Proteus syndrome
Encyclopedia
Proteus syndrome, also known as Wiedemann's syndrome (named after the German paediatrician Hans-Rudolf Wiedemann), is a congenital disorder
that causes skin
overgrowth and atypical bone
development, often accompanied by tumor
s 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 is a progressive condition wherein children are usually born without any obvious deformities. Tumors and 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. Further risks may occur due to the mass of extra tissue — Joseph Merrick
, the most famous sufferer of Proteus syndrome, himself died when the weight of his head dislocated his neck while he was sleeping.
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 a mosaic state gene. This mutation was not present in more than 1,000 persons who were unaffected by this disorder.
Previous research had suggested the condition linked to PTEN
on chromosome 10, while other research pointed to chromosome 16. Prior to the determination of the cause of the disease in 2011, other researchers expressed doubt regarding the involvement of PTEN or GPC3.
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.
syndrome. The lesions appear to be distributed in a mosaic manner. It has been confirmed that the disorder is an example of genetic mosaicism.
, the 'Elephant Man'.
Mandy Sellars
has been diagnosed by some doctors as suffering from this condition. Her legs and feet have grown at a disproportionate rate since birth.
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
that causes skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
overgrowth and atypical bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
development, often accompanied by tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s over half the body.
Proteus syndrome is highly variable, and is named after the Greek sea-god Proteus
Proteus
In Greek mythology, Proteus is an early sea-god, one of several deities whom Homer calls the "Old Man of the Sea", whose name suggests the "first" , as protogonos is the "primordial" or the "firstborn". He became the son of Poseidon in the Olympian theogony In Greek mythology, Proteus (Πρωτεύς)...
, 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
Michael Cohen (doctor)
M. Michael Cohen, Jr., the first doctor to diagnose Proteus syndrome in 1979, is Professor Emeritus of Pediatrics, Faculty of Medicine, Dalhousie University ....
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.
Presentation
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 and 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
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
and pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
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
Mandy Sellars
Mandy Sellars is a woman diagnosed as suffering from what is believed by some doctors to be Proteus syndrome, a very rare condition thought to afflict only 120 people worldwide.-Biography:...
, a woman living with a form of Proteus syndrome. Further risks may occur due to the mass of extra tissue — Joseph Merrick
Joseph Merrick
Joseph Carey Merrick , sometimes incorrectly referred to as John Merrick, was an English man with severe deformities who was exhibited as a human curiosity named the Elephant Man. He became well known in London society after he went to live at the London Hospital...
, the most famous sufferer of Proteus syndrome, himself died when the weight of his head dislocated his neck while he was sleeping.
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.
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 kinaseAKT1
RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. Multiple alternatively spliced transcript variants have been found for this gene.- Function :...
in a mosaic state gene. This mutation was not present in more than 1,000 persons who were unaffected by this disorder.
Previous research had suggested the condition linked to PTEN
PTEN (gene)
Phosphatase and tensin homolog is a protein that, in humans, is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers....
on chromosome 10, while other research pointed to chromosome 16. Prior to the determination of the cause of the disease in 2011, other researchers expressed doubt regarding the involvement of PTEN or GPC3.
Treatment
A team of doctors in Australia have trial tested the drug RapamycinSirolimus
Sirolimus , also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. A macrolide, sirolimus was first discovered as a product of the bacterium Streptomyces hygroscopicus in a soil sample from Easter...
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.
Classification
Many sources classify Proteus syndrome to be a type of nevusNevus
Nevus is the medical term for sharply-circumscribed and chronic lesions of the skin. These lesions are commonly named birthmarks and moles. Nevi are benign by definition...
syndrome. The lesions appear to be distributed in a mosaic manner. It has been confirmed that the disorder is an example of genetic mosaicism.
Notable cases
This extremely rare condition has been proposed as the condition that affected Joseph MerrickJoseph Merrick
Joseph Carey Merrick , sometimes incorrectly referred to as John Merrick, was an English man with severe deformities who was exhibited as a human curiosity named the Elephant Man. He became well known in London society after he went to live at the London Hospital...
, the 'Elephant Man'.
Mandy Sellars
Mandy Sellars
Mandy Sellars is a woman diagnosed as suffering from what is believed by some doctors to be Proteus syndrome, a very rare condition thought to afflict only 120 people worldwide.-Biography:...
has been diagnosed by some doctors as suffering from this condition. Her legs and feet have grown at a disproportionate rate since birth.