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Werner syndrome (WS) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

Werner syndrome

MONDO:0010196

Also known as:WSWerner's syndromeadult premature ageing syndrome

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Overview

A rare inherited syndrome characterized by premature aging with onset in the third decade of life and with cardinal clinical features including bilateral cataracts, short stature, graying and thinning of scalp hair, characteristic skin disorders and premature onset of additional age-related disorders.

GeneticsAutosomal recessive · WRN (chr 8)

OnsetADULT

TreatmentsNo approved treatments · 1 in pipeline

Clinical Trials1 registered

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Achilles tendon calcification, Bird-like facies, Body ache, and Hyperglycemia and others; and very common findings: Short stature, Premature arteriosclerosis, Meningioma, and Retinal degeneration and others. 31 total HPO annotations.

Organ System	Phenotype Count	Example Features
Skin	4	Subcutaneous calcification, Alopecia of scalp, Nail dystrophy

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

WRN function has not been fully characterized.

Werner syndrome is caused by mutations in the WRN gene on chromosome 8.

GeneReviews

Clinical Guidance

The chronologic order of the onset of signs and symptoms is similar in all individuals with Werner syndrome regardless of the specific WRN pathogenic variants. The specific cell type in which cancer develops may depend on the type of WRN pathogenic variant present. In individuals of Japanese descent, papillary thyroid carcinoma has been associated with an N-terminal variant, whereas follicular thyroid carcinoma is more frequently observed with a C-terminal variant . This finding clearly contradicts the original assumption that all identified WRN pathogenic variants result in truncation of the nuclear localization signal of WRN protein and thereby act as null variants.

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

The diagnosis of Werner syndrome should be suspected in individuals who have the following cardinal signs :

Bilateral ocular cataracts (present in 99%)*
Premature graying and/or thinning of scalp hair (100%)
Characteristic dermatologic pathology (96%)

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for Werner syndrome. An additional 1 compound holds orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for Werner syndrome, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for Werner syndrome. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with Werner Syndrome

System/Concern

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

1 clinical trial registered. Interventions under study include drug therapy. Pipeline includes 1 PHASE2. Research is primarily industry-sponsored.

157 publications have been identified in PubMed for Werner syndrome. Research spans Basic Science / Preclinical (27%), Review / Meta-Analysis (25%), and Gene Therapy / Novel Therapeutics (16%).

Research Type	Count	% of Total
Laboratory research	43	27%

Data assembled from 10 of 12 sources · Last updated Sep 20, 2026, 11:11 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:277700

Orphanet

European rare disease database

Orphanet:902

GARD

Genetic and Rare Diseases Info Center

GARD:7885

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are any of the 1 active clinical trial a good fit for my situation?
→What is the current development status of Progerinin, and when might it become available?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Differential Diagnosis

The differential diagnosis depends on the presenting symptoms and age of onset. Table 2. Genetic Disorders in the Differential Diagnosis of Werner Syndrome

