MCID: INT274
MIFTS: 36

Intermediate Congenital Nemaline Myopathy

Categories: Bone diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Intermediate Congenital Nemaline Myopathy

MalaCards integrated aliases for Intermediate Congenital Nemaline Myopathy:

Name: Intermediate Congenital Nemaline Myopathy 20
Intermediate Nemaline Myopathy 20 58
Intermediate Congenital Nm 20

Characteristics:

Orphanet epidemiological data:

58
intermediate nemaline myopathy
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Neonatal; Age of death: any age;

Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Intermediate Congenital Nemaline Myopathy

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 171433 Definition Intermediate nemaline myopathy is a type of nemaline myopathy (NM; see this term) that shows features of typical NM (see this term) in neonates with a more severe progression. Epidemiology The annual incidence of NM has been estimated at 1/50,000 live births, and intermediate NM might represent 20% of all cases. Clinical description Neonates with intermediate NM present with spontaneous anti-gravity movements and active respiratory muscles, but with a progressive generalized weakness which prevents achievement of gross motor milestones or leads to loss of ambulation and/or independent respiration by age 11 years. Children often develop joint contractures. Etiology The ACTA1 (1q42.13), NEB (2q22) or TPM3 (1q21.2) genes have been associated with intermediate NM and the transmission pattern of the disease is autosomal recessive or dominant.

MalaCards based summary : Intermediate Congenital Nemaline Myopathy, also known as intermediate nemaline myopathy, is related to foot drop and cap myopathy. An important gene associated with Intermediate Congenital Nemaline Myopathy is TPM3 (Tropomyosin 3), and among its related pathways/superpathways is Striated Muscle Contraction. Affiliated tissues include skeletal muscle, and related phenotypes are nemaline bodies and severe muscular hypotonia

Related Diseases for Intermediate Congenital Nemaline Myopathy

Diseases in the Nemaline Myopathy family:

Nemaline Myopathy 3 Nemaline Myopathy 2
Nemaline Myopathy 5 Nemaline Myopathy 6
Nemaline Myopathy 1 Nemaline Myopathy 4
Nemaline Myopathy 7 Nemaline Myopathy 8
Nemaline Myopathy 9 Nemaline Myopathy 10
Nemaline Myopathy 11, Autosomal Recessive Adult-Onset Nemaline Myopathy
Intermediate Congenital Nemaline Myopathy Severe Congenital Nemaline Myopathy
Congenital Nemaline Myopathy

Diseases related to Intermediate Congenital Nemaline Myopathy via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 21)
# Related Disease Score Top Affiliating Genes
1 foot drop 9.9 NEB ACTA1
2 cap myopathy 9.9 TPM3 ACTA1
3 hyaline body myopathy 9.9 NEB ACTA1
4 myopathy, congenital, with fiber-type disproportion 9.8 TPM3 ACTA1
5 centronuclear myopathy 9.8 NEB ACTA1
6 cardiomyopathy, familial hypertrophic, 1 9.7 TPM3 NEB
7 myofibrillar myopathy 9.7 NEB ACTA1
8 nemaline myopathy 2 9.7 NEB KLHL41
9 multiple pterygium syndrome, escobar variant 9.7 NEB KLHL41
10 camptodactyly-arthropathy-coxa vara-pericarditis syndrome 9.6 TPM3 NEB ACTA1
11 batten-turner congenital myopathy 9.6 TPM3 NEB ACTA1
12 distal arthrogryposis 9.6 TPM3 NEB ACTA1
13 neuromuscular disease 9.6 NEB ACTA1
14 typical congenital nemaline myopathy 9.5 NEB KLHL41 ACTA1
15 nemaline myopathy 3 9.5 NEB KLHL41 ACTA1
16 severe congenital nemaline myopathy 9.5 NEB KLHL41 ACTA1
17 nemaline myopathy 9.2 TPM3 NEB KLHL41 ACTA1
18 myopathy 9.2 TPM3 NEB KLHL41 ACTA1
19 childhood-onset nemaline myopathy 9.2 TPM3 NEB KLHL41 ACTA1
20 congenital structural myopathy 9.2 TPM3 NEB KLHL41 ACTA1
21 congenital fiber-type disproportion 9.2 TPM3 NEB KLHL41 ACTA1

