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Werner syndrome
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:
a) atherosclerosis
b) cancer, benign tumors (meningioma)
c) non-insulin-dependent diabetes mellitus
d) cataracts
e) 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:
1) hypogonadism occurs in both sexes
2) malignancies occur in 10% of patients
a) meningiomas
b) sarcomas
3) habitus
a) short-stature secondary to absence of normal adolescent growth spurt
b) slender limbs
c) stocky trunk
4) facies
a) widened and prematurely aged facies
b) beaked nose
5) premature graying & loss of hair
6) scleroderma-like skin changes, especially in extremities
a) atrophy
b) hyperkeratosis
c) subcutaneous calcification
d) ulcerations around feet
7) squeaky voice
8) atrophy of muscles
9) diabetes mellitus
10) cataracts
11) premature arteriosclerosis
12) 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
Related
multiple endocrine neoplasia type-1 (MEN-1); multiple endocrine adenomatosis; Wermer Syndrome
WRN (Werner's syndrome) gene
General
progeroid syndrome
Database Correlations
OMIM correlations
MORBIDMAP 604611
References
- OMIM 277700
- Cecil Textbook of Medicine, Wyngaarden & Smith eds,
WB Saunders, Philadelphia, 1985, 1172