Stone man’s disease, or progressive ossifying fibrodysplasia (FOP) is a very rare and severely disabling genetic disease. The muscles and tendons of affected people gradually ossify: the body is gradually trapped in a bone matrix. There is currently no cure, but the discovery of the offending gene has paved the way for promising research.

Definition

Progressive ossifying fibrodysplasia (PFO), better known under the name of stone man disease, is a severely crippling hereditary disease. It is characterized by congenital malformations of the big toes and by progressive ossification of certain extraskeletal soft tissues.

This ossification is said to be heterotopic: qualitatively normal bone is formed where it does not exist, within striated muscles, tendons, ligaments and connective tissues called fascias and aponeuroses. Eye muscles, diaphragm, tongue, pharynx, larynx and smooth muscles are spared.

Stone man’s disease progresses in flare-ups, which gradually reduce mobility and independence, leading to ankylosis of the joints and deformities.

Causes

The gene in question, located on the second chromosome, was discovered in April 2006. Called ACVR1 / ALK2, it governs the production of a protein receptor to which growth factors that stimulate bone formation bind. A single mutation – one “letter” “mistake” in the genetic code – is enough to trigger the disease.

In most cases, this mutation appears sporadically and is not passed on to the offspring. However, a small number of hereditary cases are known.

Diagnostic

Diagnosis is based on physical examination, supplemented by standard x-rays that show bone abnormalities. 

A medical genetic consultation is useful to benefit from the molecular study of the genome. This will make it possible to identify the mutation in question in order to benefit from adequate genetic counseling. Indeed, if the classic forms of this pathology are always linked to the same mutation, atypical forms associated with other mutations remain possible.

Prenatal screening is not yet available.

The people concerned

FOP affects less than one in 2 million people worldwide (2500 cases diagnosed according to the Association FOP France), without distinction of sex or ethnicity. In France, 89 people are today concerned.

The signs of the disease are progressive onset. 

Deformities of the big toes

At birth, children are normal except for the presence of congenital malformations of the big toes. Most often, these are short and deviated inward (“false hallux valgus”), due to a malformation affecting the 1st metatarsal, the long bone of the foot articulated with the first phalanx.

This malformation can be associated with a mono phalangism; sometimes, too, this is the only sign of the disease. 

Pushes

The successive ossifications of muscles and tendons generally occur in the first twenty years of life, following a progression from the upper body downwards and from the back to the anterior face. They are preceded by the appearance of more or less hard, painful and inflammatory swelling. These inflammatory flare-ups can be precipitated by trauma (injury or direct shock), intramuscular injection, viral infection, muscle stretching, or even fatigue or stress.

Other anomalies

Bone abnormalities such as abnormal bone production in the knees or fusion of the cervical vertebrae sometimes appear in the early years.

Hearing loss can appear from puberty.

Evolution

The formation of a “second skeleton” gradually reduces mobility. In addition, respiratory complications may appear as a result of progressive ossification of the intercostal and back muscles and deformities. The loss of mobility also increases the risk of thromboembolic events (phlebitis or pulmonary embolism).

The average life expectancy is around 40 years.

At present, no curative treatment is available. The discovery of the gene in question, however, allowed a major advance in research. The researchers are exploring in particular a promising therapeutic route, which would make it possible to silence the mutation of the gene by using the interfering RNA technique.

Symptomatic treatment

Within the first 24 hours of an outbreak, high dose corticosteroid therapy may be initiated. Administered for 4 days, it can provide some relief to patients by reducing the intense inflammatory and edematous reaction observed in the early stages of the disease.

Pain relievers and muscle relaxants can help with severe pain.

Patient support

All the necessary human and technical aids must be implemented to allow people suffering from the disease of the stone man to maintain a maximum of autonomy and to integrate educationally then professionally.

Unfortunately, preventing the onset of FOP is not possible. But precautionary measures can be taken to slow down its development.

Prophylaxis of relapses

Education as well as environmental adjustments should be aimed at preventing injuries and falls. Wearing a helmet may be recommended for young children. 

People suffering from stone man disease should also avoid exposure to viral infections and be very careful with their dental hygiene, as invasive dental care can cause flare-ups.

Any invasive medical procedure (biopsies, surgical procedures, etc.) is prohibited except in cases of extreme necessity. Intramuscular injections (vaccines, etc.) are also excluded.

Physical therapies

The mobilization of the body by gentle movements helps to fight against the loss of mobility. In particular, swimming pool rehabilitation can be beneficial.

Respiratory training techniques are also useful in preventing respiratory deterioration.

Other measures

• Hearing monitoring
• Prevention of phlebitis (raised lower limbs when lying down, compression stockings, low-dose aspirin after puberty)