Abstract
Abstract Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant genetic condition characterised by progressive extra-skeletal bone formation in connective tissues. Over time, heterotopic ossification entombs patients within a second skeleton, drastically impairing their mobility and autonomy. Mutations in the ACVR1 gene have been identified as the cause of FOP. The single nucleotide missense mutation in ACVR1, c.617G > A, causes a single amino acid substitution, p.R206H, and is found in >90% of all patients. Heterotopic bone formation in FOP mimics embryonic skeletal endochondral ossification, with cartilage forming after fibroproliferative tissue condensation as an intermediate stage prior to osteogenesis and tissue ossification. In contrast to normal embryonic endochondral ossification, heterotopic ossification in FOP involves an inflammatory phase that precedes cartilage and bone formation. New insights into the mechanisms of action of heterotopic bone formation in FOP have led to the discovery of new potential treatment targets including inhibitors of BMP signalling, activin A inhibitors, and mTOR inhibitors. This review summarises the current knowledge on mutations causing FOP, as well as the molecular basis of heterotopic ossification and the therapeutic options that result from these discoveries.
Highlights
Fibrodysplasia ossificans progressiva (FOP, OMIM #135100) is an autosomal dominant genetic disease that has an estimated prevalence of 1 in 1–2 million and affects individuals regardless of gender, race, ethnicity or geographical location
This review summarises the current knowledge on mutations causing FOP, as well as the molecular basis of heterotopic ossification and the therapeutic options that result from these discoveries
Many are working to translate these efforts into effective therapies that will benefit FOP patients, allowing them to conduct simple actions of daily life and to maintain mobility and autonomous living throughout their lives
Summary
Fibrodysplasia ossificans progressiva (FOP, OMIM #135100) is an autosomal dominant genetic disease that has an estimated prevalence of 1 in 1–2 million and affects individuals regardless of gender, race, ethnicity or geographical location. A recent MRI study of 13 patients (11 with the R206H variant, 2 with non-R206H mutations) indicated various changes in the brain of FOP patients, including small lesions in the dorsal medulla and ventral pons, minor dysmorphism of the brainstem, and an enlarged origin of the vestibulocochlear nerves. All of these alterations were asymptomatic [12].
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have