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: 171430 Definition Severe congenital nemaline myopathy is a severe form of nemaline myopathy (NM; see this term) characterized by severe hypotonia with little spontaneous movement in neonates. Epidemiology The 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 description Neonates 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. Etiology The ACTA1 (1q42.13) and NEB (2q22) genes are associated with this form of NM. Genetic counseling NM is transmitted in an autosomal recessive fashion or occurs sporadically.

MalaCards based summary : Severe Congenital Nemaline Myopathy, also known as severe congenital nm, is related to nemaline myopathy and 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 myopathy 29.2 NEB LMOD3 KLHL41 KLHL40 ACTA1
3 nemaline myopathy 2 29.1 NEB LMOD3 KLHL41 KLHL40
4 nemaline myopathy 3 28.6 NEB LMOD3 KLHL41 KLHL40 ACTA1
5 batten-turner congenital myopathy 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 9.0 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:

(show all 13)
# Title Authors PMID Year
1
Founder Mutation c.1516A>C in KLHL40 Is a Frequent Cause of Nemaline Myopathy With Hyponatremia in Ethnic Chinese. 6
31360996 2019
2
Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management. 6
28973083 2017
3
Identification of KLHL40 mutations by targeted next-generation sequencing facilitated a prenatal diagnosis in a family with three consecutive affected fetuses with fetal akinesia deformation sequence. 6
27762439 2016
4
Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8). 6
27528495 2016
5
Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. 6
23746549 2013
6
[Clinical features and gene mutation analysis of severe congenital nemaline myopathy in one neonate]. 61
31104670 2019
7
Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive TNNT3 splice variant. 61
29266598 2018
8
Severe congenital nemaline myopathy with primary pulmonary lymphangiectasia: unusual clinical presentation and review of the literature. 61
25890230 2015
9
Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing. 61
22407809 2012
10
Mutations in the nebulin gene can cause severe congenital nemaline myopathy. 61
12207937 2002
11
Severe congenital nemaline myopathy: a personal perspective. 61
9526359 1998
12
A new case of severe congenital nemaline myopathy. 61
8155933 1993
13
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 188)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KLHL40 NM_152393.4(KLHL40):c.1498C>T (p.Arg500Cys) SNV Pathogenic 423767 rs758188096 GRCh37: 3:42730437-42730437
GRCh38: 3:42688945-42688945
2 KLHL40 NM_152393.4(KLHL40):c.818dup (p.Lys275fs) Duplication Pathogenic 650910 rs1575218831 GRCh37: 3:42727926-42727927
GRCh38: 3:42686434-42686435
3 KLHL40 NM_152393.4(KLHL40):c.631del (p.Ala211fs) Deletion Pathogenic 658674 rs752734208 GRCh37: 3:42727740-42727740
GRCh38: 3:42686248-42686248
4 KLHL40 NM_152393.4(KLHL40):c.1516A>C (p.Thr506Pro) SNV Pathogenic 846771 GRCh37: 3:42730455-42730455
GRCh38: 3:42688963-42688963
5 KLHL40 NM_152393.4(KLHL40):c.211G>T (p.Glu71Ter) SNV Pathogenic 961304 GRCh37: 3:42727321-42727321
GRCh38: 3:42685829-42685829
6 KLHL40 NM_152393.4(KLHL40):c.703G>T (p.Glu235Ter) SNV Pathogenic 1029197 GRCh37: 3:42727813-42727813
