MCID: SVR040
MIFTS: 37

Severe Congenital Nemaline Myopathy

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

Aliases & Classifications for Severe Congenital Nemaline Myopathy

MalaCards integrated aliases for Severe Congenital Nemaline Myopathy:

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

Characteristics:

Orphanet epidemiological data:

58
severe congenital nemaline myopathy
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Severe 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: 171430DefinitionSevere congenital nemaline myopathy is a severe form of nemaline myopathy (NM; see this term) characterized by severe hypotonia with little spontaneous movement in neonates.EpidemiologyThe annual incidence of NM has been estimated at 1/50,000 live births and the severe congenital form might represent 10-20% of all cases.Clinical descriptionNeonates have sucking and swallowing difficulties, and gastroesophageal reflux, which leads to failure to thrive. Involvement of diaphragm and intercostal muscles contributes to respiratory insufficiency. Cardiomyopathy and arthrogryposis may occur. Survival after infancy is rare.EtiologyThe ACTA1 (1q42.13) and NEB (2q22) genes are associated with this form of NM.Genetic counselingNM is transmitted in an autosomal recessive fashion or occurs sporadically.Visit the Orphanet disease page for more resources.

MalaCards based summary : Severe Congenital Nemaline Myopathy, also known as severe congenital nm, is related to nemaline myopathy and batten-turner congenital myopathy. An important gene associated with Severe Congenital Nemaline Myopathy is KLHL40 (Kelch Like Family Member 40), and among its related pathways/superpathways is Striated Muscle Contraction. Affiliated tissues include skeletal muscle, and related phenotypes are dysphagia and skeletal muscle atrophy

Related Diseases for Severe 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 Severe Congenital Nemaline Myopathy via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 32)
# Related Disease Score Top Affiliating Genes
1 nemaline myopathy 30.1 NEB KLHL41 ACTA1
2 batten-turner congenital myopathy 29.2 NEB LMOD3 KLHL40 ACTA1
3 myopathy 29.2 NEB LMOD3 KLHL41 KLHL40 ACTA1
4 nemaline myopathy 2 29.1 NEB LMOD3 KLHL41 KLHL40
5 nemaline myopathy 3 28.6 NEB LMOD3 KLHL41 KLHL40 ACTA1
6 congenital nemaline myopathy 10.5
7 hypotonia 10.2
8 minicore myopathy with external ophthalmoplegia 10.1
9 muscular disease 10.1
10 neuromuscular disease 10.1
11 muscular dystrophy 10.1
12 lymphangiectasis 10.1
13 congenital amyoplasia 10.1
14 myopathy, spheroid body 9.9 NEB LMOD3
15 foot drop 9.9 NEB ACTA1
16 nemaline myopathy 8 9.9 LMOD3 KLHL40
17 hyaline body myopathy 9.9 NEB ACTA1
18 camptodactyly-arthropathy-coxa vara-pericarditis syndrome 9.8 NEB ACTA1
19 myofibrillar myopathy 9.8 NEB ACTA1
20 nemaline myopathy 11, autosomal recessive 9.8 LMOD3 KLHL41
21 fetal akinesia deformation sequence 1 9.7 KLHL40 ACTA1
22 centronuclear myopathy 9.6 NEB KLHL40 ACTA1
23 distal arthrogryposis 9.6 NEB ACTA1
24 respiratory failure 9.5 LMOD3 KLHL40 ACTA1
25 nemaline myopathy 9 9.5 LMOD3 KLHL41 KLHL40
26 nemaline myopathy 10 9.5 LMOD3 KLHL41 KLHL40
27 intermediate congenital nemaline myopathy 9.5 NEB KLHL41 ACTA1
28 childhood-onset nemaline myopathy 9.5 NEB KLHL41 ACTA1
29 multiple pterygium syndrome, escobar variant 9.3 NEB LMOD3 KLHL41 KLHL40
30 typical congenital nemaline myopathy 9.2 NEB LMOD3 KLHL41 ACTA1
31 congenital structural myopathy 8.9 NEB LMOD3 KLHL41 KLHL40 ACTA1
32 congenital fiber-type disproportion 8.9 NEB LMOD3 KLHL41 KLHL40 ACTA1

