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.
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.