Dipl.-Biol. Christina Sofeso, Dr. rer. nat. Christoph Marschall
Hypochondroplasia (HCH) is an autosomal dominant inherited form of disproportionate dwarfism and is, like achondroplasia, mainly characterized by rhizomelic shortening of the extremities. However, the characteristic form is significantly milder than achondroplasia and other FGFR3 diseases. HCH patients do not display deformation of the tibia or elongation of the fibula and the growth curves overlap with those of healthy children.
The disease is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene (FGFR3) resulting in direct activation or dimerization of the receptor and thus constitutive activation (gain of function). Various signal transduction pathways cause dysregulation of the endochondral ossification and therefore growth inhibition. The most common HCH causal variant is Asn540Lys, which is detected in around 60% of patients.
Since severe cases of hypochondroplasia (HCH) caused by Asn540Lys and mild cases of achondroplasia caused by Gly380Arg are clinically very similar and easily confused, diagnostics involves investigating both changes in the first instance.
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