Achondroplasia 2/8/04. By Richard Twyman Achondroplasia is an inherited disorder of bone development that results in short-limb dwarfism.

Overview

Achondroplasia is the most common form of short-limb dwarfism, a developmental disorder in which bone tissue does not develop properly in the long bones of the arms and legs. The condition affects about 1 in 25 000 individuals of all ethnic groups. Achondroplasia cannot be cured, but the symptoms can be treated with surgery.

Genetics

Achondroplasia is a single gene disorder caused by certain mutations in the gene on chromosome 4. The disease is described as dominant because only one copy of the gene need be mutated before symptoms develop.

The FGFR3 gene encodes the fibroblast growth factor receptor number 3. Growth factors are proteins that control cell growth and behaviour, but in order to work they must bind to receptors on the surface of responding cells. When the receptors are absent or not working properly, the growth factors cannot carry out their normal functions. The FGFR3 protein is concentrated in the cartilage and the central nervous system, so mutations in the FGFR3 gene predominantly affect these parts of the body.

Other mutations in the same gene cause more severe developmental disorders such as Crouzon syndrome, while mutations in other genes can also cause skeletal disorders – disorders such as multiple epiphyseal dysplasia and pseudoachondroplasia.

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Symptoms

Achondroplasia is primarily a disorder of bone development, in which cartilage fails to turn into bone. The bones most severely affected are those of the thighs and upper arms, resulting in profound shortening. The lower legs and forearms are affected to a lesser degree, and the hands and feet are also short with unusual separation between the third and fourth digits. Affected individuals reach a maximum height of about four feet (120 cm). The torso develops to its proper size, but the head may be larger than normal with a prominent forehead and flat nose.

Affected children usually learn to sit, crawl and walk later than their unaffected peers, and often develop a curved spine and bowed legs. Adults can suffer from back and leg pain. The abnormal development of the head sometimes results in narrow internal passages that can lead to persistent infections and hearing loss.

In the worst cases, the abnormal structure of the skull and vertebrae can cause compression of the spinal cord, resulting in paralysis and breathing difficulties. Babies with achondroplasia occasionally die in their sleep for this reason.

Diagnosis

Achondroplasia in newborns and children is generally diagnosed by bone measurement during a physical examination or by studying X-ray images. Prenatal diagnosis is recommended where one or both parents are already affected, but in the majority of cases, achondroplasia occurs spontaneously (the parents are unaffected and the mutation occurs in the cells making eggs or sperm).

Treatment

There is no cure for achondroplasia, but growth hormone can help to achieve moderate growth in some children, and surgery can be used in some cases to increase leg length by up to 30 cm. It is sometimes necessary to test affected children for hydrocephalus and, if necessary, to drain fluid and relieve pressure on the brain. Surgery can also be used to prevent spinal compression and correct bowed legs.