Desminopathy

General Information (adopted from Orphanet):

Synonyms, Signs: DRM
Desmin-related myofibrillar myopathy
desmin-related myopathy
myopathy, myofibrillar, desmin-related
CMD1F and LGMD1D, formerly
myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy
ARVD7, formerly
cardiomyopathy, dilated, 1F and limb-girdle muscular dystrophy type 1D, formerly
ARVC7, formerly
ibm1, formerly
cdcd3, formerly
mfm1
desmin-related myopathy with arrhythmogenic right ventricular cardiomyopathy
arrhythmogenic right ventricular cardiomyopathy 7, formerly
desminopathy, primary
arrhythmogenic right ventricular dysplasia, familial, 7, formerly
inclusion body myopathy 1, autosomal dominant, formerly
cardiomyopathy, dilated, with conduction defect and muscular dystrophy
Number of Symptoms 38
OrphanetNr: 98909
OMIM Id: 601419
ICD-10: G71.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant
Monogenic
Autosomal recessive
Sporadic
20718792 [IBIS]
Age of onset: All ages
20718792 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Autosomal dominant distal myopathy
 -Rare genetic disease
 -Rare neurologic disease
Familial restrictive cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Inclusion myopathy
 -Rare genetic disease
 -Rare neurologic disease
Myofibrillar myopathy
 -Rare genetic disease
 -Rare neurologic disease
Neuromuscular disease with dilated cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Qualitative or quantitative defects of desmin
 -Rare genetic disease

Comment:

Desmin-related myofibrillar myopathy (desminopathy) is caused by different mutations in DES (PMID:20718792).

Symptom Information: Sort by abundance 

1
 (HPO:0010628) Facial palsy 9697706 IBIS 146 / 7739
2
 (HPO:0000467) Neck muscle weakness 8122252 IBIS 29 / 7739
3
 (HPO:0002600) Hyporeflexia of lower limbs 8114783 IBIS 13 / 7739
4
 (HPO:0002019) Constipation 17221859 IBIS 194 / 7739
5
 (HPO:0002014) Diarrhea 17221859 IBIS 225 / 7739
6
 (HPO:0011713) Left bundle branch block 20718792 IBIS 30 / 7739
7
 (HPO:0001638) Cardiomyopathy Frequent [IBIS] 47% (n=138) 20718792 IBIS 192 / 7739
8
 (HPO:0001678) Atrioventricular block 10970245 IBIS 59 / 7739
9
 (HPO:0001645) Sudden cardiac death Occasional [IBIS] 26% (n=27) 20718792 IBIS 84 / 7739
10
 (HPO:0004756) Ventricular tachycardia 20718792 IBIS 55 / 7739
11
 (HPO:0005110) Atrial fibrillation 20718792 IBIS 71 / 7739
12
 (HPO:0011711) Left anterior fascicular block 20718792 IBIS 7 / 7739
13
 (HPO:0005130) Restrictive heart failure Occasional [IBIS] 12% (n=138) 20718792 IBIS 2 / 7739
14
 (HPO:0001639) Hypertrophic cardiomyopathy Rare [IBIS] 6% (n=138) 22275259 IBIS 137 / 7739
15
 (HPO:0011663) Right ventricular cardiomyopathy 10970245 IBIS 17 / 7739
16
 (HPO:0001644) Dilated cardiomyopathy Occasional [IBIS] 17% (n=138) 20718792 IBIS 141 / 7739
17
 (HPO:0011675) Arrhythmia Frequent [IBIS] 60% (n=159) 20718792 IBIS 226 / 7739
18
 (HPO:0011712) Right bundle branch block 20718792 IBIS 34 / 7739
19
 (HPO:0011715) Trifascicular block 20718792 IBIS 1 / 7739
20
 (HPO:0002747) Respiratory insufficiency due to muscle weakness Occasional [IBIS] 26% (n=110) 20718792 IBIS 48 / 7739
21
 (HPO:0002460) Distal muscle weakness Occasional [IBIS] 27% (n=106) 20718792 IBIS 122 / 7739
22
 (HPO:0003756) Skeletal myopathy Frequent [IBIS] 70% (n=159) 20718792 IBIS 8 / 7739
23
 (HPO:0001283) Bulbar palsy 8114783 IBIS 31 / 7739
24
 (HPO:0003701) Proximal muscle weakness Rare [IBIS] 6% (n=106) 20718792 IBIS 105 / 7739
25
 (HPO:0003458) EMG: myopathic abnormalities 18061454 IBIS 38 / 7739
26
 (HPO:0003694) Late-onset proximal muscle weakness 8509778 IBIS 3 / 7739
27
 (OMIM) Affected muscles show atrophy 9697706 IBIS 1 / 7739
28
 (OMIM) Smooth muscle may also become involved 17221859 IBIS 1 / 7739
29
 (MedDRA:10003668) Atrial tachycardia 20718792 IBIS 3 / 7739
30
 (OMIM) Diarrhea due to smooth muscle involvement 17221859 IBIS 1 / 7739
31
 (MedDRA:10057393) Bifascicular block 20718792 IBIS 4 / 7739
32
 (OMIM) Conduction abnormalities 9382102 IBIS 2 / 7739
33
 (OMIM) Arrhythmogenic right ventricular cardiomyopathy Rare [IBIS] 1% (n=138) 20718792 IBIS 3 / 7739
34
 (OMIM) Constipation due to smooth muscle involvement 17221859 IBIS 1 / 7739
35
 (OMIM) Biopsy shows degenerative changes consistent with myopathy 10970245 IBIS 1 / 7739
36
 (OMIM) Proximal muscle weakness occurs later 17720647 IBIS 3 / 7739
37
 (HPO:0040081) Abnormal levels of creatine kinase in blood Frequent [IBIS] 57% (n=159) 20718792 IBIS 2 / 7739
38
 (OMIM) Intrasarcoplasmic dense granulofilamentous aggregates that are immunoreactive with desmin 10970245, 7672786 IBIS 1 / 7739

