Osteogenesis Imperfecta

Sandra R Silva, MD Philippe Jeanty, MD, PhD

Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-07-07 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonyms: Osteogenesis imperfecta congenital, Van der Hoeve syndrome, Lobstein disease, trias fragilitas osseum, brittle bone disease, and Vrolik disease[2].

Definition: Heterogeneous group of genetic disorders (classically divided in four types assessed by Sillence: I, II or congenital, III, and IV) characterized by severe bone fragility, leading to abnormal ossification and multiple fractures[1]. The 4 types are:

·         Type I: does not present prenatal deformities, and the diagnosis is made after birth when the limb deformities start to develop.

·         Type II: the most severe form: presents with multiple skeletal malformations, such as bone shortening and angulation, due to multiple fractures, demineralization of the skull, narrow and bell-shaped chest caused by fractures of the ribs, decreased fetal movement, wrinkling of the surface of the bones due to multiple fractures.

·         Type III: less severe form than type II, usually presents multiple fractures at birth, with development of progressive bone deformities from neonatal period to adolescence. Detectable as early as second trimester in the Type IIIc.

·         Type IV: this is the mildest presentation of the disorder, not detectable prenatally. It usually involved premature osteoporosis in the 4-5th decades of life.

Incidence: 0.4:10,000 live births and about half of it (0.19:10,000) represents Type II[3].

Etiology: In the majority of the cases of both Types I and IV, an autosomal dominant pattern is involved. Type II is a de novo dominant mutation (with a few reports of autosomal recessive pattern), and Type III is either autosomal recessive or dominant[4].

Recurrence risk: Depends on the form of transmission. In general, it ranges from 2-5% for type II, if it is not caused by a spontaneous mutation1.

Diagnosis: The sonographic findings that may be present (in particular in type II) include broad, short, fractured long bones (figs. 1-2), with a wrinkled appearance caused by callus formation, decreased ossification of the skull (fig. 3), with increased visualization of the intracranial structures, small bell-shaped chest (figs. 4-5), abnormal skull shape, broad irregular ribs, angulation of the long bones, abnormal face. A typical finding of OI type II is the ability to see both corticals of a bone. Normally the distal cortical is shadowed out by the proximal, but not in the severe deminaralization of OI (achondrogenesis and hypophosphatasia may present the same finding). Most of the anomalies can be detected in utero by ultrasound in early second trimester. A normal ultrasound for a high risk patient does not exclude the disorder. In general, if the fractures do not occur in utero, the diagnosis is made only after birth1[5].

7565-118 fig 1

75651110 fig 2

Fig. 1&2: The humerus is 13mm and the femur measures 14mm (below the 5th centile).

7565-115 fig 3

Fig. 3: The skull demonstrates markedly decreased echogenicity and is readily compressible even with moderate transducer pressure (left).

75651112 fig 4

Fig. 4: The ribs are soft and the chest has a bell-shape configuration.

75651115 fig 5

Fig. 5: Frontal X-rays of the fetus. Note the poor mineralization and the numerous fractures.

Genetic anomaly: A disorder in one of the two genes responsible for the Type I collagen production (COLIA1 and COLIA2) is the cause of the disease.

Pathogenes:  A defect of formation, organization, and chemical composition in Type I collagen (which is found in skin, ligaments, tendons, demineralized bone and dentine) is responsible for decreased mineralization and bone fragility6.

Associated anomalies: Kyphoscoliosis, deafness, hypotonia, inguinal hernias, hydrocephalus, hydrops, prenatal grown deficiency4.

Differential diagnosis: Hypophosphatasia (infantile form), Achondrogenesis, and other short-limbed dwarfisms1.

Prognosis: Type II osteogenesis imperfecta is uniformly lethal, and the most frequents causes are cerebral hemorrhage and respiratory failure. The other forms develop after birth, progressive deformities of the long bones, and short stature1 5.

Management: Due to the uniformly fatal outcome, termination of pregnancy could be offered at any stage of the gestation when type II is diagnosed. For the other forms, termination could be offered before viability. If continuing the pregnancy is opted for, standard prenatal care should not be altered.


[1] Kennon JC, Vitsky JL, Tiller GE, Jeanty P.  Osteogenesis imperfecta. Fetus 1994, 4(4): 11-14.

[2] Hale AV, Medford E, Izquierdo LA, Curet L. Osteogenesis imperfecta. Fetus 1992, 2(6): 5-10.

[3] Romero R, Pilu GL, Jeanty P: Prenatal diagnosis of congenital anomalies. CT Appleton and Lange, Norwalk, l988.

[4] Jones KL. Osteogenesis Imperfecta syndrome, Type I in Smith’s recognizable patterns of human malformation.WB Saunders Company – Philadelphia, 1997, 486-487.

[5] Benacerraf BR. Osteogenesis Imperfecta in Ultrasound of fetal syndromes. Churchill Livingstone - New York, 1998, 229-235.

[6] Prockop DJ: Mutations in collagen genes as a cause of connective tissue diseases. N Engl J Med 1992, 326:8.

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