Synonyms

• WS
• adult progeria
• progeria adultorum

Category

Syndrome

Gender

Both equally

Epidemiology

• Autosomal recessive genetic disorder
• WRN helicase gene mutations
• Rare: 1 in 200,000 (Higher in Japan)
• Premature ageing Syndrome
• Increased malignancy risk (sarcomas, skin cancers, others)

Clinical Features

• Premature ageing starting 2nd-3rd decade
• Hair greying and loss
• Skin atrophy and pigmentation
• Short stature
• Osteoporosis and Bone pathology
• Type II diabetes
• Atherosclerosis

Location

• Skeletal: osteoporosis, atrophy
• Soft tissues: atrophy
• Increased sarcoma risk (especially osteosarcoma)

Imaging

• Baseline Bone density assessment (DEXA)
• Skeletal surveillance for sarcoma

Pathology

• Bone atrophy in skeleton
• Sarcoma histology if malignancy develops

Genetics

• WRN helicase gene mutations
• Autosomal recessive inheritance
• DNA repair defect

Treatment

• Surveillance for malignancy
• Management of metabolic complications (diabetes, atherosclerosis)
• Standard sarcoma treatment if malignancy develops

Prognosis

• Premature ageing with median survival 47 years
• Common causes of death: malignancy, cardiovascular disease
• Sarcoma risk increased 1000-fold

Key Points

• WRN mutations cause DNA repair defect
• Premature ageing Syndrome
• VERY High malignancy risk

Workup - Blood Tests

• WRN genetic testing
• Glucose (diabetes screening)
• Lipid panel, cardioVascular assessment

Workup - Local Imaging

• Baseline DEXA: Bone density
• Baseline skeletal survey
• Annual surveillance for sarcoma
• Cardiovascular imaging as indicated

Workup - Biopsy

If malignancy develops

Workup - Other

• Genetics consultation
• Endocrinology: diabetes management
• Cardiology: cardiovascular risk management

Follow-up Summary

• Annual full-body imaging
• Surveillance for osteosarcoma (High risk)
• Monitor for other malignancies
• Metabolic management: diabetes, cholesterol
• Cardiovascular surveillance