A case of antenatal-suspected thanatophoric dysplasia type 1 turning out as rather osteogenesis imperfecta type 2

Case: A 26 year old patient 2 gravida, 0 para was referred to our prenatal diagnosis unit at 22 weeks' gestation because of a previous scan showing strong suspicion of thanatophoric dysplasia type 1. The parents were nonrelated. Family history was unremarkable.

Material and methods: Abdominal sonography was performed using GE Voluson E8 RSA. Chromosome analysis from a sample of amniotic fluid was performed by optical microscopy. Amniotic fluid cells were subjected to a mutation analysis regarding the FGFR3-gene. A postpartum fetogramm was performed.

Results: Fetal ultrasound scan showed skeletal abnormalities with short limbs and ribs, a hypoechogenic cloverleaf skull, a narrow chest encasing hypoplastic lungs, gyration anomalies and rocker-bottom feet typical for thanatophoric dysplasia. The amniotic fluid index, umbilical artery doppler and fetal echocardiography were normal. After excessive interdisciplinary counselling, the patient opted for a fetocide. The stillborn girl of 205 g macroscopically exhibited the predicted features. Interestingly, a postpartum fetogramm hinted to osteogenesis imperfecta type 2 as the underlying pathology, displaying fractures of the upper extremities as well as multiple consolidated rib fractures and a retardation in the development of the frontal bone and the base of the skull as signs of bone fragility. Flattened vertebral bodies as typical for thanatophoric dysplasia were lacking. The postpartum cytogenetic report yielded unremarkable findings regarding the fetal karyotype. A molecular genetic analysis of the amniotic fluid cell culture regarding a mutation of the FGFR3-gene pathognomonic for thanatophoric dysplasia turned out to be inconspicuous.

Conclusion: The feasibility of prenatal ultrasound for the diagnosis of lethal skeletal dysplasias is confirmed. Nevertheless differentiation might be difficult between thanatophoric dysplasia and osteogenesis imperfecta type II. The fetogramm proved to be helpful. For further confirmation an analysis of COL1A1/COL1A2-genes mutations, typical for osteogenesis imperfecta, might be considered.