Fibrodysplasia Ossificans Progressiva A Distinctive Bone Forming

Leo Migdal

-Dec 5, 2025, 4:39 PM

fibrodysplasia ossificans progressiva a distinctive bone forming

A 3-month-old white female presented with a bone-forming lesion of the soft tissue of the left cheek. Skeletal survey revealed numerous associated radiographic abnormalities, predominantly involving the phalanges. Mineral metabolism and endocrine function were within normal limits. Multiple operations were performed over a 17-year period for palliation of sequelae arising from inability to open the mouth due to ankylosis of the temporomandibular joint by the progressively ossifying lesion. Histologically, the pathologic material had features resembling those of periosteal grafts, with all stages of membranous bone formation and a tendency for more mature lesions later in the course. .The clinico-pathologic features are those of fibrodysplasia ossificans progressiva (FOP).

The differential diagnosis of this rare condition from other bone-forming lesions of the soft tissue such as myositis ossificans, extra-skeletal osteosarcoma and osseous metaplasia is discussed. Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition where bone gradually replaces muscles and connective tissues. Injury or illness causes new bone growth, which can be painful and lead to a shortened lifespan. Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services.

Policy Pronunciation for the genetic condition fibrodysplasia ossificans progressiva is “fi-bro-dis-play-see-ah os-sif-eh-cans pro-gres-see-vah.” Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Fibrodysplasia ossificans progressiva (FOP) is a genetic condition where people are born with bunions and their body’s muscle tissue and connective tissues, like tendons and ligaments, turn into bone on the outside of their... This condition restricts movement and can cause a loss of mobility over time in people diagnosed with the condition. Symptoms of FOP appear during childhood and usually begin at the neck and shoulders before moving to other areas of the body. Fibrodysplasia ossificans progressiva is a disorder in which muscle tissue and connective tissue such as tendons and ligaments are gradually replaced by bone (ossified), forming bone outside the skeleton (extra-skeletal or heterotopic bone) that... This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs. Extra-skeletal bone formation causes progressive loss of mobility as the joints become affected.

Inability to fully open the mouth may cause difficulty in speaking and eating. Over time, people with this disorder may experience malnutrition due to their eating problems. They may also have breathing difficulties as a result of extra bone formation around the rib cage that restricts expansion of the lungs. Any trauma to the muscles of an individual with fibrodysplasia ossificans progressiva, such as a fall or invasive medical procedures, may trigger episodes of muscle swelling and inflammation (myositis) followed by more rapid ossification... Flare-ups may also be caused by viral illnesses such as influenza. People with fibrodysplasia ossificans progressiva are generally born with malformed big toes.

This abnormality of the big toes is a characteristic feature that helps to distinguish this disorder from other bone and muscle problems. Affected individuals may also have short thumbs and other skeletal abnormalities. Fibrodysplasia ossificans progressiva is a very rare disorder, believed to occur in approximately 1 in 1 million people worldwide. Several hundred cases have been reported. Fibrodysplasia ossificans progressiva (/ˌfaɪbroʊdɪˈspleɪʒ(i)ə ɒˈsɪfɪkænz prəˈɡrɛsɪvə/;[1] abbr. FOP), also called Münchmeyer disease or formerly myositis ossificans progressiva, is an extremely rare connective tissue disease.

Fibrous connective tissue such as muscle, tendons, and ligaments ossify into bone tissue. The condition ultimately immobilises sufferers as new bone replaces musculature and fuses with the existing skeleton. This has earned FOP the nickname "stone man disease".[2] FOP is caused by a mutation of the gene ACVR1, affecting the body's repair mechanism. Fibrous tissue including muscle, tendons, and ligaments ossify, either spontaneously or when damaged by trauma. In many cases, otherwise minor injuries can cause joints to permanently fuse as new bone forms, replacing the damaged muscle tissue.

