Proteus syndrome is a rare genetic disorder[Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. .] The clinical symptoms and Radiography findings of Proteus syndrome are highly variable, as are its orthopedic manifestations.
Only a few more than 200 cases have been confirmed worldwide, with estimates that about 120 people are currently alive with the condition.[ Woman's 11-stone legs may be lost at BBC] 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.
The syndrome 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 Samia Temtamy and John Rogers in 1976.
Signs and symptoms
Proteus syndrome causes an overgrowth of skin, bones, muscles, fatty tissues, and blood and . 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 typically in early childhood. The musculoskeletal manifestations are cardinal for the diagnosis of Proteus syndrome.[ The severity and locations of these 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. Further risks may occur due to the mass of extra tissue.
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The disorder does not uniformly cause learning impairments: the distribution of intelligence deficits among those with Proteus syndrome appears higher than that of the general population. This is difficult to determine with statistical significance.
Affected individuals are at increased risk for developing certain tumors including unilateral ovarian cystadenomas, , , and monomorphic of the parotid gland.
Hemimegalencephaly is often found to be associated.
Orthopaedic features
The musculoskeletal manifestations of Proteus syndrome are frequent and recognizable. Patients tend to demonstrate a unique pattern of skeletal abnormalities. The orthopaedic features are usually bilateral, asymmetrical, and progressive, and involve all four limbs and the spine. Affected patients usually have localized periarticular limb distortions, limb length discrepancy, and spine deformity. Patients with Proteus syndrome can have regular bone configuration and contours despite the bone enlargement.[
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Genetics
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.
Previous research had suggested the condition was linked to PTEN on chromosome 10,
Diagnosis
Differential diagnosis
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Macrodystrophia lipomatosa
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Fibrolipomatous hamartoma
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Neurofibromatosis type 1
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Klippel–Trénaunay syndrome
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Parkes Weber syndrome
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Sotos syndrome
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Hemangiomas
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Beckwith-Wiedemann syndrome
Classification
Many sources classify Proteus syndrome as a type of nevus syndrome. The appear to be distributed in a mosaic manner.[
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Treatment
A team of doctors in Australia has 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.
The Arqule Corporation developed the AKT1 inhibitor ARQ 092, which is being tested by a research team in the National Human Genome Research Institute at the United States National Institutes of Health in a Phase 0 dose-finding trial. In earlier tests on tissue and cell samples obtained from patients, ARQ 092 reduced phosphorylation of AKT and downstream targets of AKT in as little as two hours.
Notable cases
In a 1986 article in the The BMJ, Michael Cohen and J.A.R. Tibbles proposed the idea that Joseph Merrick (an Englishman known as the "Elephant Man") had Proteus syndrome. However, the exact condition that Joseph Merrick had is still not known with certainty.[ – Spiring P (2001). "The Improbable Elephant Man". Biologist (London) 48(3) 104., Article in The Sunday Telegraph, – BBC News, [http://www.eurekalert.org/pub_releases/2003-07/dhc-ada071803.php – Eurekalert!, Article in The Daily Telegraph]
Mandy Sellars has been diagnosed by some doctors as having this condition.
See also
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Epidermal nevus syndrome
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Mosaic (genetics)
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Overgrowth syndrome
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List of radiographic findings associated with cutaneous conditions
External links
