Thanatophoric dysplasia

Thanatophoric dysplasia type 1 and type 2 are caused by a mutation in one copy of fibroblast growth factor receptor-3 (FGFR3) gene. Normally, we have two copies of every gene. When a disease occurs with a mutation in only one copy of the gene, it is said to be dominant, whereas if the disease occurs only when there are mutations in both copies of the gene, it is said to be recessive. Thanatophoric dysplasia is a dominant disorder.

Thanatophoric dysplasia type 1 and type 2 are both caused by having a mutation in the FGFR3 gene, however, all cases of thanatophoric dysplasia type 2 have had a specific mutation called the p.Lys650Glu mutation. Although genetic testing can be helpful in confirming a diagnosis of thanatophoric dysplasia, the FGFR3 gene is a little unusual in that other types of mutations within the FGFR3 gene can also cause different types of skeletal dysplasias, including achondroplasia (OMIM 100800), Crouzon syndrome (OMIM 612247), hypochondroplasia (OMIM 146000), and Muenke syndrome (OMIM 602849).

Genetic testing should be performed by a laboratory that has expertise in the interpretation of changes to the FGFR3 gene, since different types of changes can cause overlapping, but different disorders.