Associated genes:

DES;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
DES rs121913000 pathogenic RCV000018315.24
DES rs121913001 pathogenic RCV000018316.29
DES rs121913003 pathogenic RCV000018320.28
DES rs121913004 pathogenic RCV000018324.24
DES rs121913005 pathogenic RCV000018328.29
DES rs150974575 likely pathogenic RCV000154519.1
DES rs267607482 pathogenic RCV000133502.2
DES rs267607483 pathogenic RCV000154574.1
DES rs267607495 likely pathogenic RCV000154600.1
DES rs267607499 likely pathogenic RCV000150380.1
DES rs397516698 likely pathogenic RCV000037249.2
DES rs397516698 likely pathogenic RCV000150381.1
DES rs57639980 pathogenic RCV000018319.28
DES rs57955682 pathogenic RCV000018323.28
DES rs58687088 pathogenic RCV000018326.24
DES rs59962885 pathogenic RCV000018314.23
DES rs60538473 pathogenic RCV000018317.29
DES rs62635763 pathogenic RCV000032923.28
DES rs62636495 pathogenic RCV000133501.5
DES rs727504448 likely pathogenic RCV000155417.1
DES rs730880289 pathogenic RCV000157059.2
DNAJB6 rs387907150 pathogenic RCV000179004.1

Additional Information:

Description: (OMIM) Myofibrillar myopathy (MFM) is a noncommittal term that refers to a group of morphologically homogeneous, but genetically heterogeneous chronic neuromuscular disorders. The morphologic changes in skeletal muscle in MFM result from disintegration of the sarcomeric Z disc and ...
Clinical Description OMIM Desmin-related MFM is characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, and restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. Autosomal dominant and autosomal recessive forms have ...
Genotype-Phenotype Correlations OMIM Van Spaendonck-Zwarts et al. (2011) performed a metaanalysis of 159 patients with 40 different DES mutations reported in the literature. The majority of DES mutations were missense mutations, mostly located in the 2B domain. Mutations in the 2B ...
Molecular genetics OMIM In affected members of a family with autosomal dominant inheritance of a desmin-related cardioskeletal myopathy, Goldfarb et al. (1998) identified a heterozygous mutation in the desmin gene (125660.0001). In 3 affected members of a second family with apparent ...