CNM2
MCID: MYP131
MIFTS: 40

Myopathy, Centronuclear, 2 (CNM2)

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

Aliases & Classifications for Myopathy, Centronuclear, 2

MalaCards integrated aliases for Myopathy, Centronuclear, 2:

Name: Myopathy, Centronuclear, 2 58 54 76
Autosomal Recessive Centronuclear Myopathy 54 60 30 6 74
Myopathy, Centronuclear, Autosomal Recessive 58 54 13 74
Ar-Cnm 54 60
Cnm2 58 76
Centronuclear Myopathy Autosomal Recessive 76
Myotubular Myopathy, Autosomal Recessive 58
Autosomal Recessive Myotubular Myopathy 76
Myopathy, Centronuclear, Type 2 41
Centronuclear Myopathy 2 58

Characteristics:

Orphanet epidemiological data:

60
autosomal recessive centronuclear myopathy
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable age at onset (range infancy to 30 years)
see also x-linked and autosomal dominant forms


HPO:

33
myopathy, centronuclear, 2:
Inheritance autosomal recessive inheritance
Onset and clinical course onset


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Myopathy, Centronuclear, 2

NIH Rare Diseases : 54 Autosomal recessive centronuclear myopathy (AR-CNM) is a type of centronuclear myopathy, which is a group of rare, inherited conditions that affect the muscles. In AR-CNM, specifically, affected people generally begin showing signs and symptoms during infancy or early childhood. The features of the condition can vary but may include progressive muscle weakness, foot abnormalities, high-arched palate, scoliosis, ptosis, mild to severe breathing problems, delayed motor milestones and cardiomyopathy (less commonly). Most cases of AR-CNM are caused by changes (mutations) in the BIN1 gene; however, some affected families are reported to have mutations in the SPEG, TTN, or RYR1 genes. The condition is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person and may include physical and/or occupational therapy and assistive devices to help with mobility, eating and/or breathing.

MalaCards based summary : Myopathy, Centronuclear, 2, also known as autosomal recessive centronuclear myopathy, is related to centronuclear myopathy and myopathy, and has symptoms including waddling gait, ophthalmoplegia and facial paresis. An important gene associated with Myopathy, Centronuclear, 2 is BIN1 (Bridging Integrator 1). Affiliated tissues include heart and skeletal muscle, and related phenotypes are high palate and respiratory insufficiency

UniProtKB/Swiss-Prot : 76 Myopathy, centronuclear, 2: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.

Description from OMIM: 255200

Related Diseases for Myopathy, Centronuclear, 2

Diseases in the Centronuclear Myopathy family:

Myopathy, Centronuclear, 1 Myopathy, Centronuclear, 2
Myopathy, Centronuclear, 4 Myopathy, Centronuclear, 5

Diseases related to Myopathy, Centronuclear, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 centronuclear myopathy 31.2 BIN1 RYR1 SPEG TTN
2 myopathy 30.6 RYR1 TTN
3 myopathy, centronuclear, 1 9.8 BIN1 RYR1
4 talipes equinovarus 9.7 RYR1 TTN
5 rigid spine muscular dystrophy 1 9.7 RYR1 TTN
6 neuromuscular disease 9.7 RYR1 TTN
7 muscular disease 9.7 RYR1 TTN
8 myasthenia gravis 9.7 RYR1 TTN
9 thymoma 9.6 RYR1 TTN
10 arrhythmogenic right ventricular cardiomyopathy 9.6 RYR1 TTN
11 scoliosis 9.4 RYR1 TTN

Graphical network of the top 20 diseases related to Myopathy, Centronuclear, 2:



Diseases related to Myopathy, Centronuclear, 2

Symptoms & Phenotypes for Myopathy, Centronuclear, 2

Human phenotypes related to Myopathy, Centronuclear, 2:

