A rare epilepsy phenotype in Gabriele-de Vries syndrome: A new case and literature review

Abstract

Gabriele-de Vries syndrome (GADEVS) is an extremely rare genetic syndrome characterized by mild-to-profound intellectual disability/developmental delay and a wide spectrum of clinical features. Herein, we report a case involving a rare early childhood epilepsy phenotype in a patient diagnosed with GADEVS based on the typical clinical features and the identification of a pathologic variant of the Yin Yang 1 (YY1) gene. A 3-year-old girl with global developmental delay, failure to thrive, and facial dysmorphism was referred to our rare genetic clinic. She also presented with cognitive impairment, hypotonia, hyperlaxity, strabismus, and autistic features. Whole genome sequencing identified a de novo heterozygous missense variant in the YY1 (c.1130A>G; p.His377Arg) gene. Notably, she developed afebrile seizures with abnormal electroencephalogram in early childhood. Currently, she has been seizure-free for more than 2 years with valproic acid. This case expands the epilepsy phenotypic features of GADEVS and reviews the association between the loss-of-function of the YY1 gene and epileptogenesis and possible treatment options.