What is Werner syndrome?

A progressive disorder, Werner syndrome is one of a number of rare genetic conditions that puts people at an increased risk of developing cancer—among them skin, bone (also known as sarcoma) and thyroid cancers.

Werner syndrome is also known as:

• Werner’s syndrome
• Adult progeria
• Adult premature aging syndrome
• WS

Patients with Werner syndrome age extremely rapidly. They also become susceptible to diseases associated with aging, such as:

• Cataracts
• Type 2 diabetes
• Hardening of the arteries
• Osteoporosis
• Cancer

Rarity of Werner syndrome

About one in 200,000 people in the United States are estimated to have WS, according to the U.S. National Library of Medicine. The syndrome is more common in Japan, where it affects one in 20,000 to one in 40,000 people.

Signs and symptoms of Werner syndrome

In some people, symptoms may become obvious as early as in the mid-teenage years. Others may not be diagnosed until they’re in their 30s or 40s. Typically, few signs of Werner syndrome are apparent until the early 20s or 30s. Children with the syndrome grow and develop normally until puberty—though they may be shorter than their peers.

Most people with Werner syndrome live until their 40s and 50s. Cancer and heart disease are usually what affect life expectancy.

Although WS is typically not evident until the later teen years, younger children are likely to be unusually thin and not experience typical growth spurts. They also tend to have thin arms and legs.

In their 20s, patients with WS are likely to:

• Have white or gray hair
• Experience hair loss—on the scalp, eyebrows and eyelashes
• Have sparse or no hair under the arms, in the pubic area and throughout the body
• Face decreased fertility—males typically develop a small penis and testes, and females may not menstruate or have regular menstrual cycles, and may also experience early menopause and multiple miscarriages (though successful pregnancies have also been reported)

By about 25, they also start to see:

• Skin changes, including losing the layer of fat beneath the skin—skin starts to appear shiny and waxy smooth, and the face may appear “pinched” or birdlike
• Other skin abnormalities such as ulcers and sores that are slow to heal
• Wasting of muscles within the hands, legs and feet
• Loss of bone density that may result in fractures from falls and other trauma
• Hardening of ligaments and tendons caused by an accumulation of calcium salts
• Vocal cords atrophying, resulting in a high-pitched, squeaky or hoarse voice

Other symptoms may include:

• Cataracts (median age is about 31 years old)—cataracts are often bilateral and progress rapidly
• Other eye abnormalities such as senile macular degeneration and corneal calcification
• Type 2 diabetes, which usually doesn’t develop in non-WS patients until their 50s or 60s
• Arteriosclerosis (thickening of the artery walls), which may cause chest pain and myocardial infarction (heart attack)

WS patients are predisposed to a number of cancers, including:

• Thyroid
• Skin and mucosa (malignant melanoma)
• Brain and spinal cord (meningioma)
• Soft tissues and bones (sarcomas and osteosarcoma) and primary bone tumors
• Blood cells (leukemia/myelodysplasia)

Causes of Werner syndrome

WS is caused by a faulty gene: the WRN gene. According to the National Organization for Rare Disorders, researchers have identified more than 80 different mutations of this gene in people who have this disorder.

The WRN gene tells the cells how to produce a protein responsible for maintaining and repairing DNA. The protein also helps in copying DNA, a necessary step for cell division.

We each have two copies of every gene in the body, including the WRN gene. We inherit one copy from our mother and the other from our father. A mutation is a change in a gene that causes it to no longer function.

When the WRN gene mutates, the protein it produces doesn’t work properly and breaks down more quickly. Researchers suspect the flawed protein causes cells to divide more slowly or stop earlier than they should, resulting in growth problems. As the damage to the DNA builds, it causes the health issues associated with WS.

WS is autosomal recessive, meaning the patient has inherited two mutated copies of each gene, one from each parent. Because each parent has only one mutated copy of the WRN gene, neither parent will show symptoms. A parent who has one mutated copy of the WRN gene is considered a carrier. According to the Genetic and Rare Diseases Information Center, when both parents are carriers, every child they have has a:

• 1 in 4 chance of inheriting the disorder
• 1 in 2 chance of being an unaffected carrier like their parents
• 1 in 4 chance of being unaffected and not a carrier like their parents

How WS is diagnosed

Health-care providers may look for the telltale signs: short stature, premature graying, hair loss, skin changes, cataracts. They also may ask questions about medical history.

Some laboratory tests and imaging studies may be used to confirm or characterize abnormalities associated with the disease, such as:

• Ophthalmoscopy, to look for and measure cataracts
• Blood sugar testing, to detect and monitor diabetes
• Specialized cardiac tests, to look for abnormalities and calcium deposits in blood vessels

Genetic testing to confirm mutation of the WRN gene is also helpful.

Related disorders

A number of conditions or diseases have signs and symptoms similar to Werner syndrome. Although most are extremely rare, doctors may order testing to rule them out when diagnosing WS.

These include:

• Hutchinson-Gilford progeria syndrome. By about age 10, children with this disorder show signs of premature aging and have grown only as tall as most 3-year-olds. They’re also likely to suffer from arthritis during their childhood and young adult years.
• Gottron’s syndrome. This is another form of premature aging. People with this disease have atypically small hands and feet, with thin and delicate skin. Through much of their lives, children appear older than their real age.
• De Barsy syndrome. This disorder causes the elastic tissue in the skin to degenerate, corneas to cloud, and ears to stand out. Skin appears to wrinkle. Other characteristics include loss of muscle tone and involuntary movements of the arms and legs.
• Storm syndrome. This disease is another extremely rare one linked to both premature aging and heart disease. Patients prematurely gray and lose their eyebrows and eyelashes. Their skin also appears wrinkled, and some may have joint pain.
• Rothmund-Thomson syndrome. Patients with this inherited disorder appear to have redness of the skin. They may be small in stature and suffer from muscle loss. They also may be sensitive to light, develop cataracts in their youth, and prematurely go gray or bald.
• Combined growth factor deficiency. In addition to symptoms similar to WS, patients with these combined defects also may have joint problems, flat feet and thin, tight skin.

How WS is treated

There is no one treatment for WS. The goal is to treat the symptoms as they emerge.

WS patients will likely need an internist to guide care, as well as a number of specialists, including:

• Orthopedist, to treat problems with bones, muscles and joints
• Cardiologist, to treat abnormalities of the heart and blood vessels (medications may be prescribed to manage and minimize chest pain caused by lack of oxygen to the heart)
• Ophthalmologist, to treat cataracts and other eye problems (cataracts may need to be removed and replaced with a substitute lens)
• Endocrinologist, to treat disorders of the endocrine system, including diabetes (the diabetes in those with WS may be mild and managed with diet and medication.)

If tumors develop, doctors will determine whether these are benign or malignant and help the patient decide whether the best treatment is surgery, radiation, chemotherapy or other measures.

In addition, families with Werner syndrome are advised to seek genetic counseling. It’s best to find a specialist who has experience with WS and a medical professional who specializes in genetics.