Proteus syndrome

Proteus syndrome is also known as elattoproteus syndrome and elephant man disease. The syndrome became widely recognised after the release of the movie “The Elephant Man”, a screenplay depicting the life of Joseph Merrick who was thought to have neurofibromatosis, but is now believed to actually have had severe Proteus syndrome.

A German paediatrician named the syndrome in 1983 after the Greek god Proteus, who had the ability to change his body into different shapes.

What is Proteus syndrome?

Proteus syndrome is an extremely rare genetic disorder that is characterised by the abnormal growth of bones and blood vessels, and various skin lesions including lipomas, epidermal naevi and café au lait macules. The condition is usually not evident until late infancy or early childhood when signs and symptoms start to appear. Overgrowth of different body parts is progressive with time.

The disease occurs sporadically and rarely arises in siblings or other family members.

The gene involved was identified in 2011, AKT1. The mosaic alteration or mutation in the AKT1gene leading to this syndrome is thought to occur soon after conception. The abnormal gene is present in some cells, where it makes a abnormal protein that increases cell proliferation. Unaffected cells behave normally.

What are the signs and symptoms of Proteus syndrome?

Every patient described with Proteus syndrome presents slightly differently, but the features described below occur in many of them.

Abnormal bone and soft tissue development

• Overgrowth of limbs, digits (fingers and toes) and skull. Overgrowth is usually disproportionate and asymmetric.
• Scoliosis (curvature of the spine) from abnormal vertebral growth
• Disproportionate overgrowth and focal atrophy (wasting away) of the upper arm muscles and neck, leading to the “hunched-over” look

Abnormal skin and connective tissue development

• Raised rough skin (verrucous epidermal naevi) or flat, soft variety of epidermal naevi
• Deep lines and overgrowth of soft tissue on the soles of the feet (cerebriform connective tissue naevi)
• Local overgrowth of fat (lipomas) or invasive lipomas that produce large intra-abdominal or intrathoracic lesions that can be medically dangerous
• Abnormal growth of blood or lymphatic vessels (vascular malformations) can create vascular lesions such as port wine stains or lymphatic malformations.
• Café au lait macules are often present

Common facial features include:

• Prominent occiput (enlarged back of the head)
• Drooping eyelids
• Low nasal bridge and wide, upturned nostrils
• Long, narrow face
• Open mouth at rest

Internal organs affected include the spleen and thymus, which can become enlarged. The condition also causes quite significant physical disfigurement and learning disabilities or developmental delays. Affected individual's are prone to blood clots (thrombosis, embolus).

What is the treatment for Proteus syndrome?

There is no specific treatment for Proteus syndrome. The condition should be managed by identifying early any serious medical problems and providing prophylactic and symptomatic treatment. A multidisciplinary team of doctors is required to manage Proteus syndrome. This should include and orthopaedist, craniofacial surgeon, plastic surgeon, dermatologist, dentist, neurosurgeon, geneticist, and psychologist.

Management of skin abnormalities may include:

• Periodic evaluation of lesions to ensure lipomas and vascular malformations do not become a problem locally or internally
• Removal of cutaneous vascular markings such as port wine stains and capillary haemangiomas using laser treatment
• Surgical excision of lesions if they interfere with functional activities or for cosmetic purposes.