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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
Sources: HPO, OMIM
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).  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.\n\nAs 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
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.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A metabolic disorder characterized by abnormally high blood sugar levels due to diminished production of insulin or insulin resistance/desensitization.
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
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.
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).
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.
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
Degeneration of the retina.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Acquired Abnormality
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Abnormal hair morphology
MedGen UID:
56381
Concept ID:
C0157733
Finding
An abnormality of the hair.
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.
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).
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).
Premature arteriosclerosis
MedGen UID:
376368
Concept ID:
C1848486
Disease or Syndrome
Arteriosclerosis occurring at an age that is younger than usual.
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.

Term Hierarchy

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

Professional guidelines

PubMed

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

Suggested Reading

Recent clinical studies

Etiology

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
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Nakagami H, Sugimoto K, Ishikawa T, Koshizaka M, Fujimoto T, Kiyohara E, Hayashi M, Nakagawa Y, Ando H, Terabe Y, Takami Y, Yamamoto K, Takeya Y, Takemoto M, Ebihara T, Nakamura A, Nishikawa M, Yao XJ, Hanaoka H, Yokote K, Rakugi H
Geriatr Gerontol Int 2019 Nov;19(11):1118-1123. doi: 10.1111/ggi.13782. PMID: 31746528
Lebel M, Monnat RJ Jr
Ageing Res Rev 2018 Jan;41:82-97. Epub 2017 Nov 14 doi: 10.1016/j.arr.2017.11.003. PMID: 29146545

Diagnosis

Taniguchi A, Tanaka Y, Takemoto M, Kubota Y, Taniguchi T, Motegi SI, Nakagami H, Maezawa Y, Koshizaka M, Kato H, Tsukamoto K, Mori S, Kuzuya M, Yokote K
Geriatr Gerontol Int 2021 Feb;21(2):163-165. Epub 2020 Dec 1 doi: 10.1111/ggi.14084. PMID: 33260264
Tsukamoto K, Takemoto M, Kubota Y, Taniguchi T, Motegi SI, Taniguchi A, Nakagami H, Maezawa Y, Koshizaka M, Kato H, Mori S, Kuzuya M, Yokote K
Geriatr Gerontol Int 2021 Feb;21(2):133-138. Epub 2020 Dec 1 doi: 10.1111/ggi.14095. PMID: 33258561
Kubota Y, Takemoto M, Taniguchi T, Motegi SI, Taniguchi A, Nakagami H, Maezawa Y, Koshizaka M, Kato H, Mori S, Tsukamoto K, Kuzuya M, Yokote K
Geriatr Gerontol Int 2021 Feb;21(2):153-159. Epub 2020 Nov 22 doi: 10.1111/ggi.14096. PMID: 33225552
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Geriatr Gerontol Int 2021 Feb;21(2):139-141. Epub 2020 Nov 9 doi: 10.1111/ggi.14076. PMID: 33169468
Li H, Yang M, Shen H, Wang S, Cai H
Endocr J 2021 Mar 28;68(3):261-267. Epub 2020 Oct 20 doi: 10.1507/endocrj.EJ20-0448. PMID: 33087645

Therapy

Aumailley L, Lebel M
Antioxid Redox Signal 2021 Apr 10;34(11):856-874. Epub 2020 Nov 17 doi: 10.1089/ars.2020.8147. PMID: 33202145
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Geriatr Gerontol Int 2021 Feb;21(2):142-145. Epub 2020 Nov 9 doi: 10.1111/ggi.14083. PMID: 33169495
Mori S, Takemoto M, Kubota Y, Taniguchi T, Motegi SI, Taniguchi A, Nakagami H, Maezawa Y, Koshizaka M, Kato H, Tsukamoto K, Kuzuya M, Yokote K
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Geriatr Gerontol Int 2019 Nov;19(11):1118-1123. doi: 10.1111/ggi.13782. PMID: 31746528
Kamath-Loeb AS, Zavala-van Rankin DG, Flores-Morales J, Emond MJ, Sidorova JM, Carnevale A, Cárdenas-Cortés MD, Norwood TH, Monnat RJ, Loeb LA, Mercado-Celis GE
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Prognosis

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Clin Breast Cancer 2021 Feb;21(1):57-73.e7. Epub 2020 Jul 25 doi: 10.1016/j.clbc.2020.07.013. PMID: 32919863
He G, Yan Z, Sun L, Lv Y, Guo W, Gang X, Wang G
Endocr J 2019 Nov 28;66(11):961-969. Epub 2019 Jul 4 doi: 10.1507/endocrj.EJ19-0014. PMID: 31270292
Nishioka M, Kamei S, Kinoshita T, Sanada J, Fushimi Y, Irie S, Hirata Y, Tanabe A, Hirukawa H, Kimura T, Obata A, Tatsumi F, Kohara K, Shimoda M, Nakanishi S, Mune T, Kaku K, Kaneto H
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David A, Vincent M, Arrigoni PP, Barbarot S, Pistorius MA, Isidor B, Frampas E
Diagn Interv Imaging 2017 May;98(5):373-378. Epub 2016 Dec 5 doi: 10.1016/j.diii.2016.10.007. PMID: 27931782

Clinical prediction guides

Taniguchi A, Tanaka Y, Takemoto M, Kubota Y, Taniguchi T, Motegi SI, Nakagami H, Maezawa Y, Koshizaka M, Kato H, Tsukamoto K, Mori S, Kuzuya M, Yokote K
Geriatr Gerontol Int 2021 Feb;21(2):163-165. Epub 2020 Dec 1 doi: 10.1111/ggi.14084. PMID: 33260264
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
Nakagami H, Sugimoto K, Ishikawa T, Koshizaka M, Fujimoto T, Kiyohara E, Hayashi M, Nakagawa Y, Ando H, Terabe Y, Takami Y, Yamamoto K, Takeya Y, Takemoto M, Ebihara T, Nakamura A, Nishikawa M, Yao XJ, Hanaoka H, Yokote K, Rakugi H
Geriatr Gerontol Int 2019 Nov;19(11):1118-1123. doi: 10.1111/ggi.13782. PMID: 31746528
Marabitti V, Lillo G, Malacaria E, Palermo V, Sanchez M, Pichierri P, Franchitto A
Nucleic Acids Res 2019 Apr 23;47(7):3485-3502. doi: 10.1093/nar/gkz025. PMID: 30657978Free PMC Article
Ketkar A, Voehler M, Mukiza T, Eoff RL
J Biol Chem 2017 Feb 24;292(8):3154-3163. Epub 2017 Jan 9 doi: 10.1074/jbc.M116.767699. PMID: 28069813Free PMC Article

Recent systematic reviews

Lauper JM, Krause A, Vaughan TL, Monnat RJ Jr
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Martin GM
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