Sonographic and molecular diagnosis of thanatophoric dysplasia type I at 18 weeks of gestation

Thanatophoric dysplasia is the most common type of lethal skeletal dysplasi a. It can usually be diagnosed with ultrasound, but differential diagnosis with other osteochondrodysplasias is not always possible. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have been demonstrated to cause two distinct subtypes of the disorder. We describe a case of thanatop horic dysplasia type I diagnosed at 18 weeks of gestation by ultrasonograph y. Genomic DNA obtained by chorionic villus sampling showed a C to G substi tution at position 746 in the FGFR3 gene, resulting in a Ser249Cys substitu tion already known to be associated with type I disease. Implications for p erinatal management are discussed. Copyright (C) 2000 John Wiley & Sons, Lt d.