DM2
MCID: MYT020
MIFTS: 54

Myotonic Dystrophy 2 (DM2)

Categories: Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Myotonic Dystrophy 2

MalaCards integrated aliases for Myotonic Dystrophy 2:

Name: Myotonic Dystrophy 2 57 74 13
Proximal Myotonic Myopathy 57 12 75 24 53 59 74
Myotonic Dystrophy Type 2 12 24 53 59 29 6 15
Promm 57 24 53 74 55
Ricker Syndrome 57 53 59 74
Dystrophia Myotonica 2 57 74 72
Myotonic Disorders 44 72 33
Dm2 57 53 74
Myotonic Myopathy, Proximal 57 53
Proximal Myotonic Myopathy; Promm 57
Dystrophia Myotonica Type 2 53
Proximal Myotonic Dystrophy 59
Dystrophy, Myotonic, Type 2 40
Ricker Disease 59

Characteristics:

Orphanet epidemiological data:

59
proximal myotonic myopathy
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Germany),1-9/100000 (Europe),1-5/10000 (Finland),1-9/1000000 (United Kingdom); Age of onset: Adult; Age of death: elderly;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable age of onset (range 13 to 67 years, median 48 years)
no congenital form
pathogenic alleles contain 75-11,000 repeats
normal alleles contain up to 30 repeats
repeat tracts may expand as patient ages (somatic instability)
smaller repeat lengths in younger generations (reverse anticipation)
see myotonic dystonia 1 (dm1, ) for a disorder with a similar phenotype


HPO:

32
myotonic dystrophy 2:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance Disease penetrance reflects both an individual's sensitivity for his/her symptoms and a physician's ability to correctly identify and interpret signs of the disease. as affected families and their physicians become increasingly aware of the clinical features of dm2, penetrance approaches 100%....

Classifications:



External Ids:

Disease Ontology 12 DOID:0050759
ICD9CM 35 359.2
SNOMED-CT 68 41574007
ICD10 33 G71.1 G71.19
MESH via Orphanet 45 D020967
ICD10 via Orphanet 34 G71.1
UMLS via Orphanet 73 C0752354 C2931689
Orphanet 59 ORPHA606
UMLS 72 C0221055 C0553604 C0752355 more

Summaries for Myotonic Dystrophy 2

NIH Rare Diseases : 53 Myotonic dystrophy type 2, one of the two types of myotonic dystrophy, is an inherited muscular dystrophy that affects the muscles and other body systems (e.g., heart, eyes, and pancreas). It is characterized by prolonged muscle tensing (myotonia) as well as muscle weakness, pain, and stiffness. Signs and symptoms usually develop during a person's twenties or thirties. Muscles in the neck, fingers, elbows, and hips are typically affected; facial and ankle muscles are less commonly involved. The severity of myotonic dystrophy type 2 varies widely among affected people, even among family members. It is inherited in an autosomal dominant pattern and is caused by mutations in the CNBP gene. Treatment is based on each person's specific signs and symptoms.

MalaCards based summary : Myotonic Dystrophy 2, also known as proximal myotonic myopathy, is related to hyperkalemic periodic paralysis and neuromuscular disease, and has symptoms including muscle weakness, myalgia and muscle cramp. An important gene associated with Myotonic Dystrophy 2 is CNBP (CCHC-Type Zinc Finger Nucleic Acid Binding Protein). The drugs Dichlorphenamide and Lamotrigine have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, heart and eye, and related phenotypes are cataract and myotonia

Disease Ontology : 12 A myotonic disease that is characterized by myotonia and progressive, proximal muscle wasting and weakness affecting the skeletal and smooth muscles of the neck, shoulders, elbows and hips and has material basis in the autosomal dominant inheritance of the CNBP (ZNF9) gene containing an expansion of a CCTG repeat in intron one.

OMIM : 57 Myotonic dystrophy (DM) is a multisystem disorder and the most common form of muscular dystrophy in adults. Individuals with DM2 have muscle pain and stiffness, progressive muscle weakness, myotonia, male hypogonadism, cardiac arrhythmias, diabetes, and early cataracts. Other features may include cognitive dysfunction, hypersomnia, tremor, and hearing loss (summary by Heatwole et al., 2011). See also myotonic dystrophy-1 (DM1; 160900), caused by an expanded CTG repeat in the dystrophia myotonica protein kinase gene (DMPK; 605377) on 19q13. Although originally reported as 2 disorders, myotonic dystrophy-2 and proximal myotonic myopathy are now referred to collectively as DM2 (Udd et al., 2003). (602668)

UniProtKB/Swiss-Prot : 74 Dystrophia myotonica 2: A multisystem disease characterized by the association of proximal muscle weakness with myotonia, cardiac manifestations and cataract. Additional features can include hyperhidrosis, testicular atrophy, insulin resistance and diabetes and central nervous system anomalies in rare cases.

