a heterozygous pathogenic variant in NTN1 or RAD51 who have corpus callosum abnormalities.
### Genotype-Phenotype Correlations
There are no clear and validated genotype-phenotype correlations for NTN1 or RAD51.
DCC
* Pathogenic variants in the NTN1 binding interface may predispose to abnormalities in the development of the corpus callosum with or without CMM [Spencer-Smith et al 2020] (see Genetically Related Disorders).
* Males with truncating DCC pathogenic variants are more likely to present with CMM, while females with truncating DCC pathogenic variants are more likely to present with isolated ACC (see Genetically Related Disorders) [Marsh et al 2017].
### Penetrance
Penetrance is incomplete regardless of whether the causative pathogenic variant is in DCC, NTN1, or RAD51. Penetrance for the CMM phenotype was estimated to be 42% in those with a heterozygous pathogenic DCC variant – the most frequent cause of CMM [Marsh et al 2017].
### Nomenclature
The term "synkinesis" may be appropriate, although it is more often used to describe mirror movements acquired later in life, as a result of either neurodegenerative diseases or acute brain lesions [Cox et al 2012].
The term "bimanual synergia" is mentioned in OMIM as having been used by William Bateson (1861-1926) in a family with CMM of apparent autosomal dominant inheritance and incomplete penetrance (OMIM 157600).
### Prevalence
Congenital mirror movements is a very rare disorder, with an estimated prevalence of less than 1:1,000,000 (Orphanet 238722; accessed 9-21-20), although the actual prevalence could be significantly higher due to underdiagnosis, especially in individuals with milder manifestations.
## Differential Diagnosis
The differential diagnosis of congenital mirror movements (CMM) from mirror movements of other causes is mainly theoretic, as the findings in CMM are distinctive, isolated, and easily recognized.
Physiologic mirror movements. The intensity of the mirror movements and their persistence after age seven years clearly differentiate pathologic from physiologic mirror movements. Mild physiologic mirror movements are frequent in normally developing young children. They usually disappear completely before age seven years and tend to recur gradually in old age [Bonnet et al 2010, Koerte et al 2010].
Syndromes with early-onset (congenital) mirror movements. Early-onset mirror movements are not always isolated; they may be a component of complex syndromes (see Table 2) and congenital hemiplegia (the most common form of cerebral palsy) [Norton et al 2008]. Although the clinical characteristics of mirror movements have been less comprehensively investigated in these conditions, they resemble those of CMM. In practice, differential diagnosis of CMM is rarely an issue, as the associated findings are generally more significant. When the diagnosis is in doubt, brain and cervical MRI may be considered in children or adolescents with mirror movements.
### Table 2.
Syndromes with Early-Onset Mirror Movements
View in own window
DisorderGene(s)MOIMirror MovementsOther Features
ANOS1 Kallmann syndrome (KS) (See Isolated GnRH Deficiency.)ANOS1 (KAL1)XL
* MM in persons w/KS is almost always linked to ANOS1 1 (ANOS1-KS accounts for ~5%-10% of isolated GnRH deficiency).
* Prevalence of MM in KAL1-KS is 75%. 1
Hyposmia & hypogonadotropic hypogonadism
Joubert syndrome≥34 genesAR
XL 2CMM is observed in some affected persons. 3Hypoplasia of cerebellar vermis w/characteristic neuroradiologic molar tooth sign & variable accompanying neurologic symptoms
Klippel-Feil syndrome (KFS) (OMIM PS118100) 4GDF3
GDF6
MEOX1
MYO18BAD
ARMM is present in minority of persons w/KFS (MM is likely linked to cervicomedullary neuroschisis).
* Congenital fusion of cervical vertebrae
* Typical phenotype incl low posterior hairline, short neck, & ↓ amplitude of neck movements
Moebius syndrome (OMIM 157900)UnknownADMM is only occasionally reported. 5Minimum criteria are congenital, non-progressive facial weakness in assoc w/limited abduction of 1 or both eyes.
Nevoid basal cell carcinoma syndrome
(Gorlin syndrome)PTCH1
(PTCH2) 6
SUFUADMM reported in 1 person 7Multiple basal cell carcinomas, jaw keratocysts, & skeletal malformations
Seckel syndrome
(OMIM PS210600)ATR
CENPJ
CEP152
CEP63
DNA2
NIN
NSMCE2
RBBP8
TRAIPAR1 reported person w/MM 8Primary microcephaly, intellectual disability, & often prenatal-onset growth restriction
Wildervanck syndrome (OMIM 314600)UnknownXL?1 reported person w/MM 9
* Klippel-Feil syndrome w/congenital perceptive deafness & Duane syndrome 10
* Affected persons are almost exclusively female.
AD = autosomal dominant; AR = autosomal recessive; CMM = congenital mirror movements; GnRH = gonadotropin-releasing hormone; MM = mirror movements; MOI = mode of inheritance; XL = X-linked
1\.
Dodé & Hardelin [2010], Manara et al [2015]
2\.
Digenic inheritance has been reported.
3\.
Ferland et al [2004]
4\.
Tassabehji et al [2008], Mohamed et al [2013]
5\.
Webb et al [2014]
6\.
Occasional variants in PTCH2 have been found in individuals with NBCCS but these may not be conclusive (see Nevoid Basal Cell Carcinoma Syndrome).
7\.
Sag et al [2016]
8\.
Thapa & Mukherjee [2010]
9\.
Högen et al [2012]
10\.
Duane syndrome = abducens palsy with narrowing of the palpebral fissure
Acquired mirror movements. Age of onset differentiates acquired mirror movements (usually associated with neurodegenerative disorders in adults) from congenital mirror movements.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with congenital mirror movements (CMM), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 3.
Recommended Evaluations Following Initial Diagnosis in Individuals with Congenital Mirror Movements
View in own window
System/ConcernEvaluationComment
NeurologicEvals to document difficulties w/ADLConsider referral to rehab specialist.
Consider head MRI imaging.To assess for abnormalities of CC, esp in those w/pathogenic DCC variant
Consider neuropsychological eval. 1In those w/abnormalities of CC
Genetic
counselingBy genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of CMM to facilitate medical & personal decision making
Family support/
resourcesAssess:
* Use of community or online resources such as Parent to Parent;
* Need for social work involvement for parental support.
ADL = activities of daily living; CC = corpus callosum; CMM = congenital mirror movements; MOI = mode of inheritance
1\.
Spencer-Smith et al [2020]
2\.
Medical geneticist, certified genetic counselor, or certified advanced genetic nurse
### Treatment of Manifestations
### Table 4.
Treatment of Manifestations in Individuals with Congenital Mirror Movements
View in own window
Manifestation/ConcernTreatment/CounselingConsiderations/Other
MMAdaptation of school environmentIncl allocation of extra time during exams & limitation of amount of handwriting
Avoid stigmatizing children & adolescents.To assure that educational opportunities incl university are not lost as result of MM
Education of parents & teachersReassurance that intellectual disability is not typically associated
Education of affected personsEncourage a profession that does not require complex bimanual movements, repetitive or sustained hand movements, or extensive handwriting.
Developmental delay /
Neurocognitive deficitsStandard treatmentConsider referral to neurodevelopmental specialist.
MM = mirror movements
### Agents/Circumstances to Avoid
Complex bimanual movements or sustained/repetitive hand activity should be limited in order to reduce the occurrence of pain or discomfort in the upper limbs.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Botulinum toxin injections have been successfully tried in one affected individual [Allegra et al 2017] but are not usually proposed, as the risk of inducing a motor deficit generally exceeds the possible benefit.
Noninvasive modulation of brain interhemispheric communication may be a possibility in the future [Galléa et al 2014].
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.
*[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-hydroxybutyric 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
|
Congenital Mirror Movements
|
None
| 25,790 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK279760/
| 2021-01-18T21:32:46 |
{"synonyms": ["Congenital Mirror Movement Disorder"]}
|
A number sign (#) is used with this entry because Fanconi anemia of complementation group C (FANCC) is caused by homozygous or compound heterozygous mutation in the FANCC gene (613899) on chromosome 9q22.
Description
Fanconi anemia is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011).
For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650.
Pathogenesis
The pathogenesis of the bone marrow failure that is a consistent feature of Fanconi anemia was investigated by Segal et al. (1994), who pointed out that it is not known whether the pancytopenia is a direct and specific result of the inherited mutation or a consequence of accumulated stem cell losses resulting from the nonspecific DNA damage that is characteristic of the disease. They tested the hypothesis that the FACC protein plays a regulatory role in hematopoiesis by exposing normal human lymphocytes, bone marrow cells, endothelial cells, and fibroblasts to an antisense oligodeoxynucleotide (ODN) complementary to bases -4 to +14 of FACC mRNA. The mitomycin C assay demonstrated that the antisense ODN, but not missense or sense ODNs, repressed FACC gene expression in lymphocytes. The antisense ODN substantially reduced cytoplasmic levels of FACC mRNA in bone marrow cells and lymphocytes. Escalating doses of antisense ODN increasingly inhibited clonal growth of erythroid and granulocyte-macrophage progenitor cells but did not inhibit growth of fibroblasts or endothelial cells. Segal et al. (1994) concluded that while the FACC gene product plays a role in defining cellular tolerance to crosslinking agents, it also functions to regulate growth, differentiation, and/or survival of normal hematopoietic progenitor cells.
Molecular Genetics
Strathdee et al. (1992) and Gavish et al. (1992) identified a missense mutation in the FANCC gene in the Fanconi anemia complementation group C cell line HSC536N (613899.0001).
Approximately 25% of patients with Fanconi anemia have evidence of spontaneously occurring mosaicism as manifested by the presence of 2 subpopulations of lymphocytes, one of which is hypersensitive to crosslinking agents (e.g., mitomycin C) while the other behaves normally in response to these agents. In 3 patients who were compound heterozygotes for pathogenic FAC gene mutations, Lo Ten Foe et al. (1997) investigated the molecular mechanism of mosaicism by haplotype analysis. The results indicated that an intragenic mitotic recombination must have occurred leading to a segregation of a wildtype allele in the revertant cells and suggested 2 patterns of recombination. In 1 patient, a single intragenic crossover between the maternally and paternally inherited mutations occurred associated with markers located distal to the FAC gene; in the other 2 patients (sibs), the mechanism appeared to have been gene conversion resulting in segregants that had lost 1 pathogenic mutation. In 6 of 8 patients with mosaicism, the hematologic symptoms were relatively mild despite an age range of 9 to 30 years.
