Proteus syndrome (Wiedemann syndrome), is a rare congenital disorder that causes skin overgrowth and atypical bone development, often accompanied by tumors over half the body.
Proteus syndrome is highly variable, and is named after the Greek sea-god Proteus, who could change his shape.
The condition appears to have been first described in the American medical literature by Drs. Samia Temtamy and John Rogers in 1976. Dr. Michael Cohen described it in 1979. Only a few more than 200 cases have been confirmed worldwide, with estimates that about 120 people are currently alive with the condition. As attenuated forms of the disease may exist, there could be many people with Proteus syndrome who remain undiagnosed. Those most readily diagnosed are also the most severely disfigured.
Proteus syndrome causes an overgrowth of skin, bones, muscles, fatty tissues, and blood and lymphatic vessels.
Proteus syndrome is a progressive condition wherein children are usually born without any obvious deformities. Tumors of skin and bone growths appear as they age. The severity and locations of these various asymmetrical growths vary greatly but typically the skull, one or more limbs, and soles of the feet will be affected. There is a risk of premature death in affected individuals due to deep vein thrombosis and pulmonary embolism caused by the vessel malformations that are associated with this disorder. Because of carrying excess weight and enlarged limbs, arthritis and muscle pain may also be symptoms — as is the case for Mandy Sellars, a woman living with a form of Proteus syndrome (but see "Notable Cases" below). Further risks may occur due to the mass of extra tissue.
The disorder itself does not uniformly cause learning impairments: the distribution of intelligence deficits among sufferers of Proteus syndrome appears higher than that of the general population, although this is difficult to determine with statistical significance. In addition, the presence of visible deformity may have a negative effect on the social experiences of the sufferer, causing cognitive and social deficits.
Afflicted individuals are at increased risk for developing certain tumors including unilateral ovarian cystadenomas, testicular tumors, meningiomas, and monomorphic adenomas of the parotid gland.
In 2011 researchers determined the cause of Proteus syndrome. In 26 of 29 patients who met strict clinical criteria for the disorder, Lindhurst et al. identified an activating mutation in AKT1 kinase in a mosaic state gene. This mutation in the AKT1 gene was present in all 26 affected patients.
Previous research had suggested the condition linked to PTEN on chromosome 10, while other research pointed to chromosome 16. Prior to the findings regarding AKT1 in 2011, other researchers expressed doubt regarding the involvement of PTEN or GPC3, which codes for glypican 3 and may play a role in regulating cell division and growth regulation.
X-rays of the skull and a CT scan will help identify a pituitary eosinophilic adenoma, but serum growth hormone will also be elevated early, and FSH and LH may be depressed later. An MRI will be necessary to pick up microadenomas. Serum FSH and LH will be elevated in Klinefelter's syndrome. A chromosome study should be done to identify Klinefelter's syndrome, supermale, and superfemale. A serum testosterone, dihydrotestosterone, and dehydroepiandrosterone sulfate will be helpful in diagnosing sexual precocity and virilism caused by tumors and hyperplasia of the adrenal gland. Echocardiography and urinary hydroxyproline will help identify Marfan's syndrome, whereas a urine for homocystine will help diagnose homocystinuria. A thyroid profile should be done to rule out thyrotoxicosis.
A team of doctors in Australia have trial tested the drug rapamycin in the treatment of a patient said to have Proteus syndrome and have found it to be an effective remedy. However, the diagnosis of Proteus syndrome in this patient has been questioned by others.