MAX-Related Disorder: Expanding the Phenotype of the Recurrent p.Arg60Gln Variant.

Abstract

We report on two patients with four-limb postaxial polydactyly and a recurrent de novo missense variant (c.179G>A) in the MAX gene. This variant has been previously reported in four other cases of polydactyly, progressive macrocephaly, and ophthalmologic abnormalities. Our two cases represent the fifth and sixth known occurrences of this apparently rare genetic disorder. In addition to the previously reported findings, our patients exhibit novel clinical features, including orofacial clefting, congenital heart defects (coarctation of the aorta, secundum atrial septal defect), natal teeth, and sacrococcygeal teratoma. The present study emphasizes the importance of genetic testing in patients presenting with polydactyly and associated anomalies. These cases support the pathogenicity of the recurrent MAX c.179G>A (p.Arg60Gln) variant and significantly broaden the phenotypic spectrum of polydactyly-macrocephaly syndrome/MAX-related disorder.