Review Question - QID 5151

Osteogenesis imperfecta is caused by mutations in type I collagen genes COL1A1 or COL1A2 in 85% of cases.

Pathological manifestions of osteogenesis imperfecta (OI) occur because of abnormal type 1collagen . Clinical manifestations include multiple fractures, blue sclera, and scoliosis. The genes responsible for normal collagen synthesis are COL1A1/COL1A2 and many mutations have been characterized which result in OI. Quantitative collagen defects result in a milder phenotype whereas qualitative collagen defects result in more severe clinical manifestations.

Zeitlin et al. reviewed osteogenesis imperfecta. They report that bone fragility in OI stems from decreased bone mass, disturbed organization of bone tissue, and altered bone geometry (size and shape). They found that cyclical intravenous pamidronate administration reduces bone pain and fracture incidence while increasing bone density and level of ambulation with minimal side effects.

Burnei et al. review the diagnosis and treatment of OI. They report that medical treatment with bisphosphonates, even in patients younger than age 2 years, have become widely accepted in the symptomatic treatment of OI. They report alendronate has proven to beneficially decrease fracture frequency while improving vertebral bone density and quality of life.

Illustration A shows the Sillence Classification of Osteogenesis Imperfecta.

Incorrect Answers:
Answer 1: Marfan's syndrome is an autosomal dominant disorder that affects the Fibrillin-1 gene.
Answer 2: Osteopetrosis is an autosomal dominant disorder that affects the production of macrophage colony-stimulating factor.
Answer 4: Achondroplasia is an autosomal dominant disorder that affects FGFR-3.
Answer 5: Multiple Epiphyseal Dysplasia Type 1 and Type 2 are autosomal dominant diseases that affect cartilage oligomeric matrix protein and Type IX collagen, respectively.