This website is intended for US Healthcare Professionals only.
This website is intended for US Healthcare Professionals only.

Fibrodysplasia ossificans progressiva (FOP) is a progressive, disabling, ultra-rare genetic disorder characterized by cumulative and irreversible heterotopic ossification (HO) that leads to loss of mobility and shortened life expectancy.1–3

In patients with FOP, anatomically normal bone forms at extraskeletal sites within soft and connective tissues such as skeletal muscles, tendons, ligaments, fascia, and aponeuroses.3

Milestones in the history of FOP research4–6

Date chart

FOP is caused by a mutation in the ALK2/ACVR1 gene, a BMP type 1 receptor.7

Bone morphogenetic proteins (BMPs) are extracellular ligands belonging to the TGF-β superfamily, and play a key role in tissue homeostasis.8–10

Other mutations in the ALK2/ACVR1 gene have been identified in approximately 3% of patients with FOP.11

The mutation is not inherited in most cases of FOP, it arises from a spontaneous missense mutation in the ALK2/ACVR1 gene.7 It results in constitutive activation of the BMP signaling pathway and enhanced signaling through ligand-dependent mechanisms. Increased activation of the signaling pathway leads to abnormal bone formation, and in turn heterotopic ossification (HO).12,13

Mutation in the ALK2/ACVR1 gene causes FOP by changing the response to ligands12,13


In FOP, HO occurs through an endochondral pathway that transforms soft and connective tissues into bone3,14

The process of HO begins in childhood, often with injury and inflammation as a result of a bump or bruise, or even a fall.7,15 But the process can also occur spontaneously.16

Signs of FOP include congenital malformations of the great toes and tumor-like swellings3,11,20

Congenital bilateral great toe malformation in a patient with FOP
The characteristic sign of FOP is congenital bilateral great toe malformation. Almost all patients with FOP are born with this malformation.14,21

FOP toes

Swellings on the back and scalp
Other signs and symptoms of FOP begin in early childhood and include tumor-like swellings in the head, neck, or back.20,21 Another sign of FOP in young children is that instead of crawling they will scoot on their buttocks, because of limited neck movement22,23

Back Swellings

Patients living with FOP share their stories of what life is like living with this condition

Watch Danie’s Story
Danie describes her experience growing up and living
with FOP.

Watch Erin’s Story
Erin, patient living with FOP, discusses the symptoms that had the biggest impact on her quality of life.

Patients living with FOP experience sporadic and unpredictable flare-ups16

Flare-ups often present as painful soft-tissue swellings that are warm to the touch16

Patients experience episodes of soft tissue swelling, warmth, pain, stiffness and reduced movement known as flare-ups.16 Flare-ups appear spontaneously or after muscle fatigue, trauma, intramuscular injections, or viral infections.24–26 Although some flare-ups regress spontaneously, many lead to HO, which transforms soft and connective tissues, including aponeuroses, fascia, ligaments, tendons and skeletal muscles, into heterotopic bone.3

Typically, HO begins in the dorsal, proximal, axial and cranial regions of the body (neck, shoulders, back) and progresses into ventral, caudal and distal regions (trunk and limbs).24 HO develops into ribbons, sheets, and plates of extra bone throughout the body and across joints, progressively restricting movement.27

Other clinical features observed in patients with FOP are proximal medial tibial osteochondromas, cervical spine malformations, short, broad femoral necks, hearing impairment, and shortened thumbs.28

The HO process in FOP is progressive and cumulative, meaning patients suffer more and more over time

Step 1

During the first decade of life, children may experience painful soft-tissue swellings on their neck or back29

Step 2

During the second decade of life, ankylosed joints often cause patients to lose mobility29

Step 3

Most patients with FOP are confined to a wheelchair by their 30s and require caregiver assistance to perform daily living activities.
By their 40s, many patients are at risk of early death due to thoracic insufficiency syndrome or thrombosis.29

Step 4

The median age of survival is 56 years (range: 3-77 years)2, as determined by a review of comprehensive mortality reports from 2 large FOP patient registries comprising the worldwide majority of patients with FOP28

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Ipsen The information provided here is not intended to replace professional advice. This website has been developed by Ipsen in collaboration with those living with Fibrodysplasia Ossificans Progressiva and the healthcare professionals who care for them. Ipsen would like to thank everyone for their valuable insights and stories. All names used on this website are not necessarily real names. Visit our website for more information about us, or to contact us directly. Website design and development by Kanga Health Ltd. Website reference DM-0350 NON-US-002452 July 2021