Osteo- imperfecta is a rare genetic disorder which is heterogeneous in nature. The earliest patients identified with Osteo-imperfecta was most probably 1000 BC ago in the ancient Egyptian infant. The first scientific description of this disorder was given by an army surgeon Olaus Jakob Ekman in 1788 who demonstrated his thesis and gave description on 3-generation with fragile bones hereditary in nature.
Since then it was also called as Osteogenesis- Imperfecta. It mainly occurs due to the mutations in coding collagen type 1 gene. It occurs due to the disruption or changes in one of the two genes which are COL1A1 or COL1A2. It is frame shift mutation which is prevalent in 4 to 5 among 100,000 people.
It is extensive in nature not considering the age, ethnicity or the gender of person effected. It is also known commonly as ‘Brittle bone disorder’. Patients affected by this disease have various fractures since childhood and children are suffering severely due to this disorder usually die in neonatal period. It causes skeletal deformity, sclerosis and joint fractures. It leads to hearing loss, pulmonary complications and leads to deafness.
The molecular basis of the genetic osteo- imperfecta is like any other genetic disorder which is mutations detected in the genes. The genes that code for type 1 college have been compromised due these mutations lead to adverse effects on our body. Collagen is straight rod structure that is composed from a trimer subunits’ units of COL1A1 and of COL1A2.
The two chains of reoccurring Glycine-proline-hydroxyproline dextro-rotated triplet assemblies are present. The distortion in the structures of these chains is leading cause of incorrect peptide chain formation. The abnormal folding of these chains leads to imperfect collagen and eventually to osteo imperfect.
The severity depends upon the type of OI. There are VII reported type of osteo-imperfect depending upon the impact they induce in the body. Type I is the mild form of OI; given that it is the mildest form it still has implications what one cam call severe in simple language. Type II most severe in children; they are born with frog shaped legs and go though many fractures during child birth, it might get as bad fetal for children.
Type III and IV have abstemious effects on individuals and are moderate. Type V is similar to type IV is context to the frequency of the fracture that body must endure. Type VI is a rare type not observe as much. However, the types VII and VIII are recessive transferred, it bit of information was discovered in 2006. Type VII resembles to type IV while type VIII resembles to I or II
Some of the most common effects that this disorder produces on human body, that observed in all the OI patients are; common fractures, joint pains, bone deformity, low bone density, short stature, abnormal spinal curve, cardiac issues, hyperlaxity and myopia. These symptoms are present in all the patients.
In every 10,000 new born babies 1 is estimated with this disease. It is caused because of the collagen protein disorders, mutations in the collagen proteins are the reason for this disease. Detection of osteo-imperfecta is based initially on the symptoms and later it can be confirmed by DNA testing and collagen testing. There are basically 3 main sub tests of DNA testing by which it detected, nucleus testing, cytoplasmic is testing, endoplasmic testing
It is an autosomal recessive and dominant inherited disease. The phenotype of this disease is directly proportional to the age of person. Its lethality has types which differ according to the nature of type of mutants. Congenital is the state where bone fractures held at birth stage, whereas tarda is a stage where fractures occurred in later part of life.
There is no treatment, medicine or surgery till date which seems to completely remove the possibility of having it, but it can be minimize the symptoms and severity in some cases, following some physical therapies which maintains the proper functioning if the bones.
Aerobic conditioning is a usual program which helps to strengthen the muscles. Bisphosphonates are useful for OI patients, although these drugs cannot build an entire new bone, but can slow down the process of bone weakening. The basic purpose of these prevention’s is to prevent fractures and deformities.
References
- Biggin A, Munns CF: Osteogenesis imperfecta: diagnosis and treatment. Curr Osteoporos Rep. 2014; 12(3): 279–88.
- Lindahl K, Langdahl B, Ljunggren Ö, et al.: Treatment of osteogenesis imperfecta in adults. Eur J Endocrinol. 2014; 171(2): R79–90.
- Marini JC, Reich A, Smith SM: Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr. 2014; 6(4): 500–7.
- Van Dijk FS, Nesbitt IM, Zwikstra EH, et al.: PPIB mutations cause severe osteogenesis imperfecta. Am J Hum Genet. 2009; 85(4): 521–7.
- Barnes AM, Duncan G, Weis M, et al.: Kuskokwim syndrome, a recessive congenital contracture disorder, extends the phenotype of FKBP10 mutations. Hum Mutat. 2013; 34(9): 1279–88.
Authors: Maleeha Humayun, Marium Waseem, Nushrah Mujahid