Genetic: Hutchinson-Gilford Syndrome

Definition

Hutchinson-Gilford progeria syndrome, or HGPS, is a genetic disorder characterized by premature aging and early death.

Description

HGPS is a sporadic genetic disorder, which means that it usually occurs at random and occurs in families only rarely. It was first described in 1886 by Jonathan Hutchinson (1828–1913), a British surgeon, and independently reported in 1897 by Hastings Gilford (1861–1941), also a British surgeon.

Children with HGPS look normal at birth but begin to show signs of the disorder during the first two years of life. Their growth slows down; this condition is called failure to thrive or FTT. The child is short and small for his or her age, develops wrinkled skin like that of an elderly person, loses the body fat beneath the skin, and has a fragile-looking body with joints that stick out and easily dislocated hips. The child's facial features are also distinctive, with large eyes, loss of scalp hair, a beaklike nose, thin lips, a small chin, and large ears. Some children have missing teeth or teeth that are late to come in. The child'sbodyagessix to eight times faster than normal aging; however, these children do not

develop certain age-related problems like cataracts or an increased risk of cancer.

The disorder does not interfere with intellectual development or with sitting, standing, and walking. Children with HGPS can go to school with other children and participate in activities with them.

The disease leads to death at an early age from heart attack or stroke caused by premature hardening of the arteries. Children with HGPS frequently experience angina—chest pain caused by an inadequate supply of oxygen to the heart muscle. They also suffer from high blood pressure and enlargement of the heart.

Demographics

HGPS is a very rare disorder, thought to affect between one in 8 million and one in 4 million children. About 130 cases have been reported in medical journals since the disease was first described in 1886. There were seven children in the United States with progeria in 2005.

As of 2008, 97 percent of reported cases of HGPS had been found in Caucasians. The reason for this racial disparity is not yet known; since some researchers think that the disorder is misdiagnosed in some cases, it is possible that the racial difference is at least partly a matter of reporting.

HGPS affects boys slightly more often than girls; the gender ratio is about 1.5 boys for every girl.

For many years it was thought that HGPS does not run in families. Since the early 2000s, however, two families have been identified with more than one child affected by the disorder. The first is a family in India with five children with HGPS, first described by a pediatrician in Calcutta in 2005. The other is a family in Belgium with two children with HGPS that was diagnosed in 2006.

Causes and Symptoms

Hutchinson-Gilford progeria syndrome is caused by a mutation in a gene on chromosome 1 called the LMNA gene. This gene tells cells how to

make a protein called lamin A, which helps to shape the cell nucleus inside the cell. The defective gene involved in HGPS cannot give the cell proper instructions for making lamin A. As a result, the cell nucleus develops into a strange and twisted shape rather than the normal round shape. It is not known, however, just how the unstable shape of the cell nucleus is related to the characteristic symptoms of HGPS.

Diagnosis

Children with HGPS are usually diagnosed around two years of age, when the changes in their skin, their distinctive facial features, and their failure to grow normally become apparent. The diagnosis can be confirmed by a blood test that was developed in 2003 after the gene that causes the disorder was first identified.

The doctor may also take a small sample of skin to examine it under the microscope for the changes that indicate HGPS, but this test is not necessary to diagnose the disorder.

Treatment

There is no treatment that can cure HGPS. Therapy is intended to give the child as normal a life as possible. Some children are given a daily aspirin to counteract the risk of heart attack or stroke, and doctors commonly recommend a high-calorie diet to help them gain weight. Children with HGPS may also benefit from physical therapy to keep their muscles and joints from weakening.

Children with HGPS must see the doctor periodically to have the condition of their heart and major blood vessels checked and to have their food intake adjusted when necessary.

