An Overview of Proteus Syndrome

A rare genetic disorder that causes bone and other tissues to overgrow

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Proteus syndrome is an extremely rare genetic condition that causes tissues of the body, such as skin and bone, to overgrow. The overgrowth often happens disproportionately, and can severely change a person's appearance. The condition was named after the Greek god Proteus, who could take on different shapes at will.

Symptoms

Each person with Proteus syndrome is affected in different ways. Some people may have overgrown limbs while others experience overgrowth of the skull. While any part of the body can potentially be affected by the condition, the most common parts are bone, fat, and connective tissue. Blood vessels and internal organs can also be affected.

The symptoms and features of Proteus syndrome aren't present at birth. When the infant begins to grow, the condition will become apparent—typically between 6 and 18 months of age. The condition becomes more severe as the child continues to grow.

While the specifics of the condition vary, some features are typically seen in all patients who are diagnosed with Proteus syndrome.

Common Symptoms

The three characteristics common in people with Proteus syndrome include:

  1. Some parts of the body, such as the limbs or head, rapidly overgrow and are disproportionately large compared to other parts of the body. The pattern of growth usually happens in an asymmetric and "patchy" (mosaic) formation. Which parts of the body are affected will vary from person to person.
  2. Over time, the overgrowth gets more severe and can alter a person's appearance. As time goes on, a person may experience overgrowth in new areas.
  3. No one else in the person's family has the condition or any symptoms suggestive of it.

Other signs and symptoms of Proteus syndrome can include:

Some people with Proteus syndrome develop abnormalities in the central nervous syndrome which can lead to intellectual disability or seizure disorders.

People with Proteus syndrome also may have certain facial characteristics, such as a long face with wide nostrils, crossed eyes (strabismus), and drooping eyelids (ptosis). Some research suggests people with the distinctive facial features associated with Proteus syndrome are more likely to have neurological problems related to the condition. While the link between the two has been noted, it's not yet fully understood.

Causes

Proteus syndrome is not believed to be an inherited condition. Of the few hundred cases in medical literature, no person known to have Proteus syndrome has had a child with the condition.

Proteus syndrome is, however, caused by a genetic mutation. In 2011 researchers identified the gene responsible for Proteus syndrome: AKT1. The gene is involved in how cells grow and divide (proliferation) and may also keep cells from dying off when they're supposed to (apoptosis). Since it affects these cellular mechanisms, the gene has also been implicated in some forms of cancer.

Even though Proteus syndrome is linked to a gene, that doesn't mean a parent "gives" the condition to a child. The mutations happen spontaneously (sporadic) and in the early stages of fetal development.

The mutation in the AKT1 gene affects how cells grow, but not all cells will be affected by the mutation (called mosaicism). This results in some tissues growing normally and others developing the overgrowth characteristic of Proteus syndrome.

The specific symptoms a person has and their severity are usually in proportion to the ratio of normal and mutated cells they have.

How Genes Mutate and Cause Disorders

Diagnosis

Proteus syndrome is very rare: only a few hundred cases have been diagnosed worldwide and many researchers think the condition may actually be over-diagnosed. Other conditions that can cause asymmetrical or abnormal patterns of growth may be misdiagnosed as Proteus syndrome, meaning the true incidence of the disorder could be even rarer.

Doctors use a very specific set of guidelines to make a diagnosis of Proteus syndrome. Understanding the role that gene mutations play in the development of the condition has helped make the process of diagnosing it more accurate.

Together with the diagnostic criteria, which includes the presence of the physical characteristics, signs, and symptoms, a thorough workup that includes tissue biopsies, laboratory tests, imaging studies, and genetic testing is usually needed to diagnose Proteus syndrome.

Proteus syndrome was not described in medical literature until 1979. Since the condition is so rare, many doctors have never seen it. Even with strict diagnostic criteria, it can be difficult to diagnose the condition properly. Proteus syndrome does seem to affect men more often than women and has been seen in people of all racial and ethnic backgrounds.

One of the most notable cases of Proteus syndrome is that of Joseph Merrick, better known as "The Elephant Man." Throughout his life in the early 19th century, Merrick was thought to have neurofibromatosis. Many decades later, researchers now believe he actually had Proteus syndrome.

Why the Elephant Man Medical Mystery Stumped Physicians for 100 Years

Treatment

There is no cure for Proteus syndrome. Each person who has the condition will have different symptoms, and those symptoms will vary in severity. All patients with Proteus syndrome will need to work with a team of healthcare professionals to manage their medical care.

Health Needs

Some common health needs of people who have Proteus syndrome include:

  • Surgery to remove growths or excess skin
  • Dental problems, including malocclusion
  • Poor eyesight, crossed-eyes (strabismus), or vision loss resulting from neurologic disorders
  • Cosmetic procedures to correct areas of the body deformed by overgrowth
  • Monitoring of organ systems affected (heart, kidneys, brain, spine, etc)
  • Mental health, social, and educational support
  • Referrals to specialists who handle body systems that are more severely affected or that carry high risk of complications (for example: a vascular doctor that can monitor a person for blood clots or an orthopedist who can help address issues related to bone overgrowth)

Some complications of Proteus syndrome can be serious, even life-threatening. Blood clots, embolisms, and damage to internal organs can all put a person's life at risk. Rapid and relentless overgrowth of bones can require a person with Proteus syndrome to undergo many complex orthopedic procedures.

However, surgery comes with its own risks, especially for patients who are at risk of developing blood clots, as most with Proteus syndrome are. Due to this risk, deciding when, if ever, to operate can be a tricky decision for a physician to make.

Other potential problems, while they may not shorten lifespan, can certainly impact a person's quality of life. The overgrowth or growths caused by Proteus syndrome can severely alter a person's appearance. When one or more limb is affected, it can greatly impact a person's mobility. This, combined with neurological effects, may limit a person's ability to live independently. The social stigma of having a "different" appearance may cause emotional distress, anxiety, and depression.

While people with Proteus syndrome usually need a team of specialists to manage their care, since most doctors (such as general practitioners or internal medicine physicians) are not likely to have seen a case before in their career, management of a person's care is usually overseen by a specialist, such as a geneticist.

The need for routine care, follow-up, and close monitoring with specialists will depend on which areas of the body are affected, as well as the severity of a person's symptoms and the progression of the condition.

A Word From Verywell

Since Proteus syndrome is so uncommon, it can be difficult to diagnose correctly. Once a person has been diagnosed, treatment is mostly focused on addressing symptoms (which can range in severity from mild to debilitating and be physical, medical, and cosmetic) and prevent potentially life-threatening complications (such as pulmonary embolism or blood clots).

Managing Proteus syndrome can be difficult but is most successful when a person with the condition has the support of a team of medical professionals, including specialists, genetic counselors, and mental health professionals who can address all aspects of the person's life that have been affected by the condition.

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Article Sources
  • Proteus Syndrome. NORD (National Organization for Rare Disorders). Published 2018. Accessed October 10, 2018.

  • Biesecker L. The challenges of Proteus syndrome: diagnosis and management. European Journal of Human Genetics. 2006;14(11):1151-1157. DOI: 10.1038/sj.ejhg.5201638.

  • Lindhurst MJ, Sapp JC, Teer JK, et al. A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome. New England Journal of Medicine. 2011;365(7):611-619. DOI: 10.1056/nejmoa1104017.

  • Proteus syndrome. Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, National Center for Advancing Translation Medicine. Accessed October 10, 2018.