Fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP)

Also known as 'Stone man disease', progressiva is a rare genetic disorder that causes significant disability and morbidity. In this disorder, heterotopic ossification starts in the first decade of life, and a majority of such cases develop inflammatory painful soft tissue swellings. This disability progresses from upper to lower end, proximal to the distal end, and a dorsal to ventral side, i.e., from neck, spine, shoulders to elbow, knee, hip, jaw to wrists, and ankle. The wrists, ankles, elbows, knees, hips, and jaw gradually get involved till 40 years of age. There is no definitive management for this life-threatening disorder to date, and various new drugs are being tested in clinical trials. This activity reviews the presentation, evaluation, and management of fibrodysplasia ossificans progressiva and highlights the role of the interprofessional team in evaluating and managing patients with this condition.

Cause

A mutation of the ACVR1 gene causes fibrodysplasia ossificans progressiva. The ACVR1 gene gives your body instructions to make type 1 receptors for a protein called bone morphogenic protein (BMP) that reside in your muscles and cartilage. BMP controls how bones and muscles grow and develop. The mutation of ACVR1 causes symptoms of fibrodysplasia ossificans progressiva because the receptor, like a light switch, is always on when it should turn off.

Fibrodysplasia ossificans progressiva is an autosomal dominant condition, which means only one biological parent needs to pass the altered gene to the child for them to inherit it. If a parent has the gene that causes fibrodysplasia ossificans progressiva, there’s a 50% chance that the child will inherit the condition.

Most cases of fibrodysplasia ossificans progressiva occur because of a new mutation of the ACVR1 gene (de novo). This happens randomly, and there’s no link to the gene being present in a person’s family history.

Signs and symptoms

The hallmark symptom of fibrodysplasia ossificans progressiva (FOP) is a malformation of a newborn's big toe. This malformation, which is apparent at birth, consists of a short big toe with an abnormal turning of the toe called a valgus deviation.

During early childhood, most of those with FOP form painful fibrous nodules, or tumor-like swellings, over the neck, back and shoulders. These nodules often develop after a child experiences some sort of trauma to the body, such as a bump or fall. Episodes also can occur without any warning or may not occur at all. In most cases, the nodules transform into bone during a process known as heterotopic ossification.

When the body starts to generate new bone, the patient usually experiences a painful flare-up. Tissue swelling, joint stiffness and serious discomfort can occur. Some may have a low-grade fever. Flare-ups can last as long as six to eight weeks. The disease then progresses along the trunk and limbs of the body. These lesions slowly replace the body's muscles with normal-looking bone.