[P3-157] Epilepsy, Hearing Loss, and Mental Retardation Syndrome due to SPATA5 Mutation in Two Siblings in a Japanese Family
Recently, whole exome sequencing (WES) of children with developmental delay has identified a group of patients with mutations in spermatogenesis-associated protein 5 gene (SPATA5). These patients present with a phenotype of Epilepsy, hearing loss, and mental retardation syndrome (EHLMRS) in early childhood. We studied a sibling case of EHLMRS. Our aim in this presentation is to delineate the EHLMRS as a clinical entity, including the facial appearance, neurophysiological, and neuroimaging findings in comparison with previously reported cases. Using whole exome sequencing and Sanger sequencing, we identified two siblings with SPATA5 mutations in a Japanese family. They carried compound heterozygous mutations, c.989_991del (p.Thr330del) and c.2130_2133del (p.Glu711Profs*21). Sanger sequencing confirmed that c.989_991del and c.2130_2133del were inherited from the mother and father, respectively. The patients manifested microcephaly, psychomotor retardation, hypotonus or hypertonus, and bilateral hearing loss from early infancy. Common facies were a depressed nasal bridge/ridge, broad eyebrows, and retrognathia. Epileptic spasms or tonic seizures emerged at 12–14 months of age. Interictal electroencephalography showed multifocal spikes and bursts of asynchronous diffuse spike-wave complexes. Augmented amplitudes of visually evoked potentials were detected in the two siblings. Magnetic resonance imaging revealed hypomyelination, thin corpus callosum, and progressive cerebral atrophy with preserved infratentorial structures. Blood copper levels were also elevated or close to the upper normal levels in these children. Clinical delineation of the EHLMRS should improve diagnosis, facilitating further clinical and molecular investigation.