Osteogenesis imperfecta type II

Osteogenesis imperfecta type II


Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous group of inherited disorders of connective tissue frequently caused by abnormalities in type I collagen. It is characterized by bone fragility, osteopenia and progressive skeletal deformities. Associated features in some individuals include blue sclerae, dentinogenesis imperfecta, hearing loss, deformity of the spine and long bones and joint hyperextensibility. It is characterized by marked inter- and intra-familial variability, making prenatal diagnosis difficult even in families with an established diagnosis. The various forms of osteogenesis imperfecta appear to be caused by different mutations in the gene encoding type 1 collagen. Specific to type II, proteoglycans, which are regarded as inhibitors of calcification, have been found in substantial amounts in abnormally large osteocytic lacunae of OI fetal bone. The disorder is currently categorized into 4 major types, according to the phenotypic classification of Sillence. There are several sub-types as well as marked heterogeneity at the clinical, radiological and molecular level within these groups. Osteogenesis imperfecta type II is characterized by intrauterine or early neonatal death, and may be classified into 3 subgroups (A,B,C) according to Sillence on the basis of radiological appearances.


Osteogenesis type II has been diagnosed successfully prior to 20 weeks gestation. In Type IIA is there is bone shortening, diffuse hypomineralization and multiple fractures. There are short, thick, beaded ribs and a small chest. The long bones are crumpled (accordion-shaped), short and broad. Vertebrae are flattened, with broad round ilia and broad pubic bones. The facial bones and cranial vault are very poorly ossified. At birth, infants are small for gestational age and often premature. They have blue/black sclerae and marked moulding of the face and cranium. Twenty percent are stillborn, and of the remainder, only 10% are alive at 1 month. Type II A is probably the result of a new dominant mutation. Type IIB is characterized by shortening of the femur alone, mainly normal bone density and isolated fractures. There is patchy mineralisation of the skull, and the ribs are thin and wavy without beading or fractures. The femurs are short, broad and crumpled, while the tibiae are thickened and angulated. Vertebral bodies are of a more normal height than in type IIA. The mean gestational age at birth is 37 weeks and the mean survival 14 hours. Inheritance is believed to be autosomal dominant, with parental germ cell mosaicism accounting for observed sibling recurrences. Type IIC is thought to be autosomal recessive in its inheritance. There is marked hypo-ossification of the skull. Long bones are slender with inadequately modelled shafts, angulation deformities and numerous fractures. The ribs are slender and beaded, although less uniformly than in type IIA.

Differential Diagnosis

Campomelic dysplasia presents with bowing of the tibiae and femora. Associated craniofacial anomalies including macrocephaly, cleft palate, micrognathia and hypoplastic scapulae are present in over 90% of cases and should help to distinguish the two conditions.

Sonographic Features

Long bones are short, crumpled, angulated, fractured, and locally thickened, with callous formation

Ribs are fractured

The chest is small

The skull is thin and compressible

Decreased fetal movements

Hydrops fetalis may be evident

Associated Syndromes 


Sanders RC, Greyson-Fleg RT, Hogge WA et al Osteogenesis imperfecta and campomelic dysplasia: difficulties in prenatal diagnosis J Ultrasound Med 13: 691-700
Bulas DI, Stern HJ, Rosenbaum KN et al Variable prenatal appearance of osteogenesis imperfecta J Ultrasound Med 13: 419-427
Constantine G, McCormack J, McHugo J, Fowlie A Prenatal diagnosis of severe osteogenesis imperfecta Prenat Diagn 11:103-110
Sillence DO, Barlow KK, Gerber AP et al Osteogenesis imperfecta type II: delineation of the phenotype with reference to genetic heterogeneity Am J Med Genet 17:407-423
Dinno ND, Yacoub UA, Kadlec JF et al Midtrimester diagnosis of osteogenesis imperfecta, type II Birth Defects 18:125-132