Proteus syndrome Q87.22

Wiedemann HR et al. 1983

Very rare, multiform (hence the name "Proteus", named after the Greek god Proteus, who could change his shape at will) congenital clinical picture with osseous malformations, inconsistently occurring nevus flammeus (Rocha RCC et al. 2017) and various mesenchymal and epidermal tumors. Sometimes difficult differentiation from Klippel-Trénaunay syndrome.

Point mutations in the AKT1 gene are proven. The mutation leads to a genetic mosaic, which leads to overgrowth of the affected body parts. The respective mutations only occur after fertilization, apparently in the first weeks of pregnancy. This also explains why there are no sibling cases. This further explains that the AKT1 mutation, which is lethal in itself, can survive in a mosaic formation.

The genes AKT1, PIK3CA and PTEN and the proteins encoded by them belong to a common signalling pathway that controls cell growth and cell differentiation. This also explains the similarity in the characteristics of the so-called "asymmetrical large growth syndromes".

The clinical focus is on hypertrophy of individual structures, such as individual fingers or toes, a whole limb or one half of the body. Also tumour-like thickening of the fatty tissue ( lipomas) or connective tissue. Strip-shaped epidermal nevi (linear proteus nevus) or a capillary malformation(nevus flammeus) can be detected on the skin. The symptoms can lead to functional disorders of the affected organs in the course of life.

Major symptoms: Hemihypertrophia corporis (91% of patients), macrodactyly (88% of patients), subcutaneous mesodermal tumors (76%), palmo-plant cerebriform nevi (65%), exostoses (62%), epidermal nevi (50%), scoliosis (50%).

1. Bilkay U et al (2003) Proteus syndrome. Scand J Plast Reconstr Surg Hand Surg 37: 307-310
2. Cohen MM Jr, Hayden PW. A newly recognized hamartomatous syndrome. In: O'Donnell JJ, Hall BD (eds) Penetrance and variability in malformation syndromes. The National Foundation? March of Dimes. Birth Defects (Original Article Series) 15: 291-296
3. Dragieva G et al (2003) Proteus syndrome. Vasa 32: 159-163
4. Eissing M et al (2019) PTEN Hamartoma Tumor Syndrome and Immune Dysregulation. Translated Oncol 12:361-367.
5. Fraiture AL et al (2002) Proteus syndrome of the hand. Dermatology. 204: 318-320
6. Morelli F et al (2003) A minimal form of Proteus syndrome presenting with macrodactyly and hand hyperplasia. Eur J Dermatol 13: 196-198
7. Pearson H (2002) Dual identities. Nature 417: 10-11
8. Rocha RCC et al (2017) Proteus syndrome. On Bras Dermatol 92:717-720.
9. Roma P et al (2002) Proteus syndrome. J Dermatol 29: 238-241
10. Wiedemann HR et al (1983) The proteus syndrome. Partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. Eur J Pediatr 140: 5-12