To present molecular diagnosis and genetic counseling for osteogenesis imperfecta (OI) type IV in a pregnancy carried to term with favorable outcome.
A 34-year-old, primigravid woman was referred for genetic counseling in the second trimester because of advanced maternal age and a positive family history of OI type IV. Her husband had a weight of 40 kg and a height of 145 cm. Her husband had normal sclerae, moderate short stature and osteopenia, and had sustained multiple fractures with minimal trauma since childhood. The husband and his relatives including his mother, aunt, uncle, sister and nephew had suffered from OI type IV. Molecular analysis of the affected individuals in the family revealed a G to T change at position c.2197 (c.2197G>T, GGT>TGT) of the exon 37 in the COL1A2 gene leading to a change of glycine at codon 733 to cysteine (G733C). Cytogenetic analysis of cultured amniocytes revealed a karyotype of 46,XY. Molecular analysis of uncultured amniocytes revealed a missense mutation of G733C in COL1A2. Level II ultrasound at 23 weeks of gestation revealed significant shortness of the limbs. Small stature for gestation age was obvious in the third trimester. At 37 weeks of gestation, a fetal ultrasound showed curvature of the femurs. A cesarean section was performed at 38 weeks of gestation, and a male baby was delivered uneventfully. The baby had normal sclerae, a body weight of 2190 g (< 5th centile) and a body length of 46 cm (< 5th centile). X-rays showed thin clavicles and short curved femurs but no bony fractures. No fractures were noted at the age of 1 month.
The present case adds to previous examples of favorable outcome in pregnancies with non-lethal forms of OI."