Brittle bone disease or Osteogenesis Imperfecta (OI) is characterized by a fragile skeleton.
Inheritance of OI
Mutations in the genes COL1A1, COL1A2, CRTAP, and P3h2 result in OI. In most cases, the inheritance pattern is autosomal dominant and, in some cases, it could also be autosomal recessive.
The gene mutation that causes OI affects the formation and strength of the bone while also affecting other organ systems. Broken bones are very common and increase in frequency as the patient ages. As a life-long disorder, OI occurs across races irrespective of sex.
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Types of OI
There are eight major types of OI that can be classified as mild, moderate, or severe OI:
- Mild: Type I
- Moderate: Type IV, V, VI, and VII
- Severe or most severe: Type II, III, and VIII
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Mild forms of OI (type I)
Type I, which is the most common and mild form of OI that is dominantly inherited, is characterized by mild fragile bones, few fractures, and minimal malfunction of the limbs.
When a child starts to walk, the bones might fracture or the patient might experience dislocations of the shoulder and the elbow. In some children, long bones are prone to multiple fractures, whereas vertebrae may experience compression fractures. Overall, chronic pain is often a hallmark of this condition in affected children.
The time period between the fractures may vary significantly between patients with OI Type I. Even though the stature of the child with OI may be slightly shorter as compared with non-OI children, the stature will be within the normal age ranges.
The occurrence of hearing loss in these patients will be high beginning from early childhood. The collagen levels in patients with OI Type I will be lower, while the structure of the collagen will be normal.
Moderate forms of OI
Retarded growth is a significant factor that distinguishes OI Type IV from OI Type I. The severity of the retardation may vary from moderate to severe.
Typically, children with moderate forms of OI will be shorter or of less than average height for their age, with short humerus and femur. The child will have a fracture when learning to walk. Scoliosis, compression of the vertebrae, fractures in long bone, ligament laxity, and bowed long bones are common.
The inheritance pattern in OI Type IV is autosomal dominant and does not involve a type 1 collagen deficiency; however, collagen is reduced in the bone matrix. The color of the sclera is light blue in infants with varying intensities of the color. The sclera may become more white as the patient gets older.
Inherited dominantly, the fracture frequency and degree of skeletal malformation in OI Type V are comparable to OI Type IV.
OI Type VI is very rare and is characterized by distinctive mineralization defects in the bone biopsy.
Short stature, Coxa vara, and shorter leg bones, humerus, and femurs are common in Type VII OI. The appearance and symptoms in some cases of OI Type VII are analogous to OI Types IV in many aspects. The recessive inheritance of CRTAP gene mutation causes OI Type VII, which is considered to be a moderate form of OI.
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Severe forms of OI
OI Type II, which is the most severe form of OI, is characterized by low weight, soft skulls, small chests, and very small limbs in infants. The legs of these patients will be in a frog-leg position, with intrauterine fractures that can be identified in the vertebrae, long bones, and skull.
Most of the infants with OI Type II die within a few weeks of birth due to complications arising in the respiratory and cardiac systems. While a few infants may live longer, the lungs are underdeveloped; therefore, respiratory and swallowing problems are common. Type 1 collagen gene mutations or parental mosaicism is the cause of OI Type 2.
Characterized by dominant gene mutations in collagen type 1 that are spontaneous, children who stay alive in the neonatal period are prone to OI Type III.
At birth, the symptoms of OI Type III include slightly short and bowed limbs, soft calvarium, and smaller chests. Infants with this condition often have difficulties with respiration and swallowing. Due to disruption in the development of the growth plates, there is a progressive deformity in this form of OI. Children will have short stature and in adulthood, the height of the individual will be less than 3 feet.
As type I collagen is reduced in the bone matrix, many long-bone fractures can occur while the degree of fragility of the bone and the rate of fracture rate may vary significantly. Frequently, individuals who suffer from spine curvatures, scoliosis, chest abnormalities, long bone fractures, and vertebrae will experience compression fractures.
A large head, under-developed face bones, and the triangular face shape are characteristic of OI Type III. The color of the sclerae will be gray, white, purple, or tinted blue. Though Dentinogenesis imperfecta is not widespread, it is common in OI Type III.
The LEPRE1 gene mutations may lead to the absence or severe deficiency of prolyl 3-hydroxylase activity resulting in OI Type VIII. Severe deficiency in growth and under-mineralization of the skeleton will be extreme in these types.
The appearance and symptoms of OI Type VIII are analogous to OI Types II or III in terms of their appearance and symptoms, with white sclerae being the only exception.