Welander Distal Myopathy (WDM)

Categories: Bone diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Welander Distal Myopathy

MalaCards integrated aliases for Welander Distal Myopathy:

Name: Welander Distal Myopathy 57 20 72 36 29 13 6 70
Wdm 57 20 58 72
Muscular Dystrophy, Distal, Late-Onset, Autosomal Dominant 57
Late-Onset Autosomal Dominant Distal Muscular Dystrophy 72
Welander Distal Myopathy, Swedish Type 20
Distal Myopathy, Welander Type 58
Distal Myopathy, Swedish Type 20
Myopathy, Distal, Welander 39
Myopathy, Distal, Swedish 57
Swedish Distal Myopathy 72


Orphanet epidemiological data:

distal myopathy, welander type
Inheritance: Autosomal dominant; Prevalence: >1/1000 (Sweden); Age of onset: Adult; Age of death: normal life expectancy;


57 (Updated 20-May-2021)
autosomal recessive
autosomal dominant

slowly progressive
adult onset (range 40 to 60 years)
high incidence in sweden and finland
incidence of 1 in 100 in some local nordic areas
homozygotes have earlier onset and a more severe disorder


welander distal myopathy:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course adult onset slow progression


Orphanet: 58  
Rare neurological diseases

External Ids:

OMIM® 57 604454
KEGG 36 H01975
MeSH 44 D049310
MESH via Orphanet 45 C536690
ICD10 via Orphanet 33 G71.0
UMLS via Orphanet 71 C0221054 C2931290
Orphanet 58 ORPHA603
MedGen 41 C0221054
UMLS 70 C0221054

Summaries for Welander Distal Myopathy

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 603 Definition A rare distal myopathy characterized by weakness in the distal upper extremities, usually finger and wrist extensors which later progresses to all hand muscles and distal lower extremity, primarily in toe and ankle extensors. Epidemiology Distal myopathy, Welander type (WDM) prevalence is unknown. The condition is mainly restricted to a geographical area around the Baltic Sea especially in Finland and Sweden (mid-eastern region), where the estimated prevalence is 1/10,000. However, some patients have been reported in the United Kingdom. Clinical description WDM is a late adult-onset disorder (onset between 40 and 60 years) characterized by initial weakness of index finger extensors followed by extension weakness in the other fingers. Weakness slowly progresses to all hand and lower leg muscles. In the lower limb, the anterior tibial muscle and toe extensors are typically affected leading to walking difficulties and steppage gait. Proximal limb muscles are only rarely involved. Muscle stretch reflexes are preserved (except ankle reflexes which may be lost later in the disease). Cardiac muscle involvement has not been observed. Rare homozygotes individuals show an earlier onset and proximal muscle involvement with faster progression. Etiology WDM is caused by a missense change (c.1362G>A; p.E384K) in TIA1 gene (2p13) which encodes nucleolysin TIA1 isoform p40, a key component of stress granules (SGs). Under conditions of cellular stress or metabolic changes, nucleolysin TIA1 isoform p40 promotes messenger ribonucleoprotein (mRNP) complexes to assemble in SGs to repress translation. The mutation leads to reduced dynamics of the SGs and abnormal autophagic processing with rimmed vacuolar pathology. In addition, the WDM phenotype has been reported in patients with a digenic combination of a SQSTM1 mutation and TIA1 -N357S variant. Diagnostic methods Diagnosis relies on molecular genetic testing. Additional examinations include muscle biopsy of distal muscles showing dystrophic features and prominent rimmed vacuoles. Sensory examination is usually normal, although some deficits on quantitative temperature and vibration testing have been described. The serum creatine kinase (CK) level is usually normal or slightly elevated. Needle electromyography (EMG) shows small brief 'myopathic' motor units, although a mixed 'myopathic-neuropathic' pattern may be observed. Fibrillations and complex repetitive discharges are often, but not invariably, present. Muscle magnetic resonance imaging shows considerable involvement of posterior calf muscles besides fatty degenerative changes in the anterior compartment. Differential diagnosis Differential diagnosis includes sporadic inclusion body myositis (sIBM), MATR3 distal myopathy, and muscle filaminopathy. Genetic counseling WDM is inherited as an autosomal dominant trait. Where one parent is affected, there is a 50% risk of disease transmission to offspring. Penetrance is 100% by age 75 years. Management and treatment Management is mainly symptomatic and includes the help of an occupational and a physical therapists and practical tools for finger and hand weakness. Foot drop and wrist weakness may be helped by orthoses. Prognosis The progression is benign and life expectancy is normal although the fine motor hand skills are usually lost. Homozygotes exhibit earlier onset, faster progression, and patients become wheelchair-bound by the age of 50 years.

