Progeria adultorumE34.8
Synonym(s)
OMIM 277000; Pangeria; Werner syndrome
HistoryThis section has been translated automatically.
Werner, 1904
DefinitionThis section has been translated automatically.
Hereditary segmental progeria syndrome of the adult with premature regression of various organ systems, but considerable differences to the aging process (e.g. CNS is not affected; different tumor spectrum). Hence the term "segmental progeria syndrome" or "caricature of aging".
Occurrence/EpidemiologyThis section has been translated automatically.
Incidence (worldwide): 1:1 million inhabitants/year. Highly concentrated in Japan and Sardinia.
EtiopathogenesisThis section has been translated automatically.
Autosomal recessive genetic defect in the WRN gene (gene locus 8p12-p11.2) which encodes a DNA helicase of the RecQ family. This helicase is involved in the opening of DNA prior to cell division. The mutation leads to genetic instability, with increased risk of developing malignancies. Furthermore, it is associated with increased synthesis of collagen I and III.
ManifestationThis section has been translated automatically.
Mainly occurring between the ages of 20 and 30; not before the age of 10.
Clinical featuresThis section has been translated automatically.
- Prepubertal completely inconspicuous development, postpubertal growth retardation. Usually average intelligence and absence of senile brain changes.
- Integument: Atrophy of the skin with numerous telangiectasias, extensive atrophy of the subcutaneous fatty tissue in the distal tibial and the entire foot area with hyperkeratosis and tendency to trophic ulceration. On the lower legs with taut atrophy of skin and muscles starting with sclerosis of the connective tissue. Often plantar hyperkeratosis and nail dystrophy. Canities praecox (premature graying of the hair) mostly 20. to 30. LJ. Premature alopecia areata diffusa, poikiloderma, striae cutis distensae, trophic leg ulcers. Symptoms of Progeria adultorum.
- Extracutaneous manifestation: Bilateral juvenile cataracts already around 30 years of age. Hypogonadism, testicular atrophy (see also Pseudo-Klinefelter syndrome), azoospermia tendency to type II diabetes and osteoporosis, early arteriosclerosis and coronary sclerosis (heart attack). Cawing high voice, vocal cord leukoplakia, dwarfism with characteristic habitus. Bird face, loss of facial expression.
- Increased risk of tumours (sarcomas, meningiomas, fewer carcinomas). Abnormal glycosaminoglycan metabolism with increased excretion of hyaluronic acid in urine. Often metastatic calcifications.
TherapyThis section has been translated automatically.
Symptomatic, causal therapy not known.
Progression/forecastThis section has been translated automatically.
Unfavourable, death due to arteriosclerosis often before the age of 50. In 10% malignant development (especially sarcomas).
LiteratureThis section has been translated automatically.
- Cover D et al (1990) Werner syndrome with pronounced pseudoscleroderma-like skin changes and urticaria pigmentosa-a random combination? Act Dermatol 16: 280-283
- Chen L et al (2003) LMNA mutations in atypical Werner's syndrome. Lancet 362: 440-445
- Epstein CJ et al (1966) Werner's syndrome: a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine 45: 177-221
- Goto M et al (1992) Genetic linkage of Werner's syndrome to five markers on chromosomes 8th Nature 355: 735-738
- Hürlimann AF et al (1991) Werner syndrome with trophic crural ulcers. dermatologist 42: 721-725
- Opresko PL (2003) Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis 24: 791-802
- Thomas W et al (1993) A genetic analysis of the Werner syndrome region on human chromosomes 8p, Genomics16: 685-690
- Werner O (1904) About cataract in connection with scleroderma. Schmidt and Klaunig, Kiel