MCID: TYP026
MIFTS: 35

Typical Congenital Nemaline Myopathy

Categories: Neuronal diseases, Rare diseases

Aliases & Classifications for Typical Congenital Nemaline Myopathy

MalaCards integrated aliases for Typical Congenital Nemaline Myopathy:

Name: Typical Congenital Nemaline Myopathy 20
Typical Nemaline Myopathy 20 58

Characteristics:

Orphanet epidemiological data:

58
typical nemaline myopathy
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Neonatal; Age of death: normal life expectancy;

Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Typical 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: 171436 Definition Typical nemaline myopathy is a moderate neonatal form of nemaline myopathy (NM; see this term) characterized by facial and skeletal muscle weakness and mild respiratory involvement. Epidemiology The annual incidence of NM has been estimated at 1/50,000 live births and the typical form to represent about 50% of all cases. Clinical description Disease onset is in the neonatal period. Patients have a long face, a high-arched palate and a tented upper lip. Skeletal anomalies may include kyphoscoliosis, pectus carinatum and pes cavus. In the first year of life, hypotonia and facial weakness are present and often contribute to failure to thrive and delayed motor development. Anti-gravity movements are present and respiratory muscle involvement is frequent. Nocturnal hypoxia and hypercarbia and lower respiratory tract infections are common manifestations. Joint hypermobility can be observed. In a minority of children weakness is more distal. Progression is very slow or absent and most patients are able to live an independent active life. Etiology Typical NM is caused by mutations of the ACTA1 (1q42.13), NEB (2q22) or TPM2 (9p13) genes, and disease transmission can be autosomal recessive or dominant.

MalaCards based summary : Typical Congenital Nemaline Myopathy, also known as typical nemaline myopathy, is related to nemaline myopathy 3 and nemaline myopathy. An important gene associated with Typical Congenital Nemaline Myopathy is CFL2 (Cofilin 2), and among its related pathways/superpathways are Apoptosis and survival Caspase cascade and EPHA forward signaling. Affiliated tissues include skeletal muscle, and related phenotypes are high palate and respiratory insufficiency

Related Diseases for Typical Congenital Nemaline Myopathy

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



Diseases related to Typical Congenital Nemaline Myopathy

Symptoms & Phenotypes for Typical Congenital Nemaline Myopathy

Human phenotypes related to Typical Congenital Nemaline Myopathy:

58 31 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 high palate 58 31 frequent (33%) Frequent (79-30%) HP:0000218
2 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
3 neonatal hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001319
4 type 1 muscle fiber predominance 58 31 frequent (33%) Frequent (79-30%) HP:0003803
5 hyporeflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001265
6 increased variability in muscle fiber diameter 58 31 frequent (33%) Frequent (79-30%) HP:0003557
7 foot dorsiflexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009027
8 axial muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003327
9 neck flexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003722
10 limb-girdle muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003325
11 fatigable weakness of distal limb muscles 58 31 frequent (33%) Frequent (79-30%) HP:0030198
12 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
13 ptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000508
14 short neck 58 31 occasional (7.5%) Occasional (29-5%) HP:0000470
15 hyperlordosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0003307
16 myopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003198
17 genu valgum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002857
18 micrognathia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000347
19 pectus excavatum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000767
20 elevated serum creatine kinase 58 31 occasional (7.5%) Occasional (29-5%) HP:0003236
21 waddling gait 58 31 occasional (7.5%) Occasional (29-5%) HP:0002515
22 spinal rigidity 58 31 occasional (7.5%) Occasional (29-5%) HP:0003306
23 nemaline bodies 58 31 occasional (7.5%) Occasional (29-5%) HP:0003798
24 narrow face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000275
25 polyhydramnios 58 31 occasional (7.5%) Occasional (29-5%) HP:0001561
26 hip dislocation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002827
27 narrow chest 58 31 occasional (7.5%) Occasional (29-5%) HP:0000774
28 genu varum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002970
29 arthrogryposis multiplex congenita 58 31 occasional (7.5%) Occasional (29-5%) HP:0002804
30 feeding difficulties 58 31 occasional (7.5%) Occasional (29-5%) HP:0011968
31 hypokinesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002375
32 fatigable weakness of respiratory muscles 58 31 occasional (7.5%) Occasional (29-5%) HP:0030196
33 fatiguable weakness of proximal limb muscles 58 31 occasional (7.5%) Occasional (29-5%) HP:0030200
34 facial diplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001349
35 nocturnal hypoventilation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002877
36 kyphosis 58 31 very rare (1%) Very rare (<4-1%) HP:0002808
37 gait disturbance 58 Frequent (79-30%)
38 facial palsy 58 Frequent (79-30%)
39 flexion contracture 58 Occasional (29-5%)

