Proteus syndrome

Definition

Proteus syndrome is characterized by excessive growth of cells. This can result in asymmetrical growth, benign (noncancerous) tumors, and pigmented skin lesions.

Description

Proteus syndrome is a rare condition. It was first described in 1979 by Michael Cohen. Hans-Rudolf Wiedemann named the condition after the Greek god Proteus, who could assume many forms. The disorder gained wide recognition when it became publicized that Joseph (John) Merrick, the person depicted in the movie The Elephant Man, probably had Proteus syndrome.

The excess growth of tissue that characterizes Proteus syndrome is progressive. It also tends to affect some tissues and not others. This can result in asymmetrical growth in the body, such as the skull, bones, spine, hands, feet, fingers, and toes. Proteus syndrome often results in overgrowth of one side of the body and not the other. Benign tumors on the surface of the skin or inside the body may also occur. Raised brown patches on the skin and an overgrowth of tissues on the soles of the feet or the palms of the hands are common. The types of tissues and organs that are affected and the severity of the effects vary from person to person and within the course of a lifetime. Proteus syndrome is sometimes associated with mental delay.

Genetic profile

The specific cause of Proteus syndrome is unclear. Proteus syndrome appears to occur randomly, suggesting that it is not inherited. Research suggests that Proteus syndrome results from an unknown gene that is changed (mutated) in some cells, but normal in other cells of the body. This is called mosaicism.

The tissues and organs that are affected in Proteus syndrome and the severity of effects probably depend on how many cells contain the mutated gene, and what type of cells contain it. Someone with many cells containing the changed Proteus gene are more likely to have more severe effects then someone with only a few cells changed. Someone with many cells changed in a particular part of the body, such as the hand, are more likely to have excessive growth in that area. The changed Proteus gene will affect cell growth even after the baby is fully developed, since cell division continues to take place and is necessary for the growth of tissues and organs and for the replacement of damaged cells. The changed Proteus gene mainly results in excessive growth of cells and tissues from infancy to adolescence.

Demographics

Only 100 to 200 cases of Proteus syndrome have been reported around the world. Both males and females are equally likely to be affected with Proteus syndrome.

Signs and symptoms

Individuals with Proteus syndrome can have a wide range of manifestations. The effects can also range from mild to severe. The most common manifestations of Proteus syndrome include:

• overgrowth of hands, feet, fingers, or toes (gigantism)
• overgrowth of one side of the limbs, face, or body (hemihypertrophy)
• overgrowth of the connective tissue on the soles of the feet or palms of the hand or, less commonly, in the abdomen or nose (connective tissue nevi)
• darkened, discolored, and often rough and raised patches of skin (skin surface nevi)
• benign tumors on the skin surface and under the skin
• benign tumors of the fat cells (lipoma) or areas of significantly decreased or increased body fat
• abnormalities of the skull resulting in a large or asymmetrical head
• benign bony growths projecting outward from the end of the bones (exostosis)

People with Proteus syndrome can have curvature of the spine. They may also have an enlarged spleen or thymus. Approximately 12–13% of people with the disorder have cystic abnormalities of the lungs, which can interfere with the normal functioning of the lungs. Abnormalities in the blood vessels called vascular malformations, which appear as pink or red patches on the surface of the skin, are common. About one third of people with Proteus syndrome are mentally impaired; skull abnormalities are often seen in those with impairment. People with Proteus syndrome can have a distinctive facial appearance, with a long and narrow face, down-slanting eyes, wide and forward-tipping nostrils, a low nose bridge, and a mouth that remains open when at rest. Many effects can result from the presence of tumors and bony growths that affect other organs and tissues.

Sometimes mild or moderate effects of Proteus syndrome, such as benign tumors, are present at birth. As a person grows and develops, the tissue overgrowth progresses and changes. This progression is often irregular; it is characterized by periods of major overgrowth and other periods of absent overgrowth. The effects therefore change over the course of a lifetime. However, most changes occur before adolescence, since tissue over-growth tends to plateau at that time.

Diagnosis

There is no blood test available to diagnose Proteus syndrome. A diagnosis can be made only by careful observation of the individual, perhaps over a period of time, and through imaging studies. These may include x ray evaluations of the skull and skeletal system; magnetic resonance imaging (MRI) of the limbs, nervous system, and abdomen; and computed tomography (CT) scans of the chest.

The great variability of Proteus syndrome from person to person makes it hard to diagnose. There are no definitive and universal diagnostic guidelines. Some tentative guidelines were established, however, at the First National Conference on Proteus Syndrome Diagnostic Criteria.

Treatment and management

There is no cure for Proteus syndrome. Treatment largely involves the management of effects of the disorder, such as the removal of tumors or bony overgrowths. Removal of tumors is not recommended, though, unless they are causing major problems, since these tumors usually grow back. Surgery to remove an overgrown portion of the bone should be performed only if the bony over-growth is affecting normal functioning. Bony over-growths in the ear, for example, may need to be removed if they are interfering with hearing. This type of surgery, however, can sometimes increase the growth of the remaining bone. Psychological counseling to help children with Proteus syndrome deal with the disorder should be considered. In order for counseling to be effective, it is preferable that it begins at a young age.

Prognosis

The long-term prognosis of Proteus syndrome is not known. The life expectancy is likely to vary greatly from person to person. Those with tumors and bony over-growths affecting critical organs are likely to have a poorer prognosis.

Resources

PERIODICALS

Barona-Mazuera, Maria, et al. "Proteus Syndrome: New Findings in Seven Patients." Pediatric Dermatology 14, no. 1 (1997): 1–5.

Biesecker, Leslie, et al. "Proteus Syndrome: Diagnostic Criteria, Differential Diagnosis, and Patient Evaluation." American Journal of Medical Genetics 84, no. 5 (1999): 389–95.

Cavero, Juan, Evelyn Castro, and Luz Junco. "Proteus Syndrome." International Journal of Dermatology 39 (2000): 698–709.

De Becker, Inge. "Ocular Manifestations in Proteus Syndrome." American Journal of Medical Genetics 92 (2000): 350–52.

Gilbert-Barness, Enid, Michael Cohen, and John Opitz. "Multiple Meningiomas, Craniofacial Hyperostosis and Retinal Abnormalities in Proteus Syndrome." American Journal of Medical Genetics 93 (2000): 234–40.

ORGANIZATIONS

Proteus Syndrome Foundation. 6235 Whetstone Dr., Colorado Springs, CO 80918. (719)264-8445. [email protected]. <http://www.kumc.edu/gec/support/proteus.html>.

WEBSITES

McKusick, Victor A. "Proteus Syndrome." Online Mendelian Inheritance in Man. http://www3.ncbi.nlm.nih.gov/li>htbin-post/Omim/dispmim?176920. (January 2001).

Proteus Syndrome Foundation. Proteus Syndrome Newsletter. <http://www.kumc.edu/gec/support/newslet2.html>.

Lisa Maria Andres, MS, CGC