BANEFUL MALADY

Hi. Hope you guys find my last blog interesting to know something about stalking and victim consequences. This time I would like to share about a rare disease, which I came across through an article. This rare disease is called Osteogenesis imperfecta (OI).

WHAT IS OSTEOGENESIS IMPERFECTA?

It is the genetic bone disorder present at the birth of the baby or later in adults. This disease is also known as brittle bone disease. A child born with this disorder may have soft bones, abnormal growth of bones, or other related issues. The problem ranges from mild to severe based on the signs and symptoms diagnosed.

The term osteogenesis represents “Imperfect bone formation.” In most of the cases, the child may have fracture easily with no proper reason, and even before birth fractures of bone may occur. Mild cases are the person may face a bone fracture in their lifetime.

TYPES OF OSTEOGENESIS IMPERFECTA

There are 19 types of imperfecta which is represented as type I through type XIX. Most of the symptoms overlaps (remains the similar).

Type 1: It is known to be the mildest form of OI. In this case, bone fractures are occurred during childhood or adulthood which might be very minor injury. In adults, the rate of injury is not recurrent. People who suffer with paltry condition may have blue or grey tint (slight or pale coloration) to the part of the eye. This abnormal condition occurs on the white outer layer of the eyeball (Sclera). This condition also develops hearing loss in adults. Affected people may be of abnormal height or near to normal height. OI occurs mostly due to the genetic changes of COL1A1 gene.

What is COL1A1 gene?

This gene plays a vital role in developing large molecule of type 1 collagen (a protein which is responsible for healthy joints, skin elasticity or stretchiness (ability to stretch or move back to original shape)).

If the individual is affected with OI, this in turn reduces the growth of type 1 collagen in the body. Also Type I OI is known to be an autosomal dominant pattern of inheritance (which can be passed down from parent to the child genetically). In the US, around 3000 to 30,000 people are affected by type I OI as per survey.

Type 2: This is known to be the most severe form of OI. This type will result in the death of the child if it is diagnosed with type II OI. It is also called perinatal lethal type (very short span and results in death before or after the child is born). This type is common in an unborn fetus.

It most commonly causes reduction in mass & density of bones (bone fragility), leading to reduction in connectivity of bones and results in fracture. Multiple ribs of bones and large bone fractures inside the mother womb; malfunctioning of body parts (especially hand or feet).

Also, this disorder can be predicted before the birth of the child by examining the x-ray of the skull. In the x-ray, the low density of the skull can be notified. The white outer layer of the eye turns dark and represents the sign of type II.

An observation was also carried out for this type II OI, a baby born to a 29-year-old woman. There was no family history of OI. No abnormalities were predicted on ultrasound. After 22 weeks of pregnancy, ultrasound detects some growth mismatch as per week; incurved limbs; narrow chests; hypomineralisation (enamel layer (outer layer) of the child's teeth is affected); fractures of multiple bones and ribs. It was advised to the parents to get rid of the baby since complications were too many and the survival rate of the baby is low. But the parents refused to do so. The diagnosis was retained confidentially. After 25 days, the newborn baby died due to respiratory failure and secondary to pulmonary hypoplasia (underdeveloped lungs not only affects breathing but also affects heart function, ability to eat & hear and overall growth). The estimation of the number of people affected by type II is still in progress.

Type 3: This type can be diagnosed only shortly after the birth of the child. The handling of the baby would be a greater task. It may result in bone fragility (increases the risk of bone fracture without any prior condition) since the bone of the child can get fractured, malformation of the bones may occur, short stature (condition in which the child or the teen is below their average height compared to his or her peers), dental problems (dentinogenesis imperfect: no proper development of tooth), macrocephaly (head of the baby is higher than usual), other common underlying complications (hearing loss and blue sclera). This is also due to changes in the collagen 1 or 2 gene growth. It can be an inherited disorder.

In the US, around 300 to 3,000 people are affected by type III OI as per surveys.

Type 4: This type is considered to be a variable form (symptoms don’t remain constant or other related issues). It ranges from moderate, mild, and severe outcomes. It is difficult to diagnose this type of disorder. Comparing with other types, the possibility of bone fracture occurs before puberty; no proper tooth development or other dental problems; height mismatch; adult-onset problem; and hearing loss along with white sclera. The major cause is improper growth of collagen genes (1 and 2). In the US, around 3,000 to 30,000 people are affected by type III OI as per survey.

Type 5: This type occurs due to improper growth of genes. The major outcome of this type is it results in calcification (it is the process of calcium built up in the body tissue which in turn hardens the tissue) of the forearm interosseous membrane (sheet that connects the two joints i.e., radius and ulna), dislocation of radial head (just below the elbow), affects the growth of the neck bone, also new bulge layer formation over the fractured bone (hyperplastic callus).

Type 6: This type results in bone weakening and further leads to bone damage (break) easily. While examining the disease under microscope, the bone tissue appears to be like a “fish scale” patter. Also, a child affected with type 6 OI remains healthy until six months (after birth). After six months, the child will experience the symptoms of OI. This is mainly caused by the SERPINF1 gene (it is a multifunctional secreted protein) which has anti-angiogenic (helps to stop the growth of tumors), anti-tumorigenic (oppose the formation of normal cells into cancer cells), and neurotrophic functions (provides required nutrition to the nerve tissue). If the SERPINF1 gene undergoes any of the genetic changes, it results in type 6 OI.

