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

Hypochondroplasia (HCH)

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

Scientific Background

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.


Arenas et al. 2018, J Pediatr Endocrinol Metab 31:1279 / Ornitz et Legeai-Mallet 2017, Dev Dyn 246:291 / Massart et al. 2015, Pharmacogenomics 16:1965 / Pinto et al. 2014, Horm Res Paediatr 82:355 / Heuertz et al. 2006, Eur J Hum Genet 14:1240 / Zabel 2004, medgen 16:8 / Van Esch et al. 2004, Genet Counsel 15:375 / Wilkin 2001 in: The Metabolic & Molecular Basis of Inherited Disease 5379 / Vajo et al. 2000, Endocr Rev 21:23 / Shiang et al. 1994, Cell 78:335 / Rousseau et al. 1994, Nature 371:252