FGFR3-related short limb skeletal dysplasia [DS:H00505]
Description
Thanatophoric dysplasia (TD) is a congenital skeletal dysplasia characterized by marked underdevelopment of the skeletal system and short-limb dwarfism. It is the most common form of lethal skeletal dysplasia syndromes. Two types of TD have been described. Type I TD (TDI) is associated with curved and short femurs. The shortness of the bones in type II TD (TDII) is not as significant as in TDI. TDII is characterized by straight femurs and cloverleaf skull deformity. Other features common to type I and type II include short ribs, narrow thorax, macrocephaly, distinctive facial features, brachydactyly, hypotonia, and redundant skin folds along the limbs. Most affected infants die of respiratory insufficiency shortly after birth. Both TDI and TDII are caused by heterozygous fibroblast growth factor receptor 3 (FGFR3) missense mutations. Its incidence is 1 in 20 000 to 50 000 births and it is an autosomal dominant condition. The mutation in most TD cases is de novo.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD24 Syndromes with skeletal anomalies as a major feature
H01750 Thanatophoric dysplasia
TDI is known to arise because of five different mutations, all involving the substitution of an amino acid with a cysteine in FGFR3: Arg248Cys, Ser249Cys, Gly370Cys, Ser371Cys, and Tyr373Cys.
See also H00505 FGFR3-related short limb skeletal dysplasias.
