Learning About Progeria

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


Learning About Progeria

What do we know about heredity and progeria?

Progeria is an extremely rare genetic disease of childhood characterized by dramatic, premature aging. The condition, which derives its name from "geras," the Greek word for old age, is estimated to affect one in 4 million newborns worldwide.

The most severe form of the disease is Hutchinson-Gilford progeria syndrome, recognizing the efforts of Dr. Jonathan Hutchinson, who first described the disease in 1886, and Dr. Hastings Gilford who did the same in 1904.

As newborns, children with progeria usually appear normal. However, within a year, their growth rate slows and they soon are much shorter and weigh much less than others their age. While possessing normal intelligence, affected children develop a distinctive appearance characterized by baldness, aged-looking skin, a pinched nose, and a small face and jaw relative to head size. They also often suffer from symptoms typically seen in much older people: stiffness of joints, hip dislocations and severe, progressive cardiovascular disease. However, various other features associated with the normal aging process, such as cataracts and osteoarthritis, are not seen in children with progeria.

Some children with progeria have undergone coronary artery bypass surgery and/or angioplasty in attempts to ease the life-threatening cardiovascular complications caused by progressive atherosclerosis. However, there currently is no treatment or cure for the underlying condition. Death occurs on average at age 13, usually from heart attack or stroke.

In 2003, NHGRI researchers, together with colleagues at the Progeria Research Foundation, the New York State Institute for Basic Research in Developmental Disabilities, and the University of Michigan, discovered that Hutchinson-Gilford progeria is caused by a tiny, point mutation in a single gene, known as lamin A (LMNA). Parents and siblings of children with progeria are virtually never affected by the disease. In accordance with this clinical observation, the genetic mutation appears in nearly all instances to occur in the sperm prior to conception. It is remarkable that nearly all cases are found to arise from the substitution of just one base pair among the approximately 25,000 DNA base pairs that make up the LMNA gene.

The LMNA gene codes for two proteins, lamin A and lamin C, that are known to play a key role in stabilizing the inner membrane of the cell's nucleus. In laboratory tests involving cells taken from progeria patients, researchers have found that the mutation responsible for Hutchinson-Gilford progeria causes the LMNA gene to produce an abnormal form of the lamin A protein. That abnormal protein appears to destabilize the cell's nuclear membrane in a way that may be particularly harmful to tissues routinely subjected to intense physical force, such as the cardiovascular and musculoskeletal systems.

Interestingly, different mutations in the same LMNA gene have been shown to be responsible for at least a half-dozen other genetic disorders, including two rare forms of muscular dystrophy.

In addition to its implications for diagnosis and possible treatment of progeria, the discovery of the underlying genetics of this model of premature aging may help to shed new light on humans' normal aging process.

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Is there a test for progeria?

A genetic test for Hutchinson-Gilford progeria syndrome, also called HGPS, is currently available. In the past, doctors had to base a diagnosis of progeria solely on physical symptoms, such as skin changes and a failure to gain weight, that were not fully apparent until a child's first or second year of life. This genetic test now enables doctors to diagnose a child at a younger age and initiate treatment early in the disease process.

This genetic test for Hutchinson-Gilford progeria syndrome also serves to reassure parents of affected children that their disorder stems from a sporadic genetic mutation and that therefore it is unlikely that any future offspring would have the condition.

To learn more about the genetic test for progeria, go to The Progeria Research Foundation Diagnostic Testing Program.

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NHGRI Clinical Research on Progeria

Researchers at NHGRI and their collaborators in the Progeria Research Consortium are currently exploring the next steps in understanding the cause of this disease, and possible ways of developing new treatments. This work includes creation of a mouse model of the disease, as well as the possibility of using existing drugs to block or reduce production of the abnormal lamin A protein in children with progeria. Another approach being contemplated is the use of high-throughput screening technology to identify chemical compounds that might reverse nuclear membrane abnormalities of the type seen in the cells of children with progeria.

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Additional Resources for Progeria Information

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Last Updated: December 27, 2013