A Novel Neuroimaging Phenotype in the X-Linked Intellectual Disability with a Missense Mutation of CNKSR2 Gene

Mental retardation, X-linked, syndromic, Houge type (MRXSHG) is a form of mental retardation characterized by intellectual disability, speech and language impairments, and early-onset seizures. It has been recently recorded in Online Mendelian Inheritance in Man (OMIM), and only 10 cases have been reported in the literature so far.

To highlight the novel neuroimaging findings in the pediatric X-linked intellectual disability with a missense mutation of connector enhancer of kinase suppressor of RAS2 (CNKSR2) gene.

We present a case of intellectual disability, refractory epilepsy, speech and language delay with subtle dysmorphism, and behavioral issues in an 11-year-old boy with novel neuroimaging findings in a CNKSR2 gene with missense mutation.

Brain MRI revealed involvement of the basal ganglia, predominantly the neostriatum, and along with the subependymal aspects with focal cavitations involving, especially the bilateral caudate heads. There was relative sparing of the globus pallidi and posterior putamina bilaterally. Whole-exome sequencing identified a hemizygous missense pathogenic variant in the CNKSR2 gene. The mother was found to be an asymptomatic carrier.

This case report highlights the rare missense mutation in the CNKSR2 gene and abnormal neuroimaging findings, which further provide information about the phenotypic characteristics of X-linked syndromic intellectual disability.