Prenatal diagnosis and genetic analysis of type I and type II thanatophoric dysplasia

Thanatophoric dysplasia (TD) is one of the most common neonatal lethal skel etal dysplasias. Prenatal sonographic and molecular genetic diagnoses of th ree cases of TD type I (TD1) and one case of TD type II (TD2) are presented here. Two fetuses of TD1 were characterized by polyhydramnios, macrocephal y, short limbs, a narrow thoracic cage and curved short femora, but without a cloverleaf skull at 27 and 31 weeks' gestation, respectively. The third fetus with TDI was, however, not associated with macrocephaly, polyhydramni os, chest narrowing and severe femoral bowing on prenatal ultrasound at 18 weeks' gestation. The TD2 fetus was characterized by polyhydramnios, short limbs, a narrow thoracic cage, straight short femora, hydrocephalus and a c loverleaf skull at 24 weeks' gestation. Three-dimensional ultrasound was ab le to enhance the visualization or thickened, redundant skin folds and cran iofacial and limb deformities associated with TD. Molecular analysis of the fibroblast growth factor receptor 3 (FGFR3) gene by restriction enzyme dig estion analysis and direct sequencing using cultured amniotic fluid cells o r cord blood cells revealed a missense mutation of 742C -->T (Arg248Cys) in all cases with TD1 and a missense mutation of 1948A -->G (Lys650Glu) in th e case with TD2. The present report shows that adjunctive applications of m olecular genetic analysis of the FGFR3 gene and three-dimensional ultrasoun d are useful for prenatal diagnosis of TD. Copyright (C) 2001 John Wiley & Sons, Ltd.