Novel compound heterozygous GPR56 gene mutation in a twin with lissencephaly: A case report

Lissencephaly (LIS) is a malformation of cortical development with broad gyri, shallow sulci and thickened cortex characterized by developmental delays and seizures. Currently, 20 genes have been implicated in LIS. However, GRP56-related LIS has never been reported. GRP56 is considered one of the causative genes for bilateral frontoparietal polymicrogyria. Here, we report a twin infant with LIS and review the relevant literature. The twins both carried the novel compound heterozygous GPR56 mutations.

A 5-mo-old female infant was hospitalized due to repeated convulsions for 1 d. The patient had a flat head deformity that manifested as developmental delays and a sudden onset of generalized tonic-clonic seizures at 5 mo without any causes. The electroencephalography was normal. Brain magnetic resonance imaging revealed a simple brain structure with widened and thickened gyri and shallow sulci. The white matter of the brain was significantly reduced. Patchy long T1 and T2 signals could be seen around the ventricles, which were expanded, and the extracerebral space was widened. Genetic testing confirmed that the patient carried the GPR56 gene compound heterozygous mutations c.228delC (p.F76fs) and c.1820_1821delAT (p.H607fs). The unaffected father carried a heterozygous c.1820_1821delAT mutation, and the unaffected mother carried a heterozygous c.228delC mutation. The twin sister carried the same mutations as the proband. The patient was diagnosed with LIS.

This is the first case report of LIS that is likely caused by mutations of the GPR56 gene.