Waisfisz et al. (1999) demonstrated the functional correction of a pathogenic microdeletion, microinsertion, and missense mutation in homozygous Fanconi anemia patients resulting from compensatory secondary sequence alterations in cis. A mutation in the FANCC gene, 1749T to G, which resulted in a substitution of arginine for leucine-496, was altered by 1748C-to-T creating a cysteine codon (613899.0008). Although the predicted proteins were different from wildtype, their cDNAs complemented the characteristic hypersensitivity of FA cells to crosslinking agents, thus establishing a functional correction to wildtype.
Animal Model
Krasnoshtein and Buchwald (1996) used RNA in situ hybridization to study the distribution of Fac transcripts during mouse development. Fac was initially expressed (8-10 days p.c.) in the mesenchyme and its derivatives with osteogenic potential. The transcript was also apparent at later stages of bone development (13-19.5 days p.c.), localized to cells of the inner perichondrium, periosteum, and zone of endochondral ossification. In the third site, Fac transcripts were seen in cells from both osteogenic and hematopoietic lineages. Fac mRNA was also seen in intramembranous cranial and facial bones. In addition, Fac signal was detected in nonskeletal tissues: brain, whisker follicles, lung, kidney, gut, and stomach. The pattern of expression was consistent with the skeletal and non-skeletal congenital abnormalities in FA patients. The authors commented that expression in rapidly dividing progenitors is consistent with hypotheses regarding the nature of the basic defect in FA: a role of the protein in DNA repair or protection from oxygen toxicity.
Chen et al. (1996) found that mice homozygous for a disrupted Fac gene did not show developmental abnormalities or hematologic defects during observations up to 9 months of age. However, their spleen cells had dramatically increased numbers of chromosomal aberrations in response to mitomycin C (MMC) and diepoxybutane. Homozygous male and female mice also had compromised gametogenesis, leading to markedly impaired fertility, a characteristic of Fanconi anemia patients.
Whitney et al. (1996) generated mice homozygous for a targeted deletion of exon 9 of the murine FA complementation group C gene. They selected this exon for knockout since there was evidence from mutation analysis in patients with FAC that the carboxy terminus of the protein is essential for its function. Mutant mice had normal neonatal viability and gross morphology. Their cells demonstrated chromosome breakage and crosslinker sensitivity. Male and female mutant mice had reduced numbers of germ cells and females had markedly impaired fertility. No anemia was detectable during the first year of life. The colony-forming capacity of bone marrow progenitor cells was abnormal and these cells were hypersensitive to gamma-interferon (147570). Whitney et al. (1996) concluded that this abnormal sensitivity to gamma-interferon may form the basis for bone marrow failure in Fanconi anemia.
Skel \- Radial aplasia \- Thumb deformity \- Thumb aplasia \- Thumb hypoplasia \- Duplicated thumb GU \- Kidney malformation \- Absent kidney \- Duplicated kidney \- Duplicated collecting system \- Horseshoe kidney \- Renal ectopia \- Hypergonadotropic hypogonadism \- Cryptorchidism Growth \- Low birth weight \- Small stature Neuro \- Mental retardation Skin \- Anemic pallor \- Bruisability \- Pigmentary changes \- Hyperpigmentation \- Cafe-au-lait spots Cardiac \- Congenital heart defect HEENT \- Microcephaly \- Strabismus \- Microphthalmia \- Ear anomaly \- Deafness Inheritance \- Autosomal recessive with at least two loci and multiple alleles Lab \- Multiple chromosomal breaks \- Chromosomal breakage induced by diepoxybutane (DEB), and mitomycin C \- Deficient excision of UV-induced pyrimidine dimers in DNA \- Prolonged G2 phase of cell cycle Heme \- Anemia \- Neutropenia \- Thrombocytopenia \- Reticulocytopenia \- Pancytopenia \- Bleeding \- Leukemia ▲ 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-hydroxybutyric 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
|
FANCONI ANEMIA, COMPLEMENTATION GROUP C
|
c0015625
| 25,791 |
omim
|
https://www.omim.org/entry/227645
| 2019-09-22T16:27:56 |
{"doid": ["0111087"], "mesh": ["D005199"], "omim": ["227645"], "orphanet": ["84"], "synonyms": ["Alternative titles", "FACC", "FANCONI PANCYTOPENIA, TYPE 3"], "genereviews": ["NBK1401", "NBK5192"]}
|
## Description
Angioma serpiginosum (AS) is a rare benign congenital skin disorder characterized by nonpurpuric red punctate lesions seen histologically as capillary ectasias in the superficial papillary dermis. The lesions often follow Blaschko lines and are most commonly found in females (90%) (Blinkenberg et al., 2007).
See 106050 for additional phenotypic information and possible autosomal dominant inheritance or cutaneous somatic mosaicism (Chen et al., 2006; Blinkenberg et al., 2007).
Clinical Features
Blinkenberg et al. (2007) reported a Norwegian family in which 6 females spanning 4 generations had angioma serpiginosum inherited in an X-linked dominant pattern. Four were alive at the time of the report. The proband was a 46-year-old woman with an asymptomatic punctate and linear erythematous rash that had progressed slowly since birth. The rash followed the lines of Blaschko and was localized on the left shoulder, inside of both arms, the back, and the outside and back of the thighs and calves. Skin biopsy showed nests of slightly dilated and somewhat thick-walled capillaries in the dermal papillae and upper part of the dermis with areas of hyperkeratosis. There was no inflammation. The nails were slightly dysplastic with ridges and incisions, and the hair was thin and straight. Laser treatment improved the rash. Her daughter was similarly affected. The younger sister of the proband was affected but also had small papillomatous tumors in the pharynx and upper part of the esophagus. Histology showed that the tumors were composed of a central core of vascular connective tissue covered by a squamous epithelium with disturbed maturation. The proband was subsequently found to have similar esophageal tumors that were asymptomatic. There was no family history of eye problems, infertility, or spontaneous miscarriage. X-inactivation studies showed 2 patients with 100:0 and 1 patient with 96:4 X-inactivation patterns, consistent with X-linked dominant inheritance and early lethality in males. Blinkenberg et al. (2007) suggested that the disorder may be a mild variant of the Goltz-Gorlin syndrome (focal dermal hypoplasia; FDH; 305600).
Happle (2009) stated that the diagnosis in the 4-generation Norwegian family described by Blinkenberg et al. (2007) should be focal dermal hypoplasia because close inspection of photographs of the erythematous skin lesions revealed small intermingled patches of dermal hypoplasia or atrophy. Happle (2009) further argued that the diagnosis of angioma serpiginosum should have been excluded because some patients had nail dysplasia and bald patches involving the scalp, which are characteristic signs of FDH but unknown in AS, and because esophageal or hypopharyngeal papillomatosis is a typical feature of FDH but absent in AS. In addition, Happle (2009) stated that there was 'not the slightest indication' that AS could be inherited as an X-linked trait. Houge and Hennekam (2009) responded that personal investigation of affected individuals from the Norwegian family, including examination of skin biopsies of affected areas, showed no dermal hypoplasia, and that none of the patients had bald patches; rather, the sparse and thinning hair was so mild that it initially went unnoticed. Houge and Hennekam (2009) also noted that many of the common features of FDH were missing in the Norwegian patients, including ophthalmologic signs and symptoms, papillomas around orifices, clefting, thin and anteverted pinnae, prominent coccyx, and limb anomalies. In support of X-linked inheritance, they pointed out that the vast majority of AS patients are female, that affected skin following Blaschko lines had been described in several cases, and that no male-to-male transmission had been reported.
Mapping
By X-chromosome linkage analysis of a Norwegian family with X-linked dominant angioma serpiginosum, Blinkenberg et al. (2007) identified a candidate region on Xp11.3-q12, flanked by DXS8026 and DXS106 (maximum lod score of 3.31).
Cytogenetics
In all affected females in the Norwegian family with X-linked dominant angioma serpiginosum originally reported by Blinkenberg et al. (2007), Houge et al. (2008) identified a 112-kb deletion on Xp that removed the PORCN gene (300651) and 4 other genes. Houge et al. (2008) noted that this deletion was only 25 kb smaller than a deletion previously found by Grzeschik et al. (2007) in patients with focal dermal hypoplasia, and suggested that modifying genes affecting the timing of X inactivation during embryogenesis may have caused the difference in phenotypic severity.
INHERITANCE \- X-linked dominant ABDOMEN Gastrointestinal \- Benign esophageal papillomas SKIN, NAILS, & HAIR Skin \- Non-purpuric punctate and linear erythematous rash \- Subepidermal capillary ectasia \- Lesions often follow Blaschko lines \- Lesions occur on the trunk, back, arms, legs, abdomen, buttocks \- Extensive cutaneous involvement rarely occurs \- Palms, soles, and oral mucosa are not involved Skin Histology \- Nests of dilated and thick-walled capillaries in the dermal papillae \- Hyperkeratosis \- Inflammation is usually absent Electron Microscopy \- Slit-like protrusion of capillary lumen into the endothelial lining Nails \- Dystrophic nails, mild Hair \- Thin, sparse hair MISCELLANEOUS \- Onset at birth \- Slowly progressive \- Partially responsive to laser treatment ▲ 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-hydroxybutyric 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
|
ANGIOMA SERPIGINOSUM, X-LINKED
|
c0263637
| 25,792 |
omim
|
https://www.omim.org/entry/300652
| 2019-09-22T16:19:51 |
{"doid": ["4028"], "mesh": ["C536366"], "omim": ["300652"], "orphanet": ["95429"], "synonyms": []}
|
Ovarian cancer is a form of cancer that occurs due to abnormal and uncontrolled cell growth in the ovaries. Many people with early ovarian cancer have no signs or symptoms of the condition. When present, symptoms are often nonspecific and blamed on other, more common conditions. Most cases of ovarian cancer occur sporadically in people with little to no family history of the condition; however, approximately 10-25% of ovarian cancers are thought to be "hereditary." Although the underlying genetic cause of some hereditary cases is unknown, many are part of a hereditary cancer syndrome (such as BRCA1 or BRCA2 hereditary breast and ovarian cancer syndrome, Lynch syndrome and Peutz-Jeghers syndrome) and are inherited in an autosomal dominant manner. The best treatment options for ovarian cancer depend on many factors including the subtype and stage of the condition, but may include surgery, chemotherapy, radiation therapy, and/or targeted therapy (such as monoclonal antibody 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-hydroxybutyric 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
|
Ovarian cancer
|
c0677886
| 25,793 |
gard
|
https://rarediseases.info.nih.gov/diseases/7295/ovarian-cancer
| 2021-01-18T17:58:30 |
{"mesh": ["D000077216"], "omim": ["167000 "], "synonyms": ["Ovarian carcinoma"]}
|
Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome is a rare, genetic, non-syndromic developmental defect of the eye disorder characterized by the association of posterior microphthalmia, retinal dystrophy compatible with retinitis pigmentosa, localized foveal schisis and optic disc drusen. Patients present high hyperopia, usually adult-onset progressive nyctalopia and reduced visual acuity, and, on occasion, acute-angle glaucoma.