MalaCards based summary : Welander Distal Myopathy, also known as wdm, is related to myopathy and nonaka myopathy, and has symptoms including myalgia An important gene associated with Welander Distal Myopathy is TIA1 (TIA1 Cytotoxic Granule Associated RNA Binding Protein), and among its related pathways/superpathways is Translational Control. Affiliated tissues include skeletal muscle, and related phenotypes are emg: myopathic abnormalities and intrinsic hand muscle atrophy

OMIM® : 57 Welander distal myopathy is an autosomal dominant disorder characterized by adult onset of distal muscle weakness predominantly affecting the distal long extensors of the hands, with slow progression to involve all small hand muscles and the lower legs. Skeletal muscle biopsy shows myopathic changes and prominent rimmed vacuoles. Rare homozygous patients showed earlier onset, faster progression, and proximal muscle involvement. This disorder is common in Sweden and Finland (summary by Hackman et al., 2013). (604454) (Updated 20-May-2021)

KEGG : 36 Welander distal myopathy (WDM) is an autosomal dominant disorder with late onset predominantly affecting distal extensor muscles of the hands and the feet. The disorder is considered as the most common of the distal myopathies but is almost only seen in Sweden and some parts of Finland. WDM is caused by mutations in TIA1 gene which encodes a key component of stress granules.

UniProtKB/Swiss-Prot : 72 Welander distal myopathy: An autosomal dominant disorder characterized by adult onset of distal muscle weakness predominantly affecting the distal long extensors of the hands, with slow progression to involve all small hand muscles and the lower legs. Skeletal muscle biopsy shows myopathic changes and prominent rimmed vacuoles. Rare homozygous patients showed earlier onset, faster progression, and proximal muscle involvement.

Related Diseases for Welander Distal Myopathy

Graphical network of the top 20 diseases related to Welander Distal Myopathy:

Diseases related to Welander Distal Myopathy

Symptoms & Phenotypes for Welander Distal Myopathy

Human phenotypes related to Welander Distal Myopathy:

58 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 emg: myopathic abnormalities 58 31 hallmark (90%) Very frequent (99-80%) HP:0003458
2 intrinsic hand muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008954
3 distal upper limb muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0008959
4 foot dorsiflexor weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0009027
5 weakness of long finger extensor muscles 58 31 hallmark (90%) Very frequent (99-80%) HP:0009077
6 rimmed vacuoles 58 31 frequent (33%) Frequent (79-30%) HP:0003805
7 steppage gait 58 31 frequent (33%) Frequent (79-30%) HP:0003376
8 clumsiness 58 31 frequent (33%) Frequent (79-30%) HP:0002312
9 mildly elevated creatine kinase 58 31 frequent (33%) Frequent (79-30%) HP:0008180
10 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
11 myopathy 58 Very frequent (99-80%)
12 cardiomyopathy 58 Excluded (0%)
13 distal muscle weakness 31 HP:0002460
14 distal amyotrophy 31 HP:0003693
15 distal upper limb amyotrophy 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Muscle Soft Tissue:
rimmed vacuoles
steppage gait
muscle weakness, distal
walking difficulties
muscle atrophy, distal
Laboratory Abnormalities:
mildly increased serum creatine kinase

