This disease traps the human body in a second ectopic skeleton.
Stone Man disease or Fibrodysplasia Ossificans Progressiva (FOP) is a extremely rare genetic diseasethe frequency of which is estimated at approximately 1 in 700,000 people. It is characterized by the occurrence ofprogressive ossification within the muscles, tendons and ligaments of the body.
“Signs of fibrodysplasia ossificans progressiva manifest from birth, with a deformation of the big toes which are deviated inwards and shortened (hallux valgus), explains Dr Geneviève Baujat, pediatric geneticist at Necker Hospital and specialist member of the FOP France association. During the first decade of life, before the age of 10, successive inflammatory attacks occur: they will lead to the formation of heterotopic bone, that is to say ossification present outside the normal skeleton. This heterotopic bone will develop at the level of the muscles and entheses (tendons, ligaments and aponeuroses of the muscles), in a characteristic way: it generally begins in the upper back, then progressively descends into the lower back, going from posterior to anterior and from the cephalic pole to the caudal pole, that is to say that the abnormal ossification will go from top to bottom and from back to front.” These inflammatory flare-ups vary greatly from one person to another (in terms of number and frequency) and will, or will not, result in heterotopic bone. On average, it is estimated that 80% of outbreaks result in heterotopic ossification. “Heterotopic bone causes a increasing limitation of patient mobility : ankylosis at the articular and segmental level, namely at the level of the trunk, limbs, hips, shoulders, jaw and cervical region. Patients are gradually enclosed in a second skeleton which develops little by little and will disintegrate them”, she continues.
The cause is genetic. It is almost always due to the same mutation (pathogenic variant) at the level of the ACVR1 gene which codes for a protein which is a transmembrane receptor, acting on the BMP pathway, proteins very important for ossification. “There mutation accelerates the ossification process abnormally in terms of location and temporality, under the influence of factors not yet fully elucidated, including immunological factors. In other words, there is a process of triggering bone production in a location that is not the right one”, specifies the pediatric geneticist.
“The diagnosis is often made when the child’s first attacks are observed and a swelling suddenly appears, generally in the upper back, in the shoulder blade region or at the neck, as if the child had received a big blow,” indicates the specialist. This is followed by a localized stiffness which can sometimes be painful. At the same time, the doctor notes a malformation of the big toes with hallux valgus. It differs from classic hallux valgus in that it is shortened and congenital, i.e. present from birth. “We are trying to provide education so that there is systematic detection of this hallux valgus during the examination of the newborn”she adds.
“Preventative measures are very important because flare-ups are often triggered by external factors. Any muscle injury will lead to these flare-ups and therefore this abnormal ossification,” notes Dr. Geneviève Baujat from the outset. In young children, muscle injuries are often linked to vaccination, a biopsy or even surgery. A viral infection can also cause inflammation that will be responsible for the growth of heterotopic bone. Prevention lies in limiting these triggering factors and avoiding falls, which also often cause a series of growths.
“Intellectual capacities are quite normal, even sharp”
Drug treatments : flare-ups should be treated as early as possible with two types of anti-inflammatory drugs: steroidal anti-inflammatory drugs (corticosteroids) and non-steroidal anti-inflammatory drugs, which are used differently depending on the location of the flare-up, according to a well-established treatment plan. “This helps to limit the intensity of the inflammation and to limit the installation of heterotopic bone, even if it does not completely prevent their development.” comments our expert.
Additional measures : for example at the dental level to avoid cavities; physiotherapy to learn to move, breathe and manage balance (proprioception) because movement limits the progression of heterotopic bone. Finally, the implementation of adaptation measures at home and in living spaces such as school, college and later professional life.
“Of new therapies are beginning to emerge : these are anti-ossifiers which are currently in the therapeutic trial phase with promising results. It will not be a magic wand from the outset, but these drugs should make it possible to significantly slow the progression of this pathology,” rejoices the specialist member of the FOP France association.
Today, thelife expectancy is said to be 56 years but there is actually a great deal of variability from one person to another, particularly depending on the intensity of the inflammation, the location of the flare-ups and the progression of the disease with the amount of heterotopic bone that forms. “Note that people with FOP have completely normal or even heightened intellectual abilities through the experience of this pathology. All measures aimed at promoting inclusion in the school and socio-professional environment are fundamental, with life support adapted to each person’s situation”, insists Dr Geneviève Baujat.
Link to the French Association on Fibrodysplasia Ossificans Progressive: www.fopfrance.fr