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Proteus syndrome review: molecular, clinical, and pathologic features


  • M. Michael Cohen Jr.

    Corresponding author
    1. Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
    • Corresponding author: M. Michael Cohen, Jr, Department of Pediatrics, Faculty of Medicine, Dalhousie University, 5981 University Avenue, Halifax, Nova Scotia B3H 4R2, Canada.

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  • Nothing to declare.
  • This publication is dedicated to the memory of my Fellow Bernarda Strauss, MD


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.