fibrodysplasia

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic disorder characterized by progressive heterotopic ossification of soft tissues, such as muscles, tendons, and ligaments, forming bone outside the normal skeleton. Most individuals have congenital malformation of the great toes—short or deviated hallux. Flare-ups, often triggered by minor trauma, injections, or illness, lead to new bone formation that gradually replaces soft tissue. Over time ossification follows a predictable pattern, typically beginning in the neck and shoulders and progressing to the trunk, resulting in restricted movement and, in later stages, immobilization. In many cases chest wall ossification impairs breathing.

Genetically, most cases result from a de novo gain-of-function mutation in ACVR1 (ALK2), a receptor in the BMP signaling pathway. The common mutation is R206H. FOP is inherited in an autosomal dominant manner with high penetrance, but most patients have no family history. Diagnosis is based on clinical features, radiographic evidence of heterotopic bone formation, and confirmation by genetic testing for ACVR1 mutations.

Management is supportive and multidisciplinary; there is no cure. Care emphasizes avoiding intramuscular injections and unnecessary trauma, early anti-inflammatory treatment during flare-ups, and physical therapy to preserve range of motion. Respiratory monitoring is important as chest rigidity can cause breathing problems; assistive devices and adaptive equipment may be needed. Experimental therapies include retinoic acid receptor gamma agonists such as palovarotene studied to reduce ossification; corticosteroids may help early flare-ups.

Prognosis is variable; morbidity from thoracic insufficiency and infections can occur; life expectancy is shortened relative to unaffected individuals. Prevalence is extremely low, estimated at around 1 in 2 million people. Awareness and research are supported by patient groups and medical consortia.