Proteus syndrome results from assymetric and patchy overgrowth of various tissues including bones and connective tissues. Most of the time there are no signs at birth. The overgrowth is usually not cancerous but can cause significant medical issues related to function, appearance and compression of blood vessels and organs. Most people with Proteus syndrome have a variant seen in the AKT1 gene in some, but not all cells of the body. There is no cure or specific treatment for Proteus syndrome and treatment involves medical and surgical management of symptoms.
There is usually no sign of Proteus syndrome at birth but the overgrowth starts within the first 1-2 years of life and is progressive. The overgrowth is in a patchy (or mosaic) pattern. Bones, skin and fat are most often involved. There may also be capillary malformations or prominent veins; arteriovenous malformations (AVMs) are rare. Cerebriform connective tissue nevi are very characteristic of Proteus syndrome and are almost never seen in other conditions. These are firm skin overgrowths that have deep grooves that make them look like the surface of the brain (which is why they are called cerebriform). These are usually not present until later in childhood. Legs may be sufficiently assymetric to cause difficulty walking and surgery may be recommended. Other bone and spinal deformities may occur and require close monitoring and evaluation for medical and surgical interventions. The overgrowth can cause problems with blood flow and result in blood clots in the legs or lungs, which can be life-threatening. The disfigurement may also cause psychosocial challenges.
The diagnosis may be suspected based upon physical examination. Plain x-rays should demonstrate bony overgrowth seen in Proteus syndrome but usually not seen in other overgrowth conditions. Confirmation of the diagnosis should be done by DNA testing of AKT1 from tissue biopsied from an affected body part.
Clinical exam. The physical examination includes monitoring overgrowth of body parts as well as assessments of function. Management to prevent and monitor for blood clots is needed.
Imaging. Imaging studies (x-rays) are often important to assess and monitor areas of overgrowth. No one type of imaging is best for everyone with Proteus syndrome. Some individuals may even need multiple types of imaging studies to look at different body parts or different types of overgrowth (fatty overgrowth, bone overgrowth, etc.).
Pathology. The AKT1 gene regulates growth of cells in the body. The genetic change in this gene causes the cells that have the change to grow too much and also may cause certain types of cells/tissues to grow in the wrong place.
Genetics. The genetic change in AKT1 is often only seen in cells of affected body parts and not in the blood. A biopsy (or more than one biopsy) from an area of overgrowth should be obtained for DNA testing to confirm the diagnosis.
Because individuals with Proteus syndrome may have different body parts affected in different ways, treatments may also vary between individuals. Your doctors will talk with you about what treatment, if any, is best for your child. Possible treatments may include surgeries to slow the growth of an arm or leg or remove overgrown tissues, if this is causing problems. Sclerotherapy to treat an abnormal vein or arteriovenous malformation may be recommended. Regular monitoring with imaging and laboratory studies to look for blood clots is most important, as this is the major cause of life-threatening problems.