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 have been detected. The mutation leads to a genetic mosaic, which results in 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. It also explains why the AKT1 mutation, which is lethal in itself, is compatible with survival in a mosaic association.

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

Clinically, the focus is on hypertrophy of individual structures, such as individual fingers or toes, an entire limb or one half of the body. Also tumor-like thickening of the fatty tissue ( lipomas) or connective tissue. Strip-like epidermal nevi (linear Proteus nevus) or flag-like capillary malformations(nevus flammeus) can be detected on the skin. In the course of life, the symptoms can lead to functional disorders of the affected organs.

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

Proteus syndrome is an example of an asymmetrical growth disorder that only becomes apparent during childhood. At the age of 2-4 years, individual areas of the body, for example toes or an entire limb, begin to grow excessively. A nevus cerebriformis with excessive tissue growth can occur, particularly on the soles of the feet, which superficially resembles brain furrows. In the course of the disease, severe impairments often occur due to the mosaic-like growth over the entire body. Intelligence is typically normal. Proteus syndrome is caused by a specific mosaic (GOF) mutation in the AKT1 gene .

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