NIH Rare Diseases

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 93274Disease definitionThanatophoric dysplasia, type 2 (TD2) is a form of TD (see this term) characterized by micromelia, straight long-bones, macrocephaly, brachydactyly, shortened ribs and a clover-leaf skull (kleeblattschaedel).EpidemiologyThe prevalence is unknown but it is less common than TD1 (see this term).Clinical descriptionTD2 presents in the prenatal period (in the first to second trimester) with micromelia, long-bones (femurs) that are straight and not as short as those seen in TD type 1, platyspondyly of the vertebrae, narrow thorax, and a cloverleaf (trilobed) skull. Distinctive facial features include macrocephaly, frontal bossing, low nasal bridge, large anterior fontanel and proptosis. Polyhydramnios is common. Neonates usually die shortly after birth due to respiratory insufficiency and/or spinal cord/brain stem compression.EtiologyTD2 is caused by a single missense mutation (K650E) in the fibroblast growth factor receptor 3 (FGFR3) gene, located to chromosome 4p16.3.Genetic counselingTD2 is inherited autosomal dominantly but the majority of cases are due to a de novo mutation in the proband. Genetic counseling allows families who have already had one child with TD2 to know that recurrence rate is about 2%, so their chance of having a healthy child is high. Expert reviewers: Dr. Michael Bober and Ms. Angie DukerVisit the Orphanet disease page for more resources. Last updated: 10/1/2013

MalaCards based summary

Thanatophoric Dysplasia, Type Ii, also known as td2, is related to thanatophoric dysplasia, type i and blood group, i system, and has symptoms including seizures, macrocephaly and frontal bossing. An important gene associated with Thanatophoric Dysplasia, Type Ii is FGFR3 (Fibroblast Growth Factor Receptor 3), and among its related pathways/superpathways are Negative regulation of FGFR3 signaling and MicroRNAs in cancer. The drugs Linagliptin and Benzocaine have been mentioned in the context of this disorder. Affiliated tissues include bone, brain and spinal cord, and related phenotypes are digestive/alimentary and limbs/digits/tail

OMIM

Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman et al. (1992) classified cases of TD into subtypes based on the presence of curved as opposed to straight femurs; patients with straight, relatively long femurs always had associated severe cloverleaf skull and were designated TD type II (TD2), whereas TD cases with curved, short femurs with or without cloverleaf skull were designated TD type I (TD1; 187600) (Langer et al., 1987). (187601)

UniProtKB/Swiss-Prot

Thanatophoric dysplasia 2: A neonatal lethal skeletal dysplasia causing severe shortening of the limbs, narrow thorax and short ribs. Patients with thanatophoric dysplasia type 2 have straight femurs and cloverleaf skull.