Distal Myopathy with Vocal Cord Weakness (MPD2)

Categories: Muscle diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Distal Myopathy with Vocal Cord Weakness

MalaCards integrated aliases for Distal Myopathy with Vocal Cord Weakness:

Name: Distal Myopathy with Vocal Cord Weakness 20 43
Myopathy, Distal, 2 20 6
Distal Myopathy 2 20 43
Mpd2 20 43
Vocal Cord and Pharyngeal Weakness with Distal Myopathy 43
Distal Myopathy with Vocal Cord and Pharyngeal Signs 43
Myopathia Distalis Type 2 43
Matrin 3 Distal Myopathy 43
Myopathy, Distal 2 71
Vcpdm 43


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UMLS 71 C1853723

Summaries for Distal Myopathy with Vocal Cord Weakness

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 600DefinitionVocal cord and pharyngeal distal myopathy (VCPDM) is a rare autosomal dominant distal myopathy characterized by adult onset of muscle weakness in the feet and hands (slowly progressing to involve proximal limb muscles) combined with vocal or swallowing dysfunction and frequent respiratory muscle involvement in later stages. Normal to mildly elevated creatine kinase (CK) serum levels and rimmed-vacuolated dystrophic muscle fiber changes are associated laboratory and pathologic findings.EpidemiologyWorldwide prevalence is unknown but more than 70 patients (of North American, European, and Japanese origin) have been reported to date.Clinical descriptionOnset of muscle weakness is between 30-63 years (mean in the forties) and may initially be asymmetric. It most frequently begins with involvement of ankle and toe extensors with foot drop or may manifest in the hands. Weakness in the ankles renders the gait very unstable resulting in a waddling and steppage gait. In the hands, the extensors of the fingers and the abductor pollicis brevis (with atrophy) are affected to varying degrees. Progression of muscle weakness and wasting to proximal upper and lower limb muscles is common. Bulbar involvement with dysphonia and dysphagia may be initially absent but appear as disease progresses. Initially, voice is usually nasal or hoarse and dysphagia mild (with difficulty swallowing solid food), but progressive vocal cord weakness eventually leads to aspiration. Some patients display respiratory impairment with a low vital capacity that may progress to respiratory failure. Ocular muscle involvement is not observed.EtiologyVCPDM is caused by a c.254C>G mutation in the MATR3 gene (5q31.3) which results in substitution of a conserved amino acid (S85C) in the nuclear protein Matrin-3. It harbors nuclear import and export motifs in addition to several DNA and RNA binding sites. Currently, the mechanism by which S85C alteration in Matrin-3 leads to myopathy remains largely unknown.Diagnostic methodsThe diagnosis of VCPDM is clinical and involves vocal cord examination by laryngoscopy (which reveals bowing of the vocal cords and constantly flowing secretions, resulting from incomplete closure of the glottis and pharyngeal muscle weakness). Needle EMG shows myopathic changes. Muscle biopsies reveal chronic non-inflammatory myopathy with variations in fiber size, fiber splitting and subsarcolemmal rimmed vacuoles, with pathologic changes being scant in the quadriceps and severe in the gastrocnemius. CK serum levels range from normal to an 8 fold increase. Molecular genetic screening revealing mutation in the MATR3 gene confirms diagnosis.Differential diagnosisDifferential diagnosis includes Welander distal myopathy, oculopharyngeal muscular dystrophy, and oculopharyngodistal myopathy.Genetic counselingVCPDM is inherited in an autosomal dominant manner. Genetic counseling can inform affected individuals about the 50% risk of disease transmission to their offspring.Management and treatmentCurrently, there is no cure for VCPDM. Ankle-foot orthotic braces and/or canes are used to aid in ambulation. For patients suffering from vocal cord weakness, injection of agents that add bulk and act as stiffeners (teflon, gel foam, fat), or bilateral silastic-implant medialization of the vocal folds, may aid in reducing aspiration. Ventilation or oxygen therapy may be needed if patient presents severe respiratory muscle involvement.PrognosisPrognosis of patients suffering from vocal cord and pharyngeal weakness is highly influenced by the quality of long-term respiratory care, if it is needed. Moreover, as distal upper limb muscles weaken, hand may partially curl closed, leading to a general loss of grip and dexterity. Ambulation is usually preserved.Visit the Orphanet disease page for more resources.

MalaCards based summary : Distal Myopathy with Vocal Cord Weakness, also known as myopathy, distal, 2, is related to amyotrophic lateral sclerosis 21 and miyoshi muscular dystrophy. An important gene associated with Distal Myopathy with Vocal Cord Weakness is MATR3 (Matrin 3).