GRCh38: 3:42686321-42686321
7 KLHL40 NM_152393.4(KLHL40):c.602G>A (p.Trp201Ter) SNV Pathogenic 60516 rs397509420 GRCh37: 3:42727712-42727712
GRCh38: 3:42686220-42686220
8 KLHL40 NM_152393.4(KLHL40):c.1612G>C (p.Ala538Pro) SNV Pathogenic 60515 rs397509421 GRCh37: 3:42732355-42732355
GRCh38: 3:42690863-42690863
9 KLHL40 NM_152393.4(KLHL40):c.602G>T (p.Trp201Leu) SNV Pathogenic 60514 rs397509420 GRCh37: 3:42727712-42727712
GRCh38: 3:42686220-42686220
10 KLHL40 NM_152393.4(KLHL40):c.1405G>T (p.Gly469Cys) SNV Pathogenic 60513 rs367579275 GRCh37: 3:42730193-42730193
GRCh38: 3:42688701-42688701
11 KLHL40 NM_152393.4(KLHL40):c.1582G>A (p.Glu528Lys) SNV Pathogenic 60512 rs397509419 GRCh37: 3:42730521-42730521
GRCh38: 3:42689029-42689029
12 KLHL40 NM_152393.4(KLHL40):c.544_545del (p.Ser182fs) Microsatellite Pathogenic 952701 GRCh37: 3:42727652-42727653
GRCh38: 3:42686160-42686161
13 KLHL40 NM_152393.4(KLHL40):c.1395C>A (p.Tyr465Ter) SNV Pathogenic 541327 rs139588377 GRCh37: 3:42730183-42730183
GRCh38: 3:42688691-42688691
14 KLHL40 NM_152393.4(KLHL40):c.541_547delinsGTAAG (p.Ile181fs) Indel Pathogenic 1029195 GRCh37: 3:42727651-42727657
GRCh38: 3:42686159-42686165
15 KLHL40 NM_152393.4(KLHL40):c.1489C>T (p.Gln497Ter) SNV Likely pathogenic 1029196 GRCh37: 3:42730428-42730428
GRCh38: 3:42688936-42688936
16 KLHL40 NM_152393.4(KLHL40):c.1153-2A>T SNV Likely pathogenic 541330 rs752493018 GRCh37: 3:42729632-42729632
GRCh38: 3:42688140-42688140
17 KLHL40 NM_152393.4(KLHL40):c.1152+2T>A SNV Likely pathogenic 653053 rs1575219191 GRCh37: 3:42728264-42728264
GRCh38: 3:42686772-42686772
18 KLHL40 NM_152393.4(KLHL40):c.25G>T (p.Glu9Ter) SNV Likely pathogenic 804436 rs1575218072 GRCh37: 3:42727135-42727135
GRCh38: 3:42685643-42685643
19 KLHL40 NM_152393.4(KLHL40):c.176G>C (p.Arg59Pro) SNV Likely pathogenic 807621 rs778303947 GRCh37: 3:42727286-42727286
GRCh38: 3:42685794-42685794
20 KLHL40 NM_152393.4(KLHL40):c.1421+1G>T SNV Likely pathogenic 571143 rs1186218257 GRCh37: 3:42730210-42730210
GRCh38: 3:42688718-42688718
21 KLHL40 NM_152393.4(KLHL40):c.931C>A (p.Arg311Ser) SNV Conflicting interpretations of pathogenicity 474339 rs763283033 GRCh37: 3:42728041-42728041
GRCh38: 3:42686549-42686549
22 KLHL40 NM_152393.4(KLHL40):c.1273G>A (p.Gly425Ser) SNV Conflicting interpretations of pathogenicity 474324 rs138791086 GRCh37: 3:42729754-42729754
GRCh38: 3:42688262-42688262
23 KLHL40 NM_152393.4(KLHL40):c.100G>C (p.Asp34His) SNV Conflicting interpretations of pathogenicity 640377 rs778565563 GRCh37: 3:42727210-42727210
GRCh38: 3:42685718-42685718
24 KLHL40 NM_152393.4(KLHL40):c.1414A>G (p.Ser472Gly) SNV Uncertain significance 640159 rs752099249 GRCh37: 3:42730202-42730202
GRCh38: 3:42688710-42688710
25 KLHL40 NM_152393.4(KLHL40):c.1792C>T (p.Arg598Trp) SNV Uncertain significance 566417 rs767572121 GRCh37: 3:42733411-42733411
GRCh38: 3:42691919-42691919
26 KLHL40 NM_152393.4(KLHL40):c.197C>G (p.Pro66Arg) SNV Uncertain significance 541332 rs200810691 GRCh37: 3:42727307-42727307
GRCh38: 3:42685815-42685815
27 KLHL40 NM_152393.4(KLHL40):c.1709C>T (p.Thr570Met) SNV Uncertain significance 541331 rs139268932 GRCh37: 3:42732452-42732452
GRCh38: 3:42690960-42690960
28 KLHL40 NM_152393.4(KLHL40):c.1793G>C (p.Arg598Pro) SNV Uncertain significance 846867 GRCh37: 3:42733412-42733412
