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Werner syndrome(WRN)

MedGen UID:
12147
Concept ID:
C0043119
Disease or Syndrome
Synonyms: Adult premature aging syndrome; Adult Progeria; Werner's syndrome; WRN
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Pangeria (51626007); Adult progeria (51626007); Adult premature aging syndrome (51626007); Werner syndrome (51626007); Progeria of the adult (51626007)
 
Gene: WRN
Cytogenetic location: 8p12
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]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Junko Oshima  |  George M Martin  |  Fuki M Hisama   view full author information

Additional description

From GHR
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.  http://ghr.nlm.nih.gov/condition/werner-syndrome

Clinical features

Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Osteosarcoma
MedGen UID:
505326
Concept ID:
CN002426
Finding
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.
Meningioma
MedGen UID:
505374
Concept ID:
CN002583
Finding
The presence of a meningioma, i.e., a benign tumor originating from the dura mater or arachnoid mater.
Neoplasm of the skin
MedGen UID:
428780
Concept ID:
CN007095
Finding
A tumor (abnormal growth of tissue) of the skin.
Renal neoplasm
MedGen UID:
506302
Concept ID:
CN008586
Finding
The presence of a neoplasm of the kidney.
Neoplasm of the breast
MedGen UID:
506444
Concept ID:
CN116912
Finding
A tumor (abnormal growth of tissue) of the breast.
Neoplasm of the thyroid gland
MedGen UID:
506448
Concept ID:
CN116930
Finding
A tumor (abnormal growth of tissue) of the thyroid gland.
Neoplasm of the lung
MedGen UID:
506475
Concept ID:
CN117419
Finding
Tumor of the lung.
Ovarian neoplasm
MedGen UID:
506498
Concept ID:
CN117507
Finding
The presence of a neoplasm the ovary.
Neoplasm of the oral cavity
MedGen UID:
451934
Concept ID:
CN117541
Finding
A tumor (abnormal growth of tissue) of the oral cavity.
Neoplasm of the small intestine
MedGen UID:
452045
Concept ID:
CN117722
Finding
The presence of a neoplasm of the small intestine.
Abnormality of the testis
MedGen UID:
446334
Concept ID:
CN000036
Finding
An anomaly of the testicle (the male gonad).
Hypogonadism
MedGen UID:
504359
Concept ID:
CN000131
Finding
A decreased functionality of the gonad.
Decreased fertility
MedGen UID:
504364
Concept ID:
CN000140
Finding
Secondary amenorrhea
MedGen UID:
504636
Concept ID:
CN000815
Finding
Renal neoplasm
MedGen UID:
506302
Concept ID:
CN008586
Finding
The presence of a neoplasm of the kidney.
Ovarian neoplasm
MedGen UID:
506498
Concept ID:
CN117507
Finding
The presence of a neoplasm the ovary.
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Convex nasal ridge
MedGen UID:
786052
Concept ID:
CN000415
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.
Neoplasm of the oral cavity
MedGen UID:
451934
Concept ID:
CN117541
Finding
A tumor (abnormal growth of tissue) of the oral cavity.
Abnormal retinal pigmentation
MedGen UID:
350681
Concept ID:
C1862475
Finding
Cataract
MedGen UID:
368085
Concept ID:
C1962983
Finding
Retinal degeneration
MedGen UID:
504488
Concept ID:
CN000512
Finding
A deterioration of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality.
Meningioma
MedGen UID:
505374
Concept ID:
CN002583
Finding
The presence of a meningioma, i.e., a benign tumor originating from the dura mater or arachnoid mater.
Abnormality of the cerebral vasculature
MedGen UID:
451940
Concept ID:
CN117551
Finding
Neoplasm of the breast
MedGen UID:
506444
Concept ID:
CN116912
Finding
A tumor (abnormal growth of tissue) of the breast.
Hypogonadism
MedGen UID:
504359
Concept ID:
CN000131
Finding
A decreased functionality of the gonad.
Diabetes mellitus
MedGen UID:
504609
Concept ID:
CN000766
Finding
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Secondary amenorrhea
MedGen UID:
504636
Concept ID:
CN000815
Finding
Neoplasm of the thyroid gland
MedGen UID:
506448
Concept ID:
CN116930
Finding
A tumor (abnormal growth of tissue) of the thyroid gland.
Rocker bottom foot
MedGen UID:
336761
Concept ID:
C1844713
Finding
Reduced bone mineral density
MedGen UID:
393152
Concept ID:
C2674432
Finding
Osteoporosis
MedGen UID:
776590
Concept ID:
C2911643
Finding
Abnormality of the thorax
MedGen UID:
427834
Concept ID:
CN000719
Finding
Any abnormality of the thorax (the region of the body formed by the sternum, the thoracic vertebrae and the ribs).
Chondrocalcinosis
MedGen UID:
504652
Concept ID:
CN000875
Finding
Radiographic evidence of articular calcification that represent calcium pyrophosphate depositions in soft tissue surrounding joints and at the insertions of tendons near joints (Entheses/Sharpey fibers) .
Limitation of joint mobility
MedGen UID:
446405
Concept ID:
CN001260
Finding
A reduction in the freedom of movement of one or more joints.
Osteosarcoma
MedGen UID:
505326
Concept ID:
CN002426
