Aplasia cutis congenita in a CDC42-related developmental phenotype

Am J Med Genet A. 2021 Mar;185(3):850-855. doi: 10.1002/ajmg.a.62009. Epub 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.

Keywords: CDC42; Noonan syndrome-like disorder; aplasia cutis congenita.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adult
  • Amino Acid Substitution
  • Craniofacial Abnormalities / genetics
  • Dwarfism / genetics
  • Ectodermal Dysplasia / genetics*
  • Eye Abnormalities / genetics
  • Female
  • Genetic Association Studies
  • Heart Defects, Congenital / genetics
  • Humans
  • Infant, Newborn
  • Livedo Reticularis
  • Mutation, Missense*
  • Pedigree
  • Phenotype
  • Point Mutation*
  • Scalp / pathology
  • Skin Diseases, Vascular / genetics*
  • Telangiectasis / congenital*
  • Telangiectasis / genetics
  • cdc42 GTP-Binding Protein / deficiency*
  • cdc42 GTP-Binding Protein / genetics


  • CDC42 protein, human
  • cdc42 GTP-Binding Protein

Supplementary concepts

  • Cutis marmorata telangiectatica congenita