Wiedemann?s dysmelia syndrome

Related Terms

Elephant man, gigantism, hemihypertrophy, hyperostosis, hypertrophy, macrocephaly, plantar hyperplasia, Wiedemann's dysmelia syndrome, Wiedemann's syndrome.

Background

Proteus syndrome is a rare disorder characterized by bone and skin malformations and a variety of other symptoms. The malformations result from tissue overgrowth, which can affect the bones, skin, or any other part of the body. The underlying cause of Proteus syndrome is unclear, but the condition is present from birth (congenital).
Symptoms consistent with Proteus syndrome were first described by Dr. M. Cohen, Jr. in 1979. Because patients with Proteus syndrome suffer from a wide range of malformations, the disease was named after the Greek shape-shifting deity. The disease is also known as Wiedemann's dysmelia syndrome, after Dr. H. Wiedemann, who coined the term "Proteus syndrome" in 1983.
Joseph Merrick, the patient depicted in the movie "The Elephant Man," was initially believed to have neurofibromatosis, a genetic disorder that causes tumors, skin changes, and bone deformities. However, it is now widely believed that the patient actually suffered from a severe case of Proteus syndrome.
Tissue overgrowth typically begins in infancy and can affect any part of the body. Proteus syndrome is an extremely variable condition. Disease severity is difficult to predict, and the symptoms may range from mild to severe. Connective tissue, bone, skin, and feet are commonly affected and visible effects may be different on the two sides of the body. Symptoms can also include improperly formed blood vessels, tumors, and lung disease.
It is unknown how many individuals have Proteus syndrome because not all cases are reported. It is very rare, with an estimated 100 to 200 individuals currently affected worldwide.
The long-term outcome of Proteus syndrome is not known. Life expectancy varies from person to person. In cases in which the critical organs are affected, complications of Proteus syndrome may be severe. Other cases may be mild, however, and patients may be otherwise healthy.

Signs and symptoms

People affected with Proteus syndrome may have a wide variety of symptoms, which range in frequency and severity from person to person.
Common signs include disproportionate, asymmetrical, patchy overgrowth of the hands, feet, bones, and organs. Other signs may include skeletal malformations, tumors, scoliosis (sideways curvature of the spine), abnormal blood vessels, lung disease, and skin lesions or discoloration.
Hypertrophy, an increase in the size of an organ or specific area of tissue, occurs in patients with Proteus syndrome. An overgrowth on one side of the body (hemihypertrophy) may be observed. Skull abnormalities can include a large head (macrocephaly) or an unusually shaped skull.
Deep lines and overgrowth of soft tissue on the soles of the feet (plantar hyperplasia) may occur. There may be greater or fewer than normal fat deposits throughout the body.
Tumors, which are usually benign (non-cancerous), may develop under or on the skin. These tumors may grow rapidly, remain unchanged, or show some signs of shrinking over time.
People with Proteus syndrome frequently have irregular and disorganized bone structure, including excessive bone growth, hardened connective tissue, and elongation of long bones with abnormal bone thinning.

Diagnosis

General: Due to the large range of symptoms that have been observed, Proteus syndrome is difficult to diagnose. A diagnosis can be made only through a physician's careful observation and using imaging studies. There are currently no known genetic tests to detect Proteus syndrome.
Physical exam: The diagnostic criteria for Proteus syndrome have not been clearly defined, and precise tests are not currently available. However, a rigorous physical exam may reveal random and disproportionate tissue overgrowth of arms, legs, hands, feet, fingers, toes, skull, vertebrae, spleen, or thymus. Greater or fewer than normal fat deposits may be present. Capillaries, veins, or lymph nodes may be improperly formed.
Characteristic facial features of Proteus syndrome patients include a long face, low nasal bridge (top of the nose), and a frequently open mouth.
Imaging: Imaging studies may include X-ray evaluations of the skull and bones; magnetic resonance imaging (MRI) of the limbs, nervous system, and abdomen; and computed tomography (CT) scans of the chest.

Complications

In some cases, life-threatening conditions relating to abnormal blood clotting may develop, including deep vein thrombosis (blood clots) and pulmonary embolism (blockage of lung artery).
Other complications may include central nervous system failure, tumors, lung disease, and obstructed vision.

