Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Hypochondroplasia (HCH) [Q77.4]

OMIM-Nummer: 146000, 134934 (FGFR3)

Dr. rer. nat. Christoph Marschall, Dipl.-Biol. Christine Schack,
Dipl.-Biol. Christina Sofeso

Scientific Background

Hypochondroplasia (HCH) is an autosomal dominant form of dwarfism and is, just like achondroplasia, mainly characterized by rhizomelic shortening of the extremities. It is, however, significantly milder than achondroplasia and other FGFR3 diseases. HCH patients do not display deformation of the tibia, elongation of the fibula and the growth curves overlap with the ones of healthy children.

The disease is caused by mutations in the fibroblast growth factor receptor 3 gene (FGFR3) which lead to either direct activation or to dimerization of the receptor and thus to its constitutive activation (gain of function). Various signal transduction pathways cause dysregulation of the endochondral ossification and therefore growth inhibition. Experts assume that, in comparison to mutations associated with achondroplasia, the mutations that have been associated with HCH lead to a weaker activation of the tyrosine kinase of the receptor. Causative mutations in FGFR3 are detected in approximately 70% of all HCH cases. There is, however, genetic heterogeneity.