*[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-hydroxybutyric 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
|
Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome
|
c1970236
| 25,794 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251279
| 2021-01-23T18:29:51 |
{"mesh": ["C567024"], "omim": ["611040"], "umls": ["C1970236"], "icd-10": ["Q15.8"], "synonyms": ["Nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome"]}
|
## Summary
### Clinical characteristics.
Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity.
Pathogenic variants in MT-RNR1 can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset SNHL. Hearing loss associated with aminoglycoside ototoxicity is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount (even a single dose) of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin.
Pathogenic variants in MT-TS1 are usually associated with childhood onset of SNHL that is generally nonsyndromic – although the MT-TS1 substitution m.7445A>G has been found in some families who also have palmoplantar keratoderma (scaling, hyperkeratosis, and honeycomb appearance of the skin of the palms, soles, and heels).
### Diagnosis/testing.
The diagnosis of mitochondrial nonsyndromic hearing loss and deafness is established in a proband with hearing loss and identification of a pathogenic variant in MT-RNR1 or MT-TS1, or one of the eight additional mitochondrial genes known to cause nonsyndromic hearing loss and deafness.
### Management.
Treatment of manifestations: Appropriate rehabilitation (hearing aids, speech therapy, culturally appropriate language training, cochlear implantation, educational programs for the hearing impaired). Electric acoustic stimulation for individuals with mitochondrial hearing loss with residual hearing in the lower frequencies. Lotions and emollients for mild keratoderma; dermatology referral for severe keratoderma.
Prevention of primary manifestations: Avoidance of aminoglycosides.
Surveillance: Annual audiometric assessment to evaluate stability/progression of hearing loss. Annual physical exam for related clinical findings.
Agents/circumstances to avoid: Aminoglycosides and noise exposure, especially in those with normal hearing who have the m.1555A>G or m.1494C>T MT-RNR1 pathogenic variants.
Evaluation of relatives at risk: Molecular genetic testing of at-risk maternal relatives allows for early detection of those who have inherited the mtDNA pathogenic variant and would benefit from avoiding aminoglycosides and appropriate early support and management.
### Genetic counseling.
Mitochondrial nonsyndromic hearing loss and deafness is caused by pathogenic variants in mitochondrial DNA (mtDNA) and is transmitted by maternal inheritance. The mother of a proband (usually) has the mtDNA pathogenic variant and may or may not have hearing loss. All offspring of females with a mtDNA pathogenic variant are at risk of inheriting the pathogenic variant. Offspring of males with a mtDNA pathogenic variant are not at risk of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the mtDNA pathogenic variant in the family is known. Because of mitotic segregation, the mtDNA pathogenic variant load in amniocytes and chorionic villi is unlikely to correspond to that of other fetal or adult tissues. Furthermore, the presence of the mtDNA pathogenic variant does not predict the age of onset or severity of hearing loss.
## Diagnosis
### Suggestive Findings
Mitochondrial nonsyndromic hearing loss and deafness should be suspected in a proband with the following:
* Moderate to profound hearing loss
Hearing loss graded by level of severity:
* Mild (26-40 dB)
* Moderate (41-55 dB)
* Moderately severe (56-70 dB)
* Severe (71-90 dB)
* Profound (90 dB)
Hearing is assessed by a variety of methods; see Hereditary Hearing Loss and Deafness Overview.
* Mild to moderate high-frequency hearing loss
* No other systemic findings on history or physical examination
* A family history of hearing loss suggestive of maternal inheritance (i.e., no transmission through a male)
* Onset of hearing loss following administration of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin
### Establishing the Diagnosis
The diagnosis of mitochondrial nonsyndromic hearing loss and deafness is established in a proband with the above Suggestive Findings and by identification of a pathogenic variant in one of the genes associated with mitochondrial nonsyndromic hearing loss and deafness on molecular genetic testing (see Table 1a, Table 1b).
Molecular genetic testing approaches can include targeted testing, a multigene panel, and complete mtDNA sequencing:
* Targeted testing. In individuals with hearing loss following aminoglycoside exposure, molecular testing for the pathogenic variants m.1555A>G and m.1494C>T in MT-RNR1 and m.7445A>C/T/G in MT-TS1 can be done first.
* A multigene panel that includes the mitochondrial genes listed in Table 1a and other genes of interest (see Table 1b and 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) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. (4) Some mitochondrial nonsyndromic deafness-causing pathogenic variants are heteroplasmic (i.e., both wild type and mutated mtDNA are present in a cell and/or tissue). When selecting a multigene panel, it is necessary to confirm that the test methods can identify heteroplasmic mitochondrial pathogenic variants.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
* Complete mtDNA sequencing may be considered if use of targeted testing and/or a multigene panel did not identify a pathogenic variant, clinical suspicion remains high, and there is no evidence of paternal transmission. Massively parallel DNA sequencing-based techniques are useful for identifying heteroplasmic mitochondrial pathogenic variants.
Note: This testing may be performed before a multigene panel in the case of a clear mitochondrial inheritance pattern.
### Table 1a.
Molecular Genetics of Mitochondrial Nonsyndromic Hearing Loss and Deafness: Most Common Genetic Causes
View in own window
Gene 1Proportion of Mitochondrial Nonsyndromic Hearing Loss and Deafness Attributed to Pathogenic Variants in Mitochondrial GeneProportion of Pathogenic Variants 2 Detectable by Method
Sequence analysis 3Gene-targeted deletion/duplication analysis 4
MT-RNR1~71%~100%Unknown 5
MT-TS1~29%~100%Unknown 5
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\.
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.
5\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
### Table 1b.
Molecular Genetics of Mitochondrial Nonsyndromic Hearing Loss and Deafness: Less Common Genetic Causes
View in own window
Gene 1, 2Pathogenic Variants 3 / Comments
MT-CO1m.7444G>A; located on the boundary of MT-CO1 & MT-TS1; reported in 4 individuals of Polish ancestry & 2 of Chinese ancestry w/nonsyndromic hearing loss or aminoglycoside-induced hearing loss [Zhu et al 2006, Rydzanicz et al 2011]
MT-ND1m.3388C>A; reported in a family w/maternally inherited mild-moderate hearing loss [Lévêque et al 2007]
MT-THm.12201T>C; reported in a 5-generation family w/maternally inherited hearing loss w/average onset age 29 years [Yan et al 2011]
MT-TIm.4295A>G; identified in a 3-generation family w/maternally inherited nonsyndromic hearing loss
MT-TKm.8296A>G; reported in 1/ 717 individuals w/hearing loss [Mori et al 2016]
MT-TL1m.3243A>G; identified in 5/717 individuals w/isolated hearing loss [Mori et al 2016; Author, personal communication]
MT-TS2m.12236G>A; reported in individuals from 1 family w/moderate to profound hearing loss; onset age 7-30 yrs [Lévêque et al 2007]
1\.
Pathogenic variants of any one of the genes listed in this table are reported in only a few families (i.e., <1% of mitochondrial nonsyndromic hearing loss and deafness).
2\.
See Table A. Genes and Databases for chromosome locus and protein.
3\.
Mitochondrial gene variants for nonsyndromic deafness and hearing loss in this table are limited to variants classified as "Confirmed" or "Reported" in the MITOMAP database on the basis of one or more functional analyses such as tRNA stability, respiratory complex activity, or mitochondrial protein synthesis.
## Clinical Characteristics
### Clinical Description
#### MT-RNR1-Related Hearing Loss
Aminoglycoside ototoxicity. Hearing loss occurs within a few days to weeks after administration of any amount (including a single dose) of aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin.
Hearing loss is bilateral and severe to profound [Yelverton et al 2013]. Once it appears, hearing loss is irreversible but not progressive. Hearing loss associated with the m.1555A>G pathogenic variant results from hair cell loss and dysfunction and hence is cochlear in nature [Bravo et al 2006].
Aminoglycoside ototoxicity secondary to the presence of a predisposing mtDNA pathogenic variant appears to be related to the administration of aminoglycosides (independent of dose) in contrast to "dose-related" aminoglycoside ototoxicity, which is related to the dose and/or plasma concentration of aminoglycosides in individuals who do not have a predisposing mtDNA pathogenic variant.
Vestibular symptoms are uncommon [Lu et al 2010a].
Sensorineural hearing loss (SNHL) independent of aminoglycoside exposure. MT-RNR1 pathogenic variants are also reported to be a common cause of nonsyndromic hearing loss without aminoglycoside exposure. The probability of hearing loss varies widely among reports and families (see Penetrance).
The severity, onset age, and audiometric configuration of m.1555A>G variant-related nonsyndromic hearing loss without aminoglycoside exposure are wide-ranging. The severity and onset of hearing loss in these individuals ranges from congenital profound deafness to mild to moderate progressive late-onset hearing loss. High-frequency-associated hearing loss is prevalent among individuals with mild to moderate hearing loss [Iwanicka-Pronicka et al 2015]. Zhu et al [2014] reported that the heteroplasmy level of the m.1555A>G pathogenic variant correlated with hearing loss penetrance in five families with different levels of heteroplasmy [Zhu et al 2014].
