Abstract
INTRODUCTION: Diencephalic-mesencephalic junction dysplasia syndrome is a rare neurogenetic disorder reported to be caused by variants in several genes. Phenotypic presentation is characterized by clinical findings including developmental delay, hypotonia, spasticity, and dyskinetic movements in combination with distinctive imaging features on brain magnetic resonance imaging (MRI). METHODS: Whole exome sequencing was conducted to unveil the molecular etiology of patients presenting with neurological manifestations from two unrelated families. RESULTS: To the best of our knowledge, here we report the third family affected with diencephalic-mesencephalic junction dysplasia caused by a novel variant in GSX2 and two siblings with a PCDH12 variant exhibiting a less severe phenotype. The siblings with a PCDH12 variant were positioned at the milder end of the phenotypic spectrum. Although both exhibited a clinical phenotype resembling cerebral palsy, one showed partial fusion of the hypothalamus and mesencephalon, whereas MRI was unremarkable in the other. Biallelic GSX2 variants have been implicated in basal ganglia agenesis, and similarly, our patients had basal ganglia hypoplasia along with hypothalamic-mesencephalic fusion. CONCLUSION: Identifying variants associated with the syndrome in different genes will contribute to genotype-phenotype correlation.