Clinical features from OMIM®:

604454 (Updated 20-May-2021)

UMLS symptoms related to Welander Distal Myopathy:


Drugs & Therapeutics for Welander Distal Myopathy

Search Clinical Trials , NIH Clinical Center for Welander Distal Myopathy

Genetic Tests for Welander Distal Myopathy

Genetic tests related to Welander Distal Myopathy:

# Genetic test Affiliating Genes
1 Welander Distal Myopathy 29 TIA1

Anatomical Context for Welander Distal Myopathy

MalaCards organs/tissues related to Welander Distal Myopathy:

Skeletal Muscle

Publications for Welander Distal Myopathy

Articles related to Welander Distal Myopathy:

(show all 31)
# Title Authors PMID Year
Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1. 57 6 61
23401021 2013
Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing. 61 6 57
23348830 2013
Genetic linkage of Welander distal myopathy to chromosome 2p13. 57 6 61
10482271 1999
Distal myopathy with coexisting heterozygous TIA1 and MYH7 Variants. 61 6
27282841 2016
Refined mapping of the Welander distal myopathy region on chromosome 2p13 positions the new candidate region telomeric of the DYSF locus. 57 61
12836053 2003
Welander hereditary distal myopathy, a molecular genetic comparison to hereditary myopathies with inclusion bodies. 61 57
9608564 1998
Welander distal myopathy is not linked to other defined distal myopathy gene loci. 61 57
9196908 1997
TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics. 6
28817800 2017
Distal muscular dystrophy with autosomal recessive inheritance. 57
6543900 1984
A new type of hereditary distal myopathy with characteristic sarcoplasmic bodies and intermediate (skeletin) filaments. 57
6251174 1980
Distal myopathy: electron microscopic and histochemical studies. 57
196233 1977
Histochemical and histopathological changes in skeletal muscle in late-onset hereditary distal myopathy (Welander). 57
126303 1975
Late onset hereditary distal myopathy. 57
4855680 1974
Distal muscular dystrophy in an English family. 57
5552164 1971
Hereditary distal myopathy with onset in infancy. 57
5834698 1965
Homozygous appearance of distal myopathy. 57
13469174 1957
A Lecture on Myopathy and a Distal Form: Delivered at the National Hospital for the Paralysed and Epileptic. 57
20760370 1902
A Heterologous Cell Model for Studying the Role of T-Cell Intracellular Antigen 1 in Welander Distal Myopathy. 61
30348840 2019
Whole Exome Sequencing Identifies Atypical Welander Distal Myopathy in Patient. 61
28221306 2017
Distal muscular dystrophies. 61
21496636 2011
Muscle magnetic resonance imaging shows distinct diagnostic patterns in Welander and tibial muscular dystrophy. 61
15242415 2004
A distinct phenotype of distal myopathy in a large Finnish family. 61
12847162 2003
Welander distal myopathy outside the Swedish population: phenotype and genotype. 61
12117477 2002
Distal myopathies. 61
10590885 1999
Welander distal myopathy--an overview. 61
9608565 1998
Distribution of muscle degeneration in Welander distal myopathy--a magnetic resonance imaging and muscle biopsy study. 61
8173352 1994
Muscle fibre degeneration in distal myopathy (Welander)--ultrastructure related to immunohistochemical observations on cytoskeletal proteins and Leu-19 antigen. 61
7689381 1993
Inclusion body myositis and Welander distal myopathy: a clinical, neurophysiological and morphological comparison. 61
1650819 1991
Neurogenic involvement in distal myopathy (Welander). Histochemical and morphological observations on muscle and nerve biopsies. 61
2746292 1989
Autonomic cardiovascular responses in distal myopathy (Welander). 61
3687377 1987
Sensory involvement in distal myopathy (Welander). 61
3681336 1987

