Novel ADGRV1 pathogenic variant associated to sleep-related hypermotor epilepsy

Sleep-related hypermotor epilepsy is characterized by complex seizures predominantly during sleep, marked by hyperkinetic movements and/or asymmetric tonic/dystonic posturing. The etiology often remains unknown, but when identified it is attributed to genetic and/or structural factors, implicating genes such as CHRNA4, CHRNB2, CHRNA2, KCNT1, and DEPDC5. ADGRV1 pathogenic variants are associated with an autosomal recessive form IIC of Usher syndrome and several epilepsy types, including generalized auditory-induced seizures, focal epilepsy, genetic generalized epilepsy, and epileptic encephalopathy. An association between SHE and ADGRV1 gene has never been described. Here we describe a pediatric patient with SHE harboring a de novo heterozygous pathogenic variant on the ADGRV1 gene (c.14165A>G; p.Glu4722Gly). Our findings prompt discussion about the potential phenotype expansion associated with this ADGRV1 variant and its pathogenic link with SHE.