Wikipedia : 75 Myotonic dystrophy is a long term genetic disorder that affects muscle function. Symptoms include... more...

GeneReviews: NBK1466

Related Diseases for Myotonic Dystrophy 2

Diseases in the Myotonic Dystrophy family:

Myotonic Dystrophy 1 Myotonic Dystrophy 2

Diseases related to Myotonic Dystrophy 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 129)
# Related Disease Score Top Affiliating Genes
1 hyperkalemic periodic paralysis 30.0 SCN4A CLCN1
2 neuromuscular disease 29.4 SCN4A DMPK
3 myotonia congenita 29.1 SCN4A CNBP CLCN1
4 myotonic dystrophy 28.7 MBNL1 DMPK CNBP CLCN1
5 myotonia 28.6 SCN4A DMPK CNBP CLCN1
6 myotonic dystrophy 1 28.3 MBNL1 DMPK CNBP CLCN1
7 myotonic disease 27.6 SCN4A MBNL1 DMPK CNBP CLCN1
8 muscular disease 27.3 SCN4A MBNL1 DMPK CNBP CLCN1
9 non-dystrophic myotonic disorders 12.3
10 myotonia, potassium-aggravated 11.5
11 paramyotonia congenita of von eulenburg 10.7
12 myotonia atrophica 10.4
13 schwartz-jampel syndrome, type 1 10.4
14 restless legs syndrome 10.3
15 sleep disorder 10.3
16 myositis 10.3
17 primary hyperparathyroidism 10.3
18 hyperparathyroidism 10.3
19 personality disorder 10.3
20 hypogonadism 10.3
21 hypogonadotropism 10.3
22 malignant hyperthermia 10.3
23 periodic paralysis 10.3
24 hypothyroidism 10.2
25 ataxia and polyneuropathy, adult-onset 10.2
26 sleep apnea 10.2
27 dilated cardiomyopathy 10.2
28 polyneuropathy 10.2
29 fibromyalgia 10.2
30 dysphagia 10.2
31 episodic ataxia, type 1 10.2
32 episodic ataxia 10.2
33 progressive familial heart block, type ia 10.2
34 progressive familial heart block, type ib 10.2
35 right bundle branch block 10.2
36 microvascular complications of diabetes 5 10.1
37 peripheral nervous system disease 10.1
38 neuropathy 10.1
39 muscular dystrophy 10.1
40 atrial standstill 1 10.1
41 autoimmune disease 10.1
42 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 10.1
43 autosomal dominant cerebellar ataxia 10.1
44 epilepsy 10.1
45 muscular atrophy 10.1
46 talipes equinovarus 10.1
47 dysautonomia 10.1
48 cardiac conduction defect 10.0
49 myopathy, congenital 10.0
50 glucose intolerance 10.0

Graphical network of the top 20 diseases related to Myotonic Dystrophy 2:



Diseases related to Myotonic Dystrophy 2

Symptoms & Phenotypes for Myotonic Dystrophy 2

Human phenotypes related to Myotonic Dystrophy 2:

59 32 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cataract 59 32 hallmark (90%) Very frequent (99-80%) HP:0000518
2 myotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002486
3 diabetes mellitus 32 HP:0000819
4 myalgia 32 HP:0003326
5 hypogonadism 32 HP:0000135
6 decreased circulating igg level 32 HP:0004315
7 proximal muscle weakness 32 HP:0003701
8 oligospermia 32 HP:0000798
9 neck flexor weakness 32 HP:0003722
10 elevated circulating follicle stimulating hormone level 32 HP:0008232
11 decreased circulating total igm 32 HP:0002850
12 tachycardia 32 HP:0001649
13 palpitations 32 HP:0001962
14 frontal balding 32 HP:0002292
15 type 2 muscle fiber atrophy 32 HP:0003554
16 elevated serum creatine kinase 32 HP:0003236
17 iridescent posterior subcapsular cataract 32 HP:0007889
18 insulin insensitivity 32 HP:0008189

