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 57 53 75
Autosomal Recessive Centronuclear Myopathy 53 59 29 6 73
Myopathy, Centronuclear, Autosomal Recessive 57 53 13 73
Ar-Cnm 53 59
Cnm2 57 75
Centronuclear Myopathy Autosomal Recessive 75
Myotubular Myopathy, Autosomal Recessive 57
Autosomal Recessive Myotubular Myopathy 75
Myopathy, Centronuclear, Type 2 40
Centronuclear Myopathy 2 57

Characteristics:

Orphanet epidemiological data:

59
autosomal recessive centronuclear myopathy
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
myopathy, centronuclear, 2:
Inheritance autosomal recessive inheritance
Onset and clinical course onset


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Myopathy, Centronuclear, 2

NIH Rare Diseases : 53 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, bone and skeletal muscle, and related phenotypes are high palate and dysarthria

UniProtKB/Swiss-Prot : 75 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, 3 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 31.6 SPEG RYR1 BIN1 TTN
2 myopathy 30.7 RYR1 TTN
3 myopathy, centronuclear, 1 9.9 BIN1 RYR1
4 talipes equinovarus 9.8 RYR1 TTN
5 rigid spine muscular dystrophy 1 9.8 RYR1 TTN
6 neuromuscular disease 9.8 RYR1 TTN
7 muscular disease 9.8 RYR1 TTN
8 myasthenia gravis 9.8 RYR1 TTN
9 thymoma 9.8 RYR1 TTN
10 arrhythmogenic right ventricular cardiomyopathy 9.7 RYR1 TTN
11 scoliosis 9.6 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Myopathy, Centronuclear, 2:

59 32 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 high palate 59 32 occasional (7.5%) Frequent (79-30%) HP:0000218
2 dysarthria 59 32 occasional (7.5%) Occasional (29-5%) HP:0001260
3 dysphonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001618
4 respiratory insufficiency 59 32 frequent (33%) Frequent (79-30%) HP:0002093
5 hyperlordosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003307
6 facial palsy 59 32 Frequent (79-30%) HP:0010628
7 delayed speech and language development 59 32 occasional (7.5%) Occasional (29-5%) HP:0000750
8 intellectual disability, mild 59 32 occasional (7.5%) Occasional (29-5%) HP:0001256
9 retrognathia 59 32 frequent (33%) Frequent (79-30%) HP:0000278
10 pes cavus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001761
11 waddling gait 59 32 frequent (33%) Frequent (79-30%) HP:0002515
12 scapular winging 59 32 occasional (7.5%) Occasional (29-5%) HP:0003691
13 protruding ear 59 32 occasional (7.5%) Occasional (29-5%) HP:0000411
14 motor delay 59 32 frequent (33%) Frequent (79-30%) HP:0001270
15 talipes equinovarus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001762
16 type 1 muscle fiber predominance 59 32 occasional (7.5%) Occasional (29-5%) HP:0003803
17 left ventricular hypertrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001712
18 narrow mouth 59 32 occasional (7.5%) Occasional (29-5%) HP:0000160
19 long face 59 32 occasional (7.5%) Occasional (29-5%) HP:0000276
20 areflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001284
21 hip contracture 59 32 occasional (7.5%) Occasional (29-5%) HP:0003273
22 bifid uvula 59 32 occasional (7.5%) Occasional (29-5%) HP:0000193
23 ophthalmoplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000602
24 facial diplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001349
25 generalized hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001290
26 progressive muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0003323
27 gowers sign 59 32 frequent (33%) Frequent (79-30%) HP:0003391
28 difficulty climbing stairs 59 32 frequent (33%) Frequent (79-30%) HP:0003551
29 generalized amyotrophy 59 32 frequent (33%) Frequent (79-30%) HP:0003700
30 difficulty running 59 32 frequent (33%) Frequent (79-30%) HP:0009046
31 centrally nucleated skeletal muscle fibers 59 32 occasional (7.5%) Occasional (29-5%) HP:0003687
32 long fingers 59 32 occasional (7.5%) Occasional (29-5%) HP:0100807
33 ptosis 32 HP:0000508
34 scoliosis 32 HP:0002650
35 kyphosis 32 HP:0002808
36 abnormal facial shape 59 Occasional (29-5%)
37 neonatal hypotonia 32 HP:0001319
38 flexion contracture 32 HP:0001371
39 feeding difficulties in infancy 32 HP:0008872
40 respiratory insufficiency due to muscle weakness 32 occasional (7.5%) HP:0002747
41 abnormality of the heart valves 59 Occasional (29-5%)
42 ophthalmoparesis 59 Occasional (29-5%)
43 proximal muscle weakness 32 HP:0003701
44 axial muscle weakness 32 HP:0003327
45 emg: decremental response of compound muscle action potential to repetitive nerve stimulation 59 Occasional (29-5%)
46 distal muscle weakness 32 HP:0002460
47 emg 32 occasional (7.5%) HP:0003458
48 abnormal heart valve morphology 32 occasional (7.5%) HP:0001654

