Abstracts

RATIONALE: Polymicrogyria (PMG) is a human brain malformation characterized by an irregular brain surface secondary to microgyration and a simplified 4-layered or unlayered cortical cytoarchitecture. It is one of the most common malformations of cortical development and is associated with epilepsy, cognitive impairment and motor dysfunction. The objective of this study was to define the clinical features, morphologic spectrum, associated malformations and evidence for a genetic basis for PMG using the largest series of patients collected to date.
METHODS: We have reviewed the available clinical and imaging data accumulated from three investigative groups on 220 patients with PMG. Only patients with high quality magnetic resonance images were included, and each image was reviewed by at least 2 investigators. Clinical information was obtained by medical record review.
RESULTS: We identified 8 distinct subtypes of PMG, a frequent association of PMG with other brain malformations, 15 pedigrees with multiple affected members and 9 sporadic patients with chromosomal anomalies. Males were affected more frequently than females (p=0.019). The most common distribution of PMG was bilateral and maximal in the perisylvian regions (60%). Of this group, 80% had extension of PMG beyond the immediate perisylvian region, and we have subdivided this group into grades of severity depending on the degree of extension. PMG is frequently associated with abnormalities of noncortical areas including the ventricular system (50%), corpus callosum (32%), white matter (31%), cerebellum (14%) and brainstem (4%). In a subgroup of ~ 100 patients with available clinical data, we identified a mean age of presentation of 5.6 months and a prevalence of epilepsy of 59% with mean age of onset of 13.5 months. Microcephaly was present in 51% with the majority of these children having microcephaly at birth.
CONCLUSIONS: Our data suggest that PMG is a heterogeneous disorder with a predilection for maximal involvement of the perisylvian regions although usually extending beyond the Sylvian fissures. There appear to be multiple genetic loci with best evidence for X-linked inheritance. This study now forms the basis for molecular genetic studies by both linkage analysis and physical mapping of structural rearrangements, and allows improved accuracy in syndrome delineation and prognostic and genetic counseling for affected families.