What Causes Proteus Syndrome? Are there Genes that Cause Proteus Syndrome?

Signs of Proteus Syndrome

There are no obvious signs of Proteus syndrome at birth; it is a progressive condition and problems develop over time. Some of these are: –

  • Overgrowth of skin, muscles, fatty tissues, blood and lymphatic vessels
  • Unusually large hands, feet, head
  • Benign tumours called lipomas
  • Raised rough skin
  • Deep lines on the soles of the feet
  • Deep vein thrombosis – which can be life threatening if the blood clots move to the heart or lungs

Proteus syndrome was first identified by Dr Michael Cohen in 1979. The name of the syndrome comes from Greek mythology and the god Proteus who could change his shape at will.

Causes of Proteus Syndrome

Josephmerrick1889 - image in the public domain

At the time of writing (Oct 2009) the exact cause of Proteus syndrome is unknown. The cause of some overgrowth disorders have been established i.e. Simpson-Golabi-Behmel syndrome is caused by mutations in the glypican-3 gene. The gene is one of six that belong to the glypican family and are believed to play a role in cell growth, and in shaping tissues and organs. However, no genetic link has been made with Proteus syndrome.

It has been estimated that the chances of an individual contracting the disorder is less than one in a million, even if a family member has the condition. There are no cases that have been recorded of a parent passing on the Proteus syndrome disorder to their children.

Some researchers have identified mutations in a gene called PTEN. It codes for a protein called phosphatase and tensin homolog and it acts to suppress tumours. Mutations in the gene are also involved in many cancers – where the cell cycle goes out of control. However, there is some debate about the role of PTEN in Proteus syndrome as other scientists have found no PTEN mutations in individuals with Proteus syndrome.

Another gene that has been suspected of causing the condition is the GPC3 gene. It is a member of the glypican family of genes which are involved in cell proliferation and tissue growth. Though here too some researchers have cast doubt over its involvement. The conclusion of a 2004 paper titled "Mutation analysis of the tumor suppressor PTEN and the glypican 3 (GPC3) gene in patients diagnosed with Proteus syndrome" by WD Foulkes et al was that neither PTEN nor GPC3 are likely to have major roles in the development of Proteus syndrome.

Future Research

Knowing the genetic causes of the condition could help with the development of drugs to target some of the symptoms, as well as finding answers as to why and how the syndrome occurs in the first place. As it is a progressive disease knowing which gene or genes involved could help scientists to develop ways of stabilizing it and stopping the disease from progressing any further. An ongoing research study of patients with Proteus syndrome is being carried out by the National Institutes of Health in Bethesda, Maryland, USA. As of October 2009 they are still recruiting participants.