Variations for Welander Distal Myopathy

ClinVar genetic disease variations for Welander Distal Myopathy:

6 (show top 50) (show all 54)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TIA1 NM_022173.4(TIA1):c.1150G>A (p.Glu384Lys) SNV Pathogenic 41480 rs747068278 GRCh37: 2:70439862-70439862
GRCh38: 2:70212730-70212730
2 TIA1 NM_022173.4(TIA1):c.1070A>G (p.Asn357Ser) SNV Conflicting interpretations of pathogenicity 261567 rs116621885 GRCh37: 2:70439942-70439942
GRCh38: 2:70212810-70212810
3 TIA1 NM_022173.4(TIA1):c.277+3_277+5dup Duplication Uncertain significance 656197 rs1266600719 GRCh37: 2:70456390-70456391
GRCh38: 2:70229258-70229259
4 TIA1 NM_022173.4(TIA1):c.770A>T (p.Asn257Ile) SNV Uncertain significance 656352 rs765028674 GRCh37: 2:70442621-70442621
GRCh38: 2:70215489-70215489
5 TIA1 NM_022173.4(TIA1):c.1156del (p.Gln386fs) Deletion Uncertain significance 458837 rs1553422555 GRCh37: 2:70439856-70439856
GRCh38: 2:70212724-70212724
6 TIA1 NM_022173.4(TIA1):c.1082A>C (p.Gln361Pro) SNV Uncertain significance 528489 rs556545503 GRCh37: 2:70439930-70439930
GRCh38: 2:70212798-70212798
7 TIA1 NC_000002.12:g.(?_70212709)_(70248440_?)del Deletion Uncertain significance 832328 GRCh37: 2:70439841-70475572
8 TIA1 NM_022173.4(TIA1):c.27-6T>A SNV Uncertain significance 647155 rs1573660635 GRCh37: 2:70463313-70463313
GRCh38: 2:70236181-70236181
9 TIA1 NM_022173.4(TIA1):c.223-3T>A SNV Uncertain significance 458838 rs750261656 GRCh37: 2:70456453-70456453
GRCh38: 2:70229321-70229321
10 TIA1 NM_022173.4(TIA1):c.311A>T (p.Asp104Val) SNV Uncertain significance 528490 rs143209672 GRCh37: 2:70454954-70454954
GRCh38: 2:70227822-70227822
11 TIA1 NM_022173.4(TIA1):c.209A>T (p.Lys70Met) SNV Uncertain significance 844069 GRCh37: 2:70457901-70457901
GRCh38: 2:70230769-70230769
12 TIA1 NM_022173.4(TIA1):c.1146G>T (p.Gly382=) SNV Uncertain significance 863219 GRCh37: 2:70439866-70439866
GRCh38: 2:70212734-70212734
13 TIA1 NM_022173.4(TIA1):c.398+3A>G SNV Uncertain significance 966574 GRCh37: 2:70454864-70454864
GRCh38: 2:70227732-70227732
14 TIA1 NM_022173.4(TIA1):c.154G>A (p.Glu52Lys) SNV Uncertain significance 1004185 GRCh37: 2:70457956-70457956
GRCh38: 2:70230824-70230824
15 TIA1 NM_022173.4(TIA1):c.167A>G (p.His56Arg) SNV Uncertain significance 1004639 GRCh37: 2:70457943-70457943
GRCh38: 2:70230811-70230811
16 TIA1 NM_022173.4(TIA1):c.805G>A (p.Val269Ile) SNV Uncertain significance 1006176 GRCh37: 2:70442586-70442586
GRCh38: 2:70215454-70215454
17 TIA1 NM_022173.4(TIA1):c.1078G>A (p.Val360Met) SNV Uncertain significance 651295 rs201905164 GRCh37: 2:70439934-70439934
GRCh38: 2:70212802-70212802