UMLS symptoms related to Myopathy, Centronuclear, 2:


waddling gait, ophthalmoplegia, facial paresis

MGI Mouse Phenotypes related to Myopathy, Centronuclear, 2:

46
# 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 29 BIN1

Anatomical Context for Myopathy, Centronuclear, 2

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

41
Heart, Bone, 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:

75
# Symbol AA change Variation ID SNP ID
1 BIN1 p.Lys35Asn VAR_037425 rs121909273
2 BIN1 p.Asp151Asn VAR_037426 rs121909274

ClinVar genetic disease variations for Myopathy, Centronuclear, 2:

6 (show top 50) (show all 238)
# Gene Variation Type Significance SNP ID Assembly Location
1 BIN1 NM_139343.2(BIN1): c.105G> T (p.Lys35Asn) single nucleotide variant Pathogenic rs121909273 GRCh37 Chromosome 2, 127834262: 127834262
2 BIN1 NM_139343.2(BIN1): c.105G> T (p.Lys35Asn) single nucleotide variant Pathogenic rs121909273 GRCh38 Chromosome 2, 127076686: 127076686
3 BIN1 NM_139343.2(BIN1): c.451G> A (p.Asp151Asn) single nucleotide variant Pathogenic rs121909274 GRCh37 Chromosome 2, 127826568: 127826568
4 BIN1 NM_139343.2(BIN1): c.451G> A (p.Asp151Asn) single nucleotide variant Pathogenic rs121909274 GRCh38 Chromosome 2, 127068992: 127068992
5 BIN1 NM_139343.2(BIN1): c.1723A> T (p.Lys575Ter) single nucleotide variant Pathogenic rs121909275 GRCh37 Chromosome 2, 127806161: 127806161
6 BIN1 NM_139343.2(BIN1): c.1723A> T (p.Lys575Ter) single nucleotide variant Pathogenic rs121909275 GRCh38 Chromosome 2, 127048585: 127048585
7 BIN1 NM_139343.2(BIN1): c.461G> A (p.Arg154Gln) single nucleotide variant Pathogenic rs267606681 GRCh37 Chromosome 2, 127826558: 127826558
8 BIN1 NM_139343.2(BIN1): c.461G> A (p.Arg154Gln) single nucleotide variant Pathogenic rs267606681 GRCh38 Chromosome 2, 127068982: 127068982
9 TTN NM_133378.4(TTN): c.11764+1G> A single nucleotide variant Likely pathogenic rs397517481 GRCh37 Chromosome 2, 179599054: 179599054
10 TTN NM_133378.4(TTN): c.11764+1G> A single nucleotide variant Likely pathogenic rs397517481 GRCh38 Chromosome 2, 178734327: 178734327
11 BIN1 NM_139343.2(BIN1): c.1132-7T> C single nucleotide variant Benign/Likely benign rs115938552 GRCh37 Chromosome 2, 127811595: 127811595
12 BIN1 NM_139343.2(BIN1): c.1132-7T> C single nucleotide variant Benign/Likely benign rs115938552 GRCh38 Chromosome 2, 127054019: 127054019
13 BIN1 NM_139343.2(BIN1): c.1362G> T (p.Gly454=) single nucleotide variant Conflicting interpretations of pathogenicity rs61748155 GRCh37 Chromosome 2, 127809840: 127809840
14 BIN1 NM_139343.2(BIN1): c.1362G> T (p.Gly454=) single nucleotide variant Conflicting interpretations of pathogenicity rs61748155 GRCh38 Chromosome 2, 127052264: 127052264
