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  • Updated 09.05.2020
  • Released 11.13.2001
  • Expires For CME 09.05.2023

Osteogenesis imperfecta type II: cerebral dysgenesis



In this article, the author provides the pathologic and clinical details of the perinatal lethal and usually dominant form (type II) of osteogenesis imperfecta. New mutations responsible for recessive forms are described. Abnormalities in collagen, which develop from hundreds of different mutations in type I collagen genes, lead to exceptionally brittle bones that become markedly shortened by characteristic, telescoping fractures. The calvaria is thinned, and the brain is enlarged and altered by a host of changes, chiefly neuronal migrational defects. Additional anomalies are recognized and vary among the different types of osteogenesis imperfecta. New forms of treatment are reviewed, and unresolved issues are identified.

Key points

• Osteogenesis imperfecta consists of a diverse collection of congenital and heritable (autosomal dominant or, less often, recessive) disorders of connective tissue, which result in fragile and easily fractured bone.

• Osteogenesis imperfecta type II is a perinatal lethal form that involves approximately 4% of all patients with osteogenesis imperfecta.

• In osteogenesis imperfecta type II, cerebral dysgenesis takes several forms but often involves neuronal migration defects or subcortical angiomatosis.

• In patients with nonlethal forms, therapy continues to be refined; in addition to surgery, medical treatment of bone fragility includes the use of bisphosphonate and, in the early stages of development, pre- and postnatal stem cell transplantation.

Historical note and terminology

Osteogenesis imperfecta, a congenital disease characterized by defective bone formation, has been recognized and studied for many decades. One of the earliest cases appeared in Vrolik’s Handbook of Pathological Anatomy, published between 1842 and 1844 (12). In this “brittle bone disease,” bones are abnormally thin or broad and fracture easily, often giving pathognomonic appearances radiographically. Traditionally, cases have been categorized into 4 types with additional subtypes. Some now consider osteogenesis imperfecta to exist in up to 8 forms (136; 103). For purposes of this review, a thorough tabulation of the many details of these types seems unwarranted, and discussion will be oriented toward changes associated with Type II. The group of disorders constituting osteogenesis imperfecta is heritable and presents as autosomal recessive or autosomal dominant conditions. Type II, the perinatal lethal type, can follow either pattern, but the dominant form is considerably more common. Type II is rare within the spectrum of osteogenesis imperfecta patients. In 1 study of 57 patients, only 2 had Type II (138). Type II osteogenesis imperfecta has 3 variants: A, B, and C (158). In Type IIA, long bones are short and broad, with a collapsed or telescoped appearance of multiple fractures; tibiae are angulated; ribs are focally thickened in a manner described as “continuously beaded.” In Type IIB, long bones are similarly altered, but ribs are normal or only partially beaded. In Type IIC, long bones are thin and rectangular with numerous fractures; ribs are thin and beaded. In concert with molecular and other developments, workers continue to suggest modifications to this classification (175).

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