Werner syndrome

Introduction

A 'caricature' of senescence, has been termed 'adult progeria', but is unrelated to the pediatric syndrome of progeria (Hutchinson-Gilford syndrome). Also distinguish from WerMer's syndrome (MEN-1). Mean life span is about 40-45 years.

Etiology

• deletion of nuclear localization signal in a helicase encoded by the WRN gene located on the short arm of chromosome 8

Epidemiology

rare

Pathology

• premature onset of multiple age-related disorders, including:
  • atherosclerosis
  • cancer, benign tumors (meningioma)
  • non-insulin-dependent diabetes mellitus
  • cataracts
  • osteoporosis

Genetics

• autosomal recessive
• associated with defects in WRN gene (8p12-p11.2)
• all known Werner syndrome mutations produce prematurely terminated proteins
• associated with defects in LMNA gene

Clinical manifestations

• hypogonadism occurs in both sexes
• malignancies occur in 10% of patients
  • meningiomas
  • sarcomas
• habitus
  • short-stature secondary to absence of normal adolescent growth spurt
  • slender limbs
  • stocky trunk
• facies
  • widened and prematurely aged facies
  • beaked nose
• premature graying & loss of hair
• scleroderma-like skin changes, especially in extremities
  • atrophy
  • hyperkeratosis
  • subcutaneous calcification
  • ulcerations around feet
• squeaky voice
• atrophy of muscles
• diabetes mellitus
• cataracts
• premature arteriosclerosis
• metastatic calcification

Laboratory

• altered glycosaminoglycan turnover with increased hyaluronate in urine, a non-specific finding

Complications

• major cause of death is myocardial infarction at a median age of 47 years

Management

• Caution: No local or systemic use of cortisone

More general terms

• progeroid syndrome

Additional terms

• multiple endocrine neoplasia type-1 (MEN-1); multiple endocrine adenomatosis; Wermer Syndrome
• WRN (Werner's syndrome) gene

Database

• OMIM: https://mirror.omim.org/entry/277700
• OMIM: https://mirror.omim.org/entry/604611