Treatment

General: There is no cure for Proteus syndrome. Various treatments may reduce the risks of complications. Treatment is tailored to the particular symptoms present, which may vary widely from patient to patient.
Physical therapy: People with Proteus syndrome may benefit from physical therapy. The goal of physical therapy is to improve mobility, restore function, reduce pain, and prevent further injuries. Several techniques, including exercises, stretches, traction, electrical stimulation, and massage, are used. Not all physical therapy programs are suited for everyone and patients should discuss their medical history with qualified healthcare professionals before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a licensed physical therapist. Physical therapy may aggravate pre-existing conditions, for example, persistent pain and fractures of unknown origin have been reported after physical therapy, which can also increase pain duration or limit range of motion. Both morning stiffness and bone erosion have been reported in the literature, although the cause is unclear. Erectile dysfunction has also been reported. Any therapy recommended during pregnancy or breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.
Psychotherapy: In order to manage many aspects of the disease, both physical and emotional, individuals with Proteus syndrome may benefit from psychotherapy, an interactive process between a person and a qualified mental health professional. The patient will explore thoughts, feelings, and behaviors to help with problem solving. Psychotherapy cannot always fix mental or emotional conditions, and not all therapists are qualified to work with all problems. Psychological counseling for children with Proteus syndrome should be started at a young age. The Proteus Syndrome Foundation offers networking for families affected by the condition.
Surgery: People with Proteus syndrome may opt for surgical removal of tumors. Because they may grow back after removal, however, tumors are generally not removed unless they are life-threatening. Surgery to remove an overgrown portion of the bone should be performed only if the bony overgrowth affects normal functioning because this type of surgery can sometimes increase the growth of the remaining bone.

Integrative therapies

Note: Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Proteus syndrome. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider, and should not be used to replace other proven therapies or preventive measures.
Good scientific evidence:
Physical therapy: Physical therapy has been used to treat a wide variety of pain. The goal of physical therapy is to improve mobility, restore function, reduce pain, and prevent further injuries. Several techniques, including exercises, stretches, traction, electrical stimulation, and massage, are used. Not all physical therapy programs are suited for everyone and patients should discuss their medical history with qualified healthcare professionals before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a licensed physical therapist. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported after physical therapy, which can also increase pain duration or limit range of motion. Both morning stiffness and bone erosion have been reported in the literature, although the cause is unclear. Erectile dysfunction has also been reported. Any therapy recommended during pregnancy or breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.
Psychotherapy: A broad range of psychotherapies are effective for the treatment of depression, including behavioral therapy, cognitive-behavioral therapy, and interpersonal therapy. Psychotherapy may be successful in treating mild to moderate depression. In more severe cases, psychotherapy is considered best accompanied by prescription medication. Psychotherapy is an interactive process between a person and a qualified mental health professional. The patient will explore thoughts, feelings, and behaviors to help with problem solving. Psychotherapy cannot always fix mental or emotional conditions, and not all therapists are qualified to work with all problems. Psychological counseling for children with Proteus syndrome should be started at a young age. The Proteus Syndrome Foundation offers networking for families affected by the condition.

Prevention

The cause of Proteus syndrome is unknown. It is believed that spontaneous genetic mutations occur that cause the disease. It is not known if these mutations can be inherited or prevented.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Biesecker L, Happle R, Mulliken J, et alProteus syndrome: Diagnostic criteria, differential diagnosis, and patient evaluation.Am J Med Genet. 1999 Jun 11;84(5):389-95.
Biesecker L. The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet. 2006 Nov;14(11):1151-7.
Hoeger PH, Martinez A, Maerker J, et al. Vascular anomalies in Proteus syndrome. Clin Exp Dermatol. 2004 May;29(3):222-30.
National Institutes of Health Office of Rare Diseases. .
Natural Standard: The Authority on Integrative Medicine. .
Proteus Syndrome Foundation. .
Satter E. Proteus syndrome: 2 case reports and a review of the literature. Cutis. 2007 Oct;80(4):297-302.
Turner JT, Cohen MM Jr, Biesecker LG. Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases. Am J Med Genet A. 2004 Oct 1;130(2):111-22.
University of Kansas Medical Center .

Causes

The cause of Proteus syndrome is not known. Scientists believe that it is caused by a genetic mutation or defect that becomes apparent after birth. The mutation may involve tissue growth factors or their receptors or regulators, which may explain the disease's sporadic occurrence, randomly distributed tissue overgrowth, and wide range of symptoms.
No currently known genetic mutations cause Proteus syndrome. Several scientists initially reported a PTEN gene mutation in patients with Proteus syndrome. However, these patients were later determined to have a Proteus-like syndrome, such as Cowden syndrome or Bannayan-Riley-Ruvalcaba syndrome.

Risk factors

The cause of Proteus syndrome is unknown. It is believed to be caused by spontaneous genetic mutations, occurring randomly in previously unaffected families. It is not known if these mutations can be inherited or prevented.
Proteus syndrome affects both sexes equally and has no particular racial, ethnic, or geographical distribution.