Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome with aplasia cutis congenita due to PIK3R2...

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare congenital developmental disorder characterized by megalencephaly, polymicrogyria, posterior polydactyly, and hydrocephalus and driven by PI3K-AKT-mTOR pathway dysregulation. This report presents a case of genetically confirmed MPPH in which the patient also exhibited aplasia cutis congenita (ACC), a cutaneous phenotype rarely described in this syndrome.

We describe a full-term female infant with macrocephaly [head circumference > +2 standard deviations (SDs)] and distinctive craniofacial features, including a prominent forehead, hypertelorism, and a low nasal bridge. Neuroimaging revealed bilateral perisylvian polymicrogyria, while developmental assessment indicated mild-to-moderate delay across multiple domains. Genetic testing identified a heterozygous c.1117G>A (p.G373R) mutation in PIK3R2 and confirmed it to be MPPH syndrome. Notably, a well-demarcated area of ACC was observed on the anterior neck. The patient was also found to have a patent ductus arteriosus (PDA). Such clinical findings have infrequently been described in the existing medical literature.

This report highlights the co-occurrence of ACC and PDA in a patient with PIK3R2-related MPPH, suggesting a potential expansion of the phenotypic spectrum associated with this syndrome and may provide valuable reference for early diagnosis and genetic counseling. Continued systematic documentation and synthesis of the phenotypic spectrum are vital to strengthening diagnostic consensus for this rare disease.