GRCh38: 3:42691920-42691920
29 KLHL40 NM_152393.4(KLHL40):c.1439T>C (p.Met480Thr) SNV Uncertain significance 848376 GRCh37: 3:42730378-42730378
GRCh38: 3:42688886-42688886
30 KLHL40 NM_152393.4(KLHL40):c.1246G>A (p.Val416Met) SNV Uncertain significance 848562 GRCh37: 3:42729727-42729727
GRCh38: 3:42688235-42688235
31 KLHL40 NM_152393.4(KLHL40):c.553G>C (p.Gly185Arg) SNV Uncertain significance 851342 GRCh37: 3:42727663-42727663
GRCh38: 3:42686171-42686171
32 KLHL40 NM_152393.4(KLHL40):c.1369G>C (p.Val457Leu) SNV Uncertain significance 854435 GRCh37: 3:42730157-42730157
GRCh38: 3:42688665-42688665
33 KLHL40 NM_152393.4(KLHL40):c.1160A>G (p.His387Arg) SNV Uncertain significance 855520 GRCh37: 3:42729641-42729641
GRCh38: 3:42688149-42688149
34 KLHL40 NM_152393.4(KLHL40):c.85C>T (p.His29Tyr) SNV Uncertain significance 858614 GRCh37: 3:42727195-42727195
GRCh38: 3:42685703-42685703
35 KLHL40 NM_152393.4(KLHL40):c.385T>G (p.Cys129Gly) SNV Uncertain significance 859109 GRCh37: 3:42727495-42727495
GRCh38: 3:42686003-42686003
36 KLHL40 NM_152393.4(KLHL40):c.921T>G (p.Asn307Lys) SNV Uncertain significance 863137 GRCh37: 3:42728031-42728031
GRCh38: 3:42686539-42686539
37 KLHL40 NM_152393.4(KLHL40):c.1504C>T (p.Leu502Phe) SNV Uncertain significance 936703 GRCh37: 3:42730443-42730443
GRCh38: 3:42688951-42688951
38 KLHL40 NM_152393.4(KLHL40):c.361G>C (p.Val121Leu) SNV Uncertain significance 940130 GRCh37: 3:42727471-42727471
GRCh38: 3:42685979-42685979
39 KLHL40 NM_152393.4(KLHL40):c.1183A>G (p.Met395Val) SNV Uncertain significance 943973 GRCh37: 3:42729664-42729664
GRCh38: 3:42688172-42688172
40 KLHL40 NM_152393.4(KLHL40):c.611G>A (p.Ser204Asn) SNV Uncertain significance 943974 GRCh37: 3:42727721-42727721
GRCh38: 3:42686229-42686229
41 KLHL40 NM_152393.4(KLHL40):c.1111G>C (p.Glu371Gln) SNV Uncertain significance 949223 GRCh37: 3:42728221-42728221
GRCh38: 3:42686729-42686729
42 KLHL40 NM_152393.4(KLHL40):c.1132A>T (p.Met378Leu) SNV Uncertain significance 949243 GRCh37: 3:42728242-42728242
GRCh38: 3:42686750-42686750
43 KLHL40 NM_152393.4(KLHL40):c.273A>G (p.Thr91=) SNV Uncertain significance 949568 GRCh37: 3:42727383-42727383
GRCh38: 3:42685891-42685891
44 KLHL40 NM_152393.4(KLHL40):c.1858A>C (p.Lys620Gln) SNV Uncertain significance 950017 GRCh37: 3:42733477-42733477
GRCh38: 3:42691985-42691985
45 KLHL40 NM_152393.4(KLHL40):c.1334C>T (p.Ser445Leu) SNV Uncertain significance 950737 GRCh37: 3:42730122-42730122
GRCh38: 3:42688630-42688630
46 KLHL40 NM_152393.4(KLHL40):c.1854_1857del (p.Thr619fs) Deletion Uncertain significance 950932 GRCh37: 3:42733471-42733474
GRCh38: 3:42691979-42691982
47 KLHL40 NM_152393.4(KLHL40):c.610A>G (p.Ser204Gly) SNV Uncertain significance 836423 GRCh37: 3:42727720-42727720
GRCh38: 3:42686228-42686228
48 KLHL40 NM_152393.4(KLHL40):c.108G>A (p.Val36=) SNV Uncertain significance 649408 rs533754492 GRCh37: 3:42727218-42727218
GRCh38: 3:42685726-42685726
49 KLHL40 NM_152393.4(KLHL40):c.416T>C (p.Leu139Pro) SNV Uncertain significance 642688 rs1328688864 GRCh37: 3:42727526-42727526
GRCh38: 3:42686034-42686034
50 KLHL40 NM_152393.4(KLHL40):c.296C>T (p.Ala99Val) SNV Uncertain significance 1034564 GRCh37: 3:42727406-42727406
GRCh38: 3:42685914-42685914

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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