GABRA1 and STXBP1: Novel genetic causes of Dravet syndrome

Original research article by Carvill et al. (2014).

Read the abstract here.

Dravet Syndrome is an infantile-onset epilepsy disorder that is associated with developmental delays, intellectual disability, and different types of seizures later in life, and is caused by genetic changes (mutations) in the SCN1A gene in about 75% of patients.

Carvill and her team performed whole-exome sequencing (WES) in thirteen individuals who did not have an SCN1A mutation, but were diagnosed with Dravet Syndrome. Of these thirteen individuals, three were found to have de novo (not found in either parent) mutations in the STXBP1 gene.

All three individuals had an onset of Dravet Syndrome within their first year of life, although at a later age (6-12 months) than what is usually seen in individuals with STXBP1, where onset is usually by 3 months. Two had a history of both tonic and atonic seizures, both of which are rare in the early stages of Dravet Syndrome, and all three were not observed to have epileptic spasms, which are often associated with having STXBP1. Two of the patients had severe intellectual disability (ID), while one had learning difficulties. Based on their findings, the researchers suggest that STXBP1contributes to Dravet Syndrome and should be considered for genetic testing in cases where and SCN1A mutation is not found.