Finding
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.
Short palm
MedGen UID:
425240
Concept ID:
CN003783
Finding
Short palm.
Subcutaneous calcification
MedGen UID:
506092
Concept ID:
CN006677
Finding
Deposition of calcium salts in subcutaneous tissue (i.e., the the lowermost layer of the integument).
Increased bone mineral density
MedGen UID:
451275
Concept ID:
CN116733
Finding
An abnormal increase of bone mineral density, that is, of the amount of matter per cubic centimeter of bones which is often refered to as osteosclerosis. Osteosclerosis can be detected on radiological examination as an increased whiteness (density) of affected bones.
Neoplasm of the small intestine
MedGen UID:
452045
Concept ID:
CN117722
Finding
The presence of a neoplasm of the small intestine.
Abnormality of the hair
MedGen UID:
56381
Concept ID:
C0157733
Finding
Pili torti
MedGen UID:
82670
Concept ID:
C0263491
Disease or Syndrome
Pili torti, or twisted hair, is a condition in which the hair shafts are flattened and rotated along their long axis. Hairs are fragile and break at short length. Some patients may have associated dental or nail findings, and many have resolution of the fragile hair at puberty (review by Dawber, 1996). Pili torti is also a feature in several disorders, including Bjornstad syndrome (BJS; 262000), Bazex syndrome (BZX; 301845), and Menkes disease (309400).
Lack of skin elasticity
MedGen UID:
107840
Concept ID:
C0558242
Finding
Prematurely aged appearance
MedGen UID:
346633
Concept ID:
C1857656
Finding
Abnormal hair whorl
MedGen UID:
481933
Concept ID:
C3280303
Finding
Hyperkeratosis
MedGen UID:
504662
Concept ID:
CN000900
Finding
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
White forelock
MedGen UID:
505158
Concept ID:
CN002004
Finding
A triangular depigmented region of white hairs located in the anterior midline of the scalp.
Progeroid facial appearance
MedGen UID:
428516
Concept ID:
CN004729
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.
Subcutaneous calcification
MedGen UID:
506092
Concept ID:
CN006677
Finding
Deposition of calcium salts in subcutaneous tissue (i.e., the the lowermost layer of the integument).
Aplasia/Hypoplasia of the skin
MedGen UID:
446893
Concept ID:
CN007092
Finding
Neoplasm of the skin
MedGen UID:
428780
Concept ID:
CN007095
Finding
A tumor (abnormal growth of tissue) of the skin.
Teleangiectasia of the skin
MedGen UID:
451896
Concept ID:
CN117478
Finding
Presence of small, permanently dilated blood vessels near the surface of the skin, visible as small focal red lesions.
Skin ulcer
MedGen UID:
506561
Concept ID:
CN117783
Finding
A discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis and even subcutaneous fat.
Abnormal hair quantity
MedGen UID:
489172
Concept ID:
CN167090
Finding
An abnormal amount of hair.
Abnormality of the voice
MedGen UID:
425062
Concept ID:
CN001464
Finding
Any abnormality of the voice.
Hypertension
MedGen UID:
635666
Concept ID:
C0497247
Finding
A finding of increased blood pressure; not necessarily hypertensive disorder
Premature arteriosclerosis
MedGen UID:
376368
Concept ID:
C1848486
Finding
Congestive heart failure
MedGen UID:
504881
Concept ID:
CN001488
Finding
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Coronary artery disease
MedGen UID:
504904
Concept ID:
CN001526
Finding
Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries, which increases the risk of myocardial ischemia.
Abnormality of the pulmonary artery
MedGen UID:
428461
Concept ID:
CN003909
Finding
An abnormality of the pulmonary artery.
Abnormality of the cerebral vasculature
MedGen UID:
451940
Concept ID:
CN117551
Finding
Diabetes mellitus
MedGen UID:
504609
Concept ID:
CN000766
Finding
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Laryngomalacia
MedGen UID:
504867
Concept ID:
CN001457
Finding
Laryngomalacia is a congenital abnormality of the laryngeal cartilage in which the cartilage is floppy and prolapses over the larynx during inspiration.
Abnormality of the pulmonary artery
MedGen UID:
428461
Concept ID:
CN003909
Finding
An abnormality of the pulmonary artery.
Neoplasm of the lung
MedGen UID:
506475
Concept ID:
CN117419
Finding
Tumor of the lung.
Skeletal muscle atrophy
MedGen UID:
505481
Concept ID:
CN002890
Finding
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Chondrocalcinosis
MedGen UID:
504652
Concept ID:
CN000875
Finding
Radiographic evidence of articular calcification that represent calcium pyrophosphate depositions in soft tissue surrounding joints and at the insertions of tendons near joints (Entheses/Sharpey fibers) .
Lipoatrophy
MedGen UID:
451893
Concept ID:
CN117471
Finding
Localized loss of fat tissue.
Rocker bottom foot
MedGen UID:
336761
Concept ID:
C1844713
Finding
Short palm
MedGen UID:
425240
Concept ID:
CN003783
Finding
Short palm.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews

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. [Epub ahead of print] PMID: 22258520Free PMC Article

Recent clinical studies

Etiology

Lauper JM, Krause A, Vaughan TL, Monnat RJ Jr
PLoS One 2013;8(4):e59709. Epub 2013 Apr 1 doi: 10.1371/journal.pone.0059709. PMID: 23573208Free PMC Article
Fumo G, Pau M, Patta F, Aste N, Atzori L
Dermatol Online J 2013 Mar 15;19(3):6. PMID: 23552003
Goutzanis L, Kalfarentzos EF, Petsinis V, Papadogeorgakis N
J Craniomaxillofac Surg 2013 Oct;41(7):e170-4. Epub 2013 Jan 26 doi: 10.1016/j.jcms.2012.11.045. [Epub ahead of print] PMID: 23357132
Takada-Watanabe A, Yokote K, Takemoto M, Fujimoto M, Irisuna H, Honjo S, Futami K, Furuichi Y, Saito Y
Geriatr Gerontol Int 2012 Jan;12(1):140-6. doi: 10.1111/j.1447-0594.2011.00743.x. PMID: 22188495
Ishikawa N, Nakamura K, Izumiyama-Shimomura N, Aida J, Ishii A, Goto M, Ishikawa Y, Asaka R, Matsuura M, Hatamochi A, Kuroiwa M, Takubo K
Aging (Albany NY) 2011 Apr;3(4):417-29. PMID: 21732564Free PMC Article

