Fibrodysplasia ossificans progressiveM61.1
Synonym(s)
HistoryThis section has been translated automatically.
Münchmeyer E 1869; Guy godmother 1692
DefinitionThis section has been translated automatically.
Rare (about 600 cases have been described worldwide), severe, autosomal dominant inherited systemic disease with progressive ossification of the connective and supporting tissue of the human body. Clinically it is characterized by congenital malformations of the big toes and a progressive, extraosseous, heterotopic ossification with qualitatively normal bone.
Occurrence/EpidemiologyThis section has been translated automatically.
Prevalence is estimated at <1: 2 million individuals. All ethnic groups and geographical regions are equally affected. W:m=1:1.
EtiopathogenesisThis section has been translated automatically.
Classical FOP is caused by a recurring activating mutation (617G>A; R206H) in the ACVR1/ALK2 gene (2q24.1), which codes for the activin A receptor type I/for the activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor. In atypical FOP patients, heterozygous ACVR1 missense mutations of conserved amino acids are also found. This leads to calcification after the most banal traumas and subsequently to heterotopic ossification. These ossification foci are palpable in the musculature as hard plaques or nodes. The ossifications increase over years, so that the body slowly stiffens. Those affected become wheelchair-bound.
Clinical featuresThis section has been translated automatically.
During the first decade of life sporadic episodes of painful soft tissue swelling (so-called flare-ups) occur. These are caused by injuries to the soft tissues, e.g. after banal trauma or after intramuscular injections, after viral infections, muscle strain. First affected are the muscles and the connective and supporting tissues of the neck and shoulders. Later, arms, chest, abdomen, pelvis, legs and feet are involved. With advancing age, most patients experience a restriction of lung function due to the reduced mobility of the chest. In addition, banal injuries to muscle tissue can induce extraosseous bone growth.
DiagnosisThis section has been translated automatically.
Already prenatally, shortened and twisted big toes can be detected by songropahy. The suspected diagnosis can also be confirmed by molecular genetics by detecting the mutation of ACVR1/ALK2. The newborns appear normal except for a hallux valgus, a malformed first metatarsal and/or monophalangia.
TherapyThis section has been translated automatically.
At the moment there is no reliable therapy for treatment. A short 4-day high-dose corticosteroid therapy, if started within the first 24 hours of the eruption, can reduce the severe inflammation seen in the early stages of the disease. Prophylaxis must focus on the prevention of falls, viral infections. Stimulating breathing exercises are important.
Progression/forecastThis section has been translated automatically.
The average service life is 40 years. Most patients are wheelchair-bound at the end of the second decade of life. The most common cause of death is complications due to restricted mobility of the thorax
LiteratureThis section has been translated automatically.
- Bauer AH et al (2018) Fibrodysplasia ossificans progressiva: a current review of imaging findings. Skeletal radiol 47:1043-1050.
- Kaplan FS et al (2008) Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol 22: 191-205.
- Pignolo RJ et al (2013) Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons. Pediatric Endocrinol Rev 10 Suppl 2:437-48.
- Sferopoulos NK et al (2017) Myositis ossificans in children: a review. Eur J Orthop Surg Traumatol 27:491-502.