Introduction: Polymicrogyria (PMG) is a common malformation of cortical development characterized by an excessive number of small gyri partially fused, and a disorganization of cortical lamination.  Clinical features include seizures, developmental delay, oromotor dysfunction and motor disabilities. PMG is highly heterogeneous clinically, radiologically and etiologically, rendering the identification of its cause challenging in many cases.

Methods: We studied 60 patients with all types of PMG, except those caused by environmental factors such as anoxia-ischemia and confirmed congenital infections. This included review of medical records; conventional and molecular karyotypes; targeted gene testing and, in some patients, next generation sequencing.

Results: 60 patients were included, 56 sporadic and two families with two siblings each. 34/60 (56%) had associated one or more other brain malformation(s): 8/34 corpus callosum dysgenesis, 6/34 microcephaly, 6/34 brainstem dysplasia, 6/34 nodular heterotopia, 2/34 focal cortical dysplasia, 2/34 arachnoidal cysts, 1/34 optic chiasm hypoplasia, 1/34 basal ganglia dysgenesis, 1/34 cerebellar dysgenesis, 1/34 hemimegalencephaly. One karyotype showed a reciprocal translocation 46,XY t(8;22)(p23.1;p11.2). CGH anomalies included two 22q11del, one 1p36del, (one 2p21del of unknown significance), one 6q25.1 del, one 2p13.3-p16.3dup, and one 2p16.1-p12 dup. Single gene mutations included TUBB2B, GPR56, IKBKG (NEMO), CEP290.

Conclusions: Categorization of polymicrogyria on the basis of its topography, associated brain malformations and phenotype, helps to orient the genetic testing and diagnosis. We have been able to solve 25% of the patients with an approximately equal number of chromosomal rearrangements (7/15) and single gene mutations (8/15). Next generation sequencing is still carried out in the unsolved patients.