Prenatal diagnosis of thanatophoric dysplasia by 3-D helical computed tomography and genetic analysis

We report the first case of thanatophoric dysplasia (TD) successfully diagnosed in utero by a combination of 2-D ultrasound, computed tomography (CT) 3-D imaging and genetic analysis at 26 weeks' gestation.

Prenatal sonographic examinations performed at 23 weeks' gestation revealed micromelic shortening of the limbs, reduced thoracic cavity and a presence of cloverleaf skull deformity. Based on these findings, a lethal form of skeletal dysplasia was suspected and a helical CT imaging with 3-D reconstruction depicted skeletal abnormalities which suggested TD. The prenatal diagnosis was affirmed on amniotic fluid cells by DNA mutation analysis of the fibroblast growth factor receptor 3 gene.

A missense mutation (tyrosine 373 to cysteine) was detected, and was diagnosed as TD type I.

Helical CT imaging with 3-D reconstruction and molecular testing are useful adjuncts to 2-D ultrasonography in the diagnosis of lethal skeletal dysplasias, allowing for appropriate perinatal support including genetic counseling.