TBS and ZLS form a clinical spectrum. Intellectual disability in TBS tends to be severe, whilst only mild to moderate (or even absent) in ZLS. Both syndromes feature nail abnormalities – usually aplasia or hypoplasia of the nails of the thumb and/or great toe. Gingival hypertrophy is common, but may not be seen until later in life.
Both syndromes have distinctive facial features. In TBS, the face appears myopathic while in ZLS, the face has a coarsened appearance.
TBS and ZLS are both very rare diseases. Each is an autosomal dominant condition. They arise as the result of a new (de novo) mutation in the KCNH1 gene, although at least one instance of a very mildly affected mother, who was found to be mosaic for a pathogenic variant, has been reported to subsequently have a child with TBS.
KCNH1