Epilepsy due to a MED25 Homozygous Pathogenic Founder Variant

Abstract

Previous reports have described a spectrum of clinical phenotypes in patients with MED25 pathogenic variants. One specific phenotype is the Basel-Vanagaite-Smirin-Yosef syndrome, which is a rare, autosomal recessive disorder characterized by a wide range of symptoms including eye abnormalities, cardiac abnormalities, palatal abnormalities, intellectual disability, and epilepsy. Although epilepsy appears to be common, the electroclinical phenotypes of patients with Basel-Vanagaite-Smirin-Yosef syndrome have not been well described. Here, we report 3 Basel-Vanagaite-Smirin-Yosef syndrome patients from 2 families of Lebanese descent with a homozygous MED25 founder variant from Alberta Children's Hospital, Calgary, Alberta. We describe in detail electroclinical phenotypes in each of these 3 patients. These patients developed seizures with onset between 2 and 3 years of age, multifocal and generalized discharges, as well as photoparoxysmal responses on electroencephalogram. We review the relevance of these epilepsy findings in the context of other published reports of Basel-Vanagaite-Smirin-Yosef syndrome.

Keywords: EEG; epilepsy; genetics; seizures.