Graphical network of the top 20 diseases related to Intermediate Congenital Nemaline Myopathy:



Diseases related to Intermediate Congenital Nemaline Myopathy

Symptoms & Phenotypes for Intermediate Congenital Nemaline Myopathy

Human phenotypes related to Intermediate Congenital Nemaline Myopathy:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nemaline bodies 58 31 hallmark (90%) Very frequent (99-80%) HP:0003798
2 severe muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0006829
3 generalized muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003324
4 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
5 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
6 emg: myopathic abnormalities 58 31 frequent (33%) Frequent (79-30%) HP:0003458
7 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
8 type 1 muscle fiber predominance 58 31 frequent (33%) Frequent (79-30%) HP:0003803
9 polyhydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001561
10 decreased fetal movement 58 31 frequent (33%) Frequent (79-30%) HP:0001558
11 hyporeflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001265
12 respiratory failure 58 31 frequent (33%) Frequent (79-30%) HP:0002878
13 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
14 hypokinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002375
15 myopathic facies 58 31 frequent (33%) Frequent (79-30%) HP:0002058
16 multiple prenatal fractures 58 31 frequent (33%) Frequent (79-30%) HP:0005855
17 abnormal thorax morphology 31 frequent (33%) HP:0000765
18 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
19 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
20 high, narrow palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002705
21 ophthalmoplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000602
22 long philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000343
23 areflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001284
24 premature birth 58 31 occasional (7.5%) Occasional (29-5%) HP:0001622
25 facial diplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001349
26 arthrogryposis multiplex congenita 58 31 very rare (1%) Very rare (<4-1%) HP:0002804
27 facial palsy 58 Frequent (79-30%)
28 flexion contracture 58 Frequent (79-30%)
29 abnormality of the thorax 58 Frequent (79-30%)
30 cardiomyopathy 58 Excluded (0%)

MGI Mouse Phenotypes related to Intermediate Congenital Nemaline Myopathy:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 8.92 ACTA1 KLHL41 NEB TPM3

Drugs & Therapeutics for Intermediate Congenital Nemaline Myopathy

Search Clinical Trials , NIH Clinical Center for Intermediate Congenital Nemaline Myopathy

Genetic Tests for Intermediate Congenital Nemaline Myopathy

Anatomical Context for Intermediate Congenital Nemaline Myopathy

MalaCards organs/tissues related to Intermediate Congenital Nemaline Myopathy:

40
Skeletal Muscle

Publications for Intermediate Congenital Nemaline Myopathy

Articles related to Intermediate Congenital Nemaline Myopathy:

(show all 26)
# Title Authors PMID Year
1
Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders. 6
27363342 2017
2
Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases. 6
27854218 2016
3
TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype. 6
26418456 2015
4
Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres. 6
26307083 2015
5
Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies. 6
24692096 2014
6
Congenital fiber type disproportion myopathy caused by LMNA mutations. 6
24642510 2014
7
Frequency and phenotype of patients carrying TPM2 and TPM3 gene mutations in a cohort of 94 patients with congenital myopathy. 6
24507666 2014
8
Mutations in repeating structural motifs of tropomyosin cause gain of function in skeletal muscle myopathy patients. 6
23886664 2013
9
Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene. 6
24095155 2013
10
Functional effects of congenital myopathy-related mutations in gamma-tropomyosin gene. 6
22749829 2012
11
Congenital myopathy-causing tropomyosin mutations induce thin filament dysfunction via distinct physiological mechanisms. 6
22798622 2012
12
Changes in cross-bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy. 6
21357678 2011
13
Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3. 6
20554445 2010
14
Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion. 6
19953533 2010
15
A TPM3 mutation causing cap myopathy. 6
19553118 2009
16
TPM3 mutation in one of the original cases of cap disease. 6
19487656 2009
17
Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin. 6
18382475 2008
18
Mutations in TPM3 are a common cause of congenital fiber type disproportion. 6
18300303 2008
19
A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: a clinical and pathological study. 6
17376686 2007
20
An alphaTropomyosin mutation alters dimer preference in nemaline myopathy. 6
15562513 2005
21
De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy. 6
12467750 2002
22
Mutations of the slow muscle alpha-tropomyosin gene, TPM3, are a rare cause of nemaline myopathy. 6
12196661 2002
23
Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy. 6
10619715 1999
24
A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of striated muscle force production. 6
10587521 1999
25
A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy. 6
7704029 1995
26
[Congenital myopathy with selective hypotrophy of type I fibers]. 6
1221488 1975

