Proteus syndrome

Definition: Proteus syndrome is a rare, sporadic disorder that causes postnatal overgrowth of multiple tissues in a mosaic pattern. A mosaic activating mutation in AKT1 is associated with the Proteus syndrome. (21793738)

Characteristic manifestations include: overgrowth and hypertrophy of limbs and digits, connective tissue nevus, epidermal nevus and hyperostoses. Various benign and malignant tumors and hamartomas may complicate the clinical course of patients with the syndrome.

Proteus syndrome is a highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations.

Many features of Proteus syndrome overlap with other overgrowth syndromes. The disorder might be confused with the Klippel-Trenaunay-Weber syndrome (MIM.149000) and with Ollier disease and Maffucci syndrome (MIM.166000).

PTEN-associated Proteus-like syndrome

Some authors (Zhou et al., 2000, 2001; Smith et al., 2002) have reported a ’Proteus-like’ syndrome associated with germline and tissue-specific somatic mutations in the PTEN gene (MIM.601728), which is mutated in Cowden syndrome (MIM.158350) and Bannayan-Riley-Ruvalcaba syndrome (BRRS; MIM.153480).

Synopsis

 Growth

• asymmetric overgrowth
• increased stature
• macrocephaly

 Skin & subcutaneous tissue

• thickening
• nevi
• lipomata
• lymphangiomata
• hemangiomata

 Skeletal : hemihypertrophy, bony prominences over skull, angulation defects of knees, scoliosis

 Hands & feet : macrodactyly, soft tissue hyper-trophy, which may appear as gyriform

Tumoral predisposition

 hemangiomas
 lymphangiomas
 lipomas
 tumors of the genital tract

• bilateral ovarian cystadenomas
• bilateral paraovarian villoglandular endometrioid cystadenomatous tumors of borderline malignancy of the broad ligament (11850547)

Etiology

 germline mutation in the tumor suppressor gene PTEN (MIM.601728)
 A mosaic activating mutation in AKT1 is associated with the Proteus syndrome. (21793738)

Differential diagnosis

 Klippel-Trenaunay-Weber syndrome (MIM.149000)
 Ollier disease and Maffucci syndrome (MIM.166000)

References

 A mosaic activating mutation in AKT1 associated with the Proteus syndrome. Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O’Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG. N Engl J Med. 2011 Aug 18;365(7):611-9. PMID: 21793738