Molecular Biology
and Lysosomal Disease
Diagnosis Laboratory
Center for Research and Diagnosis of Genetic Diseases
Diagnostico: Progressive Ossifying Fibrodysplasia

Progressive ossifying fibrodysplasia is a rare genetic disease that affects one individual in every two million births. Its main consequence is heterotopic ossification, i.e. formation of additional bone in abnormal locations. It is an autosomal dominant disease, usually caused by a new mutation in the ACVR1 receptor gene, which is in the signaling pathway for bone morphogenic protein. This abnormality is not related to gender, ethnicity or consanguinity.

Individuals suffering from FOP can be recognized as people who form two skeletons: one in the normal place, which develops during the embryo formation phase; and another at an abnormal site, which develops after birth. At birth, the child's skeleton is apparently normal; however, it already usually exhibits the first signs of the disease, which are varied skeletal malformations, the main one being malformation of the halluces. This characteristic is present in 95% of patients with FOP. It is also possible to find other skeletal malformations such as defects in the cervical spine, short thumbs and osteochondromas in the proximal part of the tibia.

The disease usually starts in the neck and shoulders and progresses to the back, trunk and limbs.

The symptoms start to appear before the age of 20 years, and frequently before the age of 10. They are characterized by reddish swellings in the shoulders and back that disappear with time, but that leave a bone in the place where there was inflammation. The knees and hip are commonly affected in adolescence and in early adulthood.

The bones formed by FOP are a result of the progressive transformation of soft tissues in cartilage and bone. It is a process identical to that of post-fracture bone regeneration. The body can go for months without forming new bones, as if the disease were dormant; however, without prior notice and without any injury or trauma, bones can appear in unexpected places (ligaments, muscles, tendons). As a consequence, movement in the affected areas becomes difficult or impossible. Bone neoformation is designated as a flare-up. This process is generally painful, accompanied by low fever, and there is no medication that can prevent it, once it has already started. The local edema can have various causal factors:

Occurrence of flare-ups;

Restriction of movements hindering the pumping of blood inside the ossified muscles;

Compression of veins and lymphatic vessels by the new bones;

Formation of blood clot.

According to studies, the extra bones can generate cardiopulmonary complications, especially when in association with a state of flu or infection. For this reason, all infections must be treated aggressively in these patients. Some patients may present right ventricular overload on account of the pulmonary hypertension that they develop, the so-called Cor Pulmonale

The evident radiological signs of FOP are abnormal calcifications both in fingers and in toes, generating bone malformations and trabeculae. The presence of hallux valgus and other alterations of this toe is also relevant. Moreover, there have been reports of spinal fusion and the presence of osteochondromas in these patients. Generally speaking, this “newly-formed skeleton” produces dental and morphological complications, mobility limitations, cardiopulmonary impairment and right ventricular overload.

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