Diagnosis

Oshitari T, Kitahashi M, Mizuno S, Baba T, Kubota-Taniai M, Takemoto M, Yokote K, Yamamoto S, Roy S
BMC Ophthalmol 2014 Mar 12;14:31. doi: 10.1186/1471-2415-14-31. [Epub ahead of print] PMID: 24620826Free PMC Article
Donadille B, D'Anella P, Auclair M, Uhrhammer N, Sorel M, Grigorescu R, Ouzounian S, Cambonie G, Boulot P, Laforêt P, Carbonne B, Christin-Maitre S, Bignon YJ, Vigouroux C
Orphanet J Rare Dis 2013 Jul 12;8:106. doi: 10.1186/1750-1172-8-106. [Epub ahead of print] PMID: 23849162Free PMC Article
Tadokoro T, Rybanska-Spaeder I, Kulikowicz T, Dawut L, Oshima J, Croteau DL, Bohr VA
DNA Repair (Amst) 2013 Jun 1;12(6):414-21. Epub 2013 Apr 11 doi: 10.1016/j.dnarep.2013.03.004. [Epub ahead of print] PMID: 23583337Free PMC Article
Goutzanis L, Kalfarentzos EF, Petsinis V, Papadogeorgakis N
J Craniomaxillofac Surg 2013 Oct;41(7):e170-4. Epub 2013 Jan 26 doi: 10.1016/j.jcms.2012.11.045. [Epub ahead of print] PMID: 23357132
Takemoto M, Mori S, Kuzuya M, Yoshimoto S, Shimamoto A, Igarashi M, Tanaka Y, Miki T, Yokote K
Geriatr Gerontol Int 2013 Apr;13(2):475-81. Epub 2012 Jul 23 doi: 10.1111/j.1447-0594.2012.00913.x. [Epub ahead of print] PMID: 22817610

Therapy

Oshitari T, Kitahashi M, Mizuno S, Baba T, Kubota-Taniai M, Takemoto M, Yokote K, Yamamoto S, Roy S
BMC Ophthalmol 2014 Mar 12;14:31. doi: 10.1186/1471-2415-14-31. [Epub ahead of print] PMID: 24620826Free PMC Article
Kemmanu V, Nagappa S, Hegde K, Yadav NK, Shetty BK
Indian J Ophthalmol 2012 Nov-Dec;60(6):570-2. doi: 10.4103/0301-4738.103802. PMID: 23202403Free PMC Article
Bird JL, Jennert-Burston KC, Bachler MA, Mason PA, Lowe JE, Heo SJ, Campisi J, Faragher RG, Cox LS
Biogerontology 2012 Feb;13(1):49-62. Epub 2011 Jul 24 doi: 10.1007/s10522-011-9341-8. [Epub ahead of print] PMID: 21786128
Bagley MC, Davis T, Dix MC, Fusillo V, Pigeaux M, Rokicki MJ, Kipling D
Future Med Chem 2010 Sep;2(9):1417-27. doi: 10.4155/fmc.10.217. PMID: 21426137
Massip L, Garand C, Paquet ER, Cogger VC, O'Reilly JN, Tworek L, Hatherell A, Taylor CG, Thorin E, Zahradka P, Le Couteur DG, Lebel M
FASEB J 2010 Jan;24(1):158-72. Epub 2009 Sep 9 doi: 10.1096/fj.09-137133. [Epub ahead of print] PMID: 19741171Free PMC Article

