Thanatophoric dysplasia is the most frequent form of lethal osteochondrodysplasias with an estimated frequency of nearly of 1 in 20,000 births. Thanatophoric dysplasia is classified into two types: TD type 1 patients have curved femurs with or without a cloverleaf skull, and in the second type patients always have straight femurs and a cloverleaf skull. Affected individuals usually die within minutes or days after birth.
Thanatophoric dysplasia is an autosomal dominant disorder. Prenatal diagnosis is commonly accomplished in the second-trimester scan, but occasionally thanatophoric dysplasia may not be clearly distinguished from the other osteochondrodysplasias, with consequent important prognostic implications. However, in order to confirm the diagnosis, complementary radiological, pathological and molecular studies are mandatory.
Thanatophoric dysplasia type I is associated with mutations in the transmembrane domains of the fibroblast growth factor receptor 3 (FGFR3) gene, located on the short arm of chromosome 4 (4p16.3).