Variations for Intermediate Congenital Nemaline Myopathy

ClinVar genetic disease variations for Intermediate Congenital Nemaline Myopathy:

6 (show top 50) (show all 171)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TPM3 NM_152263.4(TPM3):c.26T>G (p.Met9Arg) SNV Pathogenic 12446 rs80358247 GRCh37: 1:154164469-154164469
GRCh38: 1:154191993-154191993
2 TPM3 NM_152263.4(TPM3):c.857A>C (p.Ter286Ser) SNV Pathogenic 12447 rs199474720 GRCh37: 1:154140414-154140414
GRCh38: 1:154167938-154167938
3 TPM3 NM_152263.4(TPM3):c.855-1G>A SNV Pathogenic 12448 rs113605263 GRCh37: 1:154140417-154140417
GRCh38: 1:154167941-154167941
4 TPM3 NM_152263.4(TPM3):c.503G>A (p.Arg168His) SNV Pathogenic 12450 rs121964852 GRCh37: 1:154145447-154145447
GRCh38: 1:154172971-154172971
5 TPM3 NM_152263.4(TPM3):c.855del (p.Ter286AsnextTer?) Deletion Pathogenic 12451 rs199474719 GRCh37: 1:154140416-154140416
GRCh38: 1:154167940-154167940
6 TPM3 NM_152263.4(TPM3):c.670_672GAA[1] (p.Glu225del) Microsatellite Pathogenic 235143 rs876661406 GRCh37: 1:154143155-154143157
GRCh38: 1:154170679-154170681
7 TPM3 NM_152263.4(TPM3):c.654_656AGA[1] (p.Glu219del) Microsatellite Pathogenic 235144 rs876661407 GRCh37: 1:154143171-154143173
GRCh38: 1:154170695-154170697
8 TPM3 NM_152263.4(TPM3):c.758C>A (p.Thr253Lys) SNV Pathogenic 462142 rs1553248515 GRCh37: 1:154142893-154142893
GRCh38: 1:154170417-154170417
9 TPM3 NM_152263.4(TPM3):c.503G>A (p.Arg168His) SNV Pathogenic 12450 rs121964852 GRCh37: 1:154145447-154145447
GRCh38: 1:154172971-154172971
10 TPM3 NM_152263.4(TPM3):c.502C>T (p.Arg168Cys) SNV Pathogenic 12454 rs121964854 GRCh37: 1:154145448-154145448
GRCh38: 1:154172972-154172972
11 TPM3 NM_152263.4(TPM3):c.94C>T (p.Gln32Ter) SNV Pathogenic 12449 rs80358248 GRCh37: 1:154164401-154164401
GRCh38: 1:154191925-154191925
12 TPM3 NM_152263.4(TPM3):c.377+863_775+422del Deletion Likely pathogenic 974884 GRCh37: 1:154142454-154147728
GRCh38: 1:154169978-154175252
13 TPM3 NM_152263.4(TPM3):c.502C>G (p.Arg168Gly) SNV Likely pathogenic 12453 rs121964854 GRCh37: 1:154145448-154145448
GRCh38: 1:154172972-154172972
14 TPM3 NM_152263.4(TPM3):c.298C>G (p.Leu100Val) SNV Likely pathogenic 531180 rs121964853 GRCh37: 1:154148670-154148670
GRCh38: 1:154176194-154176194
15 TPM3 NM_152263.4(TPM3):c.43G>C (p.Asp15His) SNV Likely pathogenic 437430 rs1553251644 GRCh37: 1:154164452-154164452
GRCh38: 1:154191976-154191976
16 TPM3 NM_152263.4(TPM3):c.271C>T (p.Arg91Cys) SNV Likely pathogenic 652762 rs1571418855 GRCh37: 1:154148697-154148697
GRCh38: 1:154176221-154176221
17 TPM3 NM_152263.4(TPM3):c.43G>A (p.Asp15Asn) SNV Likely pathogenic 801549 rs1553251644 GRCh37: 1:154164452-154164452
GRCh38: 1:154191976-154191976
18 TPM3 NM_152263.4(TPM3):c.7G>C (p.Glu3Gln) SNV Likely pathogenic 801550 rs1571456678 GRCh37: 1:154164488-154164488
GRCh38: 1:154192012-154192012
19 TPM3 NM_152263.4(TPM3):c.494A>G (p.Glu165Gly) SNV Uncertain significance 842726 GRCh37: 1:154145561-154145561
GRCh38: 1:154173085-154173085
20 TPM3 NM_152263.4(TPM3):c.466G>A (p.Ala156Thr) SNV Uncertain significance 140498 rs199474714 GRCh37: 1:154145589-154145589
GRCh38: 1:154173113-154173113
21 TPM3 NM_152263.4(TPM3):c.*5795C>T SNV Uncertain significance 873749 GRCh37: 1:154134618-154134618
GRCh38: 1:154162142-154162142
22 TPM3 NM_152263.4(TPM3):c.*5266T>G SNV Uncertain significance 873798 GRCh37: 1:154135147-154135147
GRCh38: 1:154162671-154162671
23 TPM3 NM_152263.4(TPM3):c.*5239C>T SNV Uncertain significance 873799 GRCh37: 1:154135174-154135174
GRCh38: 1:154162698-154162698
24 TPM3 NM_152263.4(TPM3):c.*4806A>C SNV Uncertain significance 873855 GRCh37: 1:154135607-154135607
GRCh38: 1:154163131-154163131
