Achondroplasia is a type of genetic disorder that is a common cause of dwarfism. People with this condition have short stature, usually reaching a full adult height of around 4'0" (1.22 meters). The disorder is a result of an autosomal dominant mutation in the fibroblast growth factor receptor gene 3 (FBFR3), which causes an abnormality of cartilage formation. It occurs at a frequency of about 1 in 20,000 to 1 in 40,000 births.

Clinical features of the disease:

• dwarfism (nonproportional short stature)
• shortening of the proximal limbs (termed rhizomelic shortening)
• short fingers and toes
• a large head with prominent forehead
• small midface with a flattened nasal bridge
• spinal kyphosis (convex curvature) or lordosis (concave curvature)
• varus (bowleg) or valgus (knock knee) deformities
• frequently have ear infections (due to Eustachian tube blockages), sleep apnea (which can be central or obstructive), and hydrocephalus

People with achondroplasia have one normal copy of the fibroblast growth factor receptor 3 gene and one mutant copy. Only one copy of the gene needs to be present for the disorder to be seen. Thus, a person with achondroplasia has a 50% chance of passing on the gene to their offspring, meaning that 1 in 2 of their children will have achondroplasia. However, in 3 out of 4 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 germline mosaicism).

Achondroplasia can be detected before birth by the use of prenatal ultrasound. A DNA test can be performed before birth to detect homozygosity, where two copies of the mutant gene are inherited, a condition which is lethal and leads to stillbirths.

Growth hormone (GH) therapy has been proposed as a possible treatment for the short stature of achondroplasia. However, the people who participated in the studies on the subject have not yet reached adult size, so this type of therapy has unknown results. Early experience with surgical limb lengthening procedures resulted in a high incidence of complications, but recent experiences have improved results considerably.

For the genetic details: More than 99% of achondroplasia is caused by two different mutations in the fibroblast growth factor receptor 3 (FGFR3). In about 98% of cases, the mutation is a Gly380Arg substitution, resulting from a G to A point mutation at nucleotide 1138 of the FGFR3 gene [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.

See also

• List of rare diseases