The prevalence is approximately 1 in 25,000.
Achondroplasia is a result of an autosomal dominant mutation in the fibroblast growth factor receptor gene 3 which causes an abnormality of cartilage formation. FGFR3 normally 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.
Animals with achondroplasia have one normal copy of the fibroblast growth factor receptor 3 gene and one mutant copy. Two copies of the mutant gene are invariably fatal before, or shortly after birth. Only one copy of the gene needs to be present for the disorder to occur. Therefore, a person with achondroplasia has a 50% chance of passing on the gene to their offspring, meaning that there will be a 50% chance that each child will have achondroplasia. Since two copies (Homozygous) are fatal, if two people with achondroplasia have a child, there is a 25% chance of the child dying shortly after birth, a 50% chance the child will have achondroplasia, and a 25% chance the child will have a normal phenotype. However, in the majority of cases, people with achondroplasia are born to parents who don't have the condition. This is the result of a new mutation.
New gene mutations are associated with increasing paternal age (over 35 years). Studies have demonstrated that new gene mutations are exclusively inherited from the father and occur during spermatogenesis (as opposed to resulting from a gonadal mosaicism). More than 99% of achondroplasia is caused by two different mutations in the fibroblast growth factor receptor 3 (FGFR3). In about 98% of cases, a G to A point mutation at nucleotide 1138 of the FGFR3 gene causes a glycine to arginine substitution (Bellus et al 1995, Shiang et al 1994, Rousseau et al 1996). About 1% of cases are caused by a G to C point mutation at nucleotide 1138.
The diagnosis can be made by fetal ultrasound by progressive discordance between the femur length and biparietal diameter by age. The trident hand configuration can be seen if the fingers are fully extended.
Although used by those without achondroplasia to aid in growth, growth hormone does not help people with achondroplasia. However, if desired, the controversial surgery of limb-lengthening will lengthen the legs and arms of someone with achondroplasia, although in some cases when this surgery is undergone, some affected individuals may experience their limbs becoming "locked to their torso".
Reported by the Fox News Channel, Jyoti Amge, a 14-year-old girl from India, broke the world record for the shortest person on earth. Diagnosed with achondroplasia, she is 23 inches (58 cm) tall, and weighs 11 lbs (5 kg).
The condition was present in the pre-Columbian New World (evidence from the skeletal remains), and in documentation by skeletons, wall paintings, figurines in the ancient Egypt from pre-Dynastic times (up to 30th Dynasty). The ancient Egyptian word for people affected by the condition was nemew. They held various offices and were regarded as highly intelligent. Several of them must have been persons of importance and wealth, being found in elaborate tombs.