De novo variants in SETD1B cause intellectual disability, autism spectrum disorder, and epilepsy with myoclonic absences.

Abstract

Epilepsy with myoclonic absences is a specific seizure type characterized by bilateral rhythmic clonic jerks with impairment of consciousness. Here, we report an individual with epilepsy with myoclonic absences, mild intellectual disabilities, language disorder, and autism spectrum disorder. His interictal electroencephalogram revealed a spike‐and‐slow wave complex dominant in the frontal area. His ictal polygraphic and video‐electroencephalogram showed a characteristic diffuse synchronous 3‐Hz spike‐and‐wave burst associated with bilateral upper limb myoclonic jerks with impairment of consciousness. Using whole‐exome sequencing, we found a novel de novo variant, c.386T>G, p.(Val129Gly), in SETD1B (SET domain containing 1B). We previously reported that two individuals with a de novo SETD1B variant showed intellectual disability, epilepsy, and autism. Of note, one of those individuals and the present case showed epilepsy with myoclonic absences. Therefore, this report supports the indication that SETD1B may be a causative gene for neurodevelopmental disorders and suggests that epilepsy with myoclonic absences may be a characteristic feature of SETD1B‐related disorders.