Achondroplasia

Achondroplasia1What is achondroplasia?
Achondroplasia is a genetic disorder of bone growth that is evident at birth. It affects about 1 in 26,000 to 1 in 40,000 births, and it occurs in all races and in both sexes. Its depiction in ancient Egyptian art makes it one of the oldest recorded birth defects.
It is the most common of a group of growth defects characterized by abnormal body proportions. Affected individuals have arms and legs that are very short, while the torso is nearly normal size.
The word achondroplasia is derived from Greek and means "without cartilage formation," although individuals with achondroplasia do have cartilage. During fetal development and childhood, cartilage normally develops into bone, except in a few places, such as the nose and ears. In individuals with achondroplasia, something goes wrong during this process, especially in the long bones (such as those of the upper arms and thighs). The rate at which cartilage cells in the growth plates of the long bones turn into bone is slow, leading to short bones and reduced height.

What does a person with achondroplasia look like?
A child with achondroplasia has a relatively normal torso and short arms and legs. The upper arms and thighs are more shortened than the forearms and lower legs. Generally, the head is large, the forehead is prominent and the nose is flat at the bridge. Sometimes, the large head size reflects hydrocephalus (excess fluid in the brain) and requires surgery.

How is achondroplasia diagnosed?
At birth or during infancy, achondroplasia is generally diagnosed with x-rays and a physical examination. If there is any question about the diagnosis, genetic testing using a blood sample can be done to look for a mutation (change) in the gene that causes achondroplasia. Achondroplasia also may be detected in the fetus during an ultrasound examination, which may show shortened bones and other bone abnormalities.

How does achondroplasia affect development?
Individuals with achondroplasia usually have normal intelligence and a normal life span. However, affected children have a number of medical complications that can affect their development.
Babies with achondroplasia have poor muscle tone, often leading to delays in learning to sit, stand and walk. Before beginning to walk, a baby with achondroplasia often develops a small hump (kyphosis) on his upper back. This is due to poor muscle tone and usually goes away after the child starts walking. Babies with achondroplasia should not be placed in umbrella-type strollers or other carriers that do not provide good back support, because lack of support can contribute to development of a hump in the back. Once walking, the child usually develops a markedly curved lower spine (lordosis or sway-back), and the lower legs often become bowed. The feet are generally short, broad and flat.
Children with achondroplasia also have narrow passages in the nose that can contribute to ear infections and, without treatment, to hearing loss. Due to a small jaw, teeth may be crowded, and upper and lower teeth may be poorly aligned.
Occasionally, a baby or young child with achondroplasia may die suddenly, often during sleep. This occurs in less than 3 percent of affected babies. These deaths appear to result from compression of the upper end of the spinal cord, which can interfere with breathing. The compression is caused by abnormalities in the size and structure of the opening in the base of the skull (foramen magnum) and vertebrae in the neck through which the spinal cord descends. All babies and young children with achondroplasia should be monitored for foramen magnum compression (see below). 
Adolescents and adults with achondroplasia often develop weakness, tingling and pain in the legs or low back pain. This is often due to pressure on the spinal cord from a small spinal canal.

How is achondroplasia treated?
The growth and development of children with achondroplasia are monitored closely. Though there is currently no way to normalize skeletal development of children with the disorder, most complications can be effectively treated.
 
Infants and children with achondroplasia should be thoroughly evaluated for skeletal abnormalities by a doctor experienced with the disorder. The doctor will follow the child’s growth using special charts of head and body growth developed for children with achondroplasia.