60 33 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 high palate 60 33 occasional (7.5%) Frequent (79-30%) HP:0000218
2 respiratory insufficiency 60 33 frequent (33%) Frequent (79-30%) HP:0002093
3 retrognathia 60 33 frequent (33%) Frequent (79-30%) HP:0000278
4 waddling gait 60 33 frequent (33%) Frequent (79-30%) HP:0002515
5 motor delay 60 33 frequent (33%) Frequent (79-30%) HP:0001270
6 generalized hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0001290
7 progressive muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0003323
8 gowers sign 60 33 frequent (33%) Frequent (79-30%) HP:0003391
9 difficulty climbing stairs 60 33 frequent (33%) Frequent (79-30%) HP:0003551
10 generalized amyotrophy 60 33 frequent (33%) Frequent (79-30%) HP:0003700
11 difficulty running 60 33 frequent (33%) Frequent (79-30%) HP:0009046
12 dysarthria 60 33 occasional (7.5%) Occasional (29-5%) HP:0001260
13 dysphonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001618
14 hyperlordosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0003307
15 delayed speech and language development 60 33 occasional (7.5%) Occasional (29-5%) HP:0000750
16 intellectual disability, mild 60 33 occasional (7.5%) Occasional (29-5%) HP:0001256
17 pes cavus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001761
18 scapular winging 60 33 occasional (7.5%) Occasional (29-5%) HP:0003691
19 protruding ear 60 33 occasional (7.5%) Occasional (29-5%) HP:0000411
20 talipes equinovarus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001762
21 type 1 muscle fiber predominance 60 33 occasional (7.5%) Occasional (29-5%) HP:0003803
22 ophthalmoplegia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000602
23 left ventricular hypertrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0001712
24 narrow mouth 60 33 occasional (7.5%) Occasional (29-5%) HP:0000160
25 long face 60 33 occasional (7.5%) Occasional (29-5%) HP:0000276
26 areflexia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001284
27 hip contracture 60 33 occasional (7.5%) Occasional (29-5%) HP:0003273
28 bifid uvula 60 33 occasional (7.5%) Occasional (29-5%) HP:0000193
29 facial diplegia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001349
30 emg: decremental response of compound muscle action potential to repetitive nerve stimulation 60 33 occasional (7.5%) Occasional (29-5%) HP:0003403
31 centrally nucleated skeletal muscle fibers 60 33 occasional (7.5%) Occasional (29-5%) HP:0003687
32 long fingers 60 33 occasional (7.5%) Occasional (29-5%) HP:0100807
33 respiratory insufficiency due to muscle weakness 33 occasional (7.5%) HP:0002747
34 abnormal heart valve morphology 33 occasional (7.5%) HP:0001654
35 facial palsy 60 33 Frequent (79-30%) HP:0010628
36 ptosis 33 HP:0000508
37 scoliosis 33 HP:0002650
38 kyphosis 33 HP:0002808
39 abnormal facial shape 60 Occasional (29-5%)
40 neonatal hypotonia 33 HP:0001319
41 flexion contracture 33 HP:0001371
42 feeding difficulties in infancy 33 HP:0008872
43 abnormality of the heart valves 60 Occasional (29-5%)
44 emg: myopathic abnormalities 33 HP:0003458
45 ophthalmoparesis 60 Occasional (29-5%)
46 proximal muscle weakness 33 HP:0003701
47 axial muscle weakness 33 HP:0003327
48 distal muscle weakness 33 HP:0002460

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
ptosis
ophthalmoplegia

Skeletal Spine:
scoliosis
kyphosis
hyperlordosis

Abdomen Gastrointestinal:
feeding difficulties

Head And Neck Face:
facial muscle weakness
long face (1 patient)

Head And Neck Mouth:
high-arched palate (1 patient)

Chest Ribs Sternum Clavicles And Scapulae:
scapular winging (1 patient)

Skeletal Feet:
pes cavus (1 patient)
pes equinovarus (1 patient)

Neurologic Central Nervous System:
dysarthria
dysphonia
waddling gait
delayed motor development
mental retardation, mild (1 patient)

Muscle Soft Tissue:
neonatal hypotonia
axial muscle weakness
gowers sign
emg shows myopathic changes
distal muscle weakness may occur
more
Neurologic Peripheral Nervous System:
areflexia

Skeletal:
joint contractures

Respiratory:
respiratory insufficiency due to muscle weakness (1 patient)

Skeletal Hands:
thin hands with long fingers (1 patient)

Clinical features from OMIM:

255200

UMLS symptoms related to Myopathy, Centronuclear, 2:


waddling gait, ophthalmoplegia, facial paresis

MGI Mouse Phenotypes related to Myopathy, Centronuclear, 2:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.26 BIN1 RYR1 SPEG TTN
2 muscle MP:0005369 8.92 BIN1 RYR1 SPEG TTN

Drugs & Therapeutics for Myopathy, Centronuclear, 2

Search Clinical Trials , NIH Clinical Center for Myopathy, Centronuclear, 2

Genetic Tests for Myopathy, Centronuclear, 2

Genetic tests related to Myopathy, Centronuclear, 2:

# Genetic test Affiliating Genes
1 Autosomal Recessive Centronuclear Myopathy 30 BIN1

Anatomical Context for Myopathy, Centronuclear, 2

MalaCards organs/tissues related to Myopathy, Centronuclear, 2:

42
Heart, Skeletal Muscle

Publications for Myopathy, Centronuclear, 2

Articles related to Myopathy, Centronuclear, 2:

# Title Authors Year
1
Neuromuscular blocking effects of vecuronium in dogs with autosomal-recessive centronuclear myopathy. ( 25815571 )
2015
2
Neuromuscular blocking effects of cisatracurium and its antagonism with neostigmine in a canine model of autosomal-recessive centronuclear myopathy. ( 26582854 )
2015
3
Case report of intrafamilial variability in autosomal recessive centronuclear myopathy associated to a novel BIN1 stop mutation. ( 21129173 )
2010
4
Severe phenotype of a patient with autosomal recessive centronuclear myopathy due to a BIN1 mutation. ( 20476667 )
2009
5
[Mutations in amphiphysin 2 (BIN1) cause autosomal recessive centronuclear myopathy]. ( 18154705 )
2007
6
Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. ( 17676042 )
2007
7
SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs. ( 15829503 )
2005

Variations for Myopathy, Centronuclear, 2

UniProtKB/Swiss-Prot genetic disease variations for Myopathy, Centronuclear, 2:

76
# Symbol AA change Variation ID SNP ID
1 BIN1 p.Lys35Asn VAR_037425 rs121909273
2 BIN1 p.Asp151Asn VAR_037426 rs121909274
3 BIN1 p.Arg145Cys VAR_081082 rs124962103
4 BIN1 p.Arg154Gln VAR_081083 rs267606681
5 BIN1 p.Arg234Cys VAR_081084 rs777176261

ClinVar genetic disease variations for Myopathy, Centronuclear, 2:

6 (show top 50) (show all 240)
# Gene Variation Type Significance SNP ID Assembly Location
1 BIN1 NM_139343.2(BIN1): c.1132-7T> C single nucleotide variant Benign/Likely benign rs115938552 GRCh37 Chromosome 2, 127811595: 127811595
2 BIN1 NM_139343.2(BIN1): c.1132-7T> C single nucleotide variant Benign/Likely benign rs115938552 GRCh38 Chromosome 2, 127054019: 127054019
3 BIN1 NM_139343.2(BIN1): c.1362G> T (p.Gly454=) single nucleotide variant Conflicting interpretations of pathogenicity rs61748155 GRCh37 Chromosome 2, 127809840: 127809840
4 BIN1 NM_139343.2(BIN1): c.1362G> T (p.Gly454=) single nucleotide variant Conflicting interpretations of pathogenicity rs61748155 GRCh38 Chromosome 2, 127052264: 127052264
5 BIN1 NM_139343.2(BIN1): c.1461C> T (p.Ser487=) single nucleotide variant Uncertain significance rs34647988 GRCh37 Chromosome 2, 127808730: 127808730
6 BIN1 NM_139343.2(BIN1): c.1461C> T (p.Ser487=) single nucleotide variant Uncertain significance rs34647988 GRCh38 Chromosome 2, 127051154: 127051154
7 BIN1 NM_139343.2(BIN1): c.1595C> T (p.Thr532Met) single nucleotide variant Benign/Likely benign rs112318500 GRCh37 Chromosome 2, 127808076: 127808076
8 BIN1 NM_139343.2(BIN1): c.1595C> T (p.Thr532Met) single nucleotide variant Benign/Likely benign rs112318500 GRCh38 Chromosome 2, 127050500: 127050500
9 BIN1 NM_139343.2(BIN1): c.1625A> G (p.Lys542Arg) single nucleotide variant Benign rs138047593 GRCh37 Chromosome 2, 127808046: 127808046
10 BIN1 NM_139343.2(BIN1): c.1625A> G (p.Lys542Arg) single nucleotide variant Benign rs138047593 GRCh38 Chromosome 2, 127050470: 127050470
11 BIN1 NM_139343.2(BIN1): c.1713G> A (p.Trp571Ter) single nucleotide variant Pathogenic rs587783343 GRCh37 Chromosome 2, 127806171: 127806171
12 BIN1 NM_139343.2(BIN1): c.1713G> A (p.Trp571Ter) single nucleotide variant Pathogenic rs587783343 GRCh38 Chromosome 2, 127048595: 127048595
13 BIN1 NM_139343.2(BIN1): c.30G> A (p.Thr10=) single nucleotide variant Conflicting interpretations of pathogenicity rs35535012 GRCh37 Chromosome 2, 127864490: 127864490
14 BIN1 NM_139343.2(BIN1): c.30G> A (p.Thr10=) single nucleotide variant Conflicting interpretations of pathogenicity rs35535012 GRCh38 Chromosome 2, 127106914: 127106914
15 BIN1 NM_139343.2(BIN1): c.486T> C (p.Thr162=) single nucleotide variant Benign/Likely benign rs1060743 GRCh37 Chromosome 2, 127826533: 127826533
16 BIN1 NM_139343.2(BIN1): c.486T> C (p.Thr162=) single nucleotide variant Benign/Likely benign rs1060743 GRCh38 Chromosome 2, 127068957: 127068957
17 BIN1 NM_139343.2(BIN1): c.696C> A (p.Asn232Lys) single nucleotide variant Uncertain significance rs143820618 GRCh37 Chromosome 2, 127821511: 127821511
18 BIN1 NM_139343.2(BIN1): c.696C> A (p.Asn232Lys) single nucleotide variant Uncertain significance rs143820618 GRCh38 Chromosome 2, 127063935: 127063935
19 BIN1 NM_139343.2(BIN1): c.698+10A> G single nucleotide variant Benign/Likely benign rs72481904 GRCh37 Chromosome 2, 127821499: 127821499
20 BIN1 NM_139343.2(BIN1): c.698+10A> G single nucleotide variant Benign/Likely benign rs72481904 GRCh38 Chromosome 2, 127063923: 127063923
21 BIN1 NM_139343.2(BIN1): c.714C> T (p.Tyr238=) single nucleotide variant Benign/Likely benign rs1137845 GRCh37 Chromosome 2, 127821207: 127821207
22 BIN1 NM_139343.2(BIN1): c.714C> T (p.Tyr238=) single nucleotide variant Benign/Likely benign rs1137845 GRCh38 Chromosome 2, 127063631: 127063631
23 BIN1 NM_139343.2(BIN1): c.775-4G> A single nucleotide variant Benign/Likely benign rs61748157 GRCh37 Chromosome 2, 127819777: 127819777
24 BIN1 NM_139343.2(BIN1): c.775-4G> A single nucleotide variant Benign/Likely benign rs61748157 GRCh38 Chromosome 2, 127062201: 127062201
25 BIN1 NM_139343.2(BIN1): c.858-12C> A single nucleotide variant Benign/Likely benign rs6720741 GRCh37 Chromosome 2, 127816743: 127816743
26 BIN1 NM_139343.2(BIN1): c.858-12C> A single nucleotide variant Benign/Likely benign rs6720741 GRCh38 Chromosome 2, 127059167: 127059167
27 BIN1 NM_139343.2(BIN1): c.888C> T (p.Ser296=) single nucleotide variant Conflicting interpretations of pathogenicity rs114833236 GRCh37 Chromosome 2, 127816701: 127816701
28 BIN1 NM_139343.2(BIN1): c.888C> T (p.Ser296=) single nucleotide variant Conflicting interpretations of pathogenicity rs114833236 GRCh38 Chromosome 2, 127059125: 127059125
29 BIN1 NM_139343.2(BIN1): c.894G> A (p.Ser298=) single nucleotide variant Benign/Likely benign rs2228955 GRCh37 Chromosome 2, 127816695: 127816695
