Makindo Medical Notes

Related Subjects: |Osteoporosis |Osteogenesis Imperfecta

Osteogenesis imperfecta is a dominantly inherited disorder of collagen. Those surviving into adulthood often have the least severe form (Type I). It is characterized by fragile bones that break easily, among other systemic effects.

About:

• Brittle bones: The hallmark feature of osteogenesis imperfecta, leading to frequent fractures.
• Osteopenia/osteoporosis: A reduction in bone mass and density, which predisposes to fractures.
• Inheritance: Most cases are autosomal dominant, meaning one copy of the mutated gene from an affected parent is enough to cause the condition.
• Collagen defect: The collagen, a key structural protein, is either of poor quality or reduced in quantity, weakening the bones.

Aetiology:

• Affects approximately 6 to 7 per 100,000 people worldwide.
• Results from mutations in the COL1A1, COL1A2, CRTAP, and LEPRE1 genes, which are responsible for collagen production and quality.

Types:

• Type I (Mild): Most common and least severe form. Patients typically experience bone fractures, often before puberty. Blue sclerae (bluish tint of the whites of the eyes) may be present. Patients generally have normal or near-normal stature. Hearing loss and loose joints are common features.
• Type II (Perinatal Lethal): The most severe form, often fatal shortly after birth due to respiratory issues. Babies are born with multiple fractures, severe bone deformities, and underdeveloped lungs.
• Type III (Progressive Deforming): Progressive bone deformities with frequent fractures. Short stature, barrel-shaped rib cage, spinal curvature, and respiratory complications are often present.
• Type IV (Moderate Severe): Intermediate between Type I and Type III in terms of severity. Frequent fractures before puberty, mild to moderate bone deformities, and short stature.
• Type V: Similar to Type IV but distinguished by hypertrophic calluses at fracture sites and calcification between the radius and ulna.
• Type VI: Resembles Type IV, but with characteristic mineralization defects observed in biopsied bones.
• Type VII: A rarer form, largely confined to certain Canadian Native populations. Characterized by short stature, short humeri and femora, and coxa vara (a hip deformity).

Clinical Features:

• Fractures: Frequent fractures often occur with minimal trauma or even during normal handling in babies.
• Blue sclerae: A blue, purple, or grey tint to the whites of the eyes, particularly seen in Types I and III.
• Triangular facies: Patients may develop a triangular-shaped face, along with macrocephaly (abnormally large head).
• Hearing loss: Often begins in adolescence, due to bone abnormalities in the inner ear.
• Defective dentition: Brittle teeth prone to cavities and cracking, known as dentinogenesis imperfecta.
• Barrel chest: A rounded, protruding chest often associated with bowed legs or scoliosis (spinal curvature).
• Joint laxity: Increased flexibility of the joints, leading to frequent dislocations.
• Short stature: Patients with moderate to severe types often have significantly shorter-than-average height.

Differentials:

• Non-accidental injury (child abuse): Osteogenesis imperfecta may be misinterpreted as non-accidental injury due to frequent fractures. Detailed history and clinical assessment are important to differentiate.
• Osteoporosis: Common causes of osteoporosis should be considered in the differential diagnosis, especially in adults with frequent fractures.

Investigations:

• Radiology: X-rays typically show fractures and bone deformities. In more severe cases, healed fractures from birth may also be seen.
• Genetic testing: Confirms mutations in the COL1A1, COL1A2, or related genes, helping in diagnosis and family planning.

Management:

• Bisphosphonates: These medications slow down bone resorption, reducing the number of fractures and bone pain in children. They can be administered orally or intravenously, but require close monitoring by trained doctors.
• Immobilization: Casting, bracing, or splinting fractures is necessary to keep bones still and aligned, promoting proper healing.
• Exercise: Once fractures have healed, movement and weight-bearing exercises are encouraged to improve mobility and reduce the risk of future fractures.
• Surgery: May be necessary for scoliosis, significant deformities, or recurrent fractures. Metal rods can be inserted into long bones to strengthen them, and spinal fusion may be performed for scoliosis.
• Adults: Should avoid smoking, drinking alcohol, and prolonged use of steroids, as these can negatively impact bone density and increase the risk of fractures.

References:

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