Proteus syndrome review: molecular, clinical, and pathologic features

Clin Genet. 2014 Feb;85(2):111-9. doi: 10.1111/cge.12266. Epub 2013 Oct 23.


Proteus syndrome is caused by an activating AKT1 mutation (c.49G>A, p.Glu17Lys). Many variable features are possible in this mosaic disorder, including: (i) disproportionate, asymmetric, and distorting overgrowth; (ii) bone abnormalities different from those observed in other disorders; (iii) a characteristic cerebriform connective tissue nevus made up of highly collagenized connective tissue; (iv) epidermal nevi in early life, consisting of acanthosis and hyperkeratosis; (v) vascular malformations of the capillary, venous, or lymphatic types; (vi) dysregulated adipose tissue including lipomas, lipohypoplasia, fatty overgrowth, and localized fat deposits; (vii) other unusual features, including bullous lung alterations; specific neoplasms; a facial phenotype associated with intellectual disability and/or seizures, and/or brain malformations; and (viii) deep vein thrombosis, resulting in premature death. Concluding remarks address diagnostic criteria, natural history, management, psychosocial issues, and differential diagnosis.

Keywords: AKT1 mutation; Joseph Merrick; bullous lung alterations; cerebriform connective tissue nevus; deep vein thrombosis; diagnostic criteria; differential diagnosis; disproportionate overgrowth; dysregulated adipose tissue; epidermal nevus; management; natural history; psychosocial issues; skeletal anomalies; unusual neoplasms; vascular malformations.

Publication types

  • Review

MeSH terms

  • Diagnosis, Differential
  • Humans
  • Lipoma / genetics
  • Mutation, Missense / genetics
  • Phenotype*
  • Proteus Syndrome / diagnosis*
  • Proteus Syndrome / genetics*
  • Proteus Syndrome / pathology*
  • Proto-Oncogene Proteins c-akt / genetics*


  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt