Genetic: Achondroplasia

Definition
Description
Demographics
Causes and Symptoms
Diagnosis
Treatment
Prevention
The Future
For more information

Definition

Achondroplasia, or short-limb dwarfism, is the most common form of abnormally short stature in adults. It is caused by a mutation in a single gene on chromosome 4 that regulates the conversion of cartilage to bone. This gene is the only gene that is known to be associated with achondroplasia.

Description

Achondroplasia is basically a disorder of bone development. The skeleton of a human fetus is composed primarily of cartilage, a dense and somewhat elastic form of connective tissue that gradually turns to bone during normal development. In a person with achondroplasia, a gene that is involved in the process of bone formation produces too much of a protein that limits bone growth. As a result, the person with achondroplasia has unusually short bones in the arms and legs and other skeletal abnormalities. They also usually have difficulties with posture, joint disorders, and breathing problems in later life.

Demographics

Researchers estimate that achondroplasia occurs in one in every 15,000 to 40,000 live births. About 20 percent of cases are children who have one parent with achondroplasia; however, 75–80 percent of cases involve new

mutations of the gene responsible for the disorder. These new mutations are more likely to occur in the sperm of fathers over 35; the mother's age does not matter, as far as is presently known.

The disorder affects both sexes and all races equally.

The average adult height of people with achondroplasia is 4 feet 4 inches (1.3 meters) for men and 4 feet one-half inch (1.24 m) for women. The shortest living person with achondroplasia as of 2008 was Jyoti Amge, a teenager from Nagpur, India, who stands 23 inches (58 centimeters) tall and weighs 11 pounds (5 kilograms).

Causes and Symptoms

Achondroplasia is caused by a mutation in the FGFR3 gene on chromosome 4. A normal gene helps the body convert cartilage to bone. The mutation in the gene related to achondroplasia results in severely shortened bones and weak muscle tone in the body.

The symptoms of achondroplasia are usually obvious by the first year of life. They include:

• Poor muscle tone.
• Slowness in learning to walk; a child with achondroplasia may not walk until some point between 24 and 35 months.
• Abnormal skull structure leading to frequent ear infections, apnea (temporary slowing or stopping of breathing), and overcrowding of the teeth.
• Distinctive facial features, particularly a prominent forehead and underdevelopment of the nose and midface.
• Greater than normal separation of the little finger from the ring finger, giving the hand a distinctive trident (three-pronged) shape.
• A tendency toward obesity.
• Postural problems, including a pronounced curvature of the spine in the lower back and bowed legs.
• Back and leg pain in adult life.

Diagnosis

Babies with achondroplasia can be diagnosed before birth by ultrasound measurements of the growth of their long bones and head size. After birth, the diagnosis is usually based on x-ray studies of the child's bones and head size. The x-ray images usually reveal a small skull base, shortened growth plates in the long bones, square-shaped long bones, and normal-sized bones in the trunk area.

Billy Barty

Billy Barty (1924–2000) was an Italian-American film actor who played in a number of movies from the 1930s through 2001. He also had roles in several television series, from Alfred Hitchcock Presents and Peter Gunn to Little House on the Prairie and Frasier. Born William John Bertanzetti in Millsboro, Pennsylvania, Barty became a noted spokesperson and activist for persons with dwarfism.

In 1957 Barty gathered a group of others diagnosed with achondroplasia to meet with him in Reno, Nevada, to start an organization that would offer support and information to people with dwarfism and their families. Twenty-one people came to the meeting and formed Little People of America (LPA), an organization that has over 6,000 members as of the early 2000s.

Barty was once asked in the 1970s why he worked so tirelessly to end stereotypes and ridicule of people with dwarfism. He said, “Most of us with dwarfism prefer to be described as ‘LittlePeople.’ And please, put the emphasis on the word People. We did not spring from the pages of a story book or emerge from an enchanted forest. We are not magical beings and we are not monsters. We are parents and sons and

daughters. We are doctors and lawyers and realtors and teachers. We dream, cry, laugh, shout, fall in love, and make mistakes. We are no different from you.“

A genetic test can also be performed to confirm the diagnosis in children whose symptoms may be less clear.

Treatment

The management of achondroplasia includes careful monitoring of the child's growth, head size, and weight pattern. There are special growth charts that doctors use to evaluate the rate of growth in children with achondroplasia. It is particularly important to prevent obesity if possible. In addition, children with achondroplasia need social support because of ongoing prejudice against people with dwarfism. Organizations such as Little People of America can offer helpful advice on the education and other future plans of children with achondroplasia.

