Werner syndrome

Werner syndrome (also known as adult progeria or progeria of the adult) is a rare autosomal recessive disorder characterized by the premature appearance of features associated with aging. It is caused by mutations in the WRN gene (also called RECQL2), located on chromosome 8p12, which encodes a member of the RecQ family of DNA helicases involved in DNA repair, replication, and maintenance of genomic stability. The disease typically becomes apparent in the late teenage years or early twenties, when affected individuals fail to undergo the typical adolescent growth spurt, resulting in short stature. Key clinical features include bilateral cataracts (usually developing in the twenties), premature graying and thinning of the hair, scleroderma-like skin changes, subcutaneous tissue atrophy, and a characteristic aged facial appearance often described as "bird-like." Affected individuals frequently develop type 2 diabetes mellitus, hypogonadism, osteoporosis, atherosclerosis, and soft tissue calcifications. The voice may become high-pitched due to vocal cord atrophy. Skin ulcers, particularly around the ankles and Achilles tendon, are common and often difficult to treat. There is a significantly increased risk of malignancies, particularly soft tissue sarcomas, thyroid carcinomas, melanoma, meningiomas, and osteosarcomas, which are unusual in their distribution compared to the general population. The average life expectancy for individuals with Werner syndrome is approximately 54 years, with the most common causes of death being atherosclerotic cardiovascular disease and malignancy. There is currently no cure or treatment that reverses or halts the underlying accelerated aging process. Management is supportive and focused on surveillance and treatment of individual complications, including cataract surgery, management of diabetes and dyslipidemia, monitoring for malignancies, and wound care for skin ulcers. Werner syndrome is most prevalent in Japan, where the carrier frequency is estimated to be higher due to founder mutations.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Werner syndrome