Osteogenesis Imperfecta (OI)
Osteogenesis Imperfecta, also known as brittle bone disease, an inherited connective tissue disorder, is a group of diseases defined by similar clinical manifestations (brittle bones and blue sclerae) occurring to various degrees with a similar etiology. Most patients with OI have an autosomal dominant (AD) defect in one of the genes encoding type I collagen (COL1A1, COL1A2), which is necessary for the structure and physical properties of bone. The genetic defect causes 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, and 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, a live birth with wormian bones, short stature, and multiple fractures, or a live birth with mildly brittle bones and normal stature. The most severe forms of OI typically involve spontaneous mutations or autosomal recessive (AR) genetic defects affecting other proteins or enzymes that regulate type I collagen folding, resulting in a more severe phenotype, whereas the milder presentations are AD defects of one of the COL1A genes described above.
Sillence classification of OI
The original Sillence classification grouped OI into four clinical categories of severity, which has since been expanded to seven types. Multiple different type I collagen mutations may be responsible for each Sillence type.
Diagnosis is primarily clinical. Several laboratories can perform collagen biochemical and molecular (DNA sequencing) analysis from a skin biopsy. Bisphosphonate therapy may be beneficial, especially intravenous pamidronate and zoledronic acid. Corrective surgery, bracing, and physical therapy are also important.
Hyperflexible joints are common. Joint hypermobility decreases with age. Symptoms caused by increased joint mobility can range from arthralgias to dislocation or injury. Individuals with severe hypermobility and recurrent dislocations may have Ehlers-Danlos-Syndrom (EDS).
The Beighton score for joint laxity and hypermobility uses a simple 9-point system. A score of 5 or more indicates hypermobility.