Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Proteus syndrome

Reviewed June 2012

What is Proteus syndrome?

Proteus syndrome is a rare condition characterized by overgrowth of the bones, skin, and other tissues. Organs and tissues affected by the disease grow out of proportion to the rest of the body. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the condition. Overgrowth becomes apparent between the ages of 6 and 18 months and gets more severe with age.

In people with Proteus syndrome, the pattern of overgrowth varies greatly but can affect almost any part of the body. Bones in the limbs, skull, and spine are often affected. The condition can also cause a variety of skin growths, particularly a thick, raised, and deeply grooved lesion known as a cerebriform connective tissue nevus. This type of skin growth usually occurs on the soles of the feet and is hardly ever seen in conditions other than Proteus syndrome. Blood vessels (vascular tissue) and fat (adipose tissue) can also grow abnormally in Proteus syndrome.

Some people with Proteus syndrome have neurological abnormalities, including intellectual disability, seizures, and vision loss. Affected individuals may also have distinctive facial features such as a long face, outside corners of the eyes that point downward (down-slanting palpebral fissures), a low nasal bridge with wide nostrils, and an open-mouth expression. For reasons that are unclear, affected people with neurological symptoms are more likely to have distinctive facial features than those without neurological symptoms. It is unclear how these signs and symptoms are related to abnormal growth.

Other potential complications of Proteus syndrome include an increased risk of developing various types of noncancerous (benign) tumors and a type of blood clot called a deep venous thrombosis (DVT). DVTs occur most often in the deep veins of the legs or arms. If these clots travel through the bloodstream, they can lodge in the lungs and cause a life-threatening complication called a pulmonary embolism. Pulmonary embolism is a common cause of death in people with Proteus syndrome.

How common is Proteus syndrome?

Proteus syndrome is a rare condition with an incidence of less than 1 in 1 million people worldwide. Only a few hundred affected individuals have been reported in the medical literature.

Researchers believe that Proteus syndrome may be overdiagnosed, as some individuals with other conditions featuring asymmetric overgrowth have been mistakenly diagnosed with Proteus syndrome. To make an accurate diagnosis, most doctors and researchers now follow a set of strict guidelines that define the signs and symptoms of Proteus syndrome.

What genes are related to Proteus syndrome?

Proteus syndrome results from a mutation in the AKT1 gene. This genetic change is not inherited from a parent; it arises randomly in one cell during the early stages of development before birth. As cells continue to grow and divide, some cells will have the mutation and other cells will not. This mixture of cells with and without a genetic mutation is known as mosaicism.

The AKT1 gene helps regulate cell growth and division (proliferation) and cell death. A mutation in this gene disrupts a cell's ability to regulate its own growth, allowing it to grow and divide abnormally. Increased cell proliferation in various tissues and organs leads to the abnormal growth characteristic of Proteus syndrome. Studies suggest that an AKT1 gene mutation is more common in groups of cells that experience overgrowth than in the parts of the body that grow normally.

In some published case reports, mutations in a gene called PTEN have been associated with Proteus syndrome. However, many researchers now believe that individuals with PTEN gene mutations and asymmetric overgrowth do not meet the strict guidelines for a diagnosis of Proteus syndrome. Instead, these individuals actually have condition that is considered part of a larger group of disorders called PTEN hamartoma tumor syndrome. One name that has been proposed for the condition is segmental overgrowth, lipomatosis, arteriovenous malformations, and epidermal nevus (SOLAMEN) syndrome; another is type 2 segmental Cowden syndrome. However, some scientific articles still refer to PTEN-related Proteus syndrome.

Related Gene(s)

Changes in this gene are associated with Proteus syndrome.

  • AKT1

How do people inherit Proteus syndrome?

Because Proteus syndrome is caused by AKT1 gene mutations that occur during early development, the disorder is not inherited and does not run in families.

Where can I find information about diagnosis or management of Proteus syndrome?

These resources address the diagnosis or management of Proteus syndrome and may include treatment providers.

  • Gene Review: Proteus Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK99495)
  • Genetic Testing Registry: Proteus syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0085261)
  • Proteus Syndrome Foundation: Diagnostic Criteria and FAQs (http://www.proteus-syndrome.org/proteus-syndrome/faqs/)

You might also find information on the diagnosis or management of Proteus syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/proteus-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/proteus-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Proteus syndrome?

You may find the following resources about Proteus syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Proteus syndrome?

  • PS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Proteus syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Proteus syndrome?

adenoma ; adipose tissue ; arteriovenous ; benign ; cell ; cell proliferation ; complication ; connective tissue ; diagnosis ; disability ; embolism ; gene ; hamartoma ; incidence ; inherited ; lesion ; mosaicism ; mutation ; neurological ; ovarian ; proliferation ; pulmonary ; pulmonary embolism ; sporadic ; syndrome ; thrombosis ; tissue ; tumor ; vascular ; veins

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Biesecker L. The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet. 2006 Nov;14(11):1151-7. Epub 2006 Aug 2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16883308?dopt=Abstract)
  • Biesecker LG, Happle R, Mulliken JB, Weksberg R, Graham JM Jr, Viljoen DL, Cohen MM Jr. Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet. 1999 Jun 11;84(5):389-95. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10360391?dopt=Abstract)
  • Cohen MM Jr, Turner JT, Biesecker LG. Proteus syndrome: misdiagnosis with PTEN mutations. Am J Med Genet A. 2003 Nov 1;122A(4):323-4. (http://www.ncbi.nlm.nih.gov/pubmed/14518070?dopt=Abstract)
  • Cohen MM Jr. Proteus syndrome: an update. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):38-52. (http://www.ncbi.nlm.nih.gov/pubmed/16010681?dopt=Abstract)
  • Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O'Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG. A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med. 2011 Aug 18;365(7):611-9. doi: 10.1056/NEJMoa1104017. Epub 2011 Jul 27. (http://www.ncbi.nlm.nih.gov/pubmed/21793738?dopt=Abstract)
  • 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;130A(2):111-22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15372514?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2012
Published: November 17, 2014