Surgery may be performed if necessary to relieve pressure on the spinal cord or the brain. In some cases, there may be a buildup of fluid in the brain (hydrocephalus) that needs to be drained surgically. The child's tonsils and adenoids may be removed in order to lower the risk of apnea. The shape of bowed legs can be corrected surgically, but doctors disagree about the value of surgery intended to lengthen the legs.

Children with achondroplasia may need extra dental work because of the mismatch between the size of their teeth and the size of the jaw. In addition, they should be watched carefully for recurrent ear infections in order to minimize the risk of deafness and later learning difficulties.

There is disagreement among doctors as of the early 2000s regarding treatment with human growth hormone. It is considered an experimental treatment. Many doctors are concerned that using growth hormone in children with achondroplasia will lead to abnormal bone deposits and worsening of the spinal curvature.

Prognosis

The prognosis of a baby with achondroplasia depends on whether the defective gene is inherited from only one parent or from both. A child who inherits the gene from both parents will die before birth or shortly after birth from respiratory failure. About 3 percent of children with achondroplasia die suddenly and unexpectedly during the first year of life, usually from compression of the spinal cord.

A child who has one normal copy of the gene will usually have normal intelligence and a normal life expectancy in spite of bone and joint problems.

Prevention

There is no known way to prevent achondroplasia because the gene responsible for the condition can undergo mutation in families with no

history of the disorder, and 75–80 percent of cases result from new mutations.

The Future

Although new mutations of the gene associated with achondroplasia cannot always be foreseen, people who have the condition should seek genetic counseling before marriage. If the partner does not have the mutation, there is a 50 percent chance with each pregnancy that the child will have achondroplasia. If both spouses have the mutation, they have a 25 percent chance of a normal child with each pregnancy, a 50 percent chance that the child will have achondroplasia, and a 25 percent chance that the child will die before or shortly after birth.

SEE ALSO Childhood obesity; Ear infection; Gigantism; Hydrocephalus

WORDS TO KNOW

Apnea: A condition in which breathing slows or stops for short periods of time.

Cartilage: A dense elastic tissue that forms most of the skeleton in the human fetus but is gradually replaced by bone during normal development.

Growth plate: A cartilage plate in the long bones of children where the lengthening of bone takes place.

Hydrocephalus: An abnormal increase of cerebrospinal fluid within the brain that may cause enlargement of the skull.

Mutation: A change in the genetic material of an organism.

For more information

BOOKS

Adelson, Betty M. Dwarfism: Medical and Psychosocial Aspects of Profound Short Stature. Baltimore, MD: Johns Hopkins University Press, 2005.

Barty, Billy. Little People of America, Inc., Souvenir Book. Studio City, CA: Billy Barty Foundation, 1982.

Copeland, Michael, and Debra Copeland. Within Reach: An Inspirational Journey into the Life, Legacy, and Influence of Billy Barty. Fairfax, VA: Xulon Press, 2002.

PERIODICALS

Rabin, Roni. “It Seems the Fertility Clock Clicks for Men, Too.” New York Times, February 27, 2007. Available online at http://query.nytimes.com/gst/fullpage.html?res=9D06E4DC1E3EF934A15751C0A9619C8B63&sec=&spon=&pagewanted=all (accessed April 28, 2008). This is a news item about older men being more likely to father children with achondroplasia as well as other genetic disorders.

“Tiny Teenager Stands Tall Despite Her Height of 23 Inches.” Fox News, April 8, 2008. Available online at http://www.foxnews.com/story/0,2933,348248,00.html (accessed April 30, 2008).

Wertheimer, Ron. “Television Review: On Being Very Small in a World of Giants.” New York Times, April 28, 2001. Available online at http://query.nytimes.com/gst/fullpage.html?res=9C06E1D91039F93BA15757C0A9679C8B63 (accessed April 29, 2008). This is a review of a television show called “Dwarfs: Not a Fairy Tale,” which aired on HBO in April 2001 as part of the series America Undercover Sundays.

WEB SITES

Genetics Home Reference. Achondroplsia. Available online at http://ghr.nlm.nih.gov/condition=achondroplasia (updated June 2006; accessed April 29, 2008).

National Human Genome Research Institute (NHGRI). Learning about Achondroplasia. Available online at http://www.genome.gov/19517823 (updated February 5, 2008; accessed April 29, 2008).