Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures

Background and objective: Megalencephaly (MEG) or enlarged brain occurs as a mild familial variant with normal brain structure, but otherwise is an uncommon human brain malformation that may be associated with significant developmental and neurological problems. It has been classified into anatomic and metabolic subtypes. The clinical findings associated with anatomic megalencephaly have been variable and few distinct subtypes have been described. We report five unrelated children with severe congenital MEG associated with polymicrogyria (PMG), postaxial polydactyly (POLY) and hydrocephalus (HYD).

Methods: The clinical records and brain MRI of five patients have been reviewed.

Results: All patients had striking MEG that was symmetric in three of the five patients, and mildly asymmetric in two. The birth OFC was between +2 and +4 SD. The gyral pattern was irregular with microgyri typical of PMG, which was most severe in the perisylvian region in all five patients. Four of the five had hydrocephalus treated with a shunt. Subsequently, one of the shunted patients had small ventricles while the Others had mildly to moderately enlarged lateral ventricles. Three of the five patients had postaxial polydactyly of all four limbs. The corpus callosum was dysmorphic in one patient with a fused rostrum and genu, and intact although mildly thin in the Others. None were abnormally thick. All patients had severe mental retardation; three had seizures and another had an epileptiform EEG.

Conclusion: We believe this constellation of findings (MEG-PMG-POLY-HYD) comprises a new and distinct malformation syndrome that we designate the MPPH syndrome.