Fibrodysplasia – mysterious ossification

Fibrydysplasia (FOP) is a rare genetic disorder, in which the organism products extra bones in places where they should not develop. These bones are produced within the muscles, tendons, ligaments and other connective tissues. They cause ossification in various places hindering the normal functioning of the person.

The disease often begins to develop in the neck and progress along the back, trunk and limbs. Children born with FOP have deformed great toes (shorter than others and sometimes bent inwards). Despite the fact that FOP is a congenital disease, most of the afflicted get to know about it before the age of 10. One of the first signs of FOP are inflamed swellings, often searing, which occur usually on the arms and back. Eventually swelling disappear but leave the trail of developed bone. Because the disease is so rare, the symptoms are often misdiagnosed as cancer or fibrosis. This leads doctors to order biopsies which can actually exacerbate the growth of these lumps. Patients feel the progression of the disease variously- sometimes it is rapid and sometimes it is slow and gradual.

The process of forming of a new bone is the same as the one in which bone regenerates after the fracture and is almost identical to that in which the bone develops from the embryo. When it is fully formed it is indistinguishable from normal one beyond the fact of its unnatural distribution. It is resistant to mechanical injury and when it is broken it will heal just like any other bone.

When the body begins to create new bone there come so-called ‘Flare-ups’. They are often painful. A single symptom could last for 6-8 weeks. There may be ‘Flare-ups’ occurring simultaneously in which pain does not disappear so quickly. When the symptoms progresses, stiffness may occur overnight.

Depending on the location of concretions, Fibrodysplasia can cause, i.a., difficulty in breathing, speaking or completely block the movement.

The ossification does not disappear. The body of a person with FOP does not produce additional bone all along. The patient can survive for months and years without apparent progress. Nevertheless, there is always a risk that the bone will grow without the previous symptoms or as a result of impact or fall. Therefore, people with FOP should avoid: surgery of removal of the additional bone, intramuscular injections, dental injections, moving joints, exaggerated physical therapy, falls and injuries, contact sports, tight clothes, tight shoes and shoelaces, any pressure on the body.

In 2006, Fredrik S. Kaplan discovered that people suffering from this disease have an excess of BMP-4 in the white blood cells. BMP-4 is a protein responsible for bone formation.

In the disease when there is any wound white blood cells secrete BMP-4 which in practice means that the body is “repairing” the injured place with bone tissue. Besides, the body of patients shows a deficiency of another protein (noggin), which acts as antagonist of BMP-4, namely stops the growth of bones.

Despite this discovery there is no effective cure for FOP. There are drugs that provide relief from ‘flare-up’. One of them is Accutane. This drug is commonly used in acne treatment. It is also known due to its properties of inhibition of connective tissue cells transformation into cartilage and bone. Iontophoresis is the way of treatment in which electrodes and electrical current of low voltage is used to deliver the drug to the deeply situated tissues including muscles.

Because of the rareness of the disease pharmaceutical companies do not conduct research on a cure for Fibrodysplasia. The development of research in this area is financed only by private funds. It is assumed that about three thousands of people in the world (or approximately one person in two million) may suffer from FOP. Until now the research has resulted in approximately 600 patients with FOP worldwide (in Poland 17 people, as of July 2010).

In America there is an association of IFOPA (International FOP Association) which research activities are almost entirely financed by Fred Kaplan. This association founded in 1988 is the only important source of information and advice for patients and their families.
One of the most famous cases was that of Harry Eastlacka. He gave his skeleton for scientific purposes. It can be seen in the Mutter Museum in Philadelphia.

Written by: Anna Rej, Sandra Kryska, Mateusz Grajek

Source:
1.Fibrodysplazja, www.fop.pcp.pl,
2.Fibrodysplazja, www.ifopa.org,
3.Smith R. Fibrodysplasia (myosistis) ossificans progressiva: clinical lessons from a rare disease. Clin Orthop 1998;346:7-14. 4.Delatycki M, Rogers JG. The genetics of fybrodisplasia ossificans progressiva. Clin Orthop 1998;346:15-18.   5. Mahboubi S, Glaser DL, Shore EM, Kalpan FS. Fibrodysplasia ossificans progressiva. Pediatr Radiol 2001;31:307-314.

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