Temple–Baraitser syndrome

{{Infobox medical condition (new)

| name = Temple–Baraitser syndrome

| synonyms = Severe mental retardation and absent nails of hallux and pollex

| image = Temple_Baraitser_Hand.jpg

| caption = Small fingernails typical of Temple–Baraitser syndrome.

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| causes = Gain of function variants in KCNH1

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| differential = Zimmermann–Laband syndrome
DOOR syndrome

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| frequency = unknown

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Temple–Baraitser syndrome (TBS) is a very rare autosomal dominant genetic disorder, characterised by intellectual disability, epilepsy, small or absent nail of the thumbs and great toes, and distinct craniofacial features.{{cite web |last1=Vilain |first1=C |title=Temple-Baraitser syndrome |url=https://rarediseases.info.nih.gov/diseases/9441/temple-baraitser-syndrome |publisher=Orphanet}}

Genetics

TBS is caused by pathogenic variants (mutations) in the KCNH1 gene at chromosomal locus 1q32.2, (GRCh38): 1:210,678,313-211,134,147.{{Cite journal|last1=Simons|first1=Cas|last2=Rash|first2=Lachlan D.|last3=Crawford|first3=Joanna|last4=Ma|first4=Linlin|last5=Cristofori-Armstrong|first5=Ben|last6=Miller|first6=David|last7=Ru|first7=Kelin|last8=Baillie|first8=Gregory J.|last9=Alanay|first9=Yasemin|last10=Jacquinet|first10=A|last11=Debray|first11=FG|last12=Verloes|first12=A|last13=Shen|first13=J|last14=Yesil|first14=G|last15=Guler|first15=S|last16=Yuksel|first16=A|last17=Cleary|first17=JG|last18=Grimmond|first18=SM|last19= McGaughran|first19=J|last20=King|first20=GF|last21=Gabbett |first21=Michael T. |last22=Taft|first22=RJ.| date=January 2015|title=Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple–Baraitser syndrome and epilepsy|journal=Nature Genetics|language=en|volume=47|issue=1|pages=73–77|doi=10.1038/ng.3153|pmid=25420144|s2cid=52799681|issn=1061-4036}} It has an autosomal dominant transmission, however affected individuals are not known to reproduce, so all reported cases have been caused by de novo mutations or transmission from a mosaic parent.{{cite web |last1=Genetic Services Laboratory |title=Temple–Baraitser syndrome testing: Mutation analysis of KCNH1 |url=https://dnatesting.uchicago.edu/sites/default/files/media/documents/Temple-Baraitser%20%28KCNH1%29%20Infosheet%206-20-19.pdf |publisher=University of Chicago}}

Diagnosis

Temple–Baraitser syndrome is diagnosed by clinical examination of a person with a severe developmental disability, intellectual impairment and epilepsy. The face is often long and myopathic. Overgrown gums become apparent in late childhood. The finger and toenails are characteristically small, with complete or almost complete absence of the nails of the thumb (pollex) and great toe (hallux).{{cite journal |last1=Jacquinet |first1=Adeline |last2=Gérard |first2=Marion |last3=Gabbett |first3=Michael T. |last4=Rausin |first4=Léon |last5=Misson |first5=Jean-Paul |last6=Menten |first6=Bjorn |last7=Mortier |first7=Geert |last8=van Maldergem |first8=Lionel |last9=Verloes |first9=Alain |last10=Debray |first10=François-Guillaume |title=Temple–Baraitser Syndrome: A Rare and Possibly Unrecognized Condition |journal=Am J Med Genet A |date=2010 |volume=152A |issue=9 |pages=2322–2326 |doi=10.1002/ajmg.a.33574 |pmid=20683999 |s2cid=205313155 |url=https://doi.org/10.1002/ajmg.a.33574}}{{cite web |last1=McLaren |first1=H |title=Temple-Baraitser syndrome |url=http://www.ebi.ac.uk/efo/EFO_0009062 |website=Ontology Search |publisher=OLS |access-date=25 June 2022}} The diagnosis can be confirmed by demonstrating a gain-of-function mutation in the KCNH1 gene.{{cite web |last1=Gabbett |first1=Michael T. |title=KCNH1 - Molecular Characteristics |url=https://humandiseasegenes.nl/kcnh1/professionals/molecular-characteristics |website=Human Disease Genes Website Series |publisher=Human Disease Genes |access-date=25 June 2022}} Temple–Baraitser has clinical and genetic overlap with type 1 Zimmermann–Laband syndrome.{{cite journal |last1=Bramswig |first1=Nuria C |last2=Ockeloen |first2=CW |last3=Czeschik |first3=JC |last4=vanEssen |first4=AJ |last5=Pfundt |first5=R |last6=Smeitink |first6=J |last7=Poll-The |first7=BT |last8=Engels |first8=H |last9=Strom |first9=TM |last10=Wieczorek |first10=D |last11=Kleefstra |first11=T |last12=Lüdecke |first12=HJ |title='Splitting versus lumping': Temple-Baraitser and Zimmermann-Laband Syndromes |journal=Hum Genet |date=2015 |volume=134 |issue=10 |pages=1089–97 |doi=10.1007/s00439-015-1590-1 |pmid=26264464 |s2cid=14238362 |url=http://doi.org/10.1007/s00439-015-1590-1}}