Many individuals with progressive hearing loss commonly experience episodes of tinnitus, but vestibular symptoms are rare in these individuals. A small percentage of individuals with the m.1555A>G pathogenic variant who did not develop hearing loss had subclinical findings of a lower amplitude of response to DPOAE (distortion-product otoacoustic emission), indicating a deficit in cochlear physiology [Bravo et al 2006].
Other. Although hearing loss associated with MT-RNR1 pathogenic variants is considered nonsyndromic, a constellation of digital, spinal, and pigmentary disturbances has been reported in a family with the m.1555A>G substitution. Pigmentary findings in family members included development of gray hair with a salt-and-pepper distribution in teenagers and hypopigmented skin patches ranging in size from two to 10 cm on the wrist, knee, and groin [Nye et al 2000]. The correlation between the mitochondrial substitution and the presence of pigmentary changes remains unclear.
#### MT-TS1-Related Hearing Loss
SNHL. MT-TS1 is another hot spot for pathogenic variants associated with nonsyndromic hearing loss as well as syndromic hearing loss [Guan 2004, Zheng et al 2012]. A large number of MT-TS1 variants have been reported to cause nonsyndromic hearing loss in multiple population groups (see Molecular Genetics).
Onset of SNHL caused by the m.7445A>G pathogenic variant occurs during childhood [Yelverton et al 2013]. The severity of hearing loss is highly variable, ranging from mild to severe. Progression in the severity of hearing loss is characteristic.
Other. The m.7445A>G substitution has also been associated in some families with palmoplantar keratoderma as well as hearing loss [Sevior et al 1998, Martin et al 2000, Caria et al 2005]. The skin changes can appear as early as age four to five years and consist of scaling, hyperkeratosis, and honeycomb appearance of the skin of the palms, soles, and heels [Sevior et al 1998]. Callus formation occurs on the heels and toes. Hyperkeratosis of palms with erythema is reported in a few individuals; marked variability in the severity and extent of involvement is characteristic. Caria et al [2005] described a family with this variant; dermatosis appeared by age four to 11 years and worsened until age eight in one individual. Skin biopsy showed orthokeratotic hyperkeratosis, with some columns of parakeratosis in the inferior third of the epidermis, mild acanthosis, and focal absence of granular layer. Individuals who have both the m.7444G>A and m.1555A>G (MT-RNR1) pathogenic variants [Pandya et al 2004] or the m.7443A>G pathogenic variant alone do not have skin findings.
The m.7471dupC (previously described as m.7472insC) pathogenic variant in MT-TS1 was identified as responsible for maternally inherited nonsyndromic hearing loss, and one individual reported by Tiranti et al [1995] had syndromic hearing loss with ataxia and myoclonus. Ensink et al [1998] reported a family with this variant with early-onset SNHL and late-onset neurologic complaints.
#### Other Forms of Mitochondrial Gene-Related Hearing Loss
The m.7444G>A pathogenic variant located on the boundary of MT-CO1 and MT-TS1 has been reported to be responsible for nonsyndromic hearing loss and aminoglycoside-induced hearing loss [Zhu et al 2006, Rydzanicz et al 2011].
In addition, this pathogenic variant was co-identified with MT-RNR1 variants m.1555A>G [Pandya et al 1999, Yuan et al 2005] and m.1494C>T [Yuan et al 2007] in individuals with nonsyndromic hearing loss and aminoglycoside-induced hearing loss.
### Phenotype Correlations by Gene
See Clinical Description.
### Genotype-Phenotype Correlations
MT-TS1. The m.7445A>G pathogenic variant is associated in some families with palmoplantar keratoderma in addition to hearing loss. Individuals who have both the m.7444G>A and m.1555A>G (MT-RNR1) pathogenic variants [Pandya et al 2004] or the m.7443A>G pathogenic variant alone do not have skin findings.
### Penetrance
MT-RNR1
* Most m.1555A>G pathogenic variants occur as homoplasmic changes; the penetrance of hearing loss is believed to be 100% in those with the pathogenic variant who receive aminoglycoside antibiotics (i.e., all individuals with this pathogenic variant will become deaf with any amount of aminoglycoside in a single dose) – although neonates who were unaffected following treatment with aminoglycosides have been reported [Ealy et al 2011, Göpel et al 2014]. However, aminoglycoside exposure may increase the lifetime risk for developing deafness.
* The penetrance for hearing loss in individuals with the m.1555A>G pathogenic variant who are not exposed to aminoglycosides varies widely (0%-65%) [Bykhovskaya et al 1998, Estivill et al 1998, Ding et al 2009, Lu et al 2010b]. Zhu et al [2014] reported that the heteroplasmy level of the m.1555A>G pathogenic variant correlated with hearing loss penetrance in five families with different heteroplasmy levels; penetrance in these families was 52%, 18.2%, 10%, 26.7%, and 44%.
* The averaged penetrance of eight Chinese families harboring the m.1494C>T pathogenic variant was 31.7% when aminoglycoside-induced deafness was included and 17.5% when it was excluded [Zhao et al 2004, Chen et al 2007].
* Variants m.961T>G and m.961_962delTinsC(n) have been associated with SNHL [Guaran et al 2013] but may be either benign or low-penetrance pathogenic.
Note: It has been suggested that penetrance for hearing loss is lower in some families from China [Young et al 2005, Dai et al 2006, Tang et al 2007].
MT-TS1. The pathogenic variants exist as both homoplasmic and heteroplasmic; therefore, the severity of hearing loss and age of onset vary depending on the mutational load in an individual.
### Prevalence
The prevalence of mitochondrial nonsyndromic hearing loss and deafness has been well studied for MT-RNR1 and MT-TS1 in many populations.
In a prospective study in the Tianjin Province in China in which 58,000 newborns were screened with both audiologic and genetic methods, Zhang et al [2013] identified a pathogenic mtDNA variant in 1.8% of newborns; however, only one newborn was found to have hearing loss.
MT-RNR1. Hearing loss caused by MT-RNR1 pathogenic variant m.1555A>G has been observed worldwide (e.g., in the Arab-Israeli, Japanese, Mongolian, Zairean, Spanish, Chinese, Turkish, Balinese, Moroccan, Greek, Polish, Tunisian, and American populations) and is identified in 15% of all individuals with hearing loss and a history of aminoglycoside administration [Fischel-Ghodsian et al 1997]
The prevalence of the m.1555A>G pathogenic variant varies by population (see Table 2).
### Table 2.
Prevalence of MT-RNR1 Pathogenic Variant m.1555A>G by Population
View in own window
PopulationPrevalenceReference(s)
United States
* 2/703 (0.3%) neonates in the NICU
* 3/1,473 (0.2%) general population
* 0.8% of individuals w/adult-onset HL
* 0.3%-0.9% of individuals w/NSHL
Arnos et al [2003], Ealy et al [2011], King et al [2012], Yelverton et al [2013]
Argentina0/1,042 newbornsGravina et al [2007]
Brazil0/8,974 newbornsNivoloni Kde et al [2010]
China
* 0.14%-0.7% of general population
* 1.9%-11% of individuals w/NSHL
Lu et al [2010a], Lu et al [2010b], Chen et al [2011], Ji et al [2011], Shen et al [2011], Zhang et al [2012], Han et al [2013], Wei et al [2013], Zhang et al [2013], Xu et al [2014], Jiang et al [2015a], Jiang et al [2015b], Ding et al [2016], Ma et al [2016a]
Europe18/9,371 (0.19%) children in Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohortBitner-Glindzicz et al [2009]
Australia (European descent)6/2,856 (0.21%) general population >age 49 yearsVandebona et al [2009]
Germany12/7,056 (0.2%) LBW neonatesGöpel et al [2014]
Greece2 of 478 (0.5%) individuals w/early-onset HLKokotas et al [2009]
Italy (southern)6% of individuals w/postlingual deafnessJacobs et al [2005]
Japan
* 1.4% of individuals w/early-onset HL
* 2% of individuals w/late-onset HL
* 4.3% of maternally inherited HL
Usami et al [2012b], Yano et al [2014]
Poland1.1%-3.6% of individuals w/HLRydzanicz et al [2010], Iwanicka-Pronicka et al [2015]
South Africa1/204 (0.5%) general populationBardien et al [2009]
Spain17% of deaf individualsBravo et al [2006]
Taiwan1/1,017 (0.1%) newbornsWu et al [2011]
Tunisia2/226 (0.9%) individuals w/mitochondrial diseaseMkaouar-Rebai et al [2013]
United Kingdom6% of individuals w/postlingual deafnessJacobs et al [2005]
HL = hearing loss; LBW = low birth weight; NICU = neonatal intensive care unit; NSHL = nonsyndromic hearing loss
The prevalence of MT-RNR1 pathogenic variant m.1494C>T varies by population (see Table 3).
### Table 3.
Prevalence of MT-RNR1 Pathogenic Variant m.1494C>T by Population
View in own window
PopulationPrevalenceReference(s)
United States0.07% general populationEaly et al [2011]
Chinese
* 0.014%, 0.029%, & 0.25% of general population
* 0.18%-0.64% of individuals w/HL
Zhu et al [2009], Lu et al [2010a], Shen et al [2011], Li et al [2012], Zhang et al [2012], Han et al [2013], Wei et al [2013], Zhang et al [2013], Ma et al [2016b]
Japanese0.7% of individuals w/HLYano et al [2014]
Poland1.3% of individuals w/HLIwanicka-Pronicka et al [2015]
HL = hearing loss
The prevalence of the m.961_962delTinsC(n) pathogenic variants in deaf probands, initially determined by screening of anonymized blood spots from newborns in the state of Texas, revealed a prevalence of approximately 1% [Tang et al 2002]. More recent literature has identified varying frequencies for the three changes in this region [Guaran et al 2013, Yelverton et al 2013, Zhang et al 2013].
