Abstracts

Rationale: Polymicrogyria (PMG) is a malformation of brain cortical development. Common clinical features range from selective impairment of cognitive functions to severe encephalopathies and intractable epilepsy. It is a clinically and etiologically heterogenous condition, due to environmental causes or various genetic disorders. The aim of this study is to report the clinical phenotypes and epilepsy of several subtypes of PMG and establish genotype-phenotype correlations. Methods: Search of our brain malformation databases at the MNH/I and HUDERF hospitals, and inclusion of all types of PMG, except those associated with schizencephaly and confirmed congenital CMV/toxoplasmosis infections; detailed review of medical records; karyotype and FISH 22q11; CGH and/or SNP microarray of genomic DNA. Results: We enrolled 24 patients: 11 had symmetric bilateral perisylvian polymicrogyria (BPP), 2 asymmetrical BPP, 4 unilateral right PMG, 3 unilateral left PMG, and 4 bilateral posterior PMG. A 22q11 deletion was found in one patient with a unilateral right PMG and an associated large contralateral frontal heterotopia, congenital mitral stenosis, left hemiparesis, facial dysmorphism, moderate mental retardation and intractable epilepsy. A 2p13.3-p16.3 duplication was found in a patient with symmetric BPP. He presented with neonatal global hypotonia, feeding difficulties, and delayed psychomotor development. At the age of 10 years, physical examination revealed mild facial dysmorphic signs, mental retardation, severe language delay, attention deficit helped by methylphenidate, and growth deficiency treated with growth hormone, but no epilepsy. Conclusions: The inheritance of PMG is heterogeneous. Our observations confirm that PMG, including right-sided PMG, may be associated with deletion 22q11 (DiGeorge) syndrome and can be associated with intractable epilepsy; however, the association of a large contralateral frontal heterotopia is unusual. Altogether this suggests asymmetrical gene(s) expression between the hemispheres. Phenotypic comparison with two previously published patients harboring other types of proximal 2p duplications shows a subgroup of patients with BPP sharing a common locus narrowed to 2p16.1-p16.3, one of whom presented generalized epilepsy.