MedlinePlus Genetics : 43 Distal myopathy 2 is a condition characterized by weakness of specific muscles that begins in adulthood. It is a form of muscular dystrophy that specifically involves muscles in the throat, lower legs, and forearms. Muscles farther from the center of the body, like the muscles of the lower legs and forearms, are known as distal muscles.Muscle weakness in the ankles is usually the first symptom of distal myopathy 2. The weakness can also affect muscles in the hands, wrists, and shoulders. At first, the muscle weakness may be on only one side of the body, but both sides are eventually involved. This muscle weakness can slowly worsen and make actions like walking and lifting the fingers difficult.Another characteristic feature of distal myopathy 2 is weakness of the vocal cords and throat. This weakness initially causes the voice to sound weak or breathy (hypophonic). Eventually, the voice becomes gurgling, hoarse, and nasal. The weakness can also cause difficulty swallowing (dysphagia).

Related Diseases for Distal Myopathy with Vocal Cord Weakness

Diseases related to Distal Myopathy with Vocal Cord Weakness via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 amyotrophic lateral sclerosis 21 11.7
2 miyoshi muscular dystrophy 9.9
3 myopathy 9.9
4 distal hereditary motor neuronopathy type 7 9.9
5 spinal muscular atrophy 9.9
6 muscular atrophy 9.9
7 charcot-marie-tooth hereditary neuropathy 9.9
8 distal hereditary motor neuropathy type 7 9.9

Graphical network of the top 20 diseases related to Distal Myopathy with Vocal Cord Weakness:

Diseases related to Distal Myopathy with Vocal Cord Weakness

Symptoms & Phenotypes for Distal Myopathy with Vocal Cord Weakness

Drugs & Therapeutics for Distal Myopathy with Vocal Cord Weakness

Search Clinical Trials , NIH Clinical Center for Distal Myopathy with Vocal Cord Weakness

Genetic Tests for Distal Myopathy with Vocal Cord Weakness

Anatomical Context for Distal Myopathy with Vocal Cord Weakness

Publications for Distal Myopathy with Vocal Cord Weakness

Articles related to Distal Myopathy with Vocal Cord Weakness:

(show all 15)
# Title Authors PMID Year
Vocal cord and pharyngeal weakness with autosomal dominant distal myopathy: clinical description and gene localization to 5q31. 6 61
9837826 1998
Phenotype of matrin-3-related distal myopathy in 16 German patients. 6
25154462 2014
Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. 6
24686783 2014
Autosomal-dominant distal myopathy associated with a recurrent missense mutation in the gene encoding the nuclear matrix protein, matrin 3. 6
19344878 2009
Expanding proteome coverage with orthogonal-specificity α-lytic proteases. 61
24425750 2014
Crystal structure of silkworm Bombyx mori JHBP in complex with 2-methyl-2,4-pentanediol: plasticity of JH-binding pocket and ligand-induced conformational change of the second cavity in JHBP. 61
23437107 2013
Myotilin is not the causative gene for vocal cord and pharyngeal weakness with distal myopathy (VCPDM). 61
16674563 2006
Interactions among yeast protein-disulfide isomerase proteins and endoplasmic reticulum chaperone proteins influence their activities. 61
16002399 2005
The fission yeast ptr1+ gene involved in nuclear mRNA export encodes a putative ubiquitin ligase. 61
15094387 2004
Gene regulation in response to protein disulphide isomerase deficiency. 61
12734802 2003
Hut1 proteins identified in Saccharomyces cerevisiae and Schizosaccharomyces pombe are functional homologues involved in the protein-folding process at the endoplasmic reticulum. 61
11284010 2001
Functional differences in yeast protein disulfide isomerases. 61
11157982 2001
A new genetic method for isolating functionally interacting genes: high plo1(+)-dependent mutants and their suppressors define genes in mitotic and septation pathways in fission yeast. 61
10924454 2000
Distal spinal muscular atrophy with vocal cord paralysis (dSMA-VII) is not linked to the MPD2 locus on chromosome 5q31. 61
10922394 2000
Overproduction of Mpd2p suppresses the lethality of protein disulfide isomerase depletion in a CXXC sequence dependent manner. 61
9367834 1997

Variations for Distal Myopathy with Vocal Cord Weakness

ClinVar genetic disease variations for Distal Myopathy with Vocal Cord Weakness:

6 (show top 50) (show all 149)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MATR3 NM_018834.6(MATR3):c.254C>G (p.Ser85Cys) SNV Pathogenic 14002 rs121434591 5:138643358-138643358 5:139307669-139307669
2 MATR3 NM_018834.6(MATR3):c.1864A>G (p.Thr622Ala) SNV Pathogenic 126562 rs587777301 5:138658372-138658372 5:139322683-139322683
3 MATR3 NM_018834.6(MATR3):c.460C>T (p.Pro154Ser) SNV Pathogenic 126563 rs587777302 5:138643564-138643564 5:139307875-139307875
4 MATR3 NM_018834.6(MATR3):c.344T>G (p.Phe115Cys) SNV Pathogenic 126561 rs587777300 5:138643448-138643448 5:139307759-139307759
5 MATR3 NM_018834.6(MATR3):c.2521C>T (p.Arg841Cys) SNV Conflicting interpretations of pathogenicity 351143 rs781050726 5:138665061-138665061 5:139329372-139329372
6 MATR3 NM_018834.6(MATR3):c.2504A>G (p.Asn835Ser) SNV Conflicting interpretations of pathogenicity 351142 rs201165929 5:138665044-138665044 5:139329355-139329355
7 MATR3 NM_018834.6(MATR3):c.1132G>A (p.Ala378Thr) SNV Conflicting interpretations of pathogenicity 651450 rs201075828 5:138652744-138652744 5:139317055-139317055
8 MATR3 NM_018834.6(MATR3):c.2525G>C (p.Arg842Thr) SNV Uncertain significance 652772 rs749235364 5:138665065-138665065 5:139329376-139329376
9 MATR3 NM_018834.6(MATR3):c.304C>T (p.Arg102Cys) SNV Uncertain significance 657091 rs1327023414 5:138643408-138643408 5:139307719-139307719
10 MATR3 NM_018834.6(MATR3):c.561T>G (p.Asp187Glu) SNV Uncertain significance 658267 rs374819399 5:138643665-138643665 5:139307976-139307976
11 MATR3 NM_018834.6(MATR3):c.1363A>G (p.Thr455Ala) SNV Uncertain significance 663874 rs781213918 5:138654651-138654651 5:139318962-139318962
12 MATR3 NM_018834.6(MATR3):c.1572G>T (p.Lys524Asn) SNV Uncertain significance 664538 rs1581251198 5:138655160-138655160 5:139319471-139319471
13 MATR3 NM_018834.6(MATR3):c.2372-3dup Duplication Uncertain significance 580361 rs1561945483 5:138661848-138661849 5:139326159-139326160
14 MATR3 NM_018834.6(MATR3):c.2282A>G (p.Asn761Ser) SNV Uncertain significance 581337 rs758675030 5:138661262-138661262 5:139325573-139325573
15 MATR3 NM_018834.6(MATR3):c.2273C>A (p.Thr758Lys) SNV Uncertain significance 640602 rs757346695 5:138661253-138661253 5:139325564-139325564
16 MATR3 NM_018834.6(MATR3):c.1874A>C (p.Lys625Thr) SNV Uncertain significance 644662 rs1488614478 5:138658382-138658382 5:139322693-139322693
17 MATR3 NM_018834.6(MATR3):c.1435-10T>C SNV Uncertain significance 566721 rs772340385 5:138655013-138655013 5:139319324-139319324
18 MATR3 NM_018834.6(MATR3):c.2213A>G (p.Glu738Gly) SNV Uncertain significance 569504 rs538917496 5:138661193-138661193 5:139325504-139325504
19 MATR3 NM_018834.6(MATR3):c.2180A>G (p.Asn727Ser) SNV Uncertain significance 571163 rs1468138513 5:138661160-138661160 5:139325471-139325471
20 MATR3 NM_018834.6(MATR3):c.2234C>T (p.Ala745Val) SNV Uncertain significance 574594 rs199797401 5:138661214-138661214 5:139325525-139325525
21 MATR3 NM_018834.6(MATR3):c.1598G>A (p.Ser533Asn) SNV Uncertain significance 578420 rs1033118784 5:138655186-138655186 5:139319497-139319497
22 MATR3 NM_018834.6(MATR3):c.1948A>C (p.Met650Leu) SNV Uncertain significance 578787 rs749026971 5:138658456-138658456 5:139322767-139322767
23 MATR3 NM_018834.6(MATR3):c.2357C>G (p.Pro786Arg) SNV Uncertain significance 834625 5:138661337-138661337 5:139325648-139325648
24 MATR3 NM_018834.6(MATR3):c.628_630del (p.Glu210del) Deletion Uncertain significance 837241 5:138643730-138643732 5:139308041-139308043
25 MATR3 NM_018834.6(MATR3):c.493_495del (p.Ala165del) Deletion Uncertain significance 838160 5:138643595-138643597 5:139307906-139307908
