Pathogenic variants in TANC2 cause a neurodevelopmental disorder called "Intellectual developmental disorder with autistic features and language delay, with or without seizures" (OMIM#618906).
The TANC2 gene encodes a Tetratricopeptide repeat, ankyrin repeated and coiled-coil containing protein 2 (OMIM*615047) located on chromosome 17q23.2-q23.3. The TANC2 protein is a synapse scaffolding protein interacting with multiple PSD proteins to regulate dentritic spines and excitatory synapse formation.
Main clinical features
TANC2 individuals present a neurodevelopmental phenotype characterized by ID, ASD traits in some individuals reminiscent of the AS/Rett-like spectrum, absent speech-language delay, and facial dysmorphisms. Facial dimorphic features may include large ears with thick helices, thick eyebrows with synophrys, deep-set eye, strabismus, large nose with high nasal bridge, short and flat philtrum, large mouth with this upper lip and thicker everted lower lip, widely spaced teeth and tongue protrusion and low hairline commonly seen in individuals of European descendent. Other clinical features are motor delay, epilepsy or recurrent seizures, and systemic manifestations (eg. constipation, skeletal anomalies).
Besides NDDs, multiple significant neuropsychiatric features have been observed in adult carriers.
Inheritance
The TANC2 phenotype seems to be transmitted as an autosomal dominant condition. Affected individuals with NDDs have been found to carry de novo pathogenic SNV, scattered throughout the gene, as well as microdeletions. Mild neurodevelopmental phenotype and/or psychiatric disorders have been reported in carrier parents. A mildly affected parent carrying a microdeletion in a mosaic state has been reported in literature.
Prevalence
The TANC2-related syndrome is considered rare; its prevalence is unknown at the moment.
TANC2