Two Novel Compound Heterozygous ADGRG1/GPR56 Mutations Associated with Diffuse Cerebral Polymicrogyria

Abstract

Background Polymicrogyria (PMG) has environmental or genetic etiologies. We report a 8-year-old boy with diffuse PMG and two novel adhesion G protein-coupled receptor G1 (ADGRG1)/G protein-coupled receptor 56 (GPR56) mutations.

Case Report The proband has intellectual disability, spastic quadriparesis, and intractable epilepsy without antenatal or perinatal insults. Brain magnetic resonance imaging revealed PMG involving fronto-polar, parietal and occipital lobes with decreasing antero-posterior gradient, and a thinned-out brain stem. Targeted exome sequencing identified two novel compound heterozygote ADGRG1/GPR56 mutations (c.C209T and c.1010dupT), and each parent carries one of these mutations. Subsequent pregnancy was terminated because the fetus had the same mutations.

Conclusion The detected mutations expanded the genetic etiology of PMG and helped the family to avoid another child with this devastating condition.

Keywords

drug resistant epilepsy - intellectual disability - cortical malformations

Publication History

Received: 16 April 2020

Accepted: 27 June 2020

Article published online:
29 July 2020

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