Fibrodysplasia Ossificans Progressiva: A Disease That Turns Flesh Into Bones

The documentary Tin Soldiers which was released in 2015 was a deeply personal eye-opener into the world of people living with some of the rarest conditions and diseases. One of the main subjects of the documentary was Fibrodysplasia ossificans progressiva (FOP), a disorder that turns flesh into bones.

FOP is a disorder in which the connective tissues and muscle tissues are replaced by bone formation outside the skeleton, constraining movement. This results in the inability to move your joints and have difficulty in speaking and eating [1].

What Is Fibrodysplasia Ossificans Progressiva?

Also termed as Münchmeyer disease and previously known as myositis ossificans progressiva (MOP) is a rare, inherited disorder that is characterised by progressive fibrosis and ossification of muscles, tendons, and ligaments of multiple sites in the body [2].

The connective tissues are ossified (replaced by bone), causing the formation of bones outside the skeleton. An individual with FOP can start showing the signs from a very young age (childhood). The extra-skeletal bone formation causes progressive loss of mobility as the joints become affected, making it unable to fully open the mouth, resulting in difficulties with speaking and eating [3].

FOP is a rare disorder and occurs in approximately 1 in 2 million people worldwide, and around eight hundred cases have been reported around the globe [4].

What Causes Fibrodysplasia Ossificans Progressiva?

A single or multiple mutations in the ACVR1 gene cause fibrodysplasia ossificans progressiva. The ACVR1 gene is responsible for instructing the formation of certain proteins within your body [5].

The ACVR1 protein is found in many tissues of the body including skeletal muscle and cartilage and help to control the growth as well as the development of muscles and bones from birth to young adulthood. The ACVR1 gene mutations trigger receptor activity in the body, which in turn can cause an overgrowth of cartilage and bones, resulting in the development of FOP.

In some cases, FOP can occur from new mutations in the gene and these cases occur in people with no history of the disorder in their family.

What Are The Symptoms Of Fibrodysplasia Ossificans Progressiva?

The growth of bone outside of the skeleton structure is noticeable from early childhood, where it (additional bone growth) starts from the neck and slowly progresses to other parts of the body. Here are the signs which indicate that an individual has FOP [6]:

• Loss of mobility.
• Inability to fully open the mouth may cause difficulty in speaking and eating.
• Malnutrition caused by the inability to eat/drink.
• Breathing difficulties as a result of extra bone formation around the rib cage, restricting the expansion of the lung.
• Most people with FOP are born with malformed big toes.
• Some individuals may have short thumbs and other skeletal abnormalities.

Who Is At Risk Of Developing Fibrodysplasia Ossificans Progressiva?

Studies have found that FOP is inherited (genetic) in an autosomal dominant pattern, that is, a single copy of the faulty gene is enough to trigger the condition [7].

Note: An autosomal dominant pattern in genetics is the inheritance of genetic diseases from the parent to the offspring.

What Are The Complications Of Fibrodysplasia Ossificans Progressiva?

If an individual with FOP meets with any accident, trauma to the muscles (falls, surgeries etc.) may trigger episodes of muscle swelling and inflammation which then results in widespread and rapid ossification [8]. It can also be triggered by viral infections or diseases such as influenza. Delayed diagnosis, trauma, and infections can decrease life expectancy.

The most common cause of death in patients with fibrodysplasia ossificans progressiva is a cardiorespiratory failure from thoracic insufficiency syndrome.

How Is Fibrodysplasia Ossificans Progressiva Treated?

As FOP is rare, it is often misdiagnosed as cancer or fibrosis. The diagnosis of FOP is carried out by measuring the bone-specific alkaline phosphatase (an enzyme attached to the outer surface of the cell membrane, an excess of it can cause bone disorders) in the body.

Currently, there are no cures or approved treatments for FOP. Surgery to remove the extra bone growth is not an option because it may result in an explosive growth of new bone. Moreover, anaesthesia may trigger intubation, restrictive pulmonary disease, and changes in the electrical conduction system of the heart [9].

With proper medical management, a person with FOP may live up to 40 years. Clinical trials of several potential treatments are in progress as of 2019 [10].