The mutation affects the body's repair mechanism, causing fibrous tissue including muscle, tendons, and ligaments to become ossified, either spontaneously or when damaged as the result of trauma.

This new bone formation (known as "heterotopic ossification") eventually forms a secondary skeleton and progressively restricts the patient's ability to move.

A child with FOP will typically develop additional bones starting at the neck, then at the shoulders, arms, chest area, and finally at the feet.

Bone growth occurring during flare-ups may result in the loss of mobility to affected joints, including, if the jaw/mandible is involved, the inability to fully open the mouth, limiting speech and eating.

The binding of ACVR1 protein to BMP receptors start a signaling cascade that is crucial for inducing endochondral bone formation during development, as well as, skeletal and tissue homeostasis.

[22] Another telltale sign of FOP is a shortened great toe with a malformed distal first metatarsal and a missing or abnormal first phalanx and/or interphalangeal joint.

[25] While undergoing anesthesia, people with FOP may encounter difficulties with intubation, restrictive pulmonary disease, and changes in the electrical conduction system of the heart.

[26] Activities that increase the risk of falling or soft tissue injury should be avoided, as even minor trauma may provoke heterotopic ossification.

Currently, surgery is not usually recommended for people with FOP as it can incite rapid bone formation at incision sites or where sutures have been applied to muscle or connective tissue.

In recent studies, LNA gapmers effectively reduced the expression of the pathogenic ACVR1R206H transcript while sparing the wild-type ACVR1 gene, thus selectively suppressing osteogenic differentiation associated with FOP.

His condition began to develop at the age of ten, and by the time of his death from pneumonia in November 1973, six days before his 40th birthday, his body had completely ossified, leaving him able to move only his lips.

[32] Eastlack donated his body to science and his skeleton is now at the Mütter Museum in Philadelphia, and has proven to be an invaluable source of information in the study of FOP.

[33][34] Clinical trials of isotretinoin, etidronate with oral corticosteroids, and perhexiline maleate have failed to demonstrate effectiveness, though the variable course of the disease and small prevalence induces uncertainty.

[22] A handful of pharmaceutical companies focused on rare diseases are currently in varying stages of investigation into different therapeutic approaches for FOP.

[40] In August 2015, Clementia Pharmaceuticals also began the enrollment of children (ages 6 and above) into its Phase II clinical trial investigating palovarotene for the treatment of FOP.

[41] Preclinical studies demonstrated that palovarotene, a retinoic acid receptor gamma agonist, blocked abnormal bone formation in animal models by inhibition of secondary messenger systems in the BMP pathway.

[42] Clementia licensed palovarotene from Roche Pharmaceuticals, which previously evaluated the compound in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease.

[43] Another potential therapeutic approach involves allele-specific RNA interference that targets mutated mRNA for degradation while preserving normal ACVR1 gene expression.

Fibro/adipogenic progenitors (FAPs) may be the disease-causing cell type responsible for activin A dependent ectopic bone formation in both the muscles and tendons of mice bearing the FOP causing ACVR1(R206H) mutation.

[45] In December 2019, Ipsen issued a partial clinical hold for people under the age of 14, due to reports of early fusion of growth plates.

Recently, as of 2021[update], a potential therapeutic candidate, saracatinib, is in phase III clinical trials as a potent heterotopic ossification inhibitor in wild-type and ACVR1 mutant mice.