Werner syndrome

Werner syndrome is an inherited condition that causes many organs and tissues to age more quickly than usual, typically becoming apparent in late adolescence or early adulthood. It results from pathogenic variants in the WRN gene, which encodes a protein that helps maintain the stability of DNA. Because two altered copies of the gene are required, males and females are affected equally. The syndrome is considered rare, affecting roughly one to nine people in every million worldwide. Severity and symptoms vary widely between individuals.

People with Werner syndrome usually appear healthy in childhood but begin to notice changes in their late teens or twenties. The first clues often include short stature, premature graying or loss of scalp hair, and the early development of clouding of the eye lenses (bilateral cataracts). As time goes on, skin becomes thin, tight, and fragile, giving a prematurely aged appearance with characteristic bird-like facial features and a high-pitched voice. Multi-system involvement is typical. Eye problems center on cataracts and, in many, progressive retinal degeneration. Endocrine and metabolic changes include elevated blood sugar, diabetes mellitus, high triglyceride levels, and fatty liver findings on laboratory tests. The bones tend to become brittle, leading to reduced bone density and osteoporosis, while abnormal calcium deposits can form in tendons, especially the Achilles. Cardiovascular complications may arise from premature hardening of the arteries. Pain in the lower back and joints is common, and thickened skin on the soles (plantar hyperkeratosis) and nail changes may develop. Not all individuals experience all features, and the mix and severity of symptoms can differ considerably, even among siblings.

Werner syndrome is caused by pathogenic variants in the WRN gene. The WRN protein is a DNA helicase that participates in repairing damaged DNA and keeping chromosomes stable; when it is absent or malfunctioning, cells accumulate damage that contributes to the signs of premature aging. The disorder follows an autosomal recessive inheritance pattern, meaning an individual must inherit one altered gene copy from each parent to be affected. Parents who carry one altered copy (carriers) are typically healthy but have a 25 percent chance with each pregnancy of having a child with the condition. This condition is more common when parents share a common ancestor, because relatives are more likely to carry the same rare variant. Carrier testing may be particularly relevant for families with shared ancestry, and genetic counseling is recommended for all relatives who may be at risk.

Currently, management focuses on supportive care and symptom management. Care is typically coordinated by a multidisciplinary team that may include endocrinologists, ophthalmologists, dermatologists, orthopedic specialists, cardiologists, and physical therapists. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Examples include annual eye examinations to monitor cataracts and retinal health, periodic screening for diabetes and lipid abnormalities, imaging or bone density studies to track skeletal health, and cardiovascular evaluations to detect arteriosclerosis. Treatment of active problems follows standard medical guidelines, such as timely cataract surgery to restore vision or medications and lifestyle measures to control blood sugar and cholesterol levels. Because needs change over time, individuals should discuss personalized monitoring schedules and therapeutic options with their healthcare team, and families are encouraged to meet with a genetic counselor for ongoing guidance.

The long-term outlook for Werner syndrome depends on which complications arise and how early they are detected and treated. Many individuals remain active for years but may develop diabetes, cardiovascular disease, or bone fractures that affect quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Ongoing follow-up with knowledgeable specialists, participation in recommended monitoring plans, and early treatment of emerging issues can make a meaningful difference. Families often find it helpful to connect with expert centers and genetic counselors to stay informed about care recommendations and research opportunities.

Several clinical trials are currently investigating new treatments or ways to slow the aging-related changes seen in Werner syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.