Type 7: This type is considered to be lethal (causing death) and involves common symptoms like hearing loss, proptosis (bulging of one or both eyes. It affects the appearance and leaves the individual in a startled state), facial growth is completely affected (face dysmorphism), improper growth of teeth, and bluish sclera. Neurological development is normal until ribs of the bone are not affected. This type is mainly caused by CRTAP (Cartilage Associated Protein) acts as a protein coding gene.

Type 8: This type may cause severe damage to the child (after birth) after 18 to 24 months. It mostly causes skeletal dysplasia (a medical term used to represent 400 different conditions which affect the development of bones, neurological functions, cartilage growth (knee joints), and achondroplasia (short limbed dwarfism)).

Type 9: This type includes all common complications, like other OI. This is mainly due to an autosomal recessive form of disorder (here a child will have gene transformation from parents, where one gene would be affected, and other gene remain unaffected leads to cause for OI disorder). Here the bones are fragile and cannot resist fractures.

Type 10: This type also falls under an autosomal recessive form of disorder which includes deformities (defined as disfigurement where part of the human body will be in a different shape or size), dentinogenesis (improper growth of teeth, weaker teeth which may break easily, teeth appear to be blue-gray or yellow brown in color), generalized osteopenia (affects the mass of the body and bones get weaker. This especially results in loss in calcium levels).

Type 11: This type results in connective tissue disorder. It includes similar complications like other OI. It is caused by a heterogenous mutation (change in DNA sequence).

Type 12: This type is passed down from the parents (healthy and affected gene) to the newborn child. The child will have a mild change in the shape of the body (deformity), the boom out (eruption) of teeth will be delayed. Gradual hearing loss may occur in stages. But this type doesn’t affect tooth development after it erupts. The child will have white sclera and weak bone (bone fracture occurs if the individual tries to sneeze or cough), simple movement may lead to bone fracture.

Type 13: Similar to type 12, this type is also passed down to children from the parents gene. Here the child will have normal growth of teeth. But in turn it affects growth badly (lack of required resources). The outer layer of the eye looks a faint blue (Sclera), weakness of the bone appeared to be mild. The child may also experience about 10 to 15 (average) fractures a year (probably both upper and lower limbs will be affected). Size and shape of the body are affected to some extent.

Type 14: Similar to other types, this type also affects the newborn child because of the gene passed down from parents. It includes various and severe complications along with multiple fractures, osteopenia (a medical condition in which protein and mineral content is reduced or lower than the required range). Where in this type, the child will have normal teeth growth, sclera, and hearing capacity.

Type 15: Individuals will be affected because of the parents gene. The individual affected by this type will experience reoccurring fractures frequently (compared to other types), different size and shape of the bones, notable changes in the bone density, height of the child is affected, and blue sclera is visible in some patients. Other tooth development and hearing are normal in this type of OI.

Type 16: This type affects the child even before birth (prenatal stage). Ribs and long bones get fractured when the fetus is in the mother’s womb. The eye of the child will have blue sclera and bone formation (ossification) of the child's skull is affected. Even a child has demineralization (removes mineral ions from HA crystals of hard tissues. For example, enamel, dentin, cementum, and bone).

Type 17: This type affects the newborn child after 18 to 24 months. The child will have low bone density, trauma from a bone fracture. The severity of the disease ranges from mild to extreme complications without any bone fractures. It also leads to the death of the child.

Type 18: This type causes incomplete fractures of long tubular bones (congenital bowing) and affects mostly pediatric patients. There will be formation of additional bones in the child's skull (wormian bones), blue sclera, vertebral collapse (spine collapses, further causes severe pain, affects the size & shape of the body, and height). They will be multiple bone fragile at the duration of 1st year life period.

Type 19: This type occurs before the child is born. A child suffers with complications like bone fracture in a mother’s womb, the mineral and protein range are less than the normal level, height of adulthood will be affected completely (short stature), variable sclerosis (spine curvature is affected and grows sideways), bone formation near the chest is affected, and larger bone in lower leg is affected (this bone plays the vital role in balancing the weight of the body, knee & ankle joint functions).

As there is no cure has been identified for OI, people can still know about the causes and complications to create awareness. This blog gives brief information about the OI disorder and it types in detail. It would be tough to survive with this disorder, but I pass on my best wishes to people out there who struggle and fight back without giving up. Keep going, everything gets well soon. Just trust the future ahead.

I would like to conclude the blog with a living example, Tanya. Tanya was born in Kerala and settled in Bangalore. After she was born, she was all okay and her parents were not aware of her disorder. As days passed, Tanya started crying continuously and her parents couldn’t identify the reason behind it. They took her to different doctors, and no one diagnosed the exact reason for the child's discomfort. Finally, one doctor succeeded in diagnosing the disorder and shared the exact details about OI with Tanya’s parents.

After hearing this, both Tanya and her parents were in huge shock. Tanya was not able to walk and spend her childhood like other kids. So, she restricted herself from going to school. She spent most of her days visiting hospitals and treatments for bone fragile. She has lost hope these days. But luckily, her neighbor was fond of Tanya because of her smart nature, she liked to spend time with her along with her kids. This slowly developed self confidence in Tanya, and she joined IGNOU, the people’s university to pursue a degree. Later, she started writing articles to create awareness and increase self-confidence for all physically challenged people. As she is 29 years old, she looks like a kid who cannot move without a wheelchair. She still fights back to lead a life as she wishes.

No matter whatever situation we are in or the disease we are suffering with, just don’t give up. Be bold and fight back with full strength & courage!

Stay tuned for my next blog :)