Table 2. [Genetic Disorders in the Differential Diagnosis of Werner Syndrome]. - GeneReviews®

Presenting Symptoms	Gene	Disorder	MOI	Other Features / Comments
Progeroid features	LMNA	Atypical Werner syndrome ¹	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	AD
Cancer	BLM	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.

Presenting Symptoms

Gene

Disorder

MOI

Other Features / Comments

Progeroid features

LMNA

Atypical Werner syndrome ¹

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

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)

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)

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)

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)

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

Cancer

BLM

Bloom syndrome

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)

TP53

Li-Fraumeni syndrome (LFS)

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

May incl progeria-like facies & lipodystrophy, type 2 diabetes mellitus, cataracts, & glaucoma

Premature graying in adults

TFAP2A

Branchiooculofacial syndrome

Eye findings typically incl strabismus, coloboma, & microphthalmia; dysmorphic facial features are also present.

From: Werner Syndrome

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