18 TIA1 NM_022173.4(TIA1):c.70C>G (p.Leu24Val) SNV Uncertain significance 859902 GRCh37: 2:70463264-70463264
GRCh38: 2:70236132-70236132
19 TIA1 NM_022173.4(TIA1):c.1096C>T (p.Gln366Ter) SNV Uncertain significance 936032 GRCh37: 2:70439916-70439916
GRCh38: 2:70212784-70212784
20 TIA1 NM_022173.4(TIA1):c.98G>T (p.Cys33Phe) SNV Uncertain significance 939726 GRCh37: 2:70463236-70463236
GRCh38: 2:70236104-70236104
21 TIA1 NM_022173.4(TIA1):c.398C>T (p.Ser133Leu) SNV Uncertain significance 944740 GRCh37: 2:70454867-70454867
GRCh38: 2:70227735-70227735
22 TIA1 NM_022173.4(TIA1):c.1118A>G (p.Asn373Ser) SNV Uncertain significance 1019780 GRCh37: 2:70439894-70439894
GRCh38: 2:70212762-70212762
23 TIA1 NM_022173.4(TIA1):c.475-3C>T SNV Uncertain significance 458840 rs200499196 GRCh37: 2:70444129-70444129
GRCh38: 2:70216997-70216997
24 TIA1 NM_022173.4(TIA1):c.869T>C (p.Met290Thr) SNV Uncertain significance 578669 rs116707801 GRCh37: 2:70442522-70442522
GRCh38: 2:70215390-70215390
25 TIA1 NM_022173.4(TIA1):c.971C>G (p.Pro324Arg) SNV Uncertain significance 839978 GRCh37: 2:70441544-70441544
GRCh38: 2:70214412-70214412
26 TIA1 NM_022173.4(TIA1):c.328G>A (p.Val110Ile) SNV Uncertain significance 846033 GRCh37: 2:70454937-70454937
GRCh38: 2:70227805-70227805
27 TIA1 NM_022173.4(TIA1):c.992C>T (p.Ala331Val) SNV Uncertain significance 934669 GRCh37: 2:70441523-70441523
GRCh38: 2:70214391-70214391
28 TIA1 NM_022173.4(TIA1):c.775C>A (p.His259Asn) SNV Uncertain significance 1028743 GRCh37: 2:70442616-70442616
GRCh38: 2:70215484-70215484
29 TIA1 NM_022173.4(TIA1):c.562G>T (p.Ala188Ser) SNV Uncertain significance 1036305 GRCh37: 2:70444039-70444039
GRCh38: 2:70216907-70216907
30 TIA1 NM_022173.4(TIA1):c.277+6T>G SNV Uncertain significance 1037062 GRCh37: 2:70456390-70456390
GRCh38: 2:70229258-70229258
31 TIA1 NM_022173.4(TIA1):c.683A>T (p.Gln228Leu) SNV Uncertain significance 1043578 GRCh37: 2:70443421-70443421
GRCh38: 2:70216289-70216289
32 TIA1 NM_022173.4(TIA1):c.1006G>A (p.Gly336Ser) SNV Uncertain significance 1045764 GRCh37: 2:70441509-70441509
GRCh38: 2:70214377-70214377
33 TIA1 NM_022173.4(TIA1):c.1108A>G (p.Met370Val) SNV Uncertain significance 834552 GRCh37: 2:70439904-70439904
GRCh38: 2:70212772-70212772
34 TIA1 NM_022173.4(TIA1):c.143A>G (p.Tyr48Cys) SNV Uncertain significance 855071 GRCh37: 2:70457967-70457967
GRCh38: 2:70230835-70230835
35 TIA1 NM_022173.4(TIA1):c.689T>C (p.Met230Thr) SNV Uncertain significance 859716 GRCh37: 2:70443415-70443415
GRCh38: 2:70216283-70216283
36 TIA1 NM_022173.4(TIA1):c.1117A>G (p.Asn373Asp) SNV Uncertain significance 939077 GRCh37: 2:70439895-70439895
GRCh38: 2:70212763-70212763
37 TIA1 NM_022173.4(TIA1):c.1085C>T (p.Pro362Leu) SNV Uncertain significance 992595 GRCh37: 2:70439927-70439927