Management

Affected individuals should see a pediatrician or adult physician at least annually to monitor growth, development, seizures and general health and well-being. Developmental potential is maximized through the use of physiotherapy, occupational therapy and speech pathology. Anticonvulsants are used to control epilepsy.{{cite web |last1=Gabbett |first1=Michael T. |title=KCNH1 Management |url=https://humandiseasegenes.nl/kcnh1/professionals/management |publisher=Human Disease Genes}}

Prevalence

With fewer than 100 cases having been reported worldwide, the exact prevalence is unknown but is believed to be rare. It is likely to be underdiagnosed, with one large study identifying 2.7% of people with intellectual disability to have a mutation in KCNH1.{{cite journal |last1=Bramswig |first1=NC |last2=Ockeloen |first2=CW |last3=Czeschik |first3=JC |last4=van Essen |first4=AJ |last5=Pfundt |first5=R |last6=Smeitink |first6=J |last7=Poll-The |first7=BT |last8=Engels |first8=H |last9=Strom |first9=TM |last10=Wieczorek |first10=D |last11=Kleefstra |first11=T |last12=Lüdecke |first12=HJ |title=Splitting versus lumping': Temple–Baraitser and Zimmermann–Laband Syndromes |journal=Hum Genet |date=2015 |volume=134|issue=10 |pages=1089–1097|doi=10.1007/s00439-015-1590-1 |pmid=26264464 |s2cid=14238362 |url=https://doi.org/10.1007/s00439-015-1590-1}}

Etymology

The syndrome's named was coined by Michael Gabbett who named it after English clinical geneticists Karen Temple and Michael Baraitser.{{cite web |last1=Ward |first1=Gemma |title=Genetic test unlocks cause of Brisbane boy's rare disease |date=25 November 2014 |url=https://imb.uq.edu.au/genetic-test-unlocks-rare-disease |publisher=The University of Queensland}}{{cite web |last1=Pash |first1=Chris |title=This Brisbane Boy Is Just One Of Seven People In The World With A Rare Condition |url=https://www.thechainsaw.com/this-brisbane-boy-is-just-one-of-seven-people-in-the-world-with-a-rare-condition-2014-11 |publisher=Pedestrian Group}} Temple and Baraitser described the first case in 1991.{{cite journal |last1=Gabbett |first1=Michael T. |last2=Clark |first2=Ronald C |last3=McGaughran |first3=Julie M |title=A Second Case of Severe Mental Retardation and Absent Nails of Hallux and Pollex (Temple–Baraitser Syndrome) |journal=American Journal of Medical Genetics Part A |date=2008 |volume=146A |issue=4 |pages=450–452 |doi=10.1002/ajmg.a.32129 |pmid=18203178 |s2cid=2532859 |url=https://doi.org/10.1002/ajmg.a.32129}}{{cite journal |last1=Temple |first1=Karen I |last2=Baraitser |first2=Michael |title=Severe mental retardation and absent nails of hallux and pollex |journal=Am J Med Genet |date=1991 |volume=41|issue=2 |pages=173–175 |doi=10.1002/ajmg.1320410207 |pmid=1785628 |url=https://doi.org/10.1002/ajmg.1320410207}}

References

External links

{{Medical resources

| DiseasesDB =

| ICD10 = Q87.2

| ICD9 =

| ICDO =

| OMIM = 611816

| MedlinePlus =

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| MeshID = C567516

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| Orphanet = 420561

| SNOMED CT = 725140007

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[https://humandiseasegenes.nl/kcnh1 Human Disease Genes - KCNH1]

Category:Rare genetic syndromes

Category:Rare syndromes