Fibrodysplasia Ossificans Progressiva

Question: Discuss about the Fibrodysplasia Ossificans Progressiva. Answer: Introduction: Fibrodysplasia ossificans progressiva (FOP) is described as a rare disorder which is autosomal dominant. It can occur in any individual with the traits coming from both mother and father. In this disorder, the patient suffers from symptoms of heterotropic ossification which results in the formation of bones in the subject muscles and also in the connective tissues like tendons and ligaments. These result in prevention of smooth movements and inability to move properly (1). Along with the occurrence of heterotropic ossification, the patient also suffers from congenital malformation of his big toes. Statistical analysis has shown the presence of such disorder in 2 of a million individuals at births. Researchers are of the opinion that phenotype of this disorder is mainly linked with the markers present at the chromosome number 4. They say that disorder is mainly the reason of a particular kind of gene mutation which in turn result in the over expression of a particular type of protein called the bone morphogenetic protein other researchers have shed more light on the real genetic science behind the cause of the disease. They say that FOP can have a linkage with the chromosomal region of 2q2324. They have suggested that recurrent mutation in the particular gene that encodes the activin. A receptor called the type 1 or ACRV1 is the BMP type 1 receptor that mainly acts as the contributing factor for the disorder. BMP signalling, by acting on tetrameroc receptor complex provides signal through . this causes mesenchymal stem cell differentiation by converging at Runx2 transcription factors that prmote osteoblast differentiation and hence results in bone formation. This gene called AC RV1 is also called the activin like kinase 2 or the ALK 2 and its identification have given a huge expectation to the scientists in order to create a successful therapeutic strategy for the prevention of the disease. Moreover it would also help in early identification of the disorder as it acts as a reliable confirmatory diagnosis before the onset of any appearance of ectopic ossification. Moreover, ample researchers have been conducted which have proved that congenital great toe malformation along with the progressive swelling of different soft tissues in the body can clearly act as symptoms for genetic testing and consultation (2). Proper identification of the disorder in the primary stages can thereby inhibit the application of unnecessary therapeutic interventions which instead of curing the disorder may result in permanent damage. Moreover, correct identification of genes and their mutation resulting in such disorder and also of the various symptoms that it shows, scientists ar e now interested in development of different therapeutic agents that will tend to block the overactive behaviour of the ACVR1/ALK2 signalling (3). They are therefore very much hopeful that the therapies will help to prevent the progression of the disease. The next important thing that needs to be discussed herein is the contributing factors that result in the occurrence of such type of mutations in the genetic constitution. Both genetic and environmental factors are responsible for the occurrence of different symptoms that associate with the disorder. Different genetic determinants have been responsible for influencing the phenotype of the child mainly during the prenatal development. On the other hand, different environmental factors have been seen to influence the phenotype of child in the post natal development mainly during the progression of heterotrophic ossification. This can be very well established from the experiments that were conducted in the three pairs of monozygotic twins. It was observed in each pair of twins that malformation of the congenital toe in both the individuals in each pair was highly identical. However it also showed that when they were differentially exposed to different environments, both the individual o f each pair showed different progression to postnatal heterotropic ossification. Researchers noted that the later varied greatly due to different life history and also to different limits of environmental exposure like various soft tissue traumas and also due to different exposure to viral illnesses (4). Therapeutic treatments are still under research which aims to prevent the occurrence of the symptoms at the genetic level. However, in the present situation there is no such treatment for this disorder because researchers have not been able to establish the effectiveness of ACTH, calcium binding agents and glucorticoids in this context. Researchers have stated that they believe Sodium etidronate can be helpful in preventing the formation of ectopic bone after surgical procedures. Moreover researches are also conducted in order to establish a proper treatment method by the usage of the inferno alpha, endostatin, angiostatin and also on thalidomide (5). From the entire discussion above, one can reach a conclusion that FOP is a rare disorder which disables an individual to perform smooth movements and hampers quality life. No fruitful treatments have been established which can cure the diseases or stop its progression. Therefore it becomes extremely important to educate healthcare professionals, patients and their families about the significance of early diagnosis of the symptoms and opt for prevention of trauma to save oneself from acute distress and disability in movements. References: Shore EM, Kaplan FS. BMP Signaling in Fibrodysplasia Ossificans Progressiva, a Rare Genetic Disorder of Heterotopic Ossification. InBone Morphogenetic Proteins: Systems Biology Regulators 2017 (pp. 327-343). Springer International Publishing. Shulman, R., Ellis, J., Shore, E., Kaplan, F. S., Badell, M. (2015). Maternal Genetic Skeletal Disorders: Lessons Learned From Cases of Maternal Osteogenesis Imperfecta and Fibrodysplasia Ossificans Progressiva.Journal of Clinical Gynecology and Obstetrics,4(1), 184-187. Hatsell, S. J., Idone, V., Wolken, D. M. A., Huang, L., Kim, H. J., Wang, L., ... Das, N. (2015). ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A.Science translational medicine,7(303), 303ra137-303ra137. Morales-Piga A, Kaplan FS. Osteochondral diseases and fibrodysplasia ossificans progressiva. InRare diseases epidemiology 2010 (pp. 335-348). Springer Netherlands. Rashid U, Bari A, Maqsood A, Naz S, Ahmad TM. Fibrodysplasia Ossificans Progressiva. Journal of the College of Physicians and Surgeons--Pakistan: JCPSP. 2016 Feb 1;26(2):154-5.