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Progeria FAQ

What is it?

Progeria is commonly referred to as an "early aging disease." Although whether early aging actually occurs or whether this is a disease with many symptoms that look like aging is debated. It is also known as Hutchinson-Gilford progeria syndrome (HGPS), named after Jonathan Hutchinson, who first described the disease in 1886 and Hastings Gilford (1904), who was the first to refer to the disease as progeria (National Library of Medicine, Progeria). It is fortunately an extremely rare disease. Only somewhat more then 100 cases have been reported since it was discovered, and is estimated to affect only 1 to 2 children in 8 million. It is, however, a particularly tragic disease in that it typically strikes children before the age of 10 years, who then usually die before their teens. Patients have some characteristics of aging such as baldness, a pinched nose, delayed tooth formation, stiffness of joints, hip dislocations, cardiovascular problems, arteriosclerosis, wrinkled/aged-looking skin, and a premature cessation of growth (dwarfism). They do not, however, typically show other characteristics of aging such as Alzheimer's disease, and arthritis of the hips in these patients is a result of having been born with dislocated hips, not as an aging process.

Werner syndrome is a similar appearing disease, but it strike people in their late teens. These patients may live until their 40s. Symptoms include scaly changes, especially in the extremities, cataracts, subcutaneous calcification, premature arteriosclerosis, diabetes mellitus, and wizened and prematurely aged facial features (National Library of Medicine). They also exhibit a high frequency of cancers. As Professor George M. Martin, Pathologist and Director of the Alzheimer's Disease Research Center at the University of Washington points out, like HGPS this disease also is different from normal aging:

"Patients develop neoplasms [cancers] prematurely, but the neoplasms tend to be those derived from mesenchymal rather than epithelial cells; the latter are the main source of tumors of older people. Werner patients suffer from osteoporosis, but the distribution is unusual in that it is very severe in the long bones of the legs. They also develop unusual deposits of calcium in the soft tissues and ulcers around their elbows and ankles."

What causes it?

Progeria is an autosomal recessive disease, meaning that an individual carrying a mutation in a single gene does not show any symptoms. When two individuals with the mutant gene have a child, that child has a 1 in 4 chance of inheriting two copies of the mutation and therefore having the disease. The mutation that is responsible for the disease is in the gene for lamin A. Lamin A is a fibrous protein involved in the structure of the nuclear membrane. This results in changes in shape of the nucleus and probably in its function. It is not known how this produces the wide range of age-like changes associated with progeria. It is intriguing that mutation of the gene for lamin A is also involved in several other distinct diseases, including muscular dystrophy. Clearly, there is more to be learned about the mechanism of this disease.

The autosomal recessive gene mutation causing Werner syndrome (Gene Reviews), has been cloned. The Werner syndrome protein (WRN) codes for an enzyme in the family of enzymes called helicases. These enzymes are responsible for unwinding the double strand of DNA in each cell as the DNA is to be duplicated for cell division. Each strand of DNA has its own helicase associated with it. Although the mechanism by which a defect in this enzyme would cause Werner syndrome is not known, its normal counterpart may be responsible for DNA repair, and thus preventing cancer and cell defects.

While the gene for Werner’s syndrome has been identified the specific gene for Hutchinson-Gilford Progeria Syndrome (HGPS) has not. The exact mode of inheritance of HGPS is not known for certain.  The disease is very rare and the individuals with HGPS do not reproduce so it is not easily studied.  HGPS has been considered to be recessively inherited in the way that Werner’s is.  However, there is evidence that in at least some patients de novo mutations have occurred causing the disease to be dominantly inherited.  The following papers shed some light on this question.

Searching for clues to premature aging.   

Hutchison Gilford Progeria Syndrome

Is it curable?

So far no cure has been found for either progeria or Werner syndrome. There are organizations concerned with promoting research in these diseases such as The Progeria Research Foundation and the International Registry of Werner Syndrome.

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Last updated November 2006