MT-TS1. The prevalence of pathogenic variants is 0.8%-1.1% in deaf probands studied from the United States [Arnos et al 2003] and from Mongolia [Pandya et al 1999], and 0.68% in probands from China [Tang et al 2015]. A Japanese family with the m.7511T>C pathogenic variant has been reported [Li et al 2005].
The prevalence of pathogenic variant m.7444G>A was 0.86% in individuals with hearing loss from the United States [Yelverton et al 2013] and 0.4% in individuals with hearing loss of Polish ancestry [Rydzanicz et al 2011], but it was not identified among 513 Greek individuals [Kokotas et al 2010] or 701 Chinese individuals [Chen et al 2014].
The prevalence of m.7511T>C was 1.2% in Japanese individuals with maternally inherited hearing loss [Yano et al 2014], and 0.04% in Chinese individuals with hearing loss [Tang et al 2015].
## Differential Diagnosis
Other genetic causes of nonsyndromic hearing loss and deafness need to be considered (see Hereditary Hearing Loss and Deafness Overview and Mitochondrial Disorders Overview).
Aminoglycoside drug toxicity. The hearing loss seen after use of aminoglycosides in individuals without the MT-RNR1 pathogenic variants m.961_962delTinsC(n) or m.1555A>G results from drug toxicity and is related to the dose administered and the metabolism of the drug (i.e., the peak and trough serum concentrations).
Maternally inherited diabetes mellitus and deafness (MIDD; OMIM 520000). A single base-pair substitution of A to G at position 3243 (m.3243A>G) in MT-TL1 (NC_012920.1), which encodes tRNA leucine, is associated with MIDD [Suzuki et al 2003, Wang et al 2006]. MIDD accounts for 0.5%-2.8% of diabetes mellitus. The onset of diabetes mellitus occurs in the third decade or later in non-obese individuals. The disease can be acute or slowly progressive with or without insulin dependence, and is characterized by absence of anti-GAD (glutamic acid decarboxylase) antibodies and by rapidly progressive advanced microvascular complications. The deafness is progressive and sensorineural [Suzuki et al 2003].
Maternally inherited diabetes mellitus and deafness (MIDD) is also caused by the MT-TK pathogenic variant m.8296A>G [Kameoka et al 1998], MT-TE pathogenic variants m.14709T>C and m.14692A>G [Rigoli et al 2001, Wang et al 2016], and MT-TG pathogenic variant m.10003T>C [Liu et al 2015]. The penetrance of deafness and diabetes in individuals with MIDD is incomplete and some individuals present with isolated nonsyndromic hearing loss. It is, therefore, important to obtain a family history not only for hearing loss but also for diabetes mellitus.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of hearing loss and needs in an individual diagnosed with mitochondrial nonsyndromic hearing loss and deafness, the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:
* A complete auditory assessment (see Hereditary Hearing Loss and Deafness Overview)
* Examination of the skin for evidence of keratoderma
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Treatment includes the following:
* Appropriate rehabilitation including hearing aids, speech therapy, culturally appropriate language training, and evaluation for eligibility for cochlear implantation [Sinnathuray et al 2003]
* Electric acoustic stimulation (EAS) for individuals with mitochondrial hearing loss with residual hearing in the lower frequencies [Usami et al 2012a]
* Enrollment in educational programs appropriate for the hearing impaired
* For mild keratoderma, use of lotions and emollients; for severe keratoderma, dermatologic evaluation
### Prevention of Primary Manifestations
MT-RNR1-related aminoglycoside-induced ototoxicity. Physicians can inquire about a family history of aminoglycoside-induced hearing loss prior to the administration of aminoglycosides, either systemically or locally (e.g., into the cochlea as treatment for Meniere's disease). In individuals with a family history of aminoglycoside-induced hearing loss, alternatives to aminoglycoside treatment should be considered when possible.
In the US, aminoglycoside use is most common in the neonatal intensive care unit; however, the therapeutic imperative of treatment with antibiotics in a neonatal intensive care unit setting does not always lend itself to pre-treatment screening by molecular genetic testing.
* Bitner-Glindzicz et al [2009] report a population frequency of 0.19% for the A to G change in a European cohort of children age seven to nine years who had the pathogenic variant but did not have hearing loss because they were not exposed to aminoglycosides; they make an argument for screening on demand to avoid a preventable cause of hearing loss.
* In a commentary by Boles & Friedlich [2010], the authors suggest a prospective study into the feasibility of screening for these mitochondrial pathogenic variants (especially in busy neonatal units) in order to identify a preventable form of hearing loss.
* In the Tianjin Province in China, screening of 58,000 newborns by audiometry and molecular genetic testing determined that 1.8% of newborns had a pathogenic mitochondrial DNA variant and only one newborn had hearing loss [Zhang et al 2013].
### Surveillance
The following are appropriate:
* Annual audiometric assessment to evaluate stability or progression of hearing loss
* Annual examination by a physician to assess for related clinical findings (e.g., palmoplantar keratosis)
### Agents/Circumstances to Avoid
Aminoglycosides and noise exposure should be avoided, particularly in individuals with normal hearing who have the m.1555A>G or m.1494C>T MT-RNR1 pathogenic variant.
### Evaluation of Relatives at Risk
In a family in which the mtDNA pathogenic variant is known, prospective molecular genetic testing of at-risk maternal relatives allows early detection of those who have inherited the mtDNA pathogenic variant and would benefit from:
* Avoiding aminoglycosides to prevent onset of hearing loss
* Appropriate early support and management
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Use of aminoglycoside antibiotics during pregnancy in a mother who has the MT-RNR1 m.1555A>G or m.1494C>T pathogenic variants should be considered only in the absence of other treatment options, as these antibiotics exhibit incomplete placental transfer.
Of note, if the mother has the MT-RNR1 m.1555A>G or m.1494C>T pathogenic variant, she will pass it on to the fetus; hence, use of aminoglycosides should be avoided in the newborn.
### Therapies Under Investigation
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. 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-hydroxybutyric 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
|
Nonsyndromic Hearing Loss and Deafness, Mitochondrial
|
None
| 25,795 |
gene_reviews
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https://www.ncbi.nlm.nih.gov/books/NBK1422/
| 2021-01-18T21:07:37 |
{"synonyms": []}
|
Not to be confused with Metrorrhagia.
Heavy menstrual bleeding
Other namesHypermenorrhea, menorrhagia
SpecialtyGynecology
Symptomsbleeding more than usual
ComplicationsAnemia,
Risk factorsfamily history
Heavy menstrual bleeding, previously known as menorrhagia, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB).[1][2]
Abnormal uterine bleeding can be caused by structural abnormalities in the reproductive tract, anovulation, bleeding disorders, hormone issues (such as hypothyroidism) or cancer of the reproductive tract. Initial evaluation aims at figuring out pregnancy status, menopausal status, and the source of bleeding. One definition is bleeding lasting more than 7 days or the loss of more than 80 mL of blood heavy flow.[3]
Treatment depends on the cause, severity, and interference with quality of life.[4] Initial treatment often involve birth control pills. Tranexamic acid, danazol, progesterone IUDs, and NSAIDs are also helpful.[5] Surgery can be an effective for those whose symptoms are not well-controlled with other treatments.[6] Approximately 53 in 1000 women are affected by AUB.[7]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Consideration
* 2.2 Omega 6 and prostaglandins
* 3 Diagnosis
* 4 Treatment
* 4.1 Medications
* 4.2 Surgery
* 5 Complications
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
A normal menstrual cycle is 21–35 days in duration, with bleeding lasting an average of 5 days and total blood flow between 25 and 80 mL. Heavy menstrual bleeding is defined as total menstrual flow >80ml per cycle, soaking a pad/tampon at least every 2 hours, or bleeding lasting for >7 days.[3][1] Deviations in terms of frequency of menses, duration of menses, or volume of menses qualifies as abnormal uterine bleeding. Bleeding in between menses is also abnormal uterine bleeding and thus requires further evaluation.
Complications of heavy menstrual bleeding could also be the initial symptoms. Excessive bleeding can lead to anemia which presents as fatigue, shortness of breath, and weakness. Anemia can be diagnosed with a blood test.
## Causes[edit]
Usually, no causative abnormality can be identified and treatment is directed at the symptom, rather than a specific mechanism. However, there are known causes of abnormal uterine bleeding that need to be ruled out. Most common causes based on the nature of bleeding is listed below followed by the rare causes of bleeding (i.e. disorders of coagulation).
### Consideration[edit]
* Excessive menses but normal cycle:
* Painless:
* Fibroids (leiomyoma) — fibroids in the wall of the uterus cause increased menstrual loss if they protrude into the central cavity and thereby increase endometrial surface area.
* Coagulation defects (rare) — with the shedding of an endometrial lining's blood vessels, normal coagulation process must occur to limit and eventually stop the blood flow. Blood disorders of platelets (such as ITP) or coagulation (such as von Willebrand disease) or use of anticoagulant medication (such as warfarin) are therefore possible causes, although a rare minority of cases. Platelet function studies can also be used to ascertain platelet function abnormalities
* Endometrial cancer (cancer of the uterine lining) — bleeding can also be irregular, in between periods, or after the menopause (post-menopausal bleeding or PMB)
* Endometrial polyp
* Painful (ie associated with dysmenorrhea):
* Pelvic inflammatory disease
* Endometriosis \- extension of the endometrial tissue outside of the uterus tries to shed causing painful and abnormal bleeds
* Adenomyosis \- extension of the endometrial tissue into the wall of the uterus tries to shed causing painful and abnormal bleeds
* Pregnancy related complication (i.e. miscarriage)
* Short cycle (less than 21 days) but normal menses.
* Short cycle and excessive menses due to ovarian dysfunction and may be secondary to blockage of blood vessels by tumours.
* Polycystic ovary syndrome.[3]
* Systemic causes: thyroid disease, excessive emotional/physical stress.[3]
* Sexually transmitted infection.[3]
### Omega 6 and prostaglandins[edit]
HMB is associated with increased omega-6 AA in uterine tissues.[8] The endometrium of women with HMB have higher levels of prostaglandin (E2, F2alpha and others) when compared with women with normal menses.[9] It is thought that prostaglandins are a by product of omega 6 build up.[10]
## Diagnosis[edit]
The NICE guidelines states that: "Many women presenting to primary care with symptoms of HMB can be offered treatment without the need for further examination or investigation. However, investigation via a diagnostic technique might be warranted for women for whom history or examination suggests a structural or endometrial pathology or for whom the initial treatment has failed."[11] Diagnosis is largely achieved by obtaining a complete medical history followed by physical exam and vaginal ultrasonography. If need be, laboratory tests or hysteroscopy may be used. The following are a list of diagnostic procedures that medical professionals may use to identify the cause of the abnormal uterine bleeding.