15 BIN1 NM_139343.2(BIN1): c.1461C> T (p.Ser487=) single nucleotide variant Uncertain significance rs34647988 GRCh37 Chromosome 2, 127808730: 127808730
16 BIN1 NM_139343.2(BIN1): c.1461C> T (p.Ser487=) single nucleotide variant Uncertain significance rs34647988 GRCh38 Chromosome 2, 127051154: 127051154
17 BIN1 NM_139343.2(BIN1): c.1595C> T (p.Thr532Met) single nucleotide variant Benign/Likely benign rs112318500 GRCh37 Chromosome 2, 127808076: 127808076
18 BIN1 NM_139343.2(BIN1): c.1595C> T (p.Thr532Met) single nucleotide variant Benign/Likely benign rs112318500 GRCh38 Chromosome 2, 127050500: 127050500
19 BIN1 NM_139343.2(BIN1): c.1625A> G (p.Lys542Arg) single nucleotide variant Benign rs138047593 GRCh37 Chromosome 2, 127808046: 127808046
20 BIN1 NM_139343.2(BIN1): c.1625A> G (p.Lys542Arg) single nucleotide variant Benign rs138047593 GRCh38 Chromosome 2, 127050470: 127050470
21 BIN1 NM_139343.2(BIN1): c.1713G> A (p.Trp571Ter) single nucleotide variant Pathogenic rs587783343 GRCh37 Chromosome 2, 127806171: 127806171
22 BIN1 NM_139343.2(BIN1): c.1713G> A (p.Trp571Ter) single nucleotide variant Pathogenic rs587783343 GRCh38 Chromosome 2, 127048595: 127048595
23 BIN1 NM_139343.2(BIN1): c.30G> A (p.Thr10=) single nucleotide variant Conflicting interpretations of pathogenicity rs35535012 GRCh37 Chromosome 2, 127864490: 127864490
24 BIN1 NM_139343.2(BIN1): c.30G> A (p.Thr10=) single nucleotide variant Conflicting interpretations of pathogenicity rs35535012 GRCh38 Chromosome 2, 127106914: 127106914
25 BIN1 NM_139343.2(BIN1): c.486T> C (p.Thr162=) single nucleotide variant Benign/Likely benign rs1060743 GRCh37 Chromosome 2, 127826533: 127826533
26 BIN1 NM_139343.2(BIN1): c.486T> C (p.Thr162=) single nucleotide variant Benign/Likely benign rs1060743 GRCh38 Chromosome 2, 127068957: 127068957
27 BIN1 NM_139343.2(BIN1): c.696C> A (p.Asn232Lys) single nucleotide variant Uncertain significance rs143820618 GRCh37 Chromosome 2, 127821511: 127821511
28 BIN1 NM_139343.2(BIN1): c.696C> A (p.Asn232Lys) single nucleotide variant Uncertain significance rs143820618 GRCh38 Chromosome 2, 127063935: 127063935
29 BIN1 NM_139343.2(BIN1): c.698+10A> G single nucleotide variant Benign/Likely benign rs72481904 GRCh37 Chromosome 2, 127821499: 127821499
30 BIN1 NM_139343.2(BIN1): c.698+10A> G single nucleotide variant Benign/Likely benign rs72481904 GRCh38 Chromosome 2, 127063923: 127063923
31 BIN1 NM_139343.2(BIN1): c.714C> T (p.Tyr238=) single nucleotide variant Benign/Likely benign rs1137845 GRCh37 Chromosome 2, 127821207: 127821207
32 BIN1 NM_139343.2(BIN1): c.714C> T (p.Tyr238=) single nucleotide variant Benign/Likely benign rs1137845 GRCh38 Chromosome 2, 127063631: 127063631
33 BIN1 NM_139343.2(BIN1): c.775-4G> A single nucleotide variant Benign/Likely benign rs61748157 GRCh37 Chromosome 2, 127819777: 127819777
