Due to the mutation of the ACVR1 gene (a gene that controls bone development and repair), progressive ossifying fibrodysplasia can be a condition that the human being develops during embryonic development (more frequent eventuality) or that he inherits from one of the parents (rare).
FOP impairs the functionality of the affected joints and muscles, which over time leads to the development of walking and balance problems, breathing difficulties, chewing and speaking, etc.
Unfortunately, currently, those suffering from progressive ossifying fibrodysplasia can only count on symptomatic treatments - that is, aimed at relieving the symptoms - as there is no cure capable of canceling the mutation in ACVR1.
Progressive ossifying fibrodysplasia is a congenital condition, where congenital means that its carriers are affected from birth (even if the consequences are not evident from this moment).
Progressive ossifying fibrodysplasia is also known by the acronym FOP, whose component letters are a clear reference to the three terms used to define the conditions object of this article.
Did you know that ...
Progressive ossifying fibrodysplasia is included in the list of connective tissue diseases, such as Ehlers-Danlos syndrome or Marfan syndrome.
Epidemiology
Progressive ossifying fibrodysplasia is a rare disease; according to statistics, in fact, around the world, about one individual every 2 million is born.
According to an epidemiological data of 2017, all over the world, there are approximately 800 patients with progressive ossifying fibrodysplasia.
The first genus of ACVR1 mutation is an example of an acquired mutation and the resulting condition is called acquired type ossifying progressive fibrodysplasia; the second genus of ACVR1 mutation, on the other hand, is an example of an inherited mutation and the resulting condition is called hereditary progressive ossifying fibrodysplasia.
What are the consequences of the ACVR1 mutation?
Premise: the genes present on human chromosomes are DNA sequences that have the task of producing fundamental proteins in biological processes essential to life, including cell growth and replication.
The ACVR1 gene produces a receptor protein capable of regulating the growth, development and repair, where necessary, of the skeletal system.
In healthy people, the ACVR1 gene is activated as needed, which ensures fine control of the processes of growth, development and repair of the bones of the skeleton.
For example, the unchanged ACVR1 gene is one of the responsible for the ossification process, which characterizes the skeletal maturation of the human being, in its passage from young age to adulthood.
In people with progressive ossifying fibrodysplasia, on the other hand, the ACVR1 gene is, due to the mutation in its charge, always active (constitutive activation), which involves the loss of fine control of the processes indicated above and the occurrence of a phenomenon such as formation of bone tissue in place of connective tissue (for example, in place of cartilage, tendons, etc.) and in place of muscles.
Fibrodysplasia Ossificans Progressiva is an Autosomal Dominant Disease
To understand...
Each human gene is present in two copies, called alleles, one of maternal origin and one of paternal origin.
Progressive ossifying fibrodysplasia has all the characteristics of an autosomal dominant disease.
A genetic disease is autosomal dominant when the mutation of a single copy of the gene that causes it is sufficient to manifest itself.
As a result of all this, progressive ossifying fibrodysplasia results in a loss of mobility on the part of the muscles and joints involved, with logical repercussions on the patient's motor skills.
Did you know that ...
The lumps of bone that FOP causes outside the skeleton are called ectopic foci of ossification.
The effects of Fibrodysplasia Ossificans Progressiva: the details
As a rule, progressive ossifying fibrodysplasia attacks the human body from above; therefore, at first, it affects muscles and joints of compartments such as the head, neck, dorsal region, thorax, shoulders and upper limbs, and, subsequently, it compromises the muscle and joint function of the abdomen, pelvis, lumbar region and lower limbs.
In terms of symptoms, progressive ossifying fibrodysplasia is known to result in:
- Signs of inflammation (edema in particular) in those anatomical departments affected by the growth of extra bone tissue.
- Difficulty in chewing and speaking. They are a consequence of when the disease in question attacks the temporomandibular joint, whose correct functioning is essential for chewing and phonation.
Difficulties in chewing are responsible for malnutrition.
- Difficulty expanding the rib cage and consequent breathing problems. They are observed when FOP affects the muscles and joints of the chest through the formation of extra bone tissue.
- Difficulty moving the upper and lower limbs, resulting in problems with balance and coordination. They are a consequence of when FOP ossifies important joints such as the shoulder, elbow or knee.
Problems with balance and coordination are often the cause of accidental falls, which can further worsen the patient's state of health; in fact, all eventual muscular-joint fractures or injuries that may derive from an accidental fall are followed by unusual reparative processes, which lead to the formation of extra bone tissue. - Spinal deformations. They are the result of when the disease affects the joints present between the various vertebrae and the back muscles.
It is important to note that, in addition to the aforementioned consequences, progressive ossifying fibrodysplasia is also associated with some congenital malformations, including the presence of deformed big toes (this is a sign that characterizes practically all cases of FOP) and the presence of short thumbs (it is common, but not as common as deformed big toes).
Did you know that ...
Progressive ossifying fibrodysplasia spares some parts of the human body. For example, it does not cause the formation of unwanted bone tissue on the tongue, myocardium, smooth muscles, extraocular muscles and diaphragm.
Onset of progressive ossifying fibrodysplasia: when does it happen?
In general, progressive ossifying fibrodysplasia begins to show the first signs of its presence during early childhood; surely, under the tenth year of the patient's life, he has already given full proof of himself.
Complications
Over the years, the presence of extra bone tissue in patients with FOP becomes more and more considerable. This leads to the development of various complications, including:
- Severe breathing problems
- Immobility;
- Inability to feed followed by severe malnutrition;
- Inability to speak.
Progressive ossifying fibrodysplasia is a condition whose identification occurs, in a good percentage of cases, later than it should. This basically depends on the rarity of FOP: before thinking about the latter, in fact, doctors think of more common diseases that cause similar symptoms (eg: bone tumors, fibrous dysplasia, aggressive juvenile fibromatosis, etc.).
Medical history and physical examination
Anamnesis and physical examination essentially consist in an accurate evaluation of the symptoms exhibited by the patient.
In a context of progressive ossifying fibrodysplasia, it is in these phases of the diagnostic process that the doctor ascertains the presence of some typical consequences of the disease in question, such as:
- The deformed big toes;
- Movement difficulties;
- Problems with balance and poor coordination;
- The tendency to accidental falls;
- The sudden appearance, on the body, of signs of inflammation.
Genetic test
It is the DNA analysis aimed at detecting mutations in critical genes.
In a context of progressive ossifying fibrodysplasia, it represents the confirmatory diagnostic test, as it allows to highlight the ACVR1 mutation.
Why is surgery not one of the possible treatments?
The presence of FOP strictly excludes the use of surgery aimed at the elimination of extra bone tissue clots. This is explained by the fact that, to any bone incision, the skeleton of the patient with progressive ossifying fibrodysplasia would respond in the same anomalous way as when undergoing a fracture, ie with an overgrowth of the affected bone.
Did you know that ...
Performing a bone biopsy (ie the collection of bone tissue for a "laboratory analysis) in a patient with progressive ossifying fibrodysplasia is very dangerous, because it has the same effects as a fracture (or, absurdly, a possible intervention surgery aimed at eliminating extra bone tissue).
Activities that a FOP sufferer should avoid?
A patient with progressive ossifying fibrodysplasia should avoid:
- Intramuscular injections, such as those aimed at vaccinations;
- The practice of sporting activities;
- Overly invasive dental procedures
- Invasive surgical interventions.