Prognosis

Lauper JM, Krause A, Vaughan TL, Monnat RJ Jr
PLoS One 2013;8(4):e59709. Epub 2013 Apr 1 doi: 10.1371/journal.pone.0059709. PMID: 23573208Free PMC Article
Goutzanis L, Kalfarentzos EF, Petsinis V, Papadogeorgakis N
J Craniomaxillofac Surg 2013 Oct;41(7):e170-4. Epub 2013 Jan 26 doi: 10.1016/j.jcms.2012.11.045. [Epub ahead of print] PMID: 23357132
Gonullu E, Bilge NS, Kaşifoğlu T, Korkmaz C
Rheumatol Int 2013 May;33(5):1309-12. Epub 2012 Nov 6 doi: 10.1007/s00296-012-2564-4. [Epub ahead of print] PMID: 23129431
Takemoto M, Mori S, Kuzuya M, Yoshimoto S, Shimamoto A, Igarashi M, Tanaka Y, Miki T, Yokote K
Geriatr Gerontol Int 2013 Apr;13(2):475-81. Epub 2012 Jul 23 doi: 10.1111/j.1447-0594.2012.00913.x. [Epub ahead of print] PMID: 22817610
Takada-Watanabe A, Yokote K, Takemoto M, Fujimoto M, Irisuna H, Honjo S, Futami K, Furuichi Y, Saito Y
Geriatr Gerontol Int 2012 Jan;12(1):140-6. doi: 10.1111/j.1447-0594.2011.00743.x. PMID: 22188495

Clinical prediction guides

Donadille B, D'Anella P, Auclair M, Uhrhammer N, Sorel M, Grigorescu R, Ouzounian S, Cambonie G, Boulot P, Laforêt P, Carbonne B, Christin-Maitre S, Bignon YJ, Vigouroux C
Orphanet J Rare Dis 2013 Jul 12;8:106. doi: 10.1186/1750-1172-8-106. [Epub ahead of print] PMID: 23849162Free PMC Article
Fumo G, Pau M, Patta F, Aste N, Atzori L
Dermatol Online J 2013 Mar 15;19(3):6. PMID: 23552003
Goto M, Ishikawa Y, Sugimoto M, Furuichi Y
Biosci Trends 2013 Feb;7(1):13-22. PMID: 23524889
Heyn H, Moran S, Esteller M
Epigenetics 2013 Jan;8(1):28-33. Epub 2012 Dec 20 doi: 10.4161/epi.23366. [Epub ahead of print] PMID: 23257959Free PMC Article
Takada-Watanabe A, Yokote K, Takemoto M, Fujimoto M, Irisuna H, Honjo S, Futami K, Furuichi Y, Saito Y
Geriatr Gerontol Int 2012 Jan;12(1):140-6. doi: 10.1111/j.1447-0594.2011.00743.x. PMID: 22188495

Recent systematic reviews

Lauper JM, Krause A, Vaughan TL, Monnat RJ Jr
PLoS One 2013;8(4):e59709. Epub 2013 Apr 1 doi: 10.1371/journal.pone.0059709. PMID: 23573208Free PMC Article
Cesari M, Pahor M, Incalzi RA
Cardiovasc Ther 2010 Oct;28(5):e72-91. Epub 2010 Jul 7 doi: 10.1111/j.1755-5922.2010.00171.x. [Epub ahead of print] PMID: 20626406Free PMC Article
Pallardó FV, Lloret A, Lebel M, d'Ischia M, Cogger VC, Le Couteur DG, Gadaleta MN, Castello G, Pagano G
Biogerontology 2010 Aug;11(4):401-19. Epub 2010 Mar 18 doi: 10.1007/s10522-010-9269-4. [Epub ahead of print] PMID: 20237955
Butler RN, Warner HR, Williams TF, Austad SN, Brody JA, Campisi J, Cerami A, Cohen G, Cristofalo VJ, Drachman DA, Finch CE, Fridovich I, Harley CB, Havlik RJ, Martin GM, Miller RA, Olshansky SJ, Pereira-Smith OM, Smith JR, Sprott RL, West MD, Wilmoth JR, Wright WE
Aging Clin Exp Res 2004 Apr;16(2):104-11; discussion 111-2. PMID: 15195984
Martin GM
Natl Cancer Inst Monogr 1982;60:241-7. PMID: 6214719

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