Clinical characteristics: Werner syndrome is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Individuals with Werner syndrome develop normally until the end of the first decade. The first sign is the lack of a growth spurt during the early teen years. Early findings (usually observed in the 20s) include loss and graying of hair, hoarseness, and scleroderma-like skin changes, followed by bilateral ocular cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers, and osteoporosis in the 30s. Myocardial infarction and cancer are the most common causes of death; the mean age of death in individuals with Werner syndrome is 54 years.
Diagnosis/testing: The diagnosis of Werner syndrome is established in a proband with the following cardinal signs: bilateral ocular cataracts, premature graying and/or thinning of scalp hair, characteristic dermatologic pathology, and short stature. Identification of biallelic WRN pathogenic variants on molecular genetic testing confirms the diagnosis if clinical features are inconclusive.
Management: Treatment of manifestations: Surgical treatment of ocular cataracts using special techniques; cholesterol-lowering drugs if lipid profile is abnormal with statin treatment for those with low-density lipoprotein cholesterol levels >190 mg/dL; lifestyle counseling including tobacco avoidance, regular exercise, and maintenance of healthy weight; treatment of malignancies in a standard fashion; control of type 2 diabetes mellitus; standard treatment of osteoporosis; aggressive treatment of skin ulcers; skin care with trauma avoidance; fertility preservation treatments as needed.
Surveillance: Annual ophthalmologic examination for cataracts; ten-year atherosclerotic cardiovascular disease risk estimation, annual lipid profile, surveillance for cardiovascular risk factors such as hypertension and diabetes mellitus; physical examination including neurologic assessment with attention to signs and symptoms of malignancies common in Werner syndrome; fasting glucose level, hemoglobin A1c, or oral glucose tolerance test annually; monitoring for osteoporosis, and annual skin examination for ulcers and lentiginous melanoma.
Agents/circumstances to avoid: Smoking and obesity, which increase the risk for atherosclerosis. Smoking and alcohol increase the risk of osteoporosis and cataracts. Avoid falls, trauma to the extremities, and excessive sun exposure.
Genetic counseling: Werner syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being neither affected nor a carrier. Carrier testing for at-risk relatives and prenatal testing for a pregnancy at increased risk are possible if the pathogenic variants in the family have been identified.
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