Proteus Syndrome

What is Proteus syndrome?

Proteus syndrome is a rare genetic condition that causes excessive growth of your bones, skin, organs and/or tissues. The disease causes parts of your body to grow out of proportion with the rest of it. The overgrowth is usually asymmetrical, meaning it affects the right and left sides of your body differently.

Newborn babies with Proteus syndrome usually don’t show any signs of the condition. The atypical growth starts to appear between the ages of 6 months and 18 months. It rapidly develops within 10 years and gets more severe as you age. Along with differences in your physical appearance, some people with Proteus may experience neurological issues. People with Proteus syndrome also have an increased risk of developing blood clots and tumors.

Proteus was the Ancient Greek god of change. Scientists named the condition Proteus syndrome because it can cause your body structures to change shapes over time.

Who does Proteus syndrome affect?

Proteus syndrome can affect anyone. But some studies show it affects men and people assigned male at birth slightly more often than women and people assigned female at birth.

How common is Proteus syndrome?

Proteus syndrome is an extremely rare condition that affects fewer than 1 in 1 million people around the world. It’s difficult to diagnose the disease because it’s so rare and other conditions also cause asymmetrical overgrowth. So, it’s hard to determine the true number of people with Proteus syndrome. Researchers believe some people go undiagnosed, while others are misdiagnosed with the condition. Overall, they believe less than a few hundred people worldwide have the disease.

What are the signs and symptoms of Proteus syndrome?

The first signs of Proteus syndrome usually appear between 6 months and 18 months of age when asymmetrical overgrowth begins. Asymmetric means it may affect one side of your body more than the other. The pattern and severity of overgrowth can vary greatly. It can affect almost any part of your body, including your bones, skin, organs and tissues. The condition rapidly progresses during your first decade of life.

The bones in your arms, legs, skull and spine may develop irregularly. Your arms and legs may grow to significantly different lengths. You may have a severe curvature of your spine (scoliosis). Overgrowth may eventually affect the mobility of your joints.

Proteus syndrome can also cause abnormal skin growths. Thick, raised lesions called cerebriform connective tissue nevus often form. They’re typically found on the soles of your feet but can also affect your hands. This kind of skin growth is rarely seen in any other condition.

Abnormal growth of your blood vessels, including your capillaries and veins, may occur. Overgrowth of fat (adipose tissue) can affect your stomach, arms and legs. Mostly benign (noncancerous) tumors consisting of fatty tissue (lipomas) may develop.

Some people with Proteus syndrome have neurological abnormalities as well. These may include:

• Intellectual disabilities.
• Seizures.
• Vision loss.

Proteus syndrome can cause distinctive facial features such as:

• A long face.
• The outside corners of your eyes point downward.
• A flat nose bridge with wide nostrils.
• An open-mouth expression.

What complications can develop due to Proteus syndrome?

The most life-threatening complication of Proteus syndrome is a type of blood clot called a deep vein thrombosis (DVT). DVTs affect the deep veins of your legs or arms most often, causing pain and swelling. If a DVT travels through your bloodstream to your lungs, it can cause a dangerous condition called pulmonary embolism. People with Proteus syndrome most often die due to pulmonary embolisms.

How do you get Proteus syndrome?

A change (mutation) in the AKT1 gene causes Proteus syndrome. The AKT1 gene helps control cell growth and division. A mutation in this gene disrupts a cell’s ability to control its own growth. This allows the cell to grow and divide abnormally, leading to the overgrowth traits seen in Proteus syndrome.

Proteus syndrome isn’t an inherited condition and doesn’t run in families. The genetic mutation occurs after the fertilization of the embryo (somatic mutation). It occurs early during pregnancy when one cell in a developing fetus spontaneously mutates. As the mutated cell grows and divides, some cells will have the mutation and others won’t. This is called a mosaic gene alteration. As the AKT1 gene mutation affects only some of your body’s cells, the disease only affects part of your body.

How is Proteus syndrome diagnosed?

Your healthcare provider will perform a physical examination to diagnose Proteus syndrome. They’ll use a specific checklist of characteristics of the condition. Three general characteristics of the disease must be present for your provider to consider the diagnosis. These include:

• Mosaic distribution: Mosaic distribution means the areas of excessive growth on your body are patchy. Some body parts show signs of overgrowth and others don’t.
• Sporadic occurrence: Sporadic occurrence means no one in your family has features of the condition.
• Progressive course: Progressive course means the overgrowth has changed the look of your affected body parts significantly over time.

In addition, your healthcare provider will look at other specific characteristics. You must have specific features from each category on your provider’s checklist for them to diagnose you with Proteus syndrome.

What tests will be done to diagnose Proteus syndrome?

The genetic mutation that causes Proteus syndrome isn’t present in every cell in your body. This can make genetic testing complicated because a blood sample may not contain the mutation or only contain small traces of it.

However, healthcare providers can find the mutated gene through DNA testing of a biopsy of some of your affected tissue. They’ll use DNA from the sample to look for the mutated gene.

Is there a cure for Proteus syndrome?

There’s no cure for Proteus syndrome. Proteus syndrome treatment consists of managing your specific symptoms. You may work with a team of healthcare providers to help with your individual medical needs.

An orthopaedic surgeon may treat issues with your bones. There are many treatments available to reduce bone overgrowth in your arms, legs, fingers and toes. They can correct issues with your spine and joints as well. You’ll see a blood doctor (hematologist) before any surgeries to evaluate your risk for blood clots.

You may see a skin doctor (dermatologist) for issues with fatty overgrowth and skin changes. You may need aggressive and frequent treatment. For some issues, your healthcare provider may recommend a “wait and see” approach. This means they’ll monitor your condition before moving forward with a particular treatment.

Other healthcare providers that may be involved in your care include:

• Rehabilitation medicine doctor (physiatrist).
• Lung doctor (pulmonologist).
• Physical therapist.
• Occupational therapist.
• A person who makes shoes and other orthotics (pedorthist).

Scientists only very recently discovered the genetic cause of Proteus syndrome. This could lead to advances in testing new drugs and other therapies to treat the condition.

How can I prevent Proteus syndrome?

You can’t prevent Proteus syndrome because it’s a genetic condition. The genetic mutation that caused the condition happened randomly during fetal development. Nothing that happened before or during pregnancy caused the condition.

What is the life expectancy for Proteus syndrome?

The outlook (prognosis) for Proteus syndrome varies widely based on your affected body parts and the severity of your condition. Complications can be life-threatening and more commonly lead to death than the condition itself. Complications may include deep vein thromboses, pulmonary embolisms and cancer. Pulmonary embolism is the most common cause of death among people with Proteus syndrome.

Overall, about 25% of people with Proteus syndrome die before the age of 22. However, people with mild symptoms have a generally good prognosis with effective treatment.

How do I live with Proteus syndrome?

Proteus syndrome can cause physical differences that can be frustrating and difficult to cope with. You and your family should learn as much as you can about the condition. Talking with other people dealing with the disease and listening to their stories can help you feel less alone and more understood. Ask your healthcare provider for resources to help you manage and cope with your condition.

A note from Cleveland Clinic

Finding out you or your child has a rare genetic condition can be overwhelming and scary. It can be especially difficult if the condition causes significant physical differences. So, it’s important to find a healthcare provider that can diagnose Proteus syndrome and assemble a team of specialists. With appropriate treatment, many people have a good prognosis. It’s also important to find a support network as you cope with this difficult diagnosis.