GRCh38: 2:70212795-70212795
38 TIA1 NM_022173.4(TIA1):c.913C>T (p.Pro305Ser) SNV Uncertain significance 1058761 GRCh37: 2:70441602-70441602
GRCh38: 2:70214470-70214470
39 TIA1 NM_022173.4(TIA1):c.597G>C (p.Gln199His) SNV Uncertain significance 1059725 GRCh37: 2:70443618-70443618
GRCh38: 2:70216486-70216486
40 TIA1 NM_022173.4(TIA1):c.422T>C (p.Met141Thr) SNV Uncertain significance 571692 rs1558817897 GRCh37: 2:70451738-70451738
GRCh38: 2:70224606-70224606
41 TIA1 NM_022173.4(TIA1):c.880G>A (p.Val294Met) SNV Uncertain significance 575375 rs144296151 GRCh37: 2:70442511-70442511
GRCh38: 2:70215379-70215379
42 TIA1 NM_022173.4(TIA1):c.380C>T (p.Ala127Val) SNV Uncertain significance 580304 rs1558837955 GRCh37: 2:70454885-70454885
GRCh38: 2:70227753-70227753
43 TIA1 NM_022173.4(TIA1):c.398+10A>G SNV Likely benign 704847 rs372161184 GRCh37: 2:70454857-70454857
GRCh38: 2:70227725-70227725
44 TIA1 NM_022173.4(TIA1):c.48A>G (p.Arg16=) SNV Likely benign 704855 rs115062005 GRCh37: 2:70463286-70463286
GRCh38: 2:70236154-70236154
45 TIA1 NM_022173.4(TIA1):c.187T>C (p.Leu63=) SNV Likely benign 705011 rs374166300 GRCh37: 2:70457923-70457923
GRCh38: 2:70230791-70230791
46 TIA1 NM_022173.4(TIA1):c.33C>T (p.Val11=) SNV Likely benign 458839 rs761527779 GRCh37: 2:70463301-70463301
GRCh38: 2:70236169-70236169
47 TIA1 NM_022173.4(TIA1):c.764+10G>A SNV Likely benign 528491 rs547201931 GRCh37: 2:70443330-70443330
GRCh38: 2:70216198-70216198
48 TIA1 NM_022173.4(TIA1):c.953A>G (p.Gln318Arg) SNV Benign/Likely benign 261569 rs115611153 GRCh37: 2:70441562-70441562
GRCh38: 2:70214430-70214430
49 TIA1 NM_022173.4(TIA1):c.947C>G (p.Ala316Gly) SNV Benign 458843 rs116828570 GRCh37: 2:70441568-70441568
GRCh38: 2:70214436-70214436
50 TIA1 NM_022173.4(TIA1):c.1086G>A (p.Pro362=) SNV Benign 448688 rs72902461 GRCh37: 2:70439926-70439926
GRCh38: 2:70212794-70212794

UniProtKB/Swiss-Prot genetic disease variations for Welander Distal Myopathy:

# Symbol AA change Variation ID SNP ID
1 TIA1 p.Glu384Lys VAR_069897 rs747068278

Expression for Welander Distal Myopathy

Search GEO for disease gene expression data for Welander Distal Myopathy.

Pathways for Welander Distal Myopathy

Pathways related to Welander Distal Myopathy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.91 TIA1 SQSTM1

GO Terms for Welander Distal Myopathy

Cellular components related to Welander Distal Myopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 late endosome GO:0005770 8.62 SQSTM1 DYSF

Sources for Welander Distal Myopathy

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
69 Tocris
71 UMLS via Orphanet
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