TBC1D24: A Novel Mutation Causing Intellectual Disability and Epilepsy (P6.271)

OBJECTIVE: To describe a novel mutation causative of intellectual disability and generalized epilepsy in a sibship pair. BACKGROUND: In patients with cryptogenic epilepsy, next generation sequencing techniques are increasingly identifying causative mutations for their phenotypes. TBC1D24, a member of the RAB-GAP protein family, is highly expressed in brain and may be involved in membrane recycling, actin remodeling, and neurite development. Particularly important in early network development, mutations in this protein have been found to cause epileptic syndromes with varying phenotypic severity. DESIGN/METHODS: A case report of siblings with cryptogenic generalized epilepsy and intellectual disability, followed in our clinic for diagnosis and management of their condition. RESULTS: Whole exome sequencing in one sibling identified absence of heterozygosity and novel compound heterozygous mutations in TBC1D24. Sanger sequencing in the sister confirmed the same mutations present. After other anti-epileptics, both patients have responded to treatment with zonisamide, with complete control in one sister and reduction >50[percnt] in the other after medication initiation. CONCLUSIONS: In this case, a novel mutation in a gene previously identified to cause various epileptic syndromes elegantly describes the underlying cause of a cryptogenic familial epilepsy with intellectual disability. TBC1D24 pleiotropy in genetic epilepsies is highlighted by the diversity of phenotypic expression and by its causation of multi-systemic syndromic disorders. Disclosure: Dr. Cardon has nothing to disclose. Dr. Holder has nothing to disclose.