If the head is becoming too large, the doctor will test the child for hydrocephalus. If necessary, a neurosurgeon will insert a shunt to drain the excess fluid and relieve pressure on the brain.
The child also will be monitored for signs of upper spinal cord compression (due to foramen magnum abnormalities) using tests such as computed tomography (CT scan or CAT scan) or magnetic resonance imaging (MRI). Possible symptoms of spinal cord compression may include snoring, sleep apnea (episodes where the baby stops breathing while sleeping) and persistent low muscle tone. When necessary, surgery can widen the opening and relieve pressure on the spinal cord. Some children also may have breathing problems caused by small facial structures, large tonsils or a small chest size. Surgery to remove the tonsils and adenoids (lymph tissue near the throat) often improves these breathing problems.
If kyphosis does not go away after a child begins walking, a back brace may be used to correct it. If a brace is not effective, the child may be treated with a cast that is worn for several months or with surgery. Bowing of the legs, especially if it becomes severe or causes pain, also can be corrected with surgery.
Children with achondroplasia often require placement of middle-ear drainage tubes. This helps to prevent the hearing loss that can occur with frequent ear infections. Dental problems caused by overcrowding of teeth may require extra routine care and braces.
Children with achondroplasia tend to put on extra weight, starting in early childhood. Because excessive weight can further aggravate skeletal problems, affected children should receive nutritional guidance to help prevent obesity.
Some medical centers are evaluating the use of human growth hormone to improve the growth of children with achondroplasia. To date, some children have achieved modest increases in growth after one to two years of treatment. However, it is not yet known whether treatment will significantly increase their eventual adult height.
Leg-lengthening surgeries can increase the height of someone with achondroplasia by up to 12 to 14 inches. This procedure requires a long duration of treatment (up to 2 years), however, and is associated with many complications. Little People of America, an organization that provides information and support for individuals with short stature, regards this procedure as experimental and recommends that it be done only in a center that is well experienced in the procedure.

What is the cause of achondroplasia?
Achondroplasia is caused by a mutation in a gene (called fibroblast growth factor receptor 3) that is located on chromosome 4. In a minority of cases, a child inherits achondroplasia from a parent who also has the condition. If one parent has the condition and the other does not, there is a 50 percent chance that their child will be affected. If both parents have achondroplasia, there is a 50 percent chance that the child will inherit the condition, a 25 percent chance that the child will not have it, and a 25 percent chance that the child will inherit one abnormal gene from each parent and have severe skeletal abnormalities that lead to early death. (When both expectant parents have achondroplasia, they are usually offered prenatal tests to diagnose or rule out this fatal form of the disease.) A child who does not inherit the condition cannot pass it on to his or her own children.
In more than 80 percent of cases, however, achondroplasia is not inherited but results from a new mutation that occurs in the egg or sperm cell that forms the embryo. The parents of children with achondroplasia resulting from a new mutation are usually normal sized. Typically, these parents have no other children with achondroplasia, and the chances of their having a second affected child are extremely small.
Geneticists have observed that older-than-average fathers (age 40 and older) are more likely to have children with achondroplasia and certain other autosomal dominant conditions (disorders that occur when one gene in a gene pair is abnormal) caused by new mutations. Individuals with achondroplasia resulting from new mutations transmit the disorder to their children as described above.

Can achondroplasia be prevented?
There is no way to prevent the majority of cases of achondroplasia because they result from totally unexpected gene mutations in unaffected parents. Genetic counselingcan help adults with achondroplasia and unaffected individuals who have had an affected child make informed decisions about family planning.

What research is being done on achondroplasia?
Scientists have identified the gene, and the exact mutation (change) in the gene, that causes achondroplasia. The gene is one of a family of genes that makes proteins called fibroblast growth factor receptors. Scientists have linked these genes with several skeletal disorders.
The fibroblast growth factor receptor gene dictates the production of a protein that is located on the surface of cells of different tissue types, including cartilage. The protein
normally responds to signals from chemicals called growth factors which stimulate cell growth and maturation.
Scientists are investigating how the faulty protein actually causes the features of achondroplasia. This eventually may lead to improved treatment for this disorder, as well as improved understanding and treatment of other skeletal disorders caused by this family of genes. March of Dimes grantees and other researchers also are working to identify the genes that cause some of the other more than 100 forms of disproportionate short stature.