Proteus syndrome is currently classified as a very rare overgrowth syndrome with just a few hundred cases reported worldwide to date. The chief symptom is overgrowth of the skin and other tissues and the presence of tumors. Proteus syndrome only occurs in about one out of every one million births, and symptoms often don't present until the newborn has reached the age of 6 months.
Definition & Facts
Proteus syndrome gets its name from the Greek god Proteus, who was called the "god of change." The reference is to the marked physical changes that begin to unfold in association with Proteus syndrome.
Because of an international partnership between the National Institutes of Health (NIH), the Proteus Syndrome Foundation of the United States and its sister foundation in the United Kingdom, funding for research has yielded much useful information about what causes Proteus syndrome.
Symptoms & Complaints
A common symptom of Proteus syndrome is that the overgrowth is nearly always asymmetrical - that is, not even from one side of the body to the other (hemihypertrophy). Proteus syndrome can cause different kinds of overgrowth in affected individuals.
Here are some examples of common ways that Proteus syndrome-based overgrowth can be seen in an individual as the disorder develops:
- Overgrowth of bones (particularly in the limbs, spine and skull).
- Overgrowth of internal organs.
- Overgrowth of skin.
- Skin growths in various areas of the body.
- Abnormal growth of blood vessels and fat.
- Noticeable facial differences (including a long face, downward-slanted eyes, wide nostrils and low nasal bridge, open mouth at rest).
- Neurological disorders, including seizures, loss of vision, and sometimes disabilities of the intellect.
- Growth of benign tumors.
- Risk of deep vein thrombosis (DVT), a type of blood clot.
Because no two cases of Proteus syndrome tend to be identical, and the chief symptom of asymmetrical overgrowth is also a symptom of a number of other similarly rare disorders, it is important to take time to achieve an accurate final diagnosis by reviewing the individual's symptoms over a period of time.
Today it is known that Proteus syndrome is caused by a mosaic or unevenly occurring genetic mutation in a gene called AKT1. This gene is responsible for making a certain critical protein that controls if and how cells grow. Because the mosaic mutation of AKT1 does not occur in all cells of the body, the overgrowth seen in Proteus syndrome is asymmetrical. It occurs in some areas of the body and not in others.
Testing for Proteus syndrome is still problematic since the mutated version of AKT1 does not occur in all cells. The right set of cells must be gene sequenced during genetic testing in order to catch the mutation.
But because Proteus syndrome is not considered heritable but random, and to date no individuals who have Proteus syndrome have passed it on to their own children and the chances of having more than one child in a family born with Proteus syndrome is so low (less than 1 in 100), researchers are still working to better understand the cause of Proteus syndrome.
Diagnosis & Tests
Diagnosing Proteus syndrome has traditionally been done based on the appearance of three overarching characteristics:
- Mosaic pattern (unevenness) of overgrowth. Overgrowth appears random and asymmetrical across the individual's body.
- Random (sporadic) presentation. No other family members have symptoms of Proteus.
- Progressive symptoms. Symptoms progress and worsen over time.
However, since the discover of the mosaic gene mutation, the diagnostic process is already starting to change. Genetic testing is an important part of the diagnostic process, although it is not as simple as just running a gene sequence since the mutated gene may not be present in all cell matter equally. This means the diagnostic and testing process still predominantly relies on the above criteria and a checklist of symptoms.
Treatment & Therapy
Treatment for Proteus syndrome still focuses on managing symptoms at the moment, although this may change with earlier detection methods as genetic testing techniques develop further. Treatment typically requires a multi-disciplinary team of specialists, including the following team members:
- Dermatologist. For skin changes.
- Orthopedist. For bone overgrowth.
- Geneticist. For research and study purposes.
- Pediatrician. For children's general health issues.
- Internist. For issues related to tumor growth.
- Pulmonary specialist. For lung function.
- Physical/rehabilitative therapist. For physical therapy and movement assistance.
- Hematologist. For monitoring of DVT.
- Podiatrist. For foot and walking support devices (mobility aids).
The most immediate treatment need most individuals with Proteus syndrome have is monitoring to guard against the development of DVT. This can lead to a chief cause of death for Proteus patients - pulmonary embolism. Pulmonary embolism occurs when a DVT blood clot works itself loose and lodges in the lungs, often proving fatal.
Prevention & Prophylaxis
In the meantime, gene testing options may be preventative during the family planning process and it is expected to be helpful in earlier detection and definitive diagnosis of Proteus syndrome for prompt treatment.