This new bone formation (known as "heterotopic ossification") eventually forms a secondary skeleton progressively restricting the patient's ability to move. Circumstantial evidence suggests that the disease can cause joint degradation separate from its characteristic bone growth.[3] It is a severe, disabling disorder. Bone formed as a result of ossification is identical to "normal" bone, but in improper locations. The rate of ossified bone growth varies by patient. It is the only known medical condition in which tissue of one organ system changes into that of another.[4] Surgical removal of ossified bone causes the body to "repair" the affected area with additional bone.

FOP has no current known cure. However, there are intermittent treatments such as anti-inflammatory drugs. Promising breakthroughs include the approved treatment, Sohonos (palovarotene). Another promising treatment is Antisense-mediated therapy using allele-selective LNA gapmers. Medical reports describing individuals affected by FOP date back to Dr. Guy Patin in 1692.[5] FOP was originally called myositis ossificans progressiva and was thought to be caused by muscular inflammation (myositis) that caused bone formation.[5] In 1736, London surgeon, John Freke wrote the first...

They likewise arise from every rib of his body, and joining together in all parts of his back, as the ramifications of coral do, they make, as it were, a fixed bony pair of... McKusick in 1970 following the discovery that soft tissue other than muscles (e.g. ligaments) were also affected by the disease process.[5] Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder that causes muscles, tendons, and other soft tissues to turn permanently into bone. Extra bone forms across joints making movement difficult and sometimes impossible. This process of ossification continues throughout a patient's life.

FOP affects many areas of the body including, but not limited to, the neck, spine, chest, shoulders, elbows, wrists, hips, knees, ankles and jaw. FOP is a progressive disease, which means it typically gets worse as the patient ages. The rate of new bone formation differs for each person, and the disease's progression is generally unpredictable. FOP is known to affect about 2,500 people globally, across all ethnicities, ages, genders, and races. Because FOP is such a rare disease, experts believe that 80 percent or more of the cases are misdiagnosed and the number of people with FOP may actually be much higher. Experts in both pediatric and adult endocrinology, genetics, orthopedics, orthopedic surgery and rheumatology at UCSF Benioff Children's Hospitals are among the few in the country who readily diagnose and treat FOP.

In addition, researchers at UCSF are studying how the disease progresses and working to identify new therapies. One of the nation's best for endocrinology & diabetes care Author for correspondence (pingham@ntu.edu.sg) This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly... Heterotopic ossification (HO) is a disorder characterised by the formation of ectopic bone in soft tissue. Acquired HO typically occurs in response to trauma and is relatively common, yet its aetiology remains poorly understood.

Genetic forms, by contrast, are very rare, but provide insights into the mechanisms of HO pathobiology. Fibrodysplasia ossificans progressiva (FOP) is the most debilitating form of HO. All patients reported to date carry heterozygous gain-of-function mutations in the gene encoding activin A receptor type I (ACVR1). These mutations cause dysregulated bone morphogenetic protein (BMP) signalling, leading to HO at extraskeletal sites including, but not limited to, muscles, ligaments, tendons and fascia. Ever since the identification of the causative gene, developing a cure for FOP has been a focus of investigation, and studies have decoded the pathophysiology at the molecular and cellular levels, and explored novel... Based on the established role of BMP signalling throughout HO in FOP, therapeutic modalities that target multiple levels of the signalling cascade have been designed, and some drugs have entered clinical trials, holding out...

A potential role of other signalling pathways that could influence the dysregulated BMP signalling and present alternative therapeutic targets remains a matter of debate. Here, we review the recent FOP literature, including pathophysiology, clinical aspects, animal models and current management strategies. We also consider how this research can inform our understanding of other types of HO and highlight some of the remaining knowledge gaps. KEY WORDS: Bone morphogenetic protein, ACVR1, Fibrodysplasia ossificans progressiva, Heterotopic ossification, Inflammation Summary: Fibrodysplasia ossificans progressiva is a rare disease characterised by progressive heterotopic bone formation. Here, we present a comprehensive summary of the recent literature on this debilitating condition and discuss approaches to solving this clinical puzzle.

Fibrodysplasia Ossificans Progressiva A Distinctive Bone Forming

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