Symptoms via clinical synopsis from OMIM:

57
Endocrine Features:
diabetes mellitus
insulin insensitivity
low testosterone
elevated follicle stimulating hormone (fsh)

Genitourinary Internal Genitalia Male:
hypogonadism
oligospermia

Laboratory Abnormalities:
elevated serum creatine kinase
increased lactate dehydrogenase
elevated gamma-glutamyltransferase (ggt)
increased cholesterol
increased alt
more
Skin Nails Hair Skin:
hyperhydrosis

Head And Neck Eyes:
cataracts, posterior, subcapsular, iridescent

Muscle Soft Tissue:
myotonia
proximal muscle weakness
neck flexor weakness
muscle pain
type 2 fiber atrophy
more
Cardiovascular Heart:
tachycardia
palpitations
cardiac conduction abnormalities

Skin Nails Hair Hair:
frontal balding (male pattern baldness)

Neurologic Central Nervous System:
no mental retardation

Immunology:
decreased serum igg and igm
decreased absolute lymphocytes

Clinical features from OMIM:

602668

UMLS symptoms related to Myotonic Dystrophy 2:


muscle weakness, myalgia, muscle cramp, muscle rigidity, muscle spasticity

MGI Mouse Phenotypes related to Myotonic Dystrophy 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 8.92 CLCN1 DMPK MBNL1 SCN4A

Drugs & Therapeutics for Myotonic Dystrophy 2

Drugs for Myotonic Dystrophy 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dichlorphenamide Approved, Investigational Phase 3 120-97-8 3038
2
Lamotrigine Approved, Investigational Phase 3 84057-84-1 3878
3
Mexiletine Approved, Investigational Phase 3 31828-71-4 4178
4
Calcium Approved, Nutraceutical Phase 3 7440-70-2 271
5 Carbonic Anhydrase Inhibitors Phase 3
6 Sodium Channel Blockers Phase 3
7 Diuretics, Potassium Sparing Phase 3
8 Tranquilizing Agents Phase 3
9 Hormones Phase 3
10 Central Nervous System Depressants Phase 3
11 Antipsychotic Agents Phase 3
12 Psychotropic Drugs Phase 3
13 Calcium, Dietary Phase 3
14 Anticonvulsants Phase 3
15 calcium channel blockers Phase 3
16 Anti-Arrhythmia Agents Phase 3
17
Ranolazine Approved, Investigational Phase 1 142387-99-3, 95635-55-5 56959

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dichlorphenamide for Periodic Paralyses and Associated Sodium Channel Disorders Completed NCT00004802 Phase 3 dichlorphenamide
2 Lamotrigine as Treatment of Myotonia - a Phase 3 Randomized Controlled Trial Study Completed NCT01939561 Phase 3 Lamotrigine;Placebo
3 Efficacy and Safety of Mexiletine in Non-dystrophic Myotonias Completed NCT02336477 Phase 3 Mexiletine;placebo
4 Open Label Trial of Ranolazine in Myotonia Congenita, Paramyotonia Congenita, & Myotonic Dystrophy Type 1 Completed NCT02251457 Phase 1 Ranolazine
5 Tracking the Brain in Myotonic Dystrophies: a 5-year Longitudinal Follow-up Study Completed NCT02729597
6 Nondystrophic Myotonias: Genotype-phenotype Correlation and Longitudinal Study Completed NCT00244413
7 Observational Trial in Myotonic Dystrophy Type 2 to Define Specific Clinical Outcome Measures Recruiting NCT03603171
8 The UK National Registry for Myotonic Dystrophy Recruiting NCT04003363
9 Myotonic Dystrophy Family Registry Recruiting NCT02398786
10 National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members Recruiting NCT00082108
11 Muscle Relaxation Properties in Myopathies With Positive Muscle Phenomena: a Study Using Transcranial Magnetic Stimulation Enrolling by invitation NCT03211923

Search NIH Clinical Center for Myotonic Dystrophy 2

Cochrane evidence based reviews: myotonic disorders

Genetic Tests for Myotonic Dystrophy 2

Genetic tests related to Myotonic Dystrophy 2:

# Genetic test Affiliating Genes
1 Myotonic Dystrophy Type 2 29 CNBP

Anatomical Context for Myotonic Dystrophy 2

MalaCards organs/tissues related to Myotonic Dystrophy 2:

41
Skeletal Muscle, Heart, Eye, Pancreas, Smooth Muscle, Brain, Testes

Publications for Myotonic Dystrophy 2

Articles related to Myotonic Dystrophy 2:

(show top 50) (show all 178)
# Title Authors PMID Year
1
Myotonic dystrophy type 2: human founder haplotype and evolutionary conservation of the repeat tract. 4 8 71
14505273 2003
2
Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. 4 8 71
11486088 2001
3
Confirmation of the type 2 myotonic dystrophy (CCTG)n expansion mutation in patients with proximal myotonic myopathy/proximal myotonic dystrophy of different European origins: a single shared haplotype indicates an ancestral founder effect. 38 8 71
12970845 2003
4
Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum. 9 38 4 8
12601109 2003
5
Myotonic dystrophy type 2 in Japan: ancestral origin distinct from Caucasian families. 8 71
18057971 2008
6
Proximal myotonic myopathy (PROMM) presenting as myotonia during pregnancy. 38 4 8
10382907 1999
7
Myotonic dystrophy and proximal myotonic myophathy. 38 4 8
10399862 1999
8
Clinical and genetic characteristics of a five-generation family with a novel form of myotonic dystrophy (DM2). 38 4 8
10063831 1999
9
Linkage of proximal myotonic myopathy to chromosome 3q. 38 4 8
9921867 1999
10
Proximal myotonic myopathy: a new dominant disorder with myotonia, muscle weakness, and cataracts. 38 4 8
8058147 1994
11
Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland. 4 8
21364698 2011
12
Outcome and effect of pregnancy in myotonic dystrophy type 2. 4 8
16505316 2006
13
Sudden cardiac death in myotonic dystrophy type 2. 4 8
15623712 2004
14
Report of the 115th ENMC workshop: DM2/PROMM and other myotonic dystrophies. 3rd Workshop, 14-16 February 2003, Naarden, The Netherlands. 4 8
12921797 2003
15
Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2. 4 8
12796551 2003
16
Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM. 9 38 8
10665666 1999
17
Dominantly inherited proximal myotonic myopathy and leukoencephalopathy in a family with an incidental CLCN1 mutation. 9 38 8
9576553 1998
18
Proximal myotonic myopathy. Clinical features of a multisystem disorder similar to myotonic dystrophy. 9 38 8
7826272 1995
19
A non-DM1, non-DM2 multisystem myotonic disorder with frontotemporal dementia: phenotype and suggestive mapping of the DM3 locus to chromosome 15q21-24. 9 38 4
15215218 2004
20
Proximal myotonic myopathy (PROMM) and other proximal myotonic syndromes. 38 8
9829283 1998
21
Myotonic dystrophy phenotype without expansion of (CTG)n repeat: an entity distinct from proximal myotonic myopathy (PROMM)? 38 8
8923304 1996
22
Myotonic dystrophies type 1 and 2: anesthetic care. 38 4
23384336 2013
23
Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel. 8
22140091 2012
24
Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene. 8
21204798 2011
25
Clinical, electrophysiologic and pathologic findings in 10 patients with myotonic dystrophy 2. 38 4
22332444 2011
26
Laboratory abnormalities in patients with myotonic dystrophy type 2. 8
21911698 2011
27
Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. 8
21623381 2011
28
RNA-mediated neurodegeneration in repeat expansion disorders. 8
20373340 2010
29
Premutation allele pool in myotonic dystrophy type 2. 8
19020295 2009
30
Myotonic Dystrophy Type 2 71
20301639 2006
31
Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease. 8
16301494 2005
32
Musculoskeletal pain in patients with myotonic dystrophy type 2. 38 4
15596616 2004
33
Muscle pathology in 57 patients with myotonic dystrophy type 2. 38 4
14755494 2004
34
Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy (PROMM/DM-2). 38 4
14678804 2003
35
PROMM and deafness: exclusion of ZNF9 as the disease gene in DFNA18 suggests a polygenic origin of the PROMM/DM2 phenotype. 8
12519376 2003
36
Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. 8
12150905 2002
37
Proximal myotonic myopathy: a syndrome with a favourable prognosis? 38 4
11790388 2002
38
Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2. 8
11590133 2001
39
Proximal myotonic myopathy: evidence for anticipation in families with linkage to chromosome 3q. 38 4
10932272 2000
40
Hypothyroidism unmasking proximal myotonic myopathy. 38 4
10734262 2000
41
Reduced cerebral blood flow and impaired visual-spatial function in proximal myotonic myopathy. 38 4
10496264 1999
42
The myotonic dystrophies. 38 4
10711986 1999
43
Genetic mapping of a second myotonic dystrophy locus. 8
9620781 1998
44
Proximal myotonic myopathy with MRI white matter abnormalities of the brain. 38 4
9008490 1997
45
Proximal myotonic myopathy: mini-review of a recently delineated clinical disorder. 38 4
8664567 1996
46
Thornton-Griggs-Moxley disease: myotonic dystrophy type 2. 8
7979231 1994
47
Myotonic dystrophy with no trinucleotide repeat expansion. 8
8122879 1994
48
The frequency and severity of cardiac involvement in myotonic dystrophy type 2 (DM2): long-term outcomes. 4
23266299 2013
49
Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2. 4
22643181 2012
50
Nuclear ribonucleoprotein-containing foci increase in size in non-dividing cells from patients with myotonic dystrophy type 2. 4
22706481 2012

