Further delineation of phenotype and genotype of primary microcephaly syndrome with cortical malformations associated with mutations in the wdr62 gene

Type 2 congenital microcephaly (MCPH2) is a brain development disorder characterized by primary microcephaly with or without brain malformations. MCPH2 is caused by mutations in the WDR62 gene. We present three new patients with MCPH2 and compound heterozygous mutations in the WDR62 gene. In all the cases, the parents were healthy and unrelated. All children were clinically diagnosed with congenital microcephaly and retardation of motor and speech development. Sequencing results in the presented patients revealed five new variants in the WDR62 gene (c.4273C>T, c.1711_1712insTA, c.1777_1778delGA, c.1642+2T>G, c.194T>A) and one previously described in the German population (c.2864_2867delACAG). In two of the presented cases, variants in the SMAD4, DKC1, and ATRX genes were also found with unknown effects on the course of the disease. Moreover, in the article we collected and compared the most common clinical symptoms, dysmorphic features, and changes in radiographic examinations of the brain observed in 120 patients with recessive primary microcephaly type 2 caused by mutations in the WDR62 gene.