* Pelvic and rectal examination to ensure that bleeding is not from lower reproductive tract (i.e. vagina, cervix) or rectum
* Pap smear to rule out cervical neoplasia
* Pelvic ultrasound scan is the first line diagnostic tool for identifying structural abnormalities.[12]
* Endometrial biopsy in women with high risk endometrial cancer or atypical hyperplasia or malignancy.[11]
* Hysteroscopy (anaesthesia should be offered)[11]
* Thyroid-stimulating hormone and thyrotropin-releasing hormone dosage to rule out hypothyroidism [13]
## Treatment[edit]
Where an underlying cause can be identified, treatment may be directed at this. Clearly heavy periods at menarche and menopause may settle spontaneously (the menarche being the start and menopause being the cessation of periods).
If the degree of bleeding is mild, all that may be sought by the woman is the reassurance that there is no sinister underlying cause. If anemia occurs due to bleeding then iron tablets may be used to help restore normal hemoglobin levels.[1]
The first line treatment option for women with HMB and no identified pathology, fibroids less than 3 cm in diameter, suspected or confirmed adenomyosis is the levonorgestrel-releasing intrauterine system (LNG-IUS).[11] Clinical trial evidence suggests that the LNG-IUS may be better than other medical therapy in terms of HMB and quality of life.[14]
Usually, oral combined contraceptive or progesterone only pills may be taken for a few months, but for longer-term treatment the alternatives of injected Depo Provera or the more recent progesterone releasing IntraUterine System (IUS) may be used. In particular, an oral contraceptive containing estradiol valerate and dienogest may be more effective than tranexamic acid, NSAIDs and IUDs.[15][16] Fibroids may respond to hormonal treatment, and if they do not, then surgical removal may be required. Concerning hormonal treatment, the NICE guidelines states that: "No evidence was found on MRI-guided transcutaneous focused ultrasound for uterine fibroids nor for the progestogen-only pill, injectable progestogens, or progestogen implants."[11]
NICE guidelines says that for women (with HMB and no identified pathology or fibroids less than 3 cm in diameter) who do not wish to have pharmacological treatment and who do not want to conserve their fertility, surgical options could be considered as a first-line treatment option. And options are hysterectomy and second generation endometrial ablation. With hysterectomy more effective than second generation endometrial ablation.[11]
Tranexamic acid tablets that may also reduce loss by up to 50%.[17] This may be combined with hormonal medication previously mentioned.[18]
Anti-inflammatory medication like NSAIDs may also be used. NSAIDs are the first-line medications in ovulatory heavy menstrual bleeding, resulting in an average reduction of 20-46% in menstrual blood flow. NSAIDs may be more effective than placebo in terms of reducing blood loss increasing women's subjective perception of improvement, they may be less effective than tranexamic acid. It is uncertain if there is any difference between NSAIDs and tranexamic acid in terms of women's subjective perception of bleeding.[9] For this purpose, NSAIDs are ingested for only 5 days of the menstrual cycle, limiting their most common adverse effect of dyspepsia.[19]
A definitive treatment for heavy menstrual bleeding is to perform hysterectomy (removal of the uterus). The risks of the procedure have been reduced with measures to reduce the risk of deep vein thrombosis after surgery, and the switch from the front abdominal to vaginal approach greatly minimizing the discomfort and recuperation time for the patient; however extensive fibroids may make the womb too large for removal by the vaginal approach. Small fibroids may be dealt with by local removal (myomectomy). A further surgical technique is endometrial ablation (destruction) by the use of applied heat (thermoablation).[20] The effectiveness of endometrial ablation is probably similar to that of LNG‐IUS but the evidence is uncertain if hysterectomy is better or worse than LNG-IUS for improving HMB.[14]
### Medications[edit]
These have been ranked by the UK's National Institute for Health and Clinical Excellence:[12]
* First line
* Intrauterine device with progesterone
* Second Line
* Tranexamic acid an antifibrinolytic agent
* Nonsteroidal anti-inflammatory drugs (NSAIDs).
* Combined oral contraceptive pills to prevent proliferation of the endometrium
* Third line
* Oral progestogen (e.g. norethisterone), to prevent proliferation of the endometrium
* Injected progestogen (e.g. Depo provera)
* Other options
* Gonadotropin-releasing hormone agonist
### Surgery[edit]
* Dilation and curettage (D&C) is not recommended for cases of simple heavy menstrual bleeding, having a reserved role if a spontaneous abortion is incomplete[21]
* Endometrial ablation is not recommended for women with active or recent genital or pelvic infection, known or suspected endometrial hyperplasia or malignancy.[22]
* Uterine artery embolization (UAE): The rate of serious complications is comparable to that of myomectomy or hysterectomy; however, UAE presents an increased risk of minor complications and requiring surgery within two to five years.[23]
* Hysteroscopic myomectomy to remove fibroids over 3 cm in diameter
* Hysterectomy
In the UK the use of hysterectomy for heavy menstrual bleeding has been almost halved between 1989 and 2003.[24] This has a number of causes: better medical management, endometrial ablation and particularly the introduction of IUS[25][26] which may be inserted in the community and avoid the need for specialist referral; in one study up to 64% of women cancelled surgery.[27]
## Complications[edit]
Aside from the social distress of dealing with a prolonged and heavy period, over time the blood loss may prove to be greater than the body iron reserves or the rate of blood replenishment, leading to anemia.[4] Symptoms attributable to the anemia may include shortness of breath, tiredness, weakness, tingling and numbness in fingers and toes, headaches, depression, becoming cold more easily, and poor concentration.
## See also[edit]
* Menometrorrhagia
## References[edit]
1. ^ a b c Munro MG, Critchley HO, Broder MS, Fraser IS (April 2011). "FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age". International Journal of Gynaecology and Obstetrics. 113 (1): 3–13. doi:10.1016/j.ijgo.2010.11.011. PMID 21345435. S2CID 205260568.
2. ^ Bacon JL (June 2017). "Abnormal Uterine Bleeding: Current Classification and Clinical Management". Obstetrics and Gynecology Clinics of North America. 44 (2): 179–193. doi:10.1016/j.ogc.2017.02.012. PMID 28499529.
3. ^ a b c d e O'Brien SH (2018). "Evaluation and management of heavy menstrual bleeding in adolescents: the role of the hematologist". Hematology. 30 (1): 390–398. doi:10.1182/asheducation-2018.1.390. PMC 6246024. PMID 30504337.
4. ^ a b Committee on Practice Bulletins—Gynecology (July 2013). "Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction". Obstetrics and Gynecology. 122 (1): 176–85. doi:10.1097/01.AOG.0000431815.52679.bb. PMID 23787936. S2CID 2796244.
5. ^ Bofill Rodriguez, M; Lethaby, A; Farquhar, C (19 September 2019). "Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding". The Cochrane Database of Systematic Reviews. 9: CD000400. doi:10.1002/14651858.CD000400.pub4. PMC 6751587. PMID 31535715.
6. ^ Marjoribanks J, Lethaby A, Farquhar C (January 2016). "Surgery versus medical therapy for heavy menstrual bleeding". The Cochrane Database of Systematic Reviews (1): CD003855. doi:10.1002/14651858.CD003855.pub3. PMC 7104515. PMID 26820670.
7. ^ Kjerulff KH, Erickson BA, Langenberg PW (February 1996). "Chronic gynecological conditions reported by US women: findings from the National Health Interview Survey, 1984 to 1992". American Journal of Public Health. 86 (2): 195–9. doi:10.2105/ajph.86.2.195. PMC 1380327. PMID 8633735.
8. ^ Joseph E. Pizzorno, Michael T. Murray and Herb Joiner-Bey (2015). The Clinician's Handbook of Natural Medicine. doi:10.1016/C2010-0-67298-1. ISBN 9780702055140.CS1 maint: uses authors parameter (link)
9. ^ a b Bofill Rodriguez, M; Lethaby, A; Farquhar, C (19 September 2019). "Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding". The Cochrane Database of Systematic Reviews. 9: CD000400. doi:10.1002/14651858.CD000400.pub4. PMC 6751587. PMID 31535715.
10. ^ Harel Z (December 2006). "Dysmenorrhea in adolescents and young adults: etiology and management". Journal of Pediatric and Adolescent Gynecology. 19 (6): 363–71. doi:10.1016/j.jpag.2006.09.001. PMID 17174824.
11. ^ a b c d e f NICE (2018). "Heavy menstrual bleeding (update)". National Guideline Alliance (UK). PMID 29634173.CS1 maint: uses authors parameter (link)
12. ^ a b "CG44 Heavy menstrual bleeding: Understanding NICE guidance" (PDF). National Institute for Health and Clinical Excellence (UK). 24 January 2007.
13. ^ Weeks AD (March 2000). "Menorrhagia and hypothyroidism. Evidence supports association between hypothyroidism and menorrhagia". BMJ. 320 (7235): 649. doi:10.1136/bmj.320.7235.649. PMC 1117669. PMID 10698899.
14. ^ a b Bofill Rodriguez, M; Lethaby, A; Jordan, V (12 June 2020). "Progestogen-releasing intrauterine systems for heavy menstrual bleeding". The Cochrane Database of Systematic Reviews. 6: CD002126. doi:10.1002/14651858.CD002126.pub4. PMC 7388184. PMID 32529637.
15. ^ Kaunitz AM, Meredith S, Inki P, Kubba A, Sanchez-Ramos L (May 2009). "Levonorgestrel-releasing intrauterine system and endometrial ablation in heavy menstrual bleeding: a systematic review and meta-analysis". Obstetrics and Gynecology. 113 (5): 1104–16. doi:10.1097/AOG.0b013e3181a1d3ce. PMID 19384127. S2CID 25599471.