34 BIN1 NM_139343.2(BIN1): c.775-4G> A single nucleotide variant Benign/Likely benign rs61748157 GRCh38 Chromosome 2, 127062201: 127062201
35 BIN1 NM_139343.2(BIN1): c.858-12C> A single nucleotide variant Benign/Likely benign rs6720741 GRCh37 Chromosome 2, 127816743: 127816743
36 BIN1 NM_139343.2(BIN1): c.858-12C> A single nucleotide variant Benign/Likely benign rs6720741 GRCh38 Chromosome 2, 127059167: 127059167
37 BIN1 NM_139343.2(BIN1): c.888C> T (p.Ser296=) single nucleotide variant Conflicting interpretations of pathogenicity rs114833236 GRCh37 Chromosome 2, 127816701: 127816701
38 BIN1 NM_139343.2(BIN1): c.888C> T (p.Ser296=) single nucleotide variant Conflicting interpretations of pathogenicity rs114833236 GRCh38 Chromosome 2, 127059125: 127059125
39 BIN1 NM_139343.2(BIN1): c.894G> A (p.Ser298=) single nucleotide variant Benign/Likely benign rs2228955 GRCh37 Chromosome 2, 127816695: 127816695
40 BIN1 NM_139343.2(BIN1): c.894G> A (p.Ser298=) single nucleotide variant Benign/Likely benign rs2228955 GRCh38 Chromosome 2, 127059119: 127059119
41 BIN1 NM_139343.2(BIN1): c.957C> A (p.Ala319=) single nucleotide variant Uncertain significance rs2276579 GRCh37 Chromosome 2, 127816632: 127816632
42 BIN1 NM_139343.2(BIN1): c.957C> A (p.Ala319=) single nucleotide variant Uncertain significance rs2276579 GRCh38 Chromosome 2, 127059056: 127059056
43 BIN1 NM_139343.2(BIN1): c.957C> G (p.Ala319=) single nucleotide variant Uncertain significance rs2276579 GRCh37 Chromosome 2, 127816632: 127816632
44 BIN1 NM_139343.2(BIN1): c.957C> G (p.Ala319=) single nucleotide variant Uncertain significance rs2276579 GRCh38 Chromosome 2, 127059056: 127059056
45 BIN1 NM_139343.2(BIN1): c.957C> T (p.Ala319=) single nucleotide variant Benign/Likely benign rs2276579 GRCh37 Chromosome 2, 127816632: 127816632
46 BIN1 NM_139343.2(BIN1): c.957C> T (p.Ala319=) single nucleotide variant Benign/Likely benign rs2276579 GRCh38 Chromosome 2, 127059056: 127059056
47 TTN NM_133378.4(TTN): c.68689_68692delAACA (p.Asn22897Terfs) deletion Likely pathogenic rs727504483 GRCh38 Chromosome 2, 178569736: 178569739
48 TTN NM_133378.4(TTN): c.68689_68692delAACA (p.Asn22897Terfs) deletion Likely pathogenic rs727504483 GRCh37 Chromosome 2, 179434463: 179434466
49 TTN NM_133378.4(TTN): c.98315delG (p.Gly32772Valfs) deletion no interpretation for the single variant rs727504482 GRCh38 Chromosome 2, 178530596: 178530596
50 TTN NM_133378.4(TTN): c.98315delG (p.Gly32772Valfs) deletion no interpretation for the single variant rs727504482 GRCh37 Chromosome 2, 179395323: 179395323

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

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17 ExPASy
19 FMA
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74 UMLS via Orphanet
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