What is osteogenesis imperfecta (OI)? Which organs are involved in osteogenesis imperfecta, and why?
OI, also known as “brittle bone” disease, is a group of diseases defined by similar clinical manifestations (brittle bones and blue sclerae) occurring to various degrees with a similar etiology. It affects 1 in 20,000 individuals. The inheritance pattern and penetrance are variable. Most are autosomal dominant (AD), although 35% are sporadic mutations. Most patients with OI have an AD defect in one of the genes that encode type I collagen (COL1A1, COL1A2), which accounts for the structure and physical properties of bone. The genetic defect causes a low production (50% of normal) of type I collagen which results in osteopenia and brittleness, leading to frequent fractures. Diminished type I collagen in the sclerae leads to translucency and apparent blueness, while in the teeth causes dentinogenesis imperfecta (opalescent teeth). Hearing loss can also occur.
Clinical syndromes of brittle bone disease are variable. Affected individuals may experience in utero death from fractures, live birth with wormian bones, short stature and multiple fractures, or live birth with mildly brittle bones and normal stature. The most severe forms of OI are typically spontaneous mutations or autosomal recessive (AR) genetic defects which affect proteins or enzymes that regulate type I collagen folding. Milder presentations are typically due to AD defects of one of the COL1A genes