Coping with Unfair Suffering

Although Hutchinson-Gilford syndrome is an extremely rare disorder, it played a role in the writing of a well-known book on the meaning of human suffering. When Bad Things Happen to Good People was first published in 1981 and reissued in 2001 with a new preface. The author, Harold S. Kushner, was moved to write the book following the death of his son Aaron in 1977 at the age of fourteen. Rabbi Kushner had been the spiritual leader of Temple Israel in Natick, Massachusetts, when his son was diagnosed with progeria at the age of three in 1966. He promised his dying son that he would tell his story so that Aaron would not be forgotten. Four years after Aaron's death, the book was finally ready for publication.

Written in a warm, accessible tone, When Bad Things Happen to Good People quickly became a best seller, bringing comfort to literally millions of people struggling with sorrow and loss. The book was eventually translated into fourteen languages and still prompts readers to send thank-you notes to its author. Rabbi Kushner is not, however, concerned with being remembered as an author. He told an interviewer in 2003, “I want to be remembered that, when my son was dying and in pain, I could make him laugh.”

Prognosis

HGPS is invariably fatal; 90 percent of children with the disorder die of heart attacks or stroke. The average life expectancy is thirteen years,

although some children die as young as six or seven. The longest-lived person with HGPS died at twenty-nine.

Prevention

Since HGPS is a genetic disorder, there is no known way to prevent it.

The Future

HGPS is of interest to researchers, along with such other disorders of accelerated aging as Werner syndrome, because they think these diseases may hold clues to the normal process of human aging. In regard to a possible cure for HGPS, a clinical trial of a drug called lonafarnib, originally developed to treat cancer, began in May 2007. Some researchers are experimenting with growth hormone as a possible treatment for HGPS, but the results have not been encouraging.

SEE ALSO Heart attack; Stroke

WORDS TO KNOW

Angina: Chest pain caused by an inadequate supply of blood to the heart muscle.

Failure to thrive: A term used to describe children whose present weight or rate of weight gain is markedly lower than that of other children of their age and sex.

Progeria: A disease characterized by abnormally rapid aging. The term can be used to refer specifically to Hutchinson-Gilford syndrome or to a group of diseases characterized by accelerated aging.

Werner syndrome: Another genetic disease characterized by accelerated aging.

For more information

BOOKS

Bellenir, Karen, ed. Genetic Disorders Sourcebook: Basic Consumer Health Information, 3rd ed. Detroit, MI: Omnigraphics, 2004.

PERIODICALS

Grant, Matthew. “Family Tormented by Ageing Disease.” BBC News, February 22, 2005. Available online at http://www.news.bbc.co.uk/2/hi/south_asia/4286347.stm (accessed April 5, 2008).

Smith, Carol. “Seth Cook, 1993–2007: Darrington Teen with Rare Disorder Dies.” Seattle Post-Intelligencer, June 27, 2007. Available online at http://www.seattlepi.nwsource.com/local/321200_seth26.html (accessed April 5, 2008). Page includes a video of Seth about 90 seconds in length.

Smith, Carol. “A Time to Live: A Boy Embraces Life as a Rare Disease Hastens His Aging.” Seattle Post-Intelligencer, September 16, 2004. Available online at http://www.seattlepi.nwsource.com/specials/seth/190908_progeriamain.asp (accessed April 5, 2008). This is a six-part series on the daily life of Seth Cook, a boy with HGPS who was 10 at the time the series was printed.

WEB SITES

Genetics Home Reference. Hutchinson-Gilford Progeria Syndrome. http://www.ghr.nlm.nih.gov/condition=hutchinsongilfordprogeriasyndrome (accessed April 5, 2008).

Madisons Foundation. Progeria. http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,641/ (posted October 2005; accessed April 5, 2008).

www.MayoClinic.com. Children's Health: Progeria. http://www.mayoclinic.com/health/progeria/DS00936/DSECTION=1 (accessed April 5, 2008).

Progeria Research Foundation. Progeria 101/FAQs. http://www.progeriaresearch.org/progeria_101.html (accessed April 5, 2008).