Proteus syndrome

Proteus syndrome is an extremely rare, progressive overgrowth disorder characterized by disproportionate, asymmetric, and distorting overgrowth of various tissues. The condition was named after the Greek god Proteus, who could change his shape. It is caused by a somatic mosaic activating mutation in the AKT1 gene (c.49G>A, p.Glu17Lys), meaning the mutation occurs after conception and is present only in some cells of the body. Because the mutation is mosaic, the pattern and severity of overgrowth vary widely between affected individuals. Proteus syndrome affects multiple body systems. Key clinical features include progressive, asymmetric overgrowth of the skeleton (limbs, skull, vertebrae), skin (cerebriform connective tissue nevi, particularly on the soles of the feet, epidermal nevi, and vascular malformations), adipose tissue (lipomas and regional lipohypoplasia), and internal organs. Affected individuals may also develop vascular anomalies including deep vein thrombosis and pulmonary embolism, which represent significant causes of morbidity and premature mortality. Overgrowth is typically minimal or absent at birth and becomes progressively more apparent during childhood. Other features can include cystic lung disease, renal anomalies, and certain tumors (particularly bilateral ovarian cystadenomas and parotid monomorphic adenomas). There is currently no cure for Proteus syndrome. Management is primarily supportive and symptomatic, involving orthopedic interventions for skeletal overgrowth, surgical debulking of overgrown tissues, dermatologic care, and monitoring for thromboembolic complications. Anticoagulation prophylaxis may be considered in certain clinical situations. The AKT inhibitor miransertib (ARQ 092) has been investigated in clinical trials as a targeted therapy and has shown some promise in reducing overgrowth, though it is not yet widely approved. A multidisciplinary approach involving geneticists, orthopedic surgeons, dermatologists, and other specialists is essential for optimal care.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Proteus syndrome