Rare CCND2 (p.Thr280Ile) Variant Associated With Infantile Spasms in a Patient With Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome

Background

This report describes a pediatric case of megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, a rare neurodevelopmental disorder caused by pathogenic variants in the AKT3, CCND2, or PIK3R2 genes. We present a patient with a rare CCND2 variant (c.839C>T, p.Thr280Ile), associated with infantile spasms, ventriculomegaly, polymicrogyria, and intraventricular hemorrhage (IVH).

Methods

A retrospective chart review and literature search were performed using PubMed.

Results

Our patient was found to have ventriculomegaly, grade 3 IVH, bilateral polymicrogyria, and restricted diffusion in the caudate nuclei prenatally. No polydactyly was observed. The patient developed infantile spasms at age 5 months. While high-dose prednisone treatment failed to control the spasms, they resolved with topiramate. By age 2 years, the patient continued to have significant developmental delays, including having poor tone and being nonverbal.

Conclusion

MPPH syndrome remains a rare and challenging diagnosis, with fewer than 100 cases reported. This case highlights the importance of early genetic testing and neuroimaging in the diagnosis and management of MPPH. The unique presentation of IVH and restricted diffusion warrants further investigation into the syndrome’s variable phenotypic spectrum. Early intervention and targeted therapy may help manage seizure activity and improve outcomes.