30 BIN1 NM_139343.2(BIN1): c.894G> A (p.Ser298=) single nucleotide variant Benign/Likely benign rs2228955 GRCh38 Chromosome 2, 127059119: 127059119
31 BIN1 NM_139343.2(BIN1): c.957C> A (p.Ala319=) single nucleotide variant Uncertain significance rs2276579 GRCh37 Chromosome 2, 127816632: 127816632
32 BIN1 NM_139343.2(BIN1): c.957C> A (p.Ala319=) single nucleotide variant Uncertain significance rs2276579 GRCh38 Chromosome 2, 127059056: 127059056
33 BIN1 NM_139343.2(BIN1): c.957C> G (p.Ala319=) single nucleotide variant Uncertain significance rs2276579 GRCh37 Chromosome 2, 127816632: 127816632
34 BIN1 NM_139343.2(BIN1): c.957C> G (p.Ala319=) single nucleotide variant Uncertain significance rs2276579 GRCh38 Chromosome 2, 127059056: 127059056
35 BIN1 NM_139343.2(BIN1): c.957C> T (p.Ala319=) single nucleotide variant Benign/Likely benign rs2276579 GRCh37 Chromosome 2, 127816632: 127816632
36 BIN1 NM_139343.2(BIN1): c.957C> T (p.Ala319=) single nucleotide variant Benign/Likely benign rs2276579 GRCh38 Chromosome 2, 127059056: 127059056
37 TTN NM_133378.4(TTN): c.68689_68692delAACA (p.Asn22897Terfs) deletion Likely pathogenic rs727504483 GRCh38 Chromosome 2, 178569736: 178569739
38 TTN NM_133378.4(TTN): c.68689_68692delAACA (p.Asn22897Terfs) deletion Likely pathogenic rs727504483 GRCh37 Chromosome 2, 179434463: 179434466
39 TTN NM_133378.4(TTN): c.98315delG (p.Gly32772Valfs) deletion no interpretation for the single variant rs727504482 GRCh38 Chromosome 2, 178530596: 178530596
40 TTN NM_133378.4(TTN): c.98315delG (p.Gly32772Valfs) deletion no interpretation for the single variant rs727504482 GRCh37 Chromosome 2, 179395323: 179395323
41 TTN NM_001256850.1(TTN): c.67057_67063delGCATATGinsTA (p.Ala22353Terfs) indel Pathogenic/Likely pathogenic rs794729338 GRCh37 Chromosome 2, 179438873: 179438879
42 TTN NM_001256850.1(TTN): c.67057_67063delGCATATGinsTA (p.Ala22353Terfs) indel Pathogenic/Likely pathogenic rs794729338 GRCh38 Chromosome 2, 178574146: 178574152
43 BIN1 NM_139343.2(BIN1): c.1263+11C> T single nucleotide variant Conflicting interpretations of pathogenicity rs78967885 GRCh37 Chromosome 2, 127810987: 127810987
44 BIN1 NM_139343.2(BIN1): c.1263+11C> T single nucleotide variant Conflicting interpretations of pathogenicity rs78967885 GRCh38 Chromosome 2, 127053411: 127053411
45 BIN1 NM_139343.2(BIN1): c.105G> T (p.Lys35Asn) single nucleotide variant Pathogenic rs121909273 GRCh37 Chromosome 2, 127834262: 127834262
46 BIN1 NM_139343.2(BIN1): c.105G> T (p.Lys35Asn) single nucleotide variant Pathogenic rs121909273 GRCh38 Chromosome 2, 127076686: 127076686
47 BIN1 NM_139343.2(BIN1): c.451G> A (p.Asp151Asn) single nucleotide variant Pathogenic rs121909274 GRCh37 Chromosome 2, 127826568: 127826568
48 BIN1 NM_139343.2(BIN1): c.451G> A (p.Asp151Asn) single nucleotide variant Pathogenic rs121909274 GRCh38 Chromosome 2, 127068992: 127068992
49 BIN1 NM_139343.2(BIN1): c.1723A> T (p.Lys575Ter) single nucleotide variant Pathogenic rs121909275 GRCh37 Chromosome 2, 127806161: 127806161
50 BIN1 NM_139343.2(BIN1): c.1723A> T (p.Lys575Ter) single nucleotide variant Pathogenic rs121909275 GRCh38 Chromosome 2, 127048585: 127048585

Expression for Myopathy, Centronuclear, 2

Search GEO for disease gene expression data for Myopathy, Centronuclear, 2.

Pathways for Myopathy, Centronuclear, 2

GO Terms for Myopathy, Centronuclear, 2

Cellular components related to Myopathy, Centronuclear, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 T-tubule GO:0030315 9.16 BIN1 RYR1
2 Z disc GO:0030018 9.13 BIN1 RYR1 TTN
3 I band GO:0031674 8.8 BIN1 RYR1 TTN

Biological processes related to Myopathy, Centronuclear, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 muscle contraction GO:0006936 8.96 RYR1 TTN
2 muscle cell differentiation GO:0042692 8.62 BIN1 SPEG

Molecular functions related to Myopathy, Centronuclear, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.43 RYR1 SPEG TTN
2 actin filament binding GO:0051015 9.16 BIN1 TTN
3 calmodulin binding GO:0005516 8.96 RYR1 TTN
4 protease binding GO:0002020 8.8 BIN1 RYR1 TTN

Sources for Myopathy, Centronuclear, 2

3 CDC
7 CNVD
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10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
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35 ICD10 via Orphanet
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59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
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75 UMLS via Orphanet
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