Schnabel F, Kamphausen SB, Funke R, Kaulfuß S, Wollnik B, Zenker M
American Journal of Medical Genetics Part A
Am J Med Genet A. 2020 Dec 7.
Cell division cycle 42 (CDC42) is a small Rho GTPase, which serves as a fundamental intracellular signal node regulating actin cytoskeletal dynamics and several other integral cellular processes. CDC42‐associated disorders encompass a broad clinical spectrum including Takenouchi–Kosaki syndrome, autoinflammatory syndromes and neurodevelopmental phenotypes mimicking RASopathies. Dysregulation of CDC42 signaling by genetic defects in either DOCK6 or ARHGAP31 is also considered to play a role in the pathogenesis of Adams–Oliver syndrome (AOS). Here, we report a mother and her child carrying the previously reported pathogenic CDC42 variant c.511G>A (p.Glu171Lys). Both affected individuals presented with short stature, distinctive craniofacial features, pectus deformity as well as heart and eye anomalies, similar to the recently described Noonan syndrome‐like phenotype associated with this variant. Remarkably, one of the patients additionally exhibited aplasia cutis congenita of the scalp. Multi‐gene panel sequencing of the known AOS‐causative genes and whole exome sequencing revealed no second pathogenic variant in any disease‐associated gene explaining the aplasia cutis phenotype in our patient. This observation further expands the phenotypic spectrum of CDC42‐associated disorders and underscores the role of CDC42 dysregulation in the pathogenesis of aplasia cutis congenita.