It is also typical for adults to experience numbness or tingling in their legs because of nerve compression. Some research has found that adults with achondroplasia may also experience psychosocial complications, usually associated with short stature.Pregnancy in women with achondroplasia is considered higher risk. Women with achondroplasia generally have their babies delivered through C-sections to prevent complications that could occur with a natural birth. The life expectancy of people with achondroplasia is approximately 10 years less than average. Causes
Achondroplasia is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3) gene. This gene encodes a protein called fibroblast growth factor receptor 3, which contributes to the production of collagen and other structural components in tissues and bones. When the FGFR3 gene is mutated it interferes with how this protein interacts with growth factors leading to complications with bone production. Cartilage is not able to fully develop into bone, causing the individual to be disproportionately shorter in height.In normal development FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause achondroplasia, while two copies of the mutant gene are invariably fatal (recessive lethal) before or shortly after birth (known as a lethal allele). This occurs due to respiratory failure from an underdeveloped ribcage. A person with achondroplasia thus has a 50% chance of passing dwarfism to each of their offspring.
This makes estimates of prevalence difficult, with changing and subjective diagnostic criteria over time. One detailed and long-running study in the Netherlands found that the prevalence determined at birth was only 1.3 per 100,000 live births. Another study at the same time found a rate of 1 per 10,000. A 2020 review and meta-analysis estimated a worldwide prevalence of 4.6 per 100,000. Research
As of 2019, tentative evidence has found that the experimental peptide drug vosoritide increases growth velocity in those with achondroplasia. The drug inhibits the activity of FGFR3. Animals
Based on their disproportionate dwarfism, some dog breeds traditionally have been classified as "achondroplastic". This is the case for the dachshund, basset hound, corgi and bulldog breeds. Data from whole genome association studies in short-limbed dogs reveal a strong association of this trait with a retro-gene coding for fibroblast growth factor 4 (FGF4). Therefore, it seems unlikely that dogs and humans are achondroplastic for the same reasons. However, histological studies in some achondroplastic dog breeds have shown altered cell patterns in cartilage that are very similar to those observed in humans exhibiting achondroplasia.A similar form of achondroplasia was found in a litter of piglets from a phenotypically normal Danish sow. The dwarfism was inherited dominant in the offspring from this litter. The piglets were born phenotypically normal, but became more and more symptomatic as they reached maturity. This involved a mutation of the protein collagen, type X, alpha 1, encoded by the COL10A1 gene.