Fibrodysplasia ossificans progressiva (stone man syndrome) is an extremely rare autosomal-dominant disease in which the connective tissues and muscles gradually turn into bone.
Fibrodysplasia ossificans progressiva (FOP) is a rare disorder (only one person in 2 million people in the world is affected) that causes gradual permanent substitution of the muscles and connective tissues (tendons and ligaments) by the bone tissue. This process of bone development in places where normally there are no bone tissues is known as heterotopic ossification. The disease onset takes place in early childhood, the first evidence of heterotopic bone formation may be noticed in the neck and shoulder girdle. Eventually, almost every joint may be affected. The prognosis for ill individuals is poor, the disease results in disability and reduces a person’s lifespan.
The disorder is caused by a mutation in the ACVR1 gene that is responsible for normal growth and development of the skeleton and connective tissues – the function that is disrupted in fibrodysplasia ossificans progressiva. It appears that in FOP the receptor coded by the ACVR1 gene is constantly activated causing abnormal ossification of the tissues that shouldn’t be replaced by the bone.
Fibrodysplasia ossificans progressiva is an autosomal dominant condition – it means that if a person has even a single copy of the mutated gene he/she may develop the disease and one of the parent’s had suffered from this disease as well. However, in many cases, the disease is caused by the so-called sporadic mutation – a spontaneous new mutation in the gene.
As it was already mentioned, the disease manifests early in childhood. Kids usually have hallux valgus (big toes deformity also referred to as a bunion) and short thumbs that may be suggestive of the diagnosis. Other skeletal deformities may also be present at birth. Gradually muscles, ligaments, and tendons are replaced with the bone (get ossified), usually starting from the muscles of the neck and shoulders. Eventually, abnormal ossification restrains mobility and elasticity of the body – it becomes rigid, movement in some joints is limited whereas the other joints may become completely immobile.
Even minor traumas, invasive procedures, and any viral infections provoke soft tissue edema and inflammation with subsequent bone formation at the sites of injury. These episodes are considered disease flare-ups and may last up to several days. People with FOP experience eating problems due to the inability to open the mouth leading to severe malnutrition. Breathing issues may also arise as the abnormal bones will restrict the mobility of the rib cage and limit lung inflation.
Fibrodysplasia ossificans progressiva can be diagnosed by a physician after history taking and assessment of plain X-ray scans showing abnormal bones.
Genetic testing to detect the ACVR1 mutation are also available.
There is no curative treatment for the disease. In order to delay the FOP progression low-calcium diet, glucocorticosteroids and bisphosphonates were proposed. It is recommended to start short-courses of corticosteroids every time when there is evidence of inflammation (disease flare-up) in order to prevent further ossifications. Moreover,
The life expectancy of individuals with fibrodysplasia ossificans progressiva is shortened. In general, their lifespan is about 40 years. Furthermore, quality of life is significantly reduced and many of them are wheelchair-bound due to breathing difficulties and body rigidity.