Proteus syndrome

What causes Proteus syndrome?

Proteus syndrome is caused by mutations in the AKT1 gene. These mutations are not inherited from a parent, but arise 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 others will not. Therefore, people with Proteus syndrome have an altered AKT1 gene only in some of their cells. This mixture of cells with and without a genetic mutation is known as mosaicism. The AKT1 gene codes a protein that 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. The mutated gene makes an abnormal protein. The mutation in the AKT1 gene is known as “c. 49G>A, p.Glu17Lys,” and it is a type of an “activating mutation.” This means that the AKT1 gene has a “spelling error” that causes an abnormally active protein to be made in the body. This active protein is thought to increase rates of cell growth and may prevent cells from dying off when they naturally would. Increased cell proliferation in various tissues and organs leads to the abnormal growth characteristics and to an increased risk to develop tumors.

Last updated on 05-01-20

How might Proteus syndrome be diagnosed?

The diagnosis of Proteus syndrome is based on clinical criteria that include three general characteristics and a specific symptom checklist. A mutation in the AKT1 gene can be identified in more than 90% of people meeting the diagnostic criteria.

There are three general characteristics or features that must be present for doctors to consider a diagnosis of Proteus syndrome:

  1. Mosaic distribution: This means that the areas of overgrowth are patchy and that only some body parts show signs of overgrowth while others are unaffected.
  2. Sporadic occurrence: This means that no one else in the affected person’s family has similar features of overgrowth.
  3. Progressive course: This means that the overgrowth has noticeably altered the appearance of the affected body parts over time or that new areas of overgrowth have appeared over time.

If a person has all three of these general characteristics in addition to some specific characteristics, doctors may consider a diagnosis of Proteus syndrome.

The specific characteristics are grouped into three categories: A, B, and C. A diagnosis of Proteus syndrome requires all three general features to be present and either one feature from Category A, or two features from Category B, or three features from Category C:

Category A: Cerebriform connective tissue nevus, which are skin lesion characterized by deep grooves and gyrations as seen on the surface of the brain.

Category B:

  • Patches of skin caused by an overgrowth of cells in the outermost layer of skin (Linear epidermal nevus)

  • Asymmetric, disproportionate overgrowth (at least one of the following):

    • Limbs
    • Hyperostosis of the skull
    • Hyperostosis of the external auditory canal
    • Megaspondylodysplasia
    • Viscera: spleen/thymus
  • Specific tumors before being 20 years old of age

    • Bilateral ovarian cystadenoma (a type of benign tumor in the ovary)
    • Parotid monomorphic adenoma (a benign tumor in s salivary gland)

Category C

  • Abnormal growth and/or distribution of fat (dysregulated fatty tissue overgrowth) (either of the following):
    • Fatty tumours (lipomas)
    • Lack of fat under the skin (regional lipohypoplasia)
  • Vascular malformations (differences in the blood vessels, veins, or capillaries or vessels of the immune system called the lymphatic vessels) including one of the following:
    • Capillary malformation
    • Venous malformation
    • Lymphatic malformation
    • Lung bullae
  • Facial features (all of the following):
    • A long and narrow head (dolichocephaly)
    • Long face
    • Down slanting palpebral fissures and/or minor dropping of the eyelids (ptosis)
    • Depressed nasal bridge
    • Wide or opening nares
    • Open mouth at rest

Last updated on 05-01-20

How can I learn about research opportunities at the National Institutes of Health (NIH) that are enrolling children with Proteus syndrome?

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a clinical trial titled "Study of Proteus Syndrome and Related Congenital Disorders" that may be of interest to you. Click here to view the study abstract. Review the "eligibility" criteria to determine its appropriateness. Use the study’s contact information to learn more.

You can check this site for regular updates. To do so, visit ClinicalTrials.gov and use "Proteus syndrome" as your search term.

You can also contact the Patient Recruitment and Public Liaison (PRPL) Office at the National Institutes of Health (NIH). We recommend calling the toll-free number listed below to speak with a specialist, who can help you determine if your child is eligible for any clinical trials.

Patient Recruitment and Public Liaison Office
NIH Clinical Center
Bethesda, Maryland 20892-2655
Toll-free: 800-411-1222
Fax: 301-480-9793
Email: prpl@mail.cc.nih.gov
Web site: http://clinicalcenter.nih.gov/

ClinicalTrials.gov provides a helpful guide for information about participating in a clinical trial. Resources for travel and lodging assistance are listed on the National Center for Advancing Translational Sciences Office of Rare Diseases Research (NCATS-ORDR) website, part of the National Institutes of Health (NIH).

Last updated on 05-01-20

How might Proteus syndrome be treated?

Each person with Proteus syndrome will have different medical needs that require individualized treatment. Many patients with Proteus syndrome are followed by several specialists such as a geneticist, a pediatrician, a dermatologist, and others.

Treatment of the overgrowth include orthopedic procedures to delay or stop linear bone growth and correction of skeletal deformities such as scoliosis. Developmental intervention or special education is suggested for developmental delays. Because any organ or tissue can be affected, the affected person should be monitored for any possible complication. The following are recommended: monitoring for and treating vascular problems, such as blood clot (thrombus) that forms within a vein (vein thrombosis) and blockage of an artery in the lungs by a blood clot (pulmonary embolism); monitoring and treating the lung disease; and routine monitoring for evidence of tumor development with management of the skin problems, especially for the lesions known as cerebriform connective tissue nevi.

Last updated on 05-01-20

Selected Full-Text Journal Articles

Proteus syndrome

Biesecker L. The challenges of Proteus syndrome: diagnosis and management. European Journal of Human Genetics. 2006; 14: 1151–1157.

Last updated on 04-27-20

Where To Start

Contact

Contact a Family is a UK-wide charity providing advice, information and support to individuals affected by various health conditions. They enable parents, families, and individuals to get in contact with others, on a local, national, and international basis. Each year they reach at least 275,000 families. Click on Contact a Family to view their information on Proteus syndrome.

Last updated on 04-27-20

Proteus Syndrome Foundation

The Proteus Syndrome Foundation Web site provides information on this syndrome. Click on the link to view the information page.

Last updated on 04-27-20

DermNZ Proteus syndrome

The New Zealand Dermatolgical Society's Web site has information on Proteus syndrome. Click on the link above to view this information page.

Last updated on 04-27-20

Name: Proteus Syndrome Foundation 6235 Whetstone Drive
Colorado Springs, CO, 80918, United States
Email: http://www.proteus-syndrome.org/contact/ Url: http://www.proteus-syndrome.org
Name: Proteus Syndrome Foundation, UK Tracey Whitewood-Neal, Chair 2 Watermill Close
Bexhill-on-Sea East Sussex TN39 5EJ
United Kingdom
Phone: 01424 736640 Email: tracy.whitewood_neal@virgin.net Url: http://www.proteus-syndrome.org.uk/
Proteus syndrome Genetics Home Reference (GHR). June 2012; Reference Link

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