Presenting Symptoms	Gene	Disorder	MOI	Other Features / Comments
LMNA	Atypical Werner syndrome1	AD	Usually earlier onset (early 20s or earlier) faster rate of progression of symptoms than in typical Werner syndrome	—
Hutchinson-Gilford progeria syndrome (HGPS, progeria of childhood)2	AD	Like Werner syndrome, affects multiple organs w/presentations characterized as accelerated aging. Typically healthy at birth; profound FTT occurs in 1st yr. Death (usually from complications of cardiac or cerebrovascular disease) generally by age 6-20 yrs	—	—
Mandibuloacral dysplasia w/type A lipodystrophy (OMIM 248370)	AR	Characterized by growth deficiency, mandibular hypoplasia, progressive osteolysis of distal phalanges clavicles, acral lipodystrophy w/normal fat in neck trunk	—	—
POLD1	Mandibular hypoplasia, deafness, progeroid features, lipodystrophy (MDPL) syndrome (OMIM 615381)	AD	Unlike Werner syndrome, ocular cataracts are not a feature of MDPL syndrome risk of malignancy does not appear increased.	—
ZMPSTE24	Mandibuloacral dysplasia w/type B lipodystrophy (OMIM 608612)	AR	Onset at birth or early childhood of mandibular hypoplasia w/prominent eyes, atrophic skin, acroosteolysis, lipodystrophy Young adult-onset cataracts	—
CNBP	Myotonic dystrophy type 2 (DM2)	AD	May be considered w/young-adult onset cataracts, adults may show muscle wasting, but other manifestations (e.g., myotonia or cardiac conduction abnormalities) are quite different onset is usually in adulthood. DMPK	Myotonic dystrophy type 1
Bloom syndrome	AR	May be considered if cancer is presenting symptom, but RTS Bloom syndrome are childhood-onset disorders. Also, Werner syndrome cells do not exhibit sister chromatid exchange typical of Bloom syndrome.	—	—
RECQL4	Rothmund-Thomson syndrome (RTS)	AR	—	—
TP53	Li-Fraumeni syndrome (LFS)	AD	May present w/multiple cancers, incl non-epithelial cancers similar to those in Werner syndrome, but juvenile-onset cataracts other manifestations of Werner syndrome are not part of LFS. Progeria-like facies lipodystrophy	PIK3R1
SHORT syndrome	AD	May incl progeria-like facies lipodystrophy, type 2 diabetes mellitus, cataracts, glaucoma Premature graying in adults	TFAP2A	—
Branchiooculofacial syndrome	AD	Eye findings typically incl strabismus, coloboma, microphthalmia; dysmorphic facial features are also present.	—	—

Source: GeneReviews — "Werner Syndrome"

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Werner syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Werner Syndrome

System/Concern	Evaluation	Comment
Eyes	Ophthalmologic eval incl slit lamp exam for cataracts; eval for glaucoma diabetic retinopathy	At diagnosis Cardiovascular
Integument	Skin exam for common findings, esp calluses or early ulcerations of elbows lower legs; special attn to nail beds soles of feet for lentiginous melanoma	At diagnosis
Neurologic	Head MRI if neurologic symptoms incl new-onset seizures, focal neurologic signs such as weakness or visual field defect, or symptoms such as diploplia or headache	These signs/symptoms can be indicative of meningioma, a common neoplasm in Werner syndrome.
Genetic counseling	By genetics professionals1	To inform affected persons families re nature, MOI, implications of Werner syndrome to facilitate medical personal decision making
Psychosocial	Assessment of coping psychological fitness in light of prognosis	At diagnosis MOI = mode of inheritance 1. Medical geneticist, certified genetic counselor, certified advanced genetic nurse Treatment of Manifestations Table 4.
Treatment of Manifestations in Individuals with Werner Syndrome Manifestation/Concern	Treatment	Considerations/Other
Cataracts	Surgical treatment of ocular cataracts	Cystic macular edema is a postsurgical complication .
Malignancy	Standard treatment of malignancies	Type 2 diabetes
mellitus	Control of type 2 diabetes mellitus; favorable results reported w/use of thiazolidine, metformin, sitagliptin	,
Osteoporosis	Treat osteoporosis per current guidelines . Options incl: bisphosphonates, teriparatide. In women: calcitonin, estrogen/hormone therapy.	—
Skin ulcers	Aggressive treatment of skin ulcers w/debridement, topical medication to promote moist environment wound healing, negative pressure wound therapy skin grafting or flap surgery	Bosentan
Infertility	Fertility preservation may be achieved w/oocyte cryopreservation, sperm banking, or embryo banking.	Affected persons may benefit from consultation w/reproductive endocrinology infertility specialist. LDL = low-density lipoprotein Surveillance Table 5.

Source: GeneReviews — "Werner Syndrome"

Kisho

Werner syndrome

Overview

Clinical Presentation

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Differential Diagnosis

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Werner Syndrome Masquerading as Type 2 Diabetes: A Diagnostic Odyssey Leading to Precision Medicine.

Development of an exon 27-skipping antisense oligonucleotide as a targeted therapy for refractory skin ulcers in Werner syndrome.

Werner syndrome

Overview

Clinical Presentation

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Differential Diagnosis

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Werner Syndrome Masquerading as Type 2 Diabetes: A Diagnostic Odyssey Leading to Precision Medicine.

Development of an exon 27-skipping antisense oligonucleotide as a targeted therapy for refractory skin ulcers in Werner syndrome.