Teaching Case

Female neonate delivered with elective Caesarean section at 38 weeks of gestation, because of suspicion of severe skeletal dysplasia based on prenatal ultrasound. After delivery, the neonate deceased within four hours due to respiratory failure.

Prenatal ultrasound performed at 27 weeks of gestation showed severe skeletal dysplasia with a relatively small chest and multiple intrauterine fractures (Fig. 1 a-e). After interdisciplinary discussion and genetic counselling, elective Caesarean section was performed.
Post-mortem radiographic findings revealed osteopenia and markedly decreased ossification of the skull (Fig. 2 a), disproportionally small maxillofacial structures, flattening of the occipital bone (Fig. 2 b) and platyspondyly (Fig. 3 a-c). The thoracic cage was narrowed and the ribs showed a beaded appearance (Fig. 3 b). There were multiple fractures of the long bones with surrounding callus resulting in shortening, bowing and deformity (Fig. 4).

Based on the antenatal findings on ultrasound and the postnatal radiographic findings, the diagnosis of osteogenesis imperfecta (OI) type 2 according to the Sillence and Glorieux classification was suggested. The diagnosis was confirmed postnatally by genetic testing consisting of analysis of COL1A1 and COL1A2 genes. OI is a genetic disorder characterized by bone fragility due to a defect of type I collagen. There are 7 types of OI, varying from mild to lethal (Fig. 5). The most common symptoms are bone fractures, skeletal deformity and short stature. Type 2 is a lethal form of OI incompatible with life. The cause of death is usually due to severe hypoxemia caused by pulmonary hypoplasia, leading to cardiac arrest or due to multiple fractures [1].
OI is a relatively uncommon disorder, affecting approximately 1 in 10, 000 to 20, 000 births [1]. Type 2 OI is rare, with an incidence of 1-2:100, 000 [2]. As a perinatal lethal condition it always presents as a de novo mutation [2].
Prenatal diagnosis can be made in severe forms of OI, such as type 2, by ultrasound during the second trimester. Ultrasound may show non-specific signs such as growth retardation and polyhydramnios. Other ultrasound findings include decreased echogenicity and increased plasticity of bone due to insufficient bone mineralization and micromelia. Intrauterine fractures with surrounding callus are readily detected. The role of other antenatal imaging modalities such as CT and MRI is limited [1].
Postnatal diagnosis of OI can be made solely on clinical findings only in severe cases. Conventional radiography is usually mandatory. Radiographic findings of type 2 OI consist of osteopenia of the skull with disturbance of intramembranous ossification, platyspondyly, small beaded ribs, severely deformed extremities and broad, crumpled, bent femurs [1-3].
Fig. 6. shows characteristic radiographic features of some other types of OI.
Confirmation of the diagnosis of type 2 OI can be obtained either with direct COL1A1/COL1A2 gene sequencing or biochemical analysis of type 1 collagen in cultured fibroblasts from a skin biopsy [2].
The prognosis of OI type 2 is poor, with some of the fetuses already dead in utero. Most infants will die in the perinatal period, 60% during the first day. Because of this infaust prognosis, the management is mainly supportive, with assisted ventilation and pain control [2].