MGI Mouse Phenotypes related to Typical Congenital Nemaline Myopathy:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.02 ACTA1 CFL2 KLHL41 LMOD3 NEB

Drugs & Therapeutics for Typical Congenital Nemaline Myopathy

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

Genetic Tests for Typical Congenital Nemaline Myopathy

Anatomical Context for Typical Congenital Nemaline Myopathy

MalaCards organs/tissues related to Typical Congenital Nemaline Myopathy:

40
Skeletal Muscle

Publications for Typical Congenital Nemaline Myopathy

Articles related to Typical Congenital Nemaline Myopathy:

# Title Authors PMID Year
1
Congenital myopathy caused by a novel missense mutation in the CFL2 gene. 6
22560515 2012
2
Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. 6
17160903 2007
3
Triggering typical nemaline myopathy with compound heterozygous nebulin mutations reveals myofilament structural changes as pathomechanism. 61
32483185 2020
4
Sudden cardiac arrest in a child with nemaline myopathy. 61
25888334 2015
5
The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence. 61
19232495 2009
6
Plasma and muscle carnitine levels in haemodialysis patients with morphological-ultrastructural examination of muscle samples. 61
6646296 1983

Variations for Typical Congenital Nemaline Myopathy

ClinVar genetic disease variations for Typical Congenital Nemaline Myopathy:

6 (show top 50) (show all 65)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CFL2 NM_138638.5(CFL2):c.103G>A (p.Ala35Thr) SNV Pathogenic 8160 rs80358250 GRCh37: 14:35182668-35182668
GRCh38: 14:34713462-34713462
2 CFL2 NC_000014.9:g.(?_34712845)_(34714560_?)del Deletion Pathogenic 583485 GRCh37: 14:35182051-35183766
GRCh38: 14:34712845-34714560
3 CFL2 NC_000014.9:g.(?_34710372)_(34713686_?)del Deletion Pathogenic 657372 GRCh37: 14:35179578-35182892
GRCh38: 14:34710372-34713686
4 CFL2 NM_138638.5(CFL2):c.338del (p.Ser113fs) Deletion Pathogenic 800930 rs1594784544 GRCh37: 14:35182316-35182316
GRCh38: 14:34713110-34713110
5 CFL2 NC_000014.9:g.(?_34710372)_(34713686_?)dup Duplication Uncertain significance 833241 GRCh37: 14:35179578-35182892
GRCh38:
6 CFL2 NM_138638.5(CFL2):c.*1030C>G SNV Uncertain significance 881372 GRCh37: 14:35181041-35181041
GRCh38: 14:34711835-34711835
7 CFL2 NM_138638.5(CFL2):c.*738A>G SNV Uncertain significance 881374 GRCh37: 14:35181333-35181333
GRCh38: 14:34712127-34712127
8 CFL2 NM_138638.5(CFL2):c.*720A>T SNV Uncertain significance 881375 GRCh37: 14:35181351-35181351
GRCh38: 14:34712145-34712145
9 CFL2 NM_138638.5(CFL2):c.54G>A (p.Met18Ile) SNV Uncertain significance 661578 rs1594784960 GRCh37: 14:35182717-35182717
GRCh38: 14:34713511-34713511
10 CFL2 NM_138638.5(CFL2):c.471_473AGT[1] (p.Val159del) Microsatellite Uncertain significance 662117 rs1594784265 GRCh37: 14:35182096-35182098
GRCh38: 14:34712890-34712892
11 CFL2 NC_000014.8:g.(?_35182051)_(35183766_?)dup Duplication Uncertain significance 583711 GRCh37: 14:35182051-35183766
GRCh38: 14:34712845-34714560
12 CFL2 NM_138638.5(CFL2):c.328C>T (p.Pro110Ser) SNV Uncertain significance 650607 rs1594784547 GRCh37: 14:35182326-35182326
GRCh38: 14:34713120-34713120
13 CFL2 NM_138638.5(CFL2):c.457T>G (p.Leu153Val) SNV Uncertain significance 128713 rs587780312 GRCh37: 14:35182115-35182115
GRCh38: 14:34712909-34712909
14 CFL2 NM_138638.5(CFL2):c.388G>C (p.Gly130Arg) SNV Uncertain significance 583009 rs1566525113 GRCh37: 14:35182266-35182266
GRCh38: 14:34713060-34713060
15 CFL2 NM_138638.5(CFL2):c.19G>A (p.Val7Met) SNV Uncertain significance 60554 rs397515451 GRCh37: 14:35182752-35182752
GRCh38: 14:34713546-34713546
16 CFL2 NM_138638.5(CFL2):c.*1070G>A SNV Uncertain significance 313085 rs767101584 GRCh37: 14:35181001-35181001
GRCh38: 14:34711795-34711795
17 CFL2 NM_138638.5(CFL2):c.*718A>G SNV Uncertain significance 313089 rs886050474 GRCh37: 14:35181353-35181353
GRCh38: 14:34712147-34712147
18 CFL2 NM_138638.5(CFL2):c.*1036G>A SNV Uncertain significance 313086 rs150492527 GRCh37: 14:35181035-35181035
GRCh38: 14:34711829-34711829
19 CFL2 NM_138638.5(CFL2):c.*2340T>G SNV Uncertain significance 313075 rs886050473 GRCh37: 14:35179731-35179731
GRCh38: 14:34710525-34710525
20 CFL2 NM_138638.5(CFL2):c.4-198A>G SNV Uncertain significance 313098 rs143465827 GRCh37: 14:35182965-35182965
GRCh38: 14:34713759-34713759
21 CFL2 NM_138638.5(CFL2):c.*362G>A SNV Uncertain significance 313092 rs553554454 GRCh37: 14:35181709-35181709
GRCh38: 14:34712503-34712503
22 CFL2 NM_138638.5(CFL2):c.*1885C>T SNV Uncertain significance 313081 rs775859581 GRCh37: 14:35180186-35180186
GRCh38: 14:34710980-34710980
23 CFL2 NM_138638.5(CFL2):c.*541A>G SNV Uncertain significance 313090 rs144345993 GRCh37: 14:35181530-35181530
GRCh38: 14:34712324-34712324
24 CFL2 NM_138638.5(CFL2):c.*995T>C SNV Uncertain significance 313087 rs749572493 GRCh37: 14:35181076-35181076
GRCh38: 14:34711870-34711870
25 CFL2 NM_138638.5(CFL2):c.*293G>A SNV Uncertain significance 313093 rs774843860 GRCh37: 14:35181778-35181778
GRCh38: 14:34712572-34712572
26 CFL2 NM_138638.5(CFL2):c.4-172C>T SNV Uncertain significance 313097 rs190226324 GRCh37: 14:35182939-35182939
GRCh38: 14:34713733-34713733
27 CFL2 NM_138638.5(CFL2):c.*2284C>T SNV Uncertain significance 313076 rs372609152 GRCh37: 14:35179787-35179787
GRCh38: 14:34710581-34710581
28 CFL2 NM_138638.5(CFL2):c.76C>G (p.Gln26Glu) SNV Uncertain significance 882972 GRCh37: 14:35182695-35182695
GRCh38: 14:34713489-34713489
29 CFL2 NM_138638.5(CFL2):c.*1810T>A SNV Uncertain significance 883712 GRCh37: 14:35180261-35180261
GRCh38: 14:34711055-34711055
30 CFL2 NM_138638.5(CFL2):c.*1759A>G SNV Uncertain significance 883713 GRCh37: 14:35180312-35180312
GRCh38: 14:34711106-34711106
31 CFL2 NM_138638.5(CFL2):c.*1620T>C SNV Uncertain significance 883714 GRCh37: 14:35180451-35180451
GRCh38: 14:34711245-34711245
32 CFL2 NM_138638.5(CFL2):c.*1507C>T SNV Uncertain significance 883715 GRCh37: 14:35180564-35180564
GRCh38: 14:34711358-34711358
33 CFL2 NM_138638.5(CFL2):c.24TGA[1] (p.Asp9del) Microsatellite Uncertain significance 944237 GRCh37: 14:35182742-35182744
GRCh38: 14:34713536-34713538
34 CFL2 NM_138638.5(CFL2):c.242G>A (p.Arg81Gln) SNV Uncertain significance 971564 GRCh37: 14:35182529-35182529
GRCh38: 14:34713323-34713323
35 CFL2 NM_138638.5(CFL2):c.475G>T (p.Val159Phe) SNV Uncertain significance 1001719 GRCh37: 14:35182097-35182097
GRCh38: 14:34712891-34712891
36 CFL2 NM_138638.5(CFL2):c.355A>T (p.Ser119Cys) SNV Uncertain significance 1006980 GRCh37: 14:35182299-35182299
GRCh38: 14:34713093-34713093
37 CFL2 NM_138638.5(CFL2):c.151G>A (p.Glu51Lys) SNV Uncertain significance 954174 GRCh37: 14:35182620-35182620
GRCh38: 14:34713414-34713414
38 CFL2 NM_138638.5(CFL2):c.349del (p.Tyr117fs) Deletion Uncertain significance 1017814 GRCh37: 14:35182305-35182305
GRCh38: 14:34713099-34713099
39 CFL2 NM_138638.5(CFL2):c.17C>G (p.Thr6Arg) SNV Uncertain significance 840465 GRCh37: 14:35182754-35182754
GRCh38: 14:34713548-34713548
40 CFL2 NM_138638.5(CFL2):c.312-3T>G SNV Uncertain significance 953422 GRCh37: 14:35182345-35182345
GRCh38: 14:34713139-34713139
41 CFL2 NM_138638.5(CFL2):c.169G>A (p.Val57Met) SNV Uncertain significance 954128 GRCh37: 14:35182602-35182602
GRCh38: 14:34713396-34713396
42 CFL2 NM_138638.5(CFL2):c.316C>A (p.Pro106Thr) SNV Uncertain significance 1030772 GRCh37: 14:35182338-35182338
GRCh38: 14:34713132-34713132
43 CFL2 NM_138638.5(CFL2):c.*473A>G SNV Uncertain significance 881820 GRCh37: 14:35181598-35181598
GRCh38: 14:34712392-34712392
44 CFL2 NM_138638.5(CFL2):c.*2248G>A SNV Uncertain significance 882916 GRCh37: 14:35179823-35179823
GRCh38: 14:34710617-34710617
45 CFL2 NM_138638.5(CFL2):c.*1886G>A SNV Uncertain significance 882917 GRCh37: 14:35180185-35180185
GRCh38: 14:34710979-34710979
46 CFL2 NM_138638.5(CFL2):c.*281A>G SNV Uncertain significance 882970 GRCh37: 14:35181790-35181790
GRCh38: 14:34712584-34712584
47 CFL2 NM_138638.5(CFL2):c.*40A>G SNV Likely benign 882971 GRCh37: 14:35182031-35182031
GRCh38: 14:34712825-34712825
48 CFL2 NM_138638.5(CFL2):c.495A>G (p.Pro165=) SNV Likely benign 743607 rs201619073 GRCh37: 14:35182077-35182077
GRCh38: 14:34712871-34712871
49 CFL2 NM_138638.5(CFL2):c.276A>G (p.Lys92=) SNV Likely benign 753309 rs1468647166 GRCh37: 14:35182495-35182495
GRCh38: 14:34713289-34713289
50 CFL2 NM_138638.5(CFL2):c.*1268C>T SNV Likely benign 883716 GRCh37: 14:35180803-35180803
GRCh38: 14:34711597-34711597

