The First Iranian Patient with West Syndrome Due to a RYR3 Gene Variant: A Case Report and Literature Review

Abstract

West syndrome (WS) is a severe developmental and epileptic encephalopathy of infancy, defined by the triad of epileptic spasms, hypsarrhythmic electroencephalography, and developmental delay. Recent limited studies have suggested that the RYR3 gene is involved in the pathogenesis of WS. Our study presents an Iranian patient with WS and aims to provide further evidence to support the role of RYR3 variants in this condition. The proband was a male patient aged 2 years and 2 months with drug-resistant epileptic spasms and developmental regression. Trio-based whole-exome sequencing (Trio-WES) was conducted, and a novel de novo heterozygous variant in RYR3 (NM_001036.6: c.4112T>C, p.Leu1371Pro) was identified in the proband. The variant was not found in population databases, and bioinformatics analyses also predicted the deleterious impact of the variant. This study describes a novel RYR3 variant in a patient with WS, supporting a potential pathogenic role for RYR3 in early-onset epileptic encephalopathy. Therefore, it should be considered during the genetic assessment of unexplained WS cases.

Keywords: Calcium release channel, Infantile spasm, Ryanodine receptor 3, RYR3, Syndrome, West syndrome