Temple–Baraitser syndrome (TBS) is a very rare

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

genetic disorder, characterised by

intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

, small or absent nail of the thumbs and great toes, and distinct craniofacial features.

Genetics

TBS is caused by pathogenic variants (

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s) in the ''

KCNH1 Potassium voltage-gated channel subfamily H member 1 (KV10.1, EAG1) is a protein that in humans is encoded by the ''KCNH1'' gene. Mutations in ''KCNH1'' cause genetic epilepsy and developmental encephalopathies, and aberant expression is associat ...

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

at chromosomal locus 1q32.2, (GRCh38): 1:210,678,313-211,134,147. It has an

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 A mosaic () is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/Mortar (masonry), mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and ...

parent.

Diagnosis

Temple–Baraitser syndrome is diagnosed by clinical examination of a person with a severe

developmental disability Developmental disability is a diverse group of chronic conditions, comprising mental or physical impairments that arise before adulthood. Developmental disabilities cause individuals living with them many difficulties in certain areas of life, espe ...

intellectual impairment Developmental disability is a diverse group of chronic conditions, comprising mental or physical impairments that arise before adulthood. Developmental disabilities cause individuals living with them many difficulties in certain areas of life, espe ...

and

. 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 The thumb is the first digit of the hand, next to the index finger. When a person is standing in the medical anatomical position (where the palm is facing to the front), the thumb is the outermost digit. The Medical Latin English noun for thumb ...

(pollex) and

great toe Toes are the digits of the foot of a tetrapod. Animal species such as cats that walk on their toes are described as being ''digitigrade''. Humans, and other animals that walk on the soles of their feet, are described as being ''plantigrade''; ...

(hallux). The diagnosis can be confirmed by demonstrating a

gain-of-function Gain-of-function research (GoF research or GoFR) is medical research that genetically alters an organism in a way that may enhance the biological functions of gene products. This may include an altered pathogenesis, transmissibility, or host ran ...

in the ''

'' gene. Temple–Baraitser has clinical and genetic overlap with type 1 Zimmermann–Laband syndrome.

Management

Affected individuals should see a

pediatrician Pediatrics (American English) also spelled paediatrics (British English), is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, pediatrics covers many of their youth ...

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 Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

occupational therapy Occupational therapy (OT), also known as ergotherapy, is a healthcare profession. Ergotherapy is derived from the Greek wiktionary:ergon, ergon which is allied to work, to act and to be active. Occupational therapy is based on the assumption t ...

and

speech pathology Speech is the use of the human voice as a medium for language. Spoken language combines vowel and consonant sounds to form units of meaning like words, which belong to a language's lexicon. There are many different intentional speech acts, suc ...

Anticonvulsants Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatment ...

are used to control epilepsy.

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 ''

''.

Etymology

The syndrome's named was coined by Michael Gabbett who named it after English clinical geneticists Karen Temple and Michael Baraitser. Temple and Baraitser described the first case in 1991.

References

External links

Human Disease Genes - ''KCNH1''
Rare genetic syndromes Rare syndromes {{DEFAULTSORT:Temple-Baraitser syndrome