Severe presentation and complex brain malformations in an individual carrying a CCND2 variant

BACKGROUND: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) is a developmental brain disorder characterized by megalencephaly and bilateral perisylvian polymicrogyria due to defects in genes of the PI3K-AKT pathway. Only a few patients with CCND2 mutations have been reported to date. METHODS: We describe an individual harboring a de novo variant in CCND2 undergoing neuroradiological evaluation including diffusion tensor imaging (DTI). RESULTS: The individual presented with a severe brain malformation extending to both brainstem and cerebellum with hypomyelination not previously reported in CCND2-related disorder. Severe hypoplasia and white matter disorganization were confirmed by DTI. CONCLUSION: This report expands the phenotypic spectrum of the disorder due to CCND2 variants