Expression for Typical Congenital Nemaline Myopathy

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

Pathways for Typical Congenital Nemaline Myopathy

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.42 CFL2 ACTA1
2
Show member pathways
11.02 CFL2 ACTA1
3 10.66 TPM2 NEB ACTA1

GO Terms for Typical Congenital Nemaline Myopathy

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

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.93 TPM2 NEB LMOD3 KLHL41 CFL2 ACTA1
2 Z disc GO:0030018 9.43 NEB CFL2
3 actin filament GO:0005884 9.4 TPM2 ACTA1
4 sarcomere GO:0030017 9.37 NEB ACTA1
5 myofibril GO:0030016 9.32 NEB LMOD3
6 M band GO:0031430 9.26 LMOD3 KLHL41
7 actin cytoskeleton GO:0015629 9.26 TPM2 NEB CFL2 ACTA1
8 striated muscle thin filament GO:0005865 9.16 LMOD3 ACTA1
9 cytoskeleton GO:0005856 9.1 TPM2 NEB LMOD3 KLHL41 CFL2 ACTA1

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

# Name GO ID Score Top Affiliating Genes
1 actin filament organization GO:0007015 9.5 TPM2 LMOD3 CFL2
2 sarcomere organization GO:0045214 9.43 KLHL41 CFL2
3 muscle contraction GO:0006936 9.43 TPM2 LMOD3 ACTA1
4 striated muscle contraction GO:0006941 9.4 LMOD3 KLHL41
5 myofibril assembly GO:0030239 9.37 LMOD3 KLHL41
6 skeletal muscle thin filament assembly GO:0030240 9.16 LMOD3 ACTA1
7 muscle filament sliding GO:0030049 9.13 TPM2 NEB ACTA1
8 skeletal muscle fiber development GO:0048741 8.8 LMOD3 KLHL41 ACTA1

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

# Name GO ID Score Top Affiliating Genes
1 actin binding GO:0003779 9.33 TPM2 NEB CFL2
2 structural constituent of muscle GO:0008307 8.96 TPM2 NEB
3 actin filament binding GO:0051015 8.8 TPM2 NEB CFL2

Sources for Typical 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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