Alternative titles; symbols
ORPHA: 93275; DO: 13481;
In a complete ascertainment of cases of lethal neonatal chondrodysplasia in the West of Scotland, Connor et al. (1985) identified a seemingly 'new' form resembling thanatophoric dysplasia (187600) but with recessive inheritance. The parents were healthy and not related. The features were micromelia, curved femora and humeri, hypoplasia of the iliac, pubic, and ischial bones, and death in the neonatal period. Cataracts, anemia and hepatosplenomegaly may also be features. The histopathology of the growth plate was similar to that of thanatophoric dysplasia, i.e., it was generally disrupted with inadequate columns and fibrous bands. Two female sibs were affected; the second was recognized by prenatal x-rays.
It is likely that this family represented an example of parental germinal mosaicism for a mutation in the fibroblast growth factor receptor-3 (FGFR3; 134934) gene, which was shown by Tavormina et al. (1995) to be the site of mutation in different types of thanatophoric dysplasia.
Connor, J. M., Connor, R. A. C., Sweet, E. M., Gibson, A. A. M., Patrick, W. J. A., McNay, M. B., Redford, D. H. A. Lethal neonatal chondrodysplasias in the West of Scotland 1970-1983 with a description of a thanatophoric, dysplasialike, autosomal recessive disorder, Glasgow variant. Am. J. Med. Genet. 22: 243-253, 1985. [PubMed: 3901754] [Full Text: https://doi.org/10.1002/ajmg.1320220205]
Tavormina, P. L., Shiang, R., Thompson, L. M., Zhu, Y.-Z., Wilkin, D. J., Lachman, R. S., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Wasmuth, J. J. Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nature Genet. 9: 321-328, 1995. [PubMed: 7773297] [Full Text: https://doi.org/10.1038/ng0395-321]