Werner Syndrome Health Article

Demographics

Because of the limited number of cases, the demographic distribution of Werner syndrome is difficult to determine. Estimates of the number of people affected range from one in 95,000 to one in 1,000,000 people. Unlike progeria, which can be diagnosed at birth or soon after, Werner syndrome is not usually detected prior to adolescence. It is commonly noticed only after patients have failed to undergo the normal growth spurt associated with their teen years. The full range of symptoms is not usually seen until patients reach their 20s or 30s. Werner syndrome is more common in families in which a close biological relationship exists between parents. It occurs equally in both sexes. There is no evidence of a birth-order effect.

Signs and symptoms

The cardinal signs and symptoms of Werner syndrome start to appear after the age of 10. They are:

• Cataracts. These occur in both eyes, and usually develop by age 25 or 30.
• Skin problems including tight, shiny, smooth skin, ulceration, general wasting of the skin and localized wasting of the subcutaneous area underneath it, pigmentary changes, a thickening of the horny outer layer of the skin, and a characteristic bird-like facial appearance, including a beaked or pinched nose and unusually prominent eyes.
• Shortness of stature.
• An affected sibling or a close biological relationship between parents (third cousin or closer).
• Earlier-than-usual graying and/or thinning of scalp hair, usually by age 20.
• Excess amounts of hyaluronic acid (more commonly found in the body's connective tissues and in the fluids of the eyes and joints) in the urine.

Additional signs and symptoms of Werner syndrome include the following:

• Diabetes mellitus. This is usually mild, but can be found in between 44% and 67% of Werner syndrome patients.
• Impaired function of the ovaries or testes, as indicated by small or poorly developed genitalia or reduced fertility.
• Osteoporosis, most commonly in the upper limbs and spine, as well as in the lower limbs, feet, and ankles. In patients with Werner syndrome, osteoporosis is unlikely to be found in the skull or the torso.
• Unusually high bone density in the extremities of the finger and toe bones. This must be established by an x-ray examination.
• Deposits of calcium salts in soft tissues of the body. Common locations are around the Achilles tendon and the tendons of the elbow and the knee.
• Evidence pointing to earlier-than-usual arterial disease, such as a prior heart attack or abnormal electrocardiograms, etc.

• Rare or multiple tumors, or tumors derived from the mesoderm, the middle layer of the embryo. Werner syndrome is not marked by increased occurrence of all forms of tumors, but by selectively higher proportions of certain cancers that are relatively rare.
• Changes to the voice, rendering it squeaky, hoarse, or high-pitched.
• Flat feet.

In addition to the above signs and symptoms used for formal diagnostic purposes, other clinical observations have been reported, including loss of eyelashes and eyebrow hair, nail deformities, as well as the presence of thin limbs with a stocky trunk. A possible link to lung cancer has also been proposed.

In some cases, Werner syndrome can occur in a slower and milder partial form, with only some of the symptoms present.

Diagnosis

A definite diagnosis of Werner syndrome is established by the presence of all of the cardinal signs and symptoms listed above, plus at least two of the additional signs and symptoms.

A probable diagnosis is indicated by the presence of all of the first three cardinal signs, plus any two from the additional list.

A possible diagnosis is suggested by the presence of either cataracts or the skin manifestations, plus any four of the other signs or symptoms.

Werner syndrome may be ruled out if the above signs and symptoms appear prior to adolescence. The exception to this rule is shortness of stature, because patterns of pre-adolescent growth are not sufficiently understood.

Diagnosis may involve x rays to study hormone excretion, skin biopsies, and a blood-sugar test to determine whether diabetes mellitus is present. Werner syndrome can also be diagnosed by mutational analysis of the WRN gene.

Treatment and management

There is no known cure for Werner syndrome, so treatment is related to the specific symptoms present. For example, cataracts can be corrected by surgery and skin ulcers can be treated with grafts.

Prognosis

Because it mimics the human aging process, Werner syndrome significantly reduces life expectancy in most patients. Average life expectancy for a Werner symptom patient is somewhere between 40 and 47 years. The most common causes of death are heart attacks, cerebrovascular accidents, and cancers.

BOOKS

Thoene, Jess G., ed. Physicians' Guide to Rare Diseases. 2nd ed. Montvale, NJ: Dowden Publishing Company Inc., 1995.