Variations for Myotonic Dystrophy 2

ClinVar genetic disease variations for Myotonic Dystrophy 2:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 CNBP NM_003418.4(CNBP): c.-14-833_-14-830(75_11000) NT expansion Pathogenic 3:128891444-128891447 3:129172601-129172604

Expression for Myotonic Dystrophy 2

LifeMap Discovery
Genes differentially expressed in tissues of Myotonic Dystrophy 2 patients vs. healthy controls: 35 (show all 19)
# Gene Description Tissue Up/Dn Fold Change (log2) P value
1 MAFF v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F Skeletal Muscle - 4.77 0.000
2 COL21A1 collagen, type XXI, alpha 1 Skeletal Muscle + 3.98 0.000
3 SPX spexin hormone Skeletal Muscle + 3.70 0.000
4 COL4A3 collagen, type IV, alpha 3 (Goodpasture antigen) Skeletal Muscle + 3.68 0.000
5 ATP1B4 ATPase, Na+/K+ transporting, beta 4 polypeptide Skeletal Muscle + 3.67 0.000
6 RARRES1 retinoic acid receptor responder (tazarotene induced) 1 Skeletal Muscle - 3.50 0.000
7 NEB nebulin Skeletal Muscle + 3.26 0.000
8 PPP1R3A protein phosphatase 1, regulatory subunit 3A Skeletal Muscle + 3.25 0.000
9 AQP4 aquaporin 4 Skeletal Muscle + 3.25 0.000
10 THBS1 thrombospondin 1 Skeletal Muscle - 3.21 0.000
11 CHI3L1 chitinase 3-like 1 (cartilage glycoprotein-39) Skeletal Muscle - 3.19 0.000
12 NNMT nicotinamide N-methyltransferase Skeletal Muscle - 3.14 0.000
13 PTX3 pentraxin 3, long Skeletal Muscle - 3.13 0.001
14 SCD5 stearoyl-CoA desaturase 5 Skeletal Muscle + 3.12 0.000
15 RIF1 replication timing regulatory factor 1 Skeletal Muscle + 3.10 0.000
16 SLC39A14 solute carrier family 39 (zinc transporter), member 14 Skeletal Muscle - 3.06 0.000
17 MT1M metallothionein 1M Skeletal Muscle - 3.03 0.000
18 NFIL3 nuclear factor, interleukin 3 regulated Skeletal Muscle - 3.02 0.000
19 PRPF38B pre-mRNA processing factor 38B Skeletal Muscle + 3.01 0.000
Search GEO for disease gene expression data for Myotonic Dystrophy 2.

Pathways for Myotonic Dystrophy 2

GO Terms for Myotonic Dystrophy 2

Biological processes related to Myotonic Dystrophy 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of ion transmembrane transport GO:0034765 9.16 SCN4A CLCN1
2 muscle contraction GO:0006936 8.96 SCN4A CLCN1
3 regulation of alternative mRNA splicing, via spliceosome GO:0000381 8.62 RBMY1A1 MBNL1

Molecular functions related to Myotonic Dystrophy 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA binding GO:0003723 8.92 RBMY1A1 MBNL1 EEF2 CNBP

Sources for Myotonic Dystrophy 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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