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



Diseases related to Severe Congenital Nemaline Myopathy

Symptoms & Phenotypes for Severe Congenital Nemaline Myopathy

Human phenotypes related to Severe Congenital Nemaline Myopathy:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
2 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
3 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
4 type 1 muscle fiber predominance 58 31 frequent (33%) Frequent (79-30%) HP:0003803
5 nemaline bodies 58 31 frequent (33%) Frequent (79-30%) HP:0003798
6 polyhydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001561
7 decreased fetal movement 58 31 frequent (33%) Frequent (79-30%) HP:0001558
8 severe muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0006829
9 respiratory failure 58 31 frequent (33%) Frequent (79-30%) HP:0002878
10 hypokinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002375
11 axial muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003327
12 breech presentation 58 31 frequent (33%) Frequent (79-30%) HP:0001623
13 increased connective tissue 58 31 frequent (33%) Frequent (79-30%) HP:0009025
14 multiple prenatal fractures 58 31 frequent (33%) Frequent (79-30%) HP:0005855
15 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
16 ophthalmoplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000602
17 micropenis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000054
18 hypospadias 58 31 occasional (7.5%) Occasional (29-5%) HP:0000047
19 adducted thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0001181
20 large fontanelles 58 31 occasional (7.5%) Occasional (29-5%) HP:0000239
21 arthrogryposis multiplex congenita 58 31 occasional (7.5%) Occasional (29-5%) HP:0002804
22 premature birth 58 31 occasional (7.5%) Occasional (29-5%) HP:0001622
23 pulmonary hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002089
24 thin ribs 58 31 occasional (7.5%) Occasional (29-5%) HP:0000883
25 edema of the dorsum of hands 58 31 occasional (7.5%) Occasional (29-5%) HP:0007514
26 facial diplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001349
27 abnormality of the diaphragm 58 31 occasional (7.5%) Occasional (29-5%) HP:0000775
28 facial palsy 58 Frequent (79-30%)
29 flexion contracture 58 Frequent (79-30%)
30 abnormality of the thorax 58 Frequent (79-30%)

MGI Mouse Phenotypes related to Severe Congenital Nemaline Myopathy:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.35 ACTA1 KLHL40 KLHL41 LMOD3 NEB
2 muscle MP:0005369 9.02 ACTA1 KLHL40 KLHL41 LMOD3 NEB

Drugs & Therapeutics for Severe Congenital Nemaline Myopathy

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

Genetic Tests for Severe Congenital Nemaline Myopathy

Anatomical Context for Severe Congenital Nemaline Myopathy

MalaCards organs/tissues related to Severe Congenital Nemaline Myopathy:

40
Skeletal Muscle

Publications for Severe Congenital Nemaline Myopathy

Articles related to Severe Congenital Nemaline Myopathy:

# Title Authors PMID Year
1
Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. 6
23746549 2013
2
[Clinical features and gene mutation analysis of severe congenital nemaline myopathy in one neonate]. 61
31104670 2019
3
Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive TNNT3 splice variant. 61
29266598 2018
4
Severe congenital nemaline myopathy with primary pulmonary lymphangiectasia: unusual clinical presentation and review of the literature. 61
25890230 2015
5
Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing. 61
22407809 2012
6
Mutations in the nebulin gene can cause severe congenital nemaline myopathy. 61
12207937 2002
7
Severe congenital nemaline myopathy: a personal perspective. 61
9526359 1998
8
A new case of severe congenital nemaline myopathy. 61
8155933 1993
9
Intranuclear rods in severe congenital nemaline myopathy. 61
8232959 1993

Variations for Severe Congenital Nemaline Myopathy

ClinVar genetic disease variations for Severe Congenital Nemaline Myopathy:

6 (show top 50) (show all 148)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KLHL40 NM_152393.4(KLHL40):c.602G>T (p.Trp201Leu) SNV Pathogenic 60514 rs397509420 3:42727712-42727712 3:42686220-42686220
2 KLHL40 NM_152393.4(KLHL40):c.1612G>C (p.Ala538Pro) SNV Pathogenic 60515 rs397509421 3:42732355-42732355 3:42690863-42690863
3 KLHL40 NM_152393.4(KLHL40):c.602G>A (p.Trp201Ter) SNV Pathogenic 60516 rs397509420 3:42727712-42727712 3:42686220-42686220
4 KLHL40 NM_152393.4(KLHL40):c.1498C>T (p.Arg500Cys) SNV Pathogenic 423767 rs758188096 3:42730437-42730437 3:42688945-42688945
5 KLHL40 NM_152393.4(KLHL40):c.1405G>T (p.Gly469Cys) SNV Pathogenic 60513 rs367579275 3:42730193-42730193 3:42688701-42688701
6 KLHL40 NM_152393.4(KLHL40):c.1582G>A (p.Glu528Lys) SNV Pathogenic 60512 rs397509419 3:42730521-42730521 3:42689029-42689029
7 KLHL40 NM_152393.4(KLHL40):c.1395C>A (p.Tyr465Ter) SNV Pathogenic 541327 rs139588377 3:42730183-42730183 3:42688691-42688691
8 KLHL40 NM_152393.4(KLHL40):c.818dup (p.Lys275fs) Duplication Pathogenic 650910 rs1575218831 3:42727926-42727927 3:42686434-42686435
9 KLHL40 NM_152393.4(KLHL40):c.631del (p.Ala211fs) Deletion Pathogenic 658674 rs752734208 3:42727740-42727740 3:42686248-42686248
10 KLHL40 NM_152393.4(KLHL40):c.211G>T (p.Glu71Ter) SNV Pathogenic 961304 3:42727321-42727321 3:42685829-42685829
11 KLHL40 NM_152393.4(KLHL40):c.544_545del (p.Ser182fs) Microsatellite Pathogenic 952701 3:42727652-42727653 3:42686160-42686161
12 KLHL40 NM_152393.4(KLHL40):c.1516A>C (p.Thr506Pro) SNV Pathogenic 846771 3:42730455-42730455 3:42688963-42688963
13 KLHL40 NM_152393.4(KLHL40):c.25G>T (p.Glu9Ter) SNV Likely pathogenic 804436 rs1575218072 3:42727135-42727135 3:42685643-42685643
14 KLHL40 NM_152393.4(KLHL40):c.176G>C (p.Arg59Pro) SNV Likely pathogenic 807621 rs778303947 3:42727286-42727286 3:42685794-42685794
15 KLHL40 NM_152393.4(KLHL40):c.1152+2T>A SNV Likely pathogenic 653053 rs1575219191 3:42728264-42728264 3:42686772-42686772
16 KLHL40 NM_152393.4(KLHL40):c.1421+1G>T SNV Likely pathogenic 571143 rs1186218257 3:42730210-42730210 3:42688718-42688718
17 KLHL40 NM_152393.4(KLHL40):c.1153-2A>T SNV Likely pathogenic 541330 rs752493018 3:42729632-42729632 3:42688140-42688140
18 KLHL40 NM_152393.4(KLHL40):c.931C>A (p.Arg311Ser) SNV Conflicting interpretations of pathogenicity 474339 rs763283033 3:42728041-42728041 3:42686549-42686549
19 KLHL40 NM_152393.4(KLHL40):c.100G>C (p.Asp34His) SNV Conflicting interpretations of pathogenicity 640377 rs778565563 3:42727210-42727210 3:42685718-42685718
20 KLHL40 NM_152393.4(KLHL40):c.1832T>C (p.Val611Ala) SNV Uncertain significance 640595 rs749220097 3:42733451-42733451 3:42691959-42691959
21 KLHL40 NM_152393.4(KLHL40):c.887_889AGG[1] (p.Glu297del) Microsatellite Uncertain significance 641052 rs1575218907 3:42727996-42727998 3:42686504-42686506
22 KLHL40 NM_152393.4(KLHL40):c.613G>T (p.Gly205Cys) SNV Uncertain significance 642297 rs746095931 3:42727723-42727723 3:42686231-42686231
23 KLHL40 NM_152393.4(KLHL40):c.416T>C (p.Leu139Pro) SNV Uncertain significance 642688 rs1328688864 3:42727526-42727526 3:42686034-42686034
24 KLHL40 NM_152393.4(KLHL40):c.119G>A (p.Gly40Asp) SNV Uncertain significance 642829 rs1575218183 3:42727229-42727229 3:42685737-42685737
25 KLHL40 NM_152393.4(KLHL40):c.1019G>C (p.Cys340Ser) SNV Uncertain significance 642847 rs758244161 3:42728129-42728129 3:42686637-42686637
26 KLHL40 NM_152393.4(KLHL40):c.1636G>C (p.Glu546Gln) SNV Uncertain significance 644787 rs137937929 3:42732379-42732379 3:42690887-42690887
27 KLHL40 NM_152393.4(KLHL40):c.1396G>T (p.Val466Leu) SNV Uncertain significance 646499 rs773720799 3:42730184-42730184 3:42688692-42688692
28 KLHL40 NM_152393.4(KLHL40):c.1412_1415delinsC (p.Gly471_Ser472delinsAla) Indel Uncertain significance 648873 rs1427058930 3:42730200-42730203 3:42688708-42688711
29 KLHL40 NM_152393.4(KLHL40):c.108G>A (p.Val36=) SNV Uncertain significance 649408 rs533754492 3:42727218-42727218 3:42685726-42685726
30 KLHL40 NM_152393.4(KLHL40):c.613G>A (p.Gly205Ser) SNV Uncertain significance 649999 rs746095931 3:42727723-42727723 3:42686231-42686231
31 KLHL40 NM_152393.4(KLHL40):c.1053C>A (p.His351Gln) SNV Uncertain significance 574271 rs61736693 3:42728163-42728163 3:42686671-42686671
32 KLHL40 NM_152393.4(KLHL40):c.1383G>C (p.Met461Ile) SNV Uncertain significance 574408 rs762113138 3:42730171-42730171 3:42688679-42688679
33 KLHL40 NM_152393.4(KLHL40):c.1761C>G (p.Asn587Lys) SNV Uncertain significance 574846 rs34020089 3:42733380-42733380 3:42691888-42691888
34 KLHL40 NM_152393.4(KLHL40):c.764A>G (p.Gln255Arg) SNV Uncertain significance 575376 rs139088361 3:42727874-42727874 3:42686382-42686382
35 KLHL40 NM_152393.4(KLHL40):c.1493C>G (p.Thr498Ser) SNV Uncertain significance 577365 rs761479692 3:42730432-42730432 3:42688940-42688940
36 KLHL40 NM_152393.4(KLHL40):c.1595T>C (p.Ile532Thr) SNV Uncertain significance 577617 rs368161576 3:42730534-42730534 3:42689042-42689042
37 KLHL40 NM_152393.4(KLHL40):c.1370T>A (p.Val457Glu) SNV Uncertain significance 578319 rs1559614662 3:42730158-42730158 3:42688666-42688666
38 KLHL40 NM_152393.4(KLHL40):c.1504C>A (p.Leu502Ile) SNV Uncertain significance 578731 rs766195312 3:42730443-42730443 3:42688951-42688951
39 KLHL40 NM_152393.4(KLHL40):c.1153-3C>A SNV Uncertain significance 578779 rs767265252 3:42729631-42729631 3:42688139-42688139
40 KLHL40 NM_152393.4(KLHL40):c.88G>A (p.Gly30Ser) SNV Uncertain significance 578842 rs140056720 3:42727198-42727198 3:42685706-42685706
41 KLHL40 NM_152393.4(KLHL40):c.395A>G (p.Asn132Ser) SNV Uncertain significance 579724 rs767039942 3:42727505-42727505 3:42686013-42686013
42 KLHL40 NM_152393.4(KLHL40):c.752T>A (p.Leu251Gln) SNV Uncertain significance 581235 rs928500134 3:42727862-42727862 3:42686370-42686370
43 KLHL40 NM_152393.4(KLHL40):c.1396G>A (p.Val466Ile) SNV Uncertain significance 634636 rs773720799 3:42730184-42730184 3:42688692-42688692
44 KLHL40 NM_152393.4(KLHL40):c.1414A>G (p.Ser472Gly) SNV Uncertain significance 640159 rs752099249 3:42730202-42730202 3:42688710-42688710
45 KLHL40 NM_152393.4(KLHL40):c.1097G>A (p.Gly366Asp) SNV Uncertain significance 653866 rs952832025 3:42728207-42728207 3:42686715-42686715
46 KLHL40 NM_152393.4(KLHL40):c.1381A>G (p.Met461Val) SNV Uncertain significance 546303 rs776547008 3:42730169-42730169 3:42688677-42688677
47 KLHL40 NM_152393.4(KLHL40):c.344C>T (p.Ser115Phe) SNV Uncertain significance 661064 rs371748730 3:42727454-42727454 3:42685962-42685962
48 KLHL40 NM_152393.4(KLHL40):c.1243T>C (p.Tyr415His) SNV Uncertain significance 662094 rs759757085 3:42729724-42729724 3:42688232-42688232
49 KLHL40 NM_152393.4(KLHL40):c.1405G>A (p.Gly469Ser) SNV Uncertain significance 689641 rs367579275 3:42730193-42730193 3:42688701-42688701
50 KLHL40 NM_152393.4(KLHL40):c.125G>A (p.Arg42His) SNV Uncertain significance 651143 rs907216548 3:42727235-42727235 3:42685743-42685743

