Makindo Medical Notes.com

Related Subjects: |Osteoporosis

Osteogenesis imperfecta is a dominantly inherited disorder of collagen, and those surviving to adulthood likely have the type 1 (least severe) form. Clinical features include blue sclerae (not always present), early-onset deafness and dentinogenesis imperfecta.

About

• So called 'Brittle bones'. Dentition also affected
• Osteopenia/osteoporosis lead to bone fractures
• Long bone and vertebral
• Most are autosomal dominant

Aetiology

• 6 to 7 per 100,000 people worldwide
• Mutations in the COL1A1, COL1A2, CRTAP, and LEPRE1 gen

Types

• Type I (Mild): Most common and mildest type. Bones predisposed to fracture. Most fractures occur before puberty. Normal or near-normal stature. Stature may be average or slightly shorter than average as compared with unaffected family members, but within the normal range for age. Loose joints and muscle weakness. The sclera (whites of the eyes) often have a blue, purple, or grey tint. Triangular face. The tendency toward spinal curvature. Bone deformity absent or minimal. Brittle teeth are possible. Hearing loss is possible, often beginning in teens. Collagen structure is normal, but the amount is reduced. Dominantly inherited; spontaneous mutations are common. (It can be passed from parent to child, or occur in a previously unaffected family due to a new mutation.)
• Type II (Perinatal Lethal): Most severe form. Frequently lethal at or shortly after birth, often due to respiratory problems. Numerous fractures and severe bone deformity evident at birth. Small stature with underdeveloped lungs, and low birth weight. Collagen is improperly formed. Results from new dominant mutations to type 1 collagen genes, parental mosaicism or recessive inheritance of a mutation to CRTAP gene.
• Type III (Progressive Deforming): Progressive bone deformity, often severe. Bones fracture easily. Fractures are often present at birth, and x-rays may reveal healed fractures that occurred before birth. Short stature. Sclera have a blue, purple, or gray tint. Loose joints and poor muscle development in arms and legs. Barrel-shaped rib cage. Triangular face. Spinal curvature and compression fracture of vertebrae. Respiratory problems possible. Brittle teeth are common but not universal. Hearing loss possible. Reduced amounts of poor-quality type I collagen. Results from dominant mutations in type I collagen genes, (often the result of spontaneous mutation, parental mosaicism) or recessive inheritance of a mutation to CRTAP gene.
• Type IV (Moderate Severe): Between Type I and Type III in severity. Bones fracture easily, most before puberty. Shorter than average stature for age. Sclera are white or near-white (i.e., normal in colour). Mild to moderate bone deformity. Spinal curvature and compression fracture of vertebrae. Barrel-shaped rib cage. Triangular face. Brittle teeth are possible. Hearing loss possible. Reduced amounts of poor-quality type I collagen. Results from dominant mutations in type I collagen genes, (often the result of spontaneous mutation, parental mosaicism) or recessive inheritance of a mutation to CRTAP gene.
• Types V: Similar to Type IV in appearance and symptoms of OI. Large hypertrophic calluses at fracture or surgical procedure sites. Calcification of the membrane between the radius and ulna to restrict forearm rotation. Does not have type I collagen mutation. Dominant inheritance pattern.
• Types VI: Similar to Type IV in appearance and symptoms of OI. Distinguished by a characteristic mineralization defect is seen in biopsied bone. Does not have type I collagen mutation. The mode of inheritance is unknown.
• Types VII: Limited to a set of Canadian Natives. Short humeri and femora. Short stature. Coxa vara. Results from recessive inh

Clinical

• Fractures and pain on simple handling with babies
• Blue sclerae and triangular facies, Macrocephaly and Hearing loss
• Defective dentition with brittle teeth cavities and cracking
• Barrel chest with bowed legs or progressive scoliosis
• Limb deformities and fractures, Joint laxity, Short stature

Differentials

• Non-accidental injury
• Osteoporosis and its causes

Investigations

• Radiology: show fractures and deformity

Management

• Bisphosphonates, given to the child either by mouth or intravenously, slow down bone resorption. In children with more severe osteogenesis imperfecta, bisphosphonate treatment often reduces the number of fractures and bone pain. These medications must be administered by properly trained doctors and require close monitoring.
• Immobilization. Casting, bracing, or splinting fractures is necessary to keep the bones still and in line so that healing can occur.
• Exercise. After a fracture, movement and weight-bearing are encouraged as soon as the bone has healed. Specific exercises will increase mobility and decrease the risk of future fractures.
• Surgery: for scoliosis, deformity or fractures. Metal rods may be inserted in the long bones of the arms and legs to add strength. Spinal fusion for scoliosis
• Adults with OI should avoid activities such as smoking, drinking, and taking steroids because they have a negative impact on bone density.

References

• Osteogenesis Imperfecta: A Guide for Medical Professionals, Individuals, and Families Affected by OI