16. ^ Jensen JT, Parke S, Mellinger U, Machlitt A, Fraser IS (April 2011). "Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial". Obstetrics and Gynecology. 117 (4): 777–87. doi:10.1097/AOG.0b013e3182118ac3. PMID 21422847. S2CID 40164050.
17. ^ Bonnar J, Sheppard BL (September 1996). "Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid". BMJ. 313 (7057): 579–82. doi:10.1136/bmj.313.7057.579. PMC 2352023. PMID 8806245.
18. ^ Lukes AS, Moore KA, Muse KN, Gersten JK, Hecht BR, Edlund M, Richter HE, Eder SE, Attia GR, Patrick DL, Rubin A, Shangold GA (October 2010). "Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial". Obstetrics and Gynecology. 116 (4): 865–75. doi:10.1097/AOG.0b013e3181f20177. PMID 20859150. S2CID 6977827.
19. ^ A Shaw J (2014-09-29). "Menorrhagia Treatment & Management". Medscape. Retrieved 2015-01-04.
20. ^ Bofill Rodriguez, M; Lethaby, A; Grigore, M; Brown, J; Hickey, M; Farquhar, C (22 January 2019). "Endometrial resection and ablation techniques for heavy menstrual bleeding". The Cochrane Database of Systematic Reviews. 1: CD001501. doi:10.1002/14651858.CD001501.pub5. PMC 7057272. PMID 30667064.
21. ^ Duckitt K (September 2015). "Menorrhagia". BMJ Clinical Evidence. 2015. PMC 4574688. PMID 26382038.
22. ^ Louie M, Wright K, Siedhoff MT (2018). "The case against endometrial ablation for treatment of heavy menstrual bleeding". Curr Opin Obstet Gynecol. 30 (4): 287–292. doi:10.1097/GCO.0000000000000463. PMID 29708902. S2CID 13671197.
23. ^ Gupta, Janesh K.; Sinha, Anju; Lumsden, M. A.; Hickey, Martha (2014-12-26). "Uterine artery embolization for symptomatic uterine fibroids". The Cochrane Database of Systematic Reviews (12): CD005073. doi:10.1002/14651858.CD005073.pub4. ISSN 1469-493X. PMID 25541260.
24. ^ Reid PC, Mukri F (April 2005). "Trends in number of hysterectomies performed in England for menorrhagia: examination of health episode statistics, 1989 to 2002-3". BMJ. 330 (7497): 938–9. doi:10.1136/bmj.38376.505382.AE. PMC 556338. PMID 15695496.
25. ^ Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman S, Kivelä A, Kujansuu E, Vuorma S, Yliskoski M, Paavonen J (March 2004). "Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year follow-up". JAMA. 291 (12): 1456–63. doi:10.1001/jama.291.12.1456. PMID 15039412.
26. ^ Istre O, Trolle B (August 2001). "Treatment of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection". Fertility and Sterility. 76 (2): 304–9. doi:10.1016/S0015-0282(01)01909-4. PMID 11476777.
27. ^ Stewart A, Cummins C, Gold L, Jordan R, Phillips W (January 2001). "The effectiveness of the levonorgestrel-releasing intrauterine system in menorrhagia: a systematic review". BJOG. 108 (1): 74–86. doi:10.1016/S0306-5456(00)00020-6. PMID 11213008.
## External links[edit]
Classification
D
* ICD-10: N92.0
* ICD-9-CM: 627.0
* MeSH: D008595
* DiseasesDB: 22575
External resources
* eMedicine: med/1449
* Patient UK: Heavy menstrual bleeding
* v
* t
* e
Female diseases of the pelvis and genitals
Internal
Adnexa
Ovary
* Endometriosis of ovary
* Female infertility
* Anovulation
* Poor ovarian reserve
* Mittelschmerz
* Oophoritis
* Ovarian apoplexy
* Ovarian cyst
* Corpus luteum cyst
* Follicular cyst of ovary
* Theca lutein cyst
* Ovarian hyperstimulation syndrome
* Ovarian torsion
Fallopian tube
* Female infertility
* Fallopian tube obstruction
* Hematosalpinx
* Hydrosalpinx
* Salpingitis
Uterus
Endometrium
* Asherman's syndrome
* Dysfunctional uterine bleeding
* Endometrial hyperplasia
* Endometrial polyp
* Endometriosis
* Endometritis
Menstruation
* Flow
* Amenorrhoea
* Hypomenorrhea
* Oligomenorrhea
* Pain
* Dysmenorrhea
* PMS
* Timing
* Menometrorrhagia
* Menorrhagia
* Metrorrhagia
* Female infertility
* Recurrent miscarriage
Myometrium
* Adenomyosis
Parametrium
* Parametritis
Cervix
* Cervical dysplasia
* Cervical incompetence
* Cervical polyp
* Cervicitis
* Female infertility
* Cervical stenosis
* Nabothian cyst
General
* Hematometra / Pyometra
* Retroverted uterus
Vagina
* Hematocolpos / Hydrocolpos
* Leukorrhea / Vaginal discharge
* Vaginitis
* Atrophic vaginitis
* Bacterial vaginosis
* Candidal vulvovaginitis
* Hydrocolpos
Sexual dysfunction
* Dyspareunia
* Hypoactive sexual desire disorder
* Sexual arousal disorder
* Vaginismus
* Urogenital fistulas
* Ureterovaginal
* Vesicovaginal
* Obstetric fistula
* Rectovaginal fistula
* Prolapse
* Cystocele
* Enterocele
* Rectocele
* Sigmoidocele
* Urethrocele
* Vaginal bleeding
* Postcoital bleeding
Other / general
* Pelvic congestion syndrome
* Pelvic inflammatory disease
External
Vulva
* Bartholin's cyst
* Kraurosis vulvae
* Vestibular papillomatosis
* Vulvitis
* Vulvodynia
Clitoral hood or clitoris
* Persistent genital arousal disorder
* v
* t
* e
Menstrual cycle
Events and phases
* Menstruation
* Follicular phase
* Ovulation
* Luteal phase
Life stages
* Menarche
* Menopause
Tracking
Signs
* Basal body temperature
* Cervical mucus
* Mittelschmerz
Systems
* Fertility awareness
* Calendar-based methods
* Billings Ovulation Method
* Creighton Model
Suppression
* Extended cycle combined hormonal contraceptive
* Lactational amenorrhea
Disorders
* Amenorrhea
* Anovulation
* Dysmenorrhea
* Hypomenorrhea
* Irregular menstruation
* Menometrorrhagia
* Menorrhagia
* Metrorrhagia
* Oligomenorrhea
Related events
* Folliculogenesis
* Menstrual synchrony
* Premenstrual syndrome / Premenstrual dysphoric disorder / Menstrual psychosis
* Sexual activity
In culture and religion
* Chhaupadi
* Feminine hygiene
* Sanitary napkin
* Tampon
* Menstrual cup
* Menstrual Hygiene Day
* Menstrual taboo
* Menstruation hut
* Niddah
Authority control
* GND: 4232119-0
*[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-hydroxybutyric 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
|
Heavy menstrual bleeding
|
c0025323
| 25,796 |
wikipedia
|
https://en.wikipedia.org/wiki/Heavy_menstrual_bleeding
| 2021-01-18T18:41:42 |
{"mesh": ["D008595"], "umls": ["C0025323"], "icd-9": ["627.0"], "icd-10": ["N92.0"], "wikidata": ["Q1494682"]}
|
Idiopathic pulmonary haemosiderosis
Other namesIdiopathic pulmonary hemosiderosis
SpecialtyRespirology
Idiopathic pulmonary haemosiderosis (IPH) is a lung disease of unknown cause that is characterized by alveolar capillary bleeding and accumulation of haemosiderin in the lungs. It is rare, with an incidence between 0.24[1] and 1.23[2] cases per million people.
## Contents
* 1 Pathophysiology
* 1.1 Related or similar conditions
* 2 Diagnosis
* 3 Treatment
* 4 Prognosis
* 5 History
* 6 References
* 7 External links
## Pathophysiology[edit]
Being idiopathic, IPH by definition has an unknown cause. It is thought to be an immune-mediated disease.[3][4] The lung bleeding causes accumulation of iron, which in itself causes additional lung damage. Meanwhile, there is insufficient iron for inclusion into the haemoglobin molecules inside red blood cells which carry oxygen to body tissues for cellular respiration.[citation needed]
Idiopathic pulmonary haemosiderosis can occur either as a primary lung disorder or as the sequela to other pulmonary, cardiovascular or immune system disorder.
* PH1 involves PH with circulating anti-GBM antibodies.
* PH2 involves PH with immune complex disease such as systemic lupus erythematosus, SLE.
* PH3 involves no demonstrable immune system involvement.
A distinct subset of patients with pulmonary hemosiderosis has hypersensitivity to cow's milk which result in formation of IgG antibodies against basement membrane. This is called Heiner syndrome. Mechanism of haemorrhage is similar to that observed in Goodpasture syndrome.