Expression for Severe Congenital Nemaline Myopathy

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

Pathways for Severe Congenital Nemaline Myopathy

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

# Super pathways Score Top Affiliating Genes
1 10.48 NEB ACTA1

GO Terms for Severe Congenital Nemaline Myopathy

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

# Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.67 NEB LMOD3 KLHL41 ACTA1
2 sarcomere GO:0030017 9.4 NEB ACTA1
3 myofibril GO:0030016 9.32 NEB LMOD3
4 Cul3-RING ubiquitin ligase complex GO:0031463 9.26 KLHL41 KLHL40
5 M band GO:0031430 9.16 LMOD3 KLHL41
6 A band GO:0031672 8.96 LMOD3 KLHL40
7 striated muscle thin filament GO:0005865 8.62 LMOD3 ACTA1

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

# Name GO ID Score Top Affiliating Genes
1 muscle contraction GO:0006936 9.37 LMOD3 ACTA1
2 muscle filament sliding GO:0030049 9.32 NEB ACTA1
3 striated muscle contraction GO:0006941 9.26 LMOD3 KLHL41
4 myofibril assembly GO:0030239 9.16 LMOD3 KLHL41
5 skeletal muscle thin filament assembly GO:0030240 8.96 LMOD3 ACTA1
6 skeletal muscle fiber development GO:0048741 8.92 LMOD3 KLHL41 KLHL40 ACTA1

Sources for Severe 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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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