25 TPM3 NM_152263.4(TPM3):c.*4287A>G SNV Uncertain significance 873909 GRCh37: 1:154136126-154136126
GRCh38: 1:154163650-154163650
26 TPM3 NM_152263.4(TPM3):c.*3481C>T SNV Uncertain significance 873972 GRCh37: 1:154136932-154136932
GRCh38: 1:154164456-154164456
27 TPM3 NM_152263.4(TPM3):c.*3298A>G SNV Uncertain significance 873973 GRCh37: 1:154137115-154137115
GRCh38: 1:154164639-154164639
28 TPM3 NM_152263.4(TPM3):c.*2544C>T SNV Uncertain significance 874032 GRCh37: 1:154137869-154137869
GRCh38: 1:154165393-154165393
29 TPM3 NM_152263.4(TPM3):c.*2423G>A SNV Uncertain significance 874033 GRCh37: 1:154137990-154137990
GRCh38: 1:154165514-154165514
30 TPM3 NM_152263.4(TPM3):c.*2101T>C SNV Uncertain significance 874087 GRCh37: 1:154138312-154138312
GRCh38: 1:154165836-154165836
31 TPM3 NM_152263.4(TPM3):c.*2053G>C SNV Uncertain significance 874088 GRCh37: 1:154138360-154138360
GRCh38: 1:154165884-154165884
32 TPM3 NM_152263.4(TPM3):c.*1077A>C SNV Uncertain significance 874145 GRCh37: 1:154139336-154139336
GRCh38: 1:154166860-154166860
33 TPM3 NM_152263.4(TPM3):c.776-14C>T SNV Uncertain significance 874255 GRCh37: 1:154141873-154141873
GRCh38: 1:154169397-154169397
34 TPM3 NM_152263.4(TPM3):c.*5715C>T SNV Uncertain significance 873750 GRCh37: 1:154134698-154134698
GRCh38: 1:154162222-154162222
35 TPM3 NM_152263.4(TPM3):c.*5658G>A SNV Uncertain significance 874703 GRCh37: 1:154134755-154134755
GRCh38: 1:154162279-154162279
36 TPM3 NM_152263.4(TPM3):c.*5640C>T SNV Uncertain significance 874704 GRCh37: 1:154134773-154134773
GRCh38: 1:154162297-154162297
37 TPM3 NM_152263.4(TPM3):c.*5204C>T SNV Uncertain significance 873800 GRCh37: 1:154135209-154135209
GRCh38: 1:154162733-154162733
38 TPM3 NM_152263.4(TPM3):c.665A>T (p.Tyr222Phe) SNV Uncertain significance 652272 rs142817656 GRCh37: 1:154143165-154143165
GRCh38: 1:154170689-154170689
39 TPM3 NM_152263.4(TPM3):c.262T>C (p.Ser88Pro) SNV Uncertain significance 561134 rs1558052214 GRCh37: 1:154148706-154148706
GRCh38: 1:154176230-154176230
40 TPM3 NM_152263.4(TPM3):c.855-1G>A SNV Uncertain significance 12448 rs113605263 GRCh37: 1:154140417-154140417
GRCh38: 1:154167941-154167941
41 TPM3 NM_152263.4(TPM3):c.857A>C (p.Ter286Ser) SNV Uncertain significance 12447 rs199474720 GRCh37: 1:154140414-154140414
GRCh38: 1:154167938-154167938
42 TPM3 NM_152263.4(TPM3):c.329C>T (p.Ala110Val) SNV Uncertain significance 623645 rs1558052023 GRCh37: 1:154148639-154148639
GRCh38: 1:154176163-154176163
43 TPM3 NM_152263.4(TPM3):c.761T>C (p.Ile254Thr) SNV Uncertain significance 647207 rs761036509 GRCh37: 1:154142890-154142890
GRCh38: 1:154170414-154170414
44 TPM3 NM_152263.4(TPM3):c.*5583C>T SNV Uncertain significance 292629 rs886045286 GRCh37: 1:154134830-154134830
GRCh38: 1:154162354-154162354
45 TPM3 NM_152263.4(TPM3):c.*61C>A SNV Uncertain significance 292692 rs886045317 GRCh37: 1:154140352-154140352
GRCh38: 1:154167876-154167876
46 TPM3 NM_152263.4(TPM3):c.788C>G (p.Ala263Gly) SNV Uncertain significance 462143 rs1455676920 GRCh37: 1:154141847-154141847
GRCh38: 1:154169371-154169371
47 TPM3 NM_152263.4(TPM3):c.65G>A (p.Arg22Gln) SNV Uncertain significance 462141 rs1553251640 GRCh37: 1:154164430-154164430
GRCh38: 1:154191954-154191954
48 TPM3 NM_152263.4(TPM3):c.760A>G (p.Ile254Val) SNV Uncertain significance 531179 rs1553248513 GRCh37: 1:154142891-154142891
GRCh38: 1:154170415-154170415
49 TPM3 NM_152263.4(TPM3):c.*283G>C SNV Uncertain significance 292691 rs886045316 GRCh37: 1:154140130-154140130
GRCh38: 1:154167654-154167654
50 TPM3 NM_152263.4(TPM3):c.*5755A>G SNV Uncertain significance 292626 rs777522493 GRCh37: 1:154134658-154134658
GRCh38: 1:154162182-154162182

