KCNH1-related disorders
| Temple–Baraitser syndrome | |
|---|---|
| Other names | Severe mental retardation and absent nails of hallux and pollex |
| Small fingernails typical of Temple–Baraitser syndrome. | |
| Causes | Gain of function variants in KCNH1 |
| Differential diagnosis | Zimmermann–Laband syndrome DOOR syndrome |
| Frequency | unknown |
KCNH1-related disorders are caused by gain-of-function mutations in the gene KCNH1. KCNH1-related disorders are classified as a neurodevelopmental disorder and are characterized by intellectual disability, seizures, and developmental delay. Severity of symptoms are on a wide spectrum, and many individuals also have low muscle tone as babies, distinctive facial features, nail abnormalities, hair overgrowth, and gum overgrowth. The majority of individuals with KCNH1-related disorders have a non-familial (de novo) mutation in the voltage-gated potassium channel subfamily H member 1 (KCNH1) gene that causes the voltage-gated potassium ion channel KCNH1 encodes for, Kv10.1, to be overactive in neurons of the brain. Many individuals are not diagnosed until after they begin to have seizures or miss developmental milestones, and diagnosis requires genetic sequencing. No cure for KCNH1-related disorders is currently available, and treatment focuses on alleviating symptoms. Some individuals achieve seizure control using existing anti-seizure medications.
One phenotype is called Temple–Baraitser syndrome (TBS), 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. Other phenotypes are called Zimmermann–Laband syndrome type 1.