Greek "without cartilage formation" It is one of the most common causes of dwarfism. The appearance is of short staturewith disproportionately short arms and legs and a large head. The characteristic facial features include a prominentforehead and a flattened bridge of the nose.

Although this condition can be inherited in an autosomal dominant manner, 80% of cases are due to new, sporadicmutations. Mutations involve the gene encoding fibroblast growth factor receptor 3 (FGFR3), situated on chromosome 4.Most commonly, a point mutation causes the substitution of arginine for glycine (G380R) in the transmembrane region ofthe receptor.

There is growing evidence that mutations of FGF3R confer a "gain of function". It is proposed that the normal function ofFGFR3 is to slow down the formation of bone by inhibiting the proliferation of chondrocytes, the cells that producecartilage. The mutation increases the activity of FGFR3, severely limiting bone growth.

This theory is supported by the knock-out mouse model in which the receptor is absent, and so the negative regulation ofbone formation is lost. The result is a mouse with excessively long bones and elongated vertebrae, resulting in a long tail.Achondroplastic mouse models are useful tools in developing potential treatments.