Expression for Intermediate Congenital Nemaline Myopathy

Search GEO for disease gene expression data for Intermediate Congenital Nemaline Myopathy.

Pathways for Intermediate Congenital Nemaline Myopathy

Pathways related to Intermediate Congenital Nemaline Myopathy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.66 TPM3 NEB ACTA1

GO Terms for Intermediate Congenital Nemaline Myopathy

Cellular components related to Intermediate Congenital Nemaline Myopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 actin filament GO:0005884 9.32 TPM3 ACTA1
2 stress fiber GO:0001725 9.26 TPM3 ACTA1
3 cytoskeleton GO:0005856 9.26 TPM3 NEB KLHL41 ACTA1
4 sarcomere GO:0030017 9.16 NEB ACTA1
5 actin cytoskeleton GO:0015629 8.8 TPM3 NEB ACTA1

Biological processes related to Intermediate Congenital Nemaline Myopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 muscle contraction GO:0006936 9.16 TPM3 ACTA1
2 skeletal muscle fiber development GO:0048741 8.96 KLHL41 ACTA1
3 muscle filament sliding GO:0030049 8.8 TPM3 NEB ACTA1

Molecular functions related to Intermediate Congenital Nemaline Myopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 actin filament binding GO:0051015 8.62 TPM3 NEB

Sources for Intermediate Congenital Nemaline Myopathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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