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Werner syndrome(WRN)

MedGen UID:
12147
Concept ID:
C0043119
Disease or Syndrome
Synonyms: Werner's syndrome; WRN
SNOMED CT: Pangeria (51626007); Adult progeria (51626007); Adult premature aging syndrome (51626007); Werner syndrome (51626007); Progeria of the adult (51626007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): WRN (8p12)
 
Monarch Initiative: MONDO:0010196
OMIM®: 277700
Orphanet: ORPHA902

Disease characteristics

Excerpted from the GeneReview: Werner Syndrome
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. [from GeneReviews]
Authors:
Junko Oshima  |  George M Martin  |  Fuki M Hisama   view full author information

Additional descriptions

From OMIM
Werner syndrome (WRN) is a rare autosomal recessive segmental progeroid syndrome. Patients exhibit not only an appearance of accelerated aging (premature graying, thinning of hair, skin atrophy and atrophy of subcutaneous fat), but also several disorders commonly associated with aging, including bilateral cataracts, diabetes mellitus, osteoporosis, premature arteriosclerosis, and a variety of benign and malignant neoplasms (summary by Oshima et al., 1996). See also Hutchinson-Gilford progeria syndrome (HGPS; 176670), a more severe progeroid syndrome with earlier onset caused by mutation in the LMNA gene (150330).  http://www.omim.org/entry/277700
From MedlinePlus Genetics
Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature. The characteristic aged appearance of individuals with Werner syndrome typically begins to develop when they are in their twenties and includes graying and loss of hair; a hoarse voice; and thin, hardened skin. They may also have a facial appearance described as "bird-like." Many people with Werner syndrome have thin arms and legs and a thick trunk due to abnormal fat deposition.

As Werner syndrome progresses, affected individuals may develop disorders of aging early in life, such as cloudy lenses (cataracts) in both eyes, skin ulcers, type 2 diabetes, diminished fertility, severe hardening of the arteries (atherosclerosis), thinning of the bones (osteoporosis), and some types of cancer. It is not uncommon for affected individuals to develop multiple, rare cancers during their lifetime. People with Werner syndrome usually live into their late forties or early fifties. The most common causes of death are cancer and atherosclerosis.  https://medlineplus.gov/genetics/condition/werner-syndrome

Clinical features

From HPO
Low back pain
MedGen UID:
7389
Concept ID:
C0024031
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the lower back.
Osteosarcoma
MedGen UID:
10501
Concept ID:
C0029463
Neoplastic Process
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
Premature arteriosclerosis
MedGen UID:
376368
Concept ID:
C1848486
Disease or Syndrome
Arteriosclerosis occurring at an age that is younger than usual.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Meningioma
MedGen UID:
7532
Concept ID:
C0025286
Neoplastic Process
The presence of a meningioma, i.e., a benign tumor originating from the dura mater or arachnoid mater.
High pitched voice
MedGen UID:
66836
Concept ID:
C0241703
Finding
An abnormal increase in the pitch (frequency) of the voice.
Elevated hemoglobin A1c
MedGen UID:
892798
Concept ID:
C4073162
Finding
An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Reduced bone mineral density
MedGen UID:
393152
Concept ID:
C2674432
Finding
A reduction of bone mineral density, that is, of the amount of matter per cubic centimeter of bones.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
Alopecia of scalp
MedGen UID:
658454
Concept ID:
C0574769
Finding
Bird-like facies
MedGen UID:
325243
Concept ID:
C1837758
Finding
Scleroderma
MedGen UID:
3770
Concept ID:
C0011644
Disease or Syndrome
A chronic autoimmune phenomenon characterized by fibrosis (or hardening) and vascular alterations of the skin.
Subcutaneous calcification
MedGen UID:
120484
Concept ID:
C0263625
Disease or Syndrome
Deposition of calcium salts in subcutaneous tissue (i.e., the the lowermost layer of the integument).
Prematurely aged appearance
MedGen UID:
346633
Concept ID:
C1857656
Finding
Progeroid facial appearance
MedGen UID:
341830
Concept ID:
C1857710
Finding
A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVWerner syndrome
Follow this link to review classifications for Werner syndrome in Orphanet.

Professional guidelines

PubMed

Takemoto M, Kubota Y, Taniguchi T, Motegi SI, Taniguchi A, Nakagami H, Maezawa Y, Koshizaka M, Kato H, Tsukamoto K, Mori S, Kuzuya M, Yokote K
Geriatr Gerontol Int 2021 Feb;21(2):142-145. Epub 2020 Nov 9 doi: 10.1111/ggi.14083. PMID: 33169495
Kuzuya M, Takemoto M, Kubota Y, Taniguchi T, Motegi SI, Taniguchi A, Nakagami H, Maezawa Y, Koshizaka M, Kato H, Mori S, Tsukamoto K, Yokote K
Geriatr Gerontol Int 2021 Feb;21(2):139-141. Epub 2020 Nov 9 doi: 10.1111/ggi.14076. PMID: 33169468
Compagnucci C, Bertini E
Int J Mol Sci 2017 Nov 7;18(11) doi: 10.3390/ijms18112350. PMID: 29112121Free PMC Article

Curated

Hisama FM, Kubisch C, Martin GM, Oshima J
Eur J Hum Genet 2012 May;20(5) Epub 2012 Jan 18 doi: 10.1038/ejhg.2011.265. PMID: 22258520Free PMC Article

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Diagnosis

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Therapy

Takemoto M, Kubota Y, Taniguchi T, Motegi SI, Taniguchi A, Nakagami H, Maezawa Y, Koshizaka M, Kato H, Tsukamoto K, Mori S, Kuzuya M, Yokote K
Geriatr Gerontol Int 2021 Feb;21(2):142-145. Epub 2020 Nov 9 doi: 10.1111/ggi.14083. PMID: 33169495
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Prognosis

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Geriatr Gerontol Int 2021 Feb;21(2):139-141. Epub 2020 Nov 9 doi: 10.1111/ggi.14076. PMID: 33169468
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Recent systematic reviews

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