26 MATR3 NM_018834.6(MATR3):c.2066C>A (p.Ser689Tyr) SNV Uncertain significance 842173 5:138658574-138658574 5:139322885-139322885
27 MATR3 NM_018834.6(MATR3):c.2314G>A (p.Asp772Asn) SNV Uncertain significance 843102 5:138661294-138661294 5:139325605-139325605
28 MATR3 NM_018834.6(MATR3):c.2227C>T (p.Pro743Ser) SNV Uncertain significance 855664 5:138661207-138661207 5:139325518-139325518
29 MATR3 NM_018834.6(MATR3):c.2254_2256GAT[1] (p.Asp753del) Microsatellite Uncertain significance 859218 5:138661233-138661235 5:139325544-139325546
30 MATR3 NM_018834.6(MATR3):c.272G>A (p.Ser91Asn) SNV Uncertain significance 862259 5:138643376-138643376 5:139307687-139307687
31 MATR3 NM_018834.6(MATR3):c.1885_1887del (p.Glu629del) Deletion Uncertain significance 862631 5:138658393-138658395 5:139322704-139322706
32 MATR3 NM_199189.2(MATR3):c.-563T>C SNV Uncertain significance 904479 5:138609656-138609656 5:139273967-139273967
33 MATR3 NM_199189.2(MATR3):c.-422C>T SNV Uncertain significance 904480 5:138609797-138609797 5:139274108-139274108
34 MATR3 NM_018834.6(MATR3):c.1235G>A (p.Arg412Lys) SNV Uncertain significance 904538 5:138653337-138653337 5:139317648-139317648
35 MATR3 NM_018834.6(MATR3):c.*138T>C SNV Uncertain significance 904615 5:138665222-138665222 5:139329533-139329533
36 MATR3 NM_018834.6(MATR3):c.*262A>G SNV Uncertain significance 904616 5:138665346-138665346 5:139329657-139329657
37 MATR3 NM_018834.6(MATR3):c.2114G>T (p.Ser705Ile) SNV Uncertain significance 781861 rs201970174 5:138658622-138658622 5:139322933-139322933
38 MATR3 NM_018834.6(MATR3):c.*441C>G SNV Uncertain significance 905405 5:138665525-138665525 5:139329836-139329836
39 MATR3 NM_018834.6(MATR3):c.*487C>T SNV Uncertain significance 905406 5:138665571-138665571 5:139329882-139329882
40 MATR3 NM_018834.6(MATR3):c.*493T>C SNV Uncertain significance 905407 5:138665577-138665577 5:139329888-139329888
41 MATR3 NM_018834.6(MATR3):c.*2098A>G SNV Uncertain significance 905469 5:138667182-138667182 5:139331493-139331493
42 MATR3 NM_018834.6(MATR3):c.*2142G>A SNV Uncertain significance 905470 5:138667226-138667226 5:139331537-139331537
43 MATR3 NM_018834.6(MATR3):c.*2170T>G SNV Uncertain significance 905471 5:138667254-138667254 5:139331565-139331565
44 MATR3 NM_018834.6(MATR3):c.*857C>T SNV Uncertain significance 905920 5:138665941-138665941 5:139330252-139330252
45 MATR3 NM_018834.6(MATR3):c.675A>G (p.Arg225=) SNV Uncertain significance 906860 5:138643779-138643779 5:139308090-139308090
46 MATR3 NM_018834.6(MATR3):c.2233G>C (p.Ala745Pro) SNV Uncertain significance 906938 5:138661213-138661213 5:139325524-139325524
47 MATR3 NM_018834.6(MATR3):c.1179A>G (p.Arg393=) SNV Uncertain significance 907852 5:138652791-138652791 5:139317102-139317102
48 MATR3 NM_018834.6(MATR3):c.*1143G>A SNV Uncertain significance 907990 5:138666227-138666227 5:139330538-139330538
49 MATR3 NM_018834.6(MATR3):c.857C>T (p.Pro286Leu) SNV Uncertain significance 935932 5:138643961-138643961 5:139308272-139308272
50 MATR3 NM_018834.6(MATR3):c.1904G>A (p.Gly635Asp) SNV Uncertain significance 937895 5:138658412-138658412 5:139322723-139322723

Expression for Distal Myopathy with Vocal Cord Weakness

Search GEO for disease gene expression data for Distal Myopathy with Vocal Cord Weakness.

Pathways for Distal Myopathy with Vocal Cord Weakness

GO Terms for Distal Myopathy with Vocal Cord Weakness

Sources for Distal Myopathy with Vocal Cord Weakness

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 05-Mar-2021)
61 PubMed
70 Tocris
72 UMLS via Orphanet
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