ADGRG1-related polymicrogyria syndrome: report on a large consanguineous family with a novel variant and review

Abstract

Abstract Background Polymicrogyria is a spectrum of complex cortical malformations encompassing multiple subtypes. Of these, bilateral frontoparietal polymicrogyria (BFPP) has been associated with pathogenic variants in the ADGRG1 gene, formerly known as GPR56. BFPP is characterized by cognitive impairment, motor delay, seizures, oculomotor findings, cerebellar, pyramidal signs, and brain malformations that consist of abnormal changes in the cortex, white matter, brainstem, and cerebellum. Case presentation A large consanguineous Syrian family with five affected individuals exhibiting features of BFPP, is included in this study. These patients presented with cognitive impairment, psychomotor delay, epileptic episodes, cerebellar signs, oculomotor findings, and brain malformations. Through whole exome sequencing, a novel homozygous pathogenic variant in the ADGRG1 gene (NM_201525.4: c.308T > C; p.Leu103Pro) was identified. Conclusion Here, we report a thorough literature review of cases with BFPP, and we discuss the importance of genetic counseling in families with genetic disorders, especially in underdeveloped countries.