Introduction
Fibrous dysplasia ossificans progressiva (FOP) is a rare genetic condition of the connective tissue due to abnormal development of the bone in non-bony areas such as ligaments, tendons, and skeletal muscles. This disorder causes the body to undergo a process called metamorphosis, where the body calcifies into bone, locking the joint into place and making it difficult or impossible to move. Patients with FOP are seen with stiff joints, big malformed toes at birth, and other skeletal deformities affecting the neck, back, shoulders, hips, knees, elbows, wrists, and ankles. FOP usually has an onset in early childhood and progresses with life. The gene involved in the process of FOP occurs as a result of mutation of the ACVR1 (activin A receptor type 1) gene in the bone morphogenetic protein (BMP) pathway, which involves skeletal formation and repair during and post-birth.
How Is Fibrous Dysplasia Ossificans Progressiva Clinically Seen?
Around fifty percent of patients with FOP show defects and malformations in great toes and thumbs. The first clinical signs are the skeletal changes found at birth. The skeletal changes seen in FOP are shortened big toe, malformed distal metatarsal (foot bones), short fingers and toes, and clinodactyly (bent fifth finger). The congenital malformations include tibial osteochondromas (overgrowth of the bony cartilage), malformation of the spinal bone, and abnormally short broad neck of the thigh bone extending up to the pelvis (hip bone). The bone shows the presence of firm, tender swellings on the back, neck, and shoulders. Some patients show the presence of low-grade fever along with pain and stiffness. FOP is first seen affecting the neck, back, chest, arms, and legs, progressing to affect hips, ankles, wrist bone, elbow, shoulder, and jaw. The affected individuals are also more prone to respiratory infections due to their inability to move.
How Commonly Is Fibrous Dysplasia Ossificans Progressiva Seen?
FOP is a very rare congenitally inherited disease of the tissue, which was first discovered in the eighteenth century. The incidence is seen in an average of nine hundred people per four thousand individuals. The prevalence of the disease is equally seen among men and women and is diverse among people of all ethnicities. Bone growth abnormalities are seen from birth. In rare case scenarios, it is seen in delayed onset and after adolescence or early adulthood.
How Does Fibrous Dysplasia Ossificans Progressiva Occur?
Most cases of FOP, affect a person within a family. This occurs as an autosomal dominant disorder due to a mutation of the gene on chromosome 2 called ACVR1, which affects the bone morphogenetic protein or BMP. The bone morphogenetic proteins regulate skeletal formation from the embryonic stage of life. The FOP gene is encoded by the BMP receptors on the cell surface and determines the fate of the stem cells that are expressed by passing the signals into the cells. The BMP cells also activate a receptor called activin receptor type 1A or ACVR 1. The dominant genetic disorders like these with the affected gene are passed down from the parent to the child.
How Is Fibrous Dysplasia Ossificans Progressiva Investigated?
Fibrous dysplasia ossificans progressiva is a very commonly missed out condition, and hence examining it is very important.
Clinical Examination :
The most common method of diagnosing FOP is through clinical examination. The patient is examined for short great toes, stiff joints, and limbs.
Blood Test :
The blood samples are drawn for gene sequencing, which is done to find defects in the ACVR1 gene.
What Are the Precautions to Be Followed While Treating Patients with Fibrous Dysplasia Ossificans Progressiva?
Various precautions are to be followed before treating FOP.
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Patients with FOP are contraindicated for biopsies as it may result in rapid bone formation in the area of tissue removal.
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Intramuscular injections are avoided.
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In dental treatments, local anesthetic injections are precluded by stretching the jaw.
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Infections like flu or flu-like illnesses can also provoke FOP.
How Is Fibrous Dysplasia Ossificans Progressiva Treated?
Effective treatments for FOP are still unknown and are under clinical trials. However, patients are put on painkillers or anti-inflammatory medications to relieve pain and swelling, and prophylactic antibiotics are given in patients with respiratory complications. Occupational therapy is given to ease lifestyle, and shoes, braces, and other walking aids are given for physical assistance. Genetic counseling is given to the family members of the patient with FOP for proper knowledge on treatments and eliminating opportunities.
What Are the Other Conditions Similar To Fibrous Dysplasia Ossificans Progressiva?
Few other conditions appear similar to fibrous dysplasia ossificans progressiva, and it is important to have a piece of knowledge about those diseases to rule out the other possibilities, and they are:
Aggressive Juvenile Fibromatosis: It is a clinical condition where there is an increase in fibroblast cells, which invades the adjacent cells and tissues resulting in pain and disability of function. Like FOP, children affected are also seen with toe malformation.
Progressive Osseous Heteroplasia: It is an extremely rare genetic disorder characterized by abnormal bone development. Unlike FOP, the skin becomes heteroplastic, like a callous formation, and ossifies.
What Is the Prognosis of Fibrous Dysplasia Ossificans Progressiva?
The clinical prognosis of fibrous dysplasia ossificans progressiva is generally fair to low. The clinical outcome is generally low as it is a very rare clinical condition and treatment of the disease is still in trial.
Conclusion
As discussed above, fibrous dysplasia ossificans progressiva is a very rare clinical condition affecting children or seen to occur in the womb. This condition occurs due to genetic transmission, where the disease is transmitted from the mother or father to the child. The condition shows calcification of the cartilage, tissues, muscles, etc., to ossify due to a defect in the ACVR1 gene, which alters the bone morphology patterns. Although FOP is a serious medical condition with few treatment options, physical and occupational therapy provides greater relief to the patients. Also, with the developing technologies in medicine and surgery, the chances of better and new treatments and cures can be expected for betterment.
