MCID: MYP131
MIFTS: 35

Myopathy, Centronuclear, 2

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Muscle 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 ophthalmoplegia, waddling gait and facial paresis. An important gene associated with Myopathy, Centronuclear, 2 is BIN1 (Bridging Integrator 1). Affiliated tissues include skeletal muscle, and related phenotypes are high palate and ptosis

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:

# Related Disease Score Top Affiliating Genes
1 centronuclear myopathy 29.9 BIN1 SPEG TTN
2 myopathy 28.1 BIN1 SPEG TTN

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:

32 (show all 28)
# Description HPO Frequency HPO Source Accession
1 high palate 32 occasional (7.5%) HP:0000218
2 ptosis 32 HP:0000508
3 dysarthria 32 HP:0001260
4 dysphonia 32 HP:0001618
5 scoliosis 32 HP:0002650
6 kyphosis 32 HP:0002808
7 hyperlordosis 32 HP:0003307
8 facial palsy 32 HP:0010628
9 neonatal hypotonia 32 HP:0001319
10 flexion contracture 32 HP:0001371
11 feeding difficulties in infancy 32 HP:0008872
12 intellectual disability, mild 32 occasional (7.5%) HP:0001256
13 respiratory insufficiency due to muscle weakness 32 occasional (7.5%) HP:0002747
14 pes cavus 32 occasional (7.5%) HP:0001761
15 scapular winging 32 occasional (7.5%) HP:0003691
16 long face 32 occasional (7.5%) HP:0000276
17 talipes equinovarus 32 occasional (7.5%) HP:0001762
18 areflexia 32 HP:0001284
19 motor delay 32 HP:0001270
20 ophthalmoplegia 32 HP:0000602
21 distal muscle weakness 32 HP:0002460
22 proximal muscle weakness 32 HP:0003701
23 generalized amyotrophy 32 HP:0003700
24 waddling gait 32 HP:0002515
25 axial muscle weakness 32 HP:0003327
26 centrally nucleated skeletal muscle fibers 32 HP:0003687
27 gowers sign 32 HP:0003391
28 emg 32 HP:0003458

UMLS symptoms related to Myopathy, Centronuclear, 2:


ophthalmoplegia, waddling gait, facial paresis

GenomeRNAi Phenotypes related to Myopathy, Centronuclear, 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased human cytomegalovirus (HCMV) strain AD169 replication GR00248-A 8.62 SPEG TTN

MGI Mouse Phenotypes related to Myopathy, Centronuclear, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.13 BIN1 SPEG TTN
2 muscle MP:0005369 8.8 BIN1 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
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 210)
# 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 no interpretation for the single variant rs727504483 GRCh38 Chromosome 2, 178569736: 178569739
48 TTN NM_133378.4(TTN): c.68689_68692delAACA (p.Asn22897Terfs) deletion no interpretation for the single variant 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 Z disc GO:0030018 8.96 BIN1 TTN
2 I band GO:0031674 8.62 BIN1 TTN

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

# Name GO ID Score Top Affiliating Genes
1 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 protein kinase activity GO:0004672 9.26 SPEG TTN
2 protein serine/threonine kinase activity GO:0004674 9.16 SPEG TTN
3 actin filament binding GO:0051015 8.96 BIN1 TTN
4 protease binding GO:0002020 8.62 BIN1 TTN

Sources for Myopathy, Centronuclear, 2

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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44 MeSH
45 MESH via Orphanet
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62 PubMed
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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
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74 UMLS via Orphanet
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