Incidence

1 in 10,000 births

Prevalence

6–7:100,000 persons

Genetics

• The majority of cases (∼85%) are due to autosomal dominant mutations in the genes encoding type I collagen, COL1A1 and COL1A2.
• Traditionally, OI has been classified due to clinical presentation, as initially described by Sillence. However, in the last decade, new dominant and recessive forms caused by mutations in several different genes have been described, which has altered the classification of OI. Modified classification typing is noted in parentheses below:
  • Type I (classic nondeforming OI with blue sclerae): usually normal stature, fractures infrequent, and usually in prepubertal years. No bowing of long bones. Blue sclerae. Early hypoacusia common.
  • Type II (perinatally lethal OI): death usually in perinatal period due to pulmonary hypoplasia. Intrauterine fractures, shortened long bones, and blue sclerae are common.
  • Type III (progressively deforming OI): severely shortened stature, severe deformities of long bones, prevalent vertebral fractures, scoliosis, chest deformities. Characteristic triangular face.
  • Type IV (common variable OI with normal sclerae): DI common, short stature, bowing of long bones, vertebral fractures, scoliosis, and joint laxity. Patients are usually ambulatory. Sclerae are usually normal hue.
  • Other clinical forms of OI
  • OI with calcification in interosseous membranes (type V): autosomal dominant mutations of IFITM5 gene. Patients can develop hyperplastic calluses in long bones after fracture causing tender, firm swellings over bones. Blue sclerae and DI not common.
  • Type VI: rare form of recessive OI due to mutations in SERPINF1 gene causing severe matrix mineralization defect. No blue sclerae, DI, or wormian bones. Rhizomelic shortening of extremities.
  • Type VII: recessive mutation of CRTAP gene causing rhizomelia, early fractures, and osteopenia
  • Type VIII: absence or severe deficiency of prolyl 3-hydroxylase activity due to mutations in the LEPRE1 gene
  • Type IX: moderate to severe OI caused by defects in the PPIB gene
  • Type X and XI: chaperone defects caused by SERPINH1 or FKBP10 mutations. Type XI due to FKBP10 mutations can cause progressively deforming OI or Bruck syndrome.