### Related or similar conditions[edit]
There are many pulmonary problems that may seem to mimic haemosiderosis but do not necessarily include the deposits of iron into the lung. The deposition of iron in the lungs, occurring in the form of haemosiderin, is the defining characteristic of this illness. These other conditions may occur separately or together with haemosiderosis.[citation needed]
* Pulmonary fibrosis
* Adult respiratory distress syndrome (ARDS)
* Immune complex disease
* intra-alveolar bleeding
## Diagnosis[edit]
Clinically, IPH manifests as a triad of haemoptysis, diffuse parenchymal infiltrates on chest radiographs, and iron deficiency anaemia. It is diagnosed at an average age of 4.5 plus or minus 3.5 years,[5] and it is twice as common in females.[5] The clinical course of IPH is exceedingly variable, and most of the patients continue to have episodes of pulmonary haemorrhage despite therapy. Death may occur suddenly from acute pulmonary haemorrhage or after progressive pulmonary insufficiency resulting in chronic respiratory failure.[citation needed]
## Treatment[edit]
Corticosteroids are the mainstay of treatment of IPH, though they are controversial and lack clear evidence in their favour.[6] They are thought to decrease the frequency of haemorrhage,[7][8][9] while other studies suggest that they do not have any effect on the course or prognosis of this disease.[3][7][10] In either case, steroid therapy has significant side effects. Small trials have investigated the use of other medications, but none has emerged as a clear standard of care. This includes immune modulators such as hydroxychloroquine,[11][12] azathioprine,[13][14] and cyclophosphamide.[15] 6-mercaptopurine as a long-term therapy may prevent pulmonary haemorrhage.[16] A 2007 scientific letter. reports preliminary success in preventing pulmonary haemorrhage with the anti-oxidant N-acetylcysteine.[17]
## Prognosis[edit]
Death may occur rapidly with acute, massive pulmonary bleeding or over longer periods as the result of continued pulmonary failure and right heart failure. Historically, patients had an average survival of 2.5 years after diagnosis, but today 86% may survive beyond five years.[5]
## History[edit]
The condition was first described as "brown lung induration" by Rudolf Virchow in 1864 in patients after their death. Wilhelm Ceelen later correlated his findings to the clinical symptoms of two children who died of IPH in 1931.[18] The first living patient was diagnosed by Jan Waldenström in 1944.[19] It has been given several names, including:
* Haemosiderin accumulation
* Pulmonary haemosiderosis
* Brown induration of lung
* Essential brown induration of lung
* Ceelen-Gellerstedt syndrome (after physicians Wilhelm Ceelen and Nils Gellerstedt)[20]
## References[edit]
1. ^ Kjellman B, Elinder G, Garwicz S, Svan H (September 1984). "Idiopathic pulmonary haemosiderosis in Swedish children". Acta Paediatr Scand. 73 (5): 584–8. doi:10.1111/j.1651-2227.1984.tb09978.x. PMID 6485774. S2CID 35288686.
2. ^ Ohga, S; Takahashi, K; Miyazaki, S; Kato, H; Ueda, K (1995). "Idiopathic pulmonary haemosiderosis in Japan: 39 possible cases from a survey questionnaire". European Journal of Pediatrics. 154 (12): 994–995. doi:10.1007/BF01958645. PMID 8801109. S2CID 6752082.
3. ^ a b Soergel KH, Sommers SC (1962). "Idiopathic pulmonary hemosiderosis and related syndromes". Am J Med. 32 (4): 499–511. doi:10.1016/0002-9343(62)90051-7.
4. ^ Gonzalez-Crussi F, Hull MT, Grosefeld JL (1976). "Idiopathic pulmonary hemosiderosis: evidence of capillary basement membrane abnormality". Am Rev Respir Dis. 114 (4): 689–698. doi:10.1164/arrd.1976.114.4.689 (inactive 2021-01-15). PMID 970745.CS1 maint: DOI inactive as of January 2021 (link)
5. ^ a b c Saeed, Muhammad M; Woo, Marlyn S; MacLaughlin, Eithne F; Margetis, Monique F; Keens, Thomas G (September 1999). "Prognosis in Pediatric Idiopathic Pulmonary Hemosiderosis". Chest. 116 (3): 721–725. doi:10.1378/chest.116.3.721. PMID 10492278. Archived from the original on 2013-04-14.
6. ^ Sethi, GR; Singhal, KK (Oct 2008). "Pulmonary diseases and corticosteroids". Indian Journal of Pediatrics. 75 (10): 1045–56. doi:10.1007/s12098-008-0209-0. PMC 7091456. PMID 19023529.
7. ^ a b Matsaniotis N, Karpouzas J, Apostolopoulou E, et al. (1968). "Idiopathic pulmonary hemosiderosis in children". Arch Dis Child. 43 (229): 307–309. doi:10.1136/adc.43.229.307. PMC 2019947. PMID 5652705.
8. ^ Beckerman RC, Taussig LM, Pinnas JL (June 1979). "Familial idiopathic pulmonary hemosiderosis". Am. J. Dis. Child. 133 (6): 609–11. doi:10.1001/archpedi.1979.02130060049010. PMID 375718.
9. ^ Gilman PA, Zinkham WH (1969). "Severe idiopathic pulmonary hemosiderosis in the absence of clinical or radiologic evidence of pulmonary disease". J Pediatr. 75 (1): 118–121. doi:10.1016/S0022-3476(69)80110-1. PMID 5790393.
10. ^ Boat, TF (1998). "Idiopathic pulmonary hemosiderosis". In Chernick V, Boat T (eds.). Kendig's disorders of the respiratory tract in children. Philadelphia PA: WB Saunders. pp. 628–9.
11. ^ Bush A, Sheppard MN, Warner JO (1992). "Chloroquine in idiopathic pulmonary hemosiderosis". Arch Dis Child. 67 (5): 625–627. doi:10.1136/adc.67.5.625. PMC 1793713. PMID 1599302.
12. ^ Zaki M, Al Saleh Q, Al Mutari G (1995). "Effectiveness of chloroquine therapy in idiopathic pulmonary hemosiderosis". Pediatric Pulmonology. 20 (2): 125–126. doi:10.1002/ppul.1950200213. PMID 8570303. S2CID 30052392.
13. ^ Byrd RB, Gracey DR (1973). "Immunosuppressive treatment of idiopathic pulmonary hemosiderosis". JAMA. 226 (4): 458–9. doi:10.1001/jama.226.4.458. PMID 4800237.
14. ^ Rossi GA, Balzano E, Battistini E (1992). "Long-term prednisone and azathioprine treatment of a patient with idiopathic pulmonary hemosiderosis". Pediatr Pulmonol. 13 (3): 176–180. doi:10.1002/ppul.1950130310. PMID 1437333. S2CID 42147592.
15. ^ Colombo JR, Stolz SM (1992). "Treatment of life-threatening primary pulmonary hemosiderosis with cyclophosphamide". Chest. 102 (3): 959–960. doi:10.1378/chest.102.3.959. PMID 1516434.
16. ^ Luo XQ, Ke ZY, Huang LB, Guan XQ, Zhang XL, Zhu J, Zhang YC (Nov 2008). "Maintenance therapy with dose-adjusted 6-mercaptopurine in idiopathic pulmonary hemosiderosis". Pediatric Pulmonology. 43 (11): 1067–71. doi:10.1002/ppul.20894. PMID 18972408. S2CID 206379500.
17. ^ "Idiopathic Pulmonary Haemosiderosis - World 1st Medical Treatment By Researchers At Queen Mary University London And University Of Leicester". Medical New Today. 2 June 2007.
18. ^ Ceelen, W. (1931). "Die Kreislaufstörungen der Lungen". In Henke, F.; Lubarsch, O. (eds.). Handbuch der speziellen pathologischen Anatomie und Histologie (in German). 3. Berlin: Springer. p. 10.
19. ^ Heiner, DC (1990). "Pulmonary hemosiderosis". In Chernick V, Kendig EL Jr (eds.). Disorders of the respiratory tract in children. Philadelphia PA: WB Saunders. pp. 498–509.
20. ^ Ceelen-Gellerstedt syndrome at Who Named It?
## External links[edit]
Classification
D
* ICD-9-CM: 516.1
* OMIM: 178550
* MeSH: C536281
* DiseasesDB: 29717
* Hemosiderosis at eMedicine
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Idiopathic pulmonary haemosiderosis
|
c0020807
| 25,797 |
wikipedia
|
https://en.wikipedia.org/wiki/Idiopathic_pulmonary_haemosiderosis
| 2021-01-18T19:08:52 |
{"mesh": ["C536281"], "umls": ["C0020807"], "orphanet": ["99931"], "wikidata": ["Q1052626"]}
|
Hematohidrosis is a rare condition characterized by blood oozing from intact skin and mucosa. Signs and symptoms include sweating blood, crying bloody tears, bleeding from the nose, bleeding from the ears, or oozing blood from other skin surfaces. The episodes are usually self-limiting. In some cases, the fluid appears to be blood tinged, while others resemble frank blood. It can occur on any part of the body, but most commonly appears on the face (ear, nose, and eyes). The cause is unknown. The bleeding is due to the rupture of the very small blood vessels of the skin (dermal capillaries). Some theories include increased vascular pressure leading to the passage of blood cells through the ducts of the sweat glands, inflammation of the vessels of the skin (vasculitis of dermal vessels), and intensified sympathetic activation. Some cases are associated with systemic disease, bleeding disorders, menstruation, excessive exertion, high blood pressure, fear and intense emotional stress. Treatment remains a challenge, and may include vitamin C, hemostatic drugs, anxiolytics, or antidepressants, and propranolol. Resolution of symptoms may occur spontaneously.
*[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-hydroxybutyric 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
|
Hematohidrosis
|
c0473554
| 25,798 |
gard
|
https://rarediseases.info.nih.gov/diseases/13131/hematohidrosis
| 2021-01-18T18:00:08 |
{"icd-9": ["705.89 "], "icd-10": ["L74.8"], "synonyms": ["Hematidrosis"]}
|
Mucopolysaccharidosis type IIIA (MPS IIIA) is a severe, progressive disorder that affects the central nervous system. In people with MPS IIIA, the body cannot break down a large sugar molecule called heparin sulfate. Signs and symptoms usually begin in early childhood and include severe neurological symptoms such as progressive dementia, aggressive behavior, hyperactivity, seizures, deafness, loss of vision, and an inability to sleep for more than a few hours at a time. MPS IIIA is caused by mutations in the SGSH gene and is inherited in an autosomal recessive manner. There is currently no specific treatment for MPS IIIA; affected people usually do not survive past the second decade of life.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric 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
|
Mucopolysaccharidosis type IIIA
|
c0086647
| 25,799 |
gard
|
https://rarediseases.info.nih.gov/diseases/7071/mucopolysaccharidosis-type-iiia
| 2021-01-18T17:58:57 |
{"mesh": ["D009084"], "omim": ["252900"], "umls": ["C0086647"], "orphanet": ["79269"], "synonyms": ["Mucopoly-saccharidosis type 3A", "Sanfilippo syndrome A", "Heparan sulfate sulfatase deficiency", "MPS IIIA", "MPS 3A", "Heparan sulfamidase deficiency", "MPS3A", "MPSIIIA", "Mucopolysaccharidosis type 3A", "Sanfilippo syndrome type A"]}
|
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