Abstracts

Rationale: Polymicrogyria (PMG) is a malformation of brain cortical development. Common clinical features include developmental delay, oromotor dysfunction, motor disabilities, and seizures that can be intractable. PMG is a clinically and etiologically heterogenous condition. It can be attributable to environmental causes, single gene disorders with various patterns of inheritance, or chromosomal rearrangements, usually sporadic. Our aim is to report the phenotypes, epilepsy and copy number variation (CNV) data of a cohort of PMG patients and establish genotype-phenotype correlations. Methods: Search of our brain malformation databases 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 31 patients: 13 symmetric bilateral perisylvian polymicrogyria (BPP), 2 asymmetrical BPP, 8 unilateral right PMG, 4 unilateral left PMG, 2 bilateral temporo-occipital, and 2 bilateral parieto-occipital PMG. Associated brain malformations were: microcephaly in 2 patients, nodular heterotopia in 4. CGH microarray results are available for 18 patients. A 22q11 deletion was found in two boys with unilateral right PMG. The brain MRI showed an associated large contralateral frontal heterotopia in one; he presented with moderate mental retardation, facial dysmorphism, congenital mitral valve stenosis, congenital left hemiparesis and intractable focal epilepsy. The second one had an associated large ipsilateral heterotopia; he presented with neonatal seizures from day 2 of life, severe psychomotor retardation, facial dysmorphism, and left hemiparesis. A 2p13.3-p16.3 duplication was found in a boy with symmetric BPP. He presented with neonatal global hypotonia, feeding difficulties, delayed psychomotor development. At the age of 10 years, mild facial dysmorphic signs with low set ears, mental retardation, severe language delay, attention deficit, and growth deficiency were noted. A small for gestational age boy was born with a large fontanel, thick hair texture and low hair line, his ears were low set and somewhat small. At age 14 days, brain MRI showed right perisylvian PMG, a 2p16.1-p12 duplication was found.Conclusions: The inheritance of PMG is heterogeneous. Our observations further illustrate that PMG can be due to copy number variants (CNV), here 4 patients had a chromosomal rearrangement. Unilateral PMG may be associated with deletion 22q11 (Velocardiofacial-DiGeorge syndrome). This suggests asymmetrical gene(s) expression between the hemispheres. Phenotypic and CNV comparison with previously published patients allowed us to narrow a locus for BPP to 2p16.1-p16.3. SNPs array of the second patient with 2p duplication will evidence whether his duplication region is overlapping this 2p16.1-p16.3 locus or is contiguous in which case a second gene could be involved.