Autosomal Recessive Primary Microcephaly (MCPH) and Novel Pathogenic Variants in and Genes.

Introduction: Autosomal recessive primary microcephaly (MCPH) is a disorder characterized by congenital microcephaly and intellectual disability without extra-central nervous system malformation. MCPH is a disease with heterogeneity in genotype and phenotype. For this reason, it is important to determine the genetic causes and genotype-phenotype relationship in MCPH, which causes lifelong impairment. In this study, we aimed to evaluate the clinical, genetic, and brain imaging findings of cases diagnosed with MCPH.

Methods: Electroencephalogram and brain magnetic resonance imaging were performed for all cases. We evaluated genetic results of the 39 families including cases with suspected MCPH diagnosis.

Results: Genetic diagnosis related to MCPH was provided in 11/39 (28.2%) of these families including 13/41 cases (31.7%). Variants of the gene were the most common (61.5%) cause, and variants of the gene were the second most common cause (38.5%). We have found 6 novel variants and 4 previously reported variants in and genes. Main brain imaging findings in our cases were lissencephaly, polymicrogyria, schizencephaly, pachygyria, and cortical dysplasia. Genetic counseling in 2 families whose genetic diagnosis was determined prevented them from having another child with MCPH.

Discussion/conclusion: Detection and reporting of novel variants is an important step in eliminating this disorder by providing families with appropriate genetic counseling.