MFM9
MCID: MYP153
MIFTS: 29

Myopathy, Myofibrillar, 9, with Early Respiratory Failure (MFM9)

Categories: Genetic diseases

Aliases & Classifications for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

MalaCards integrated aliases for Myopathy, Myofibrillar, 9, with Early Respiratory Failure:

Name: Myopathy, Myofibrillar, 9, with Early Respiratory Failure 58
Hereditary Myopathy with Early Respiratory Failure 58 25 26 76 30 6
Hmerf 58 25 26 76
Myopathy, Proximal, with Early Respiratory Muscle Involvement 58 26 13
Edstrom Myopathy 58 26 76
Myopathy, Distal, with Early Respiratory Failure, Autosomal Dominant 58
Myopathy, Proximal, with Early Respiratory Muscle Involvement; Mprm 58
Hereditary Myopathy with Early Respiratory Failure; Hmerf 58
Myofibrillar Myopathy with Early Respiratory Failure 25
Myopathy, Hereditary with Early Respiratory Failure 41
Mfm-Titinopathy 25
Mfm9 58
Mprm 58

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
slowly progressive
adult onset (range 20 to 70 years)
lower limb weakness is usually the presenting feature
clinical heterogeneity, even within families


HPO:

33
myopathy, myofibrillar, 9, with early respiratory failure:
Onset and clinical course variable expressivity adult onset progressive
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance Penetrance appears to depend on the pathogenic variant...

Classifications:



Summaries for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

OMIM : 58 Myofibrillar myopathy-9 with early respiratory failure (MFM9) is an autosomal dominant muscle disorder characterized by adult onset of slowly progressive muscle weakness with diaphragmatic involvement causing respiratory insufficiency. Patients present between 20 and 70 years of age with distal or proximal muscle weakness, mainly affecting the lower limbs with foot drop or difficulty walking. The age at onset is highly variable, even within families. Nearly all patients eventually develop significant proximal and distal weakness, as well as respiratory insufficiency requiring nocturnal ventilation. Additional, more variable features may include axial weakness, neck muscle weakness, and rarely, cardiac involvement. Muscle biopsy shows myopathic or dystrophic changes with fiber splitting, eosinophilic cytoplasmic inclusions consistent with myofibrillar myopathy, rimmed vacuoles, and increased connective or fatty tissue (summary by Pfeffer et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy (MFM), see MFM1 (601419). (603689)

MalaCards based summary : Myopathy, Myofibrillar, 9, with Early Respiratory Failure, also known as hereditary myopathy with early respiratory failure, is related to hereditary proximal myopathy with early respiratory failure and muscle disorders. An important gene associated with Myopathy, Myofibrillar, 9, with Early Respiratory Failure is TTN (Titin). Affiliated tissues include skeletal muscle and testes, and related phenotypes are respiratory insufficiency due to muscle weakness and skeletal muscle atrophy

Genetics Home Reference : 26 Hereditary myopathy with early respiratory failure (HMERF) is an inherited disease that affects muscles used for movement (skeletal muscles) and muscles that are needed for breathing (respiratory muscles).

UniProtKB/Swiss-Prot : 76 Hereditary myopathy with early respiratory failure: Autosomal dominant, adult-onset myopathy with early respiratory muscle involvement.

GeneReviews: NBK185330

Related Diseases for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

Diseases related to Myopathy, Myofibrillar, 9, with Early Respiratory Failure via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hereditary proximal myopathy with early respiratory failure 12.0
2 muscle disorders 10.6
3 respiratory failure 10.6
4 myopathy 10.6
5 myofibrillar myopathy 10.2

Graphical network of the top 20 diseases related to Myopathy, Myofibrillar, 9, with Early Respiratory Failure:



Diseases related to Myopathy, Myofibrillar, 9, with Early Respiratory Failure

Symptoms & Phenotypes for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

Human phenotypes related to Myopathy, Myofibrillar, 9, with Early Respiratory Failure:

33 (show all 28)
# Description HPO Frequency HPO Source Accession
1 respiratory insufficiency due to muscle weakness 33 frequent (33%) HP:0002747
2 skeletal muscle atrophy 33 frequent (33%) HP:0003202
3 emg: myopathic abnormalities 33 frequent (33%) HP:0003458
4 rimmed vacuoles 33 frequent (33%) HP:0003805
5 type 1 muscle fiber predominance 33 frequent (33%) HP:0003803
6 increased variability in muscle fiber diameter 33 frequent (33%) HP:0003557
7 neck flexor weakness 33 frequent (33%) HP:0003722
8 foot dorsiflexor weakness 33 frequent (33%) HP:0009027
9 reduced vital capacity 33 frequent (33%) HP:0002792
10 necrotizing myopathy 33 frequent (33%) HP:0008978
11 restrictive deficit on pulmonary function testing 33 frequent (33%) HP:0002111
12 muscle fiber splitting 33 frequent (33%) HP:0003555
13 internally nucleated skeletal muscle fibers 33 frequent (33%) HP:0031237
14 limited hip movement 33 frequent (33%) HP:0008800
15 orthopnea 33 frequent (33%) HP:0012764
16 elevated serum creatine kinase 33 frequent (33%) HP:0003236
17 proximal muscle weakness 33 occasional (7.5%) HP:0003701
18 calf muscle hypertrophy 33 occasional (7.5%) HP:0008981
19 tibialis muscle weakness 33 occasional (7.5%) HP:0008963
20 muscle fiber hypertrophy 33 occasional (7.5%) HP:0100293
21 falls 33 very rare (1%) HP:0002527
22 nocturnal hypoventilation 33 very rare (1%) HP:0002877
23 respiratory insufficiency 33 HP:0002093
24 pelvic girdle muscle weakness 33 HP:0003749
25 respiratory failure 33 HP:0002878
26 quadriceps muscle weakness 33 HP:0003731
27 diaphragmatic weakness 33 HP:0009113
28 shoulder girdle muscle weakness 33 HP:0003547

Symptoms via clinical synopsis from OMIM:

58
Muscle Soft Tissue:
rimmed vacuoles
difficulty walking
frequent falls
myofibrillar myopathy
muscle fiber splitting
more
Chest Diaphragm:
diaphragmatic weakness

Laboratory Abnormalities:
increased creatine kinase, mild to moderate

Respiratory:
nocturnal hypoventilation
early respiratory failure
decreased vital capacity

Cardiovascular Heart:
cardiac involvement (rare)

Clinical features from OMIM:

603689

Drugs & Therapeutics for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

Search Clinical Trials , NIH Clinical Center for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

Genetic Tests for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

Genetic tests related to Myopathy, Myofibrillar, 9, with Early Respiratory Failure:

# Genetic test Affiliating Genes
1 Hereditary Myopathy with Early Respiratory Failure 30 TTN

Anatomical Context for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

MalaCards organs/tissues related to Myopathy, Myofibrillar, 9, with Early Respiratory Failure:

42
Skeletal Muscle, Testes

Publications for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

Articles related to Myopathy, Myofibrillar, 9, with Early Respiratory Failure:

(show all 22)
# Title Authors Year
1
Hereditary myopathy with early respiratory failure (HMERF): Still rare, but common enough. ( 29361395 )
2018
2
Cardiac involvement in hereditary myopathy with early respiratory failure: A cohort study. ( 27511179 )
2016
3
Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure. ( 25253871 )
2015
4
New disease allele and de novo mutation indicate mutational vulnerability of titin exon 343 in hereditary myopathy with early respiratory failure. ( 25500009 )
2015
5
Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure. ( 23486992 )
2014
6
Reply: Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain. ( 24569025 )
2014
7
Reply: Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain. ( 24578547 )
2014
8
Hereditary myopathy with early respiratory failure is associated with misfolding of the titin fibronectin III 119 subdomain. ( 24636144 )
2014
9
Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain. ( 24231549 )
2014
10
Reply: Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain. ( 24271327 )
2014
11
A new disease allele for the p.C30071R mutation in titin causing hereditary myopathy with early respiratory failure. ( 24444549 )
2014
12
Hereditary myopathy with early respiratory failure: occurrence in various populations. ( 23606733 )
2014
13
Think worldwide: hereditary myopathy with early respiratory failure (HMERF) may not be rare. ( 23695499 )
2014
14
Exome sequencing identifies a novel TTN mutation in a family with hereditary myopathy with early respiratory failure. ( 23446887 )
2013
15
Exome sequencing identifies titin mutations causing hereditary myopathy with early respiratory failure (HMERF) in families of diverse ethnic origins. ( 23514108 )
2013
16
Titin mutation segregates with hereditary myopathy with early respiratory failure. ( 22577215 )
2012
17
Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin. ( 22577218 )
2012
18
An Italian case of hereditary myopathy with early respiratory failure (HMERF) not associated with the titin kinase domain R279W mutation. ( 20708934 )
2010
19
Subclinical semitendinosus and obturator externus involvement defines an autosomal dominant myopathy with early respiratory failure. ( 16084088 )
2005
20
The kinase domain of titin controls muscle gene expression and protein turnover. ( 15802564 )
2005
21
A novel autosomal dominant distal myopathy with early respiratory failure: clinico-pathologic characteristics and exclusion of linkage to candidate genetic loci. ( 11310621 )
2001
22
Autosomal dominant myopathy with proximal weakness and early respiratory muscle involvement maps to chromosome 2q. ( 10053013 )
1999

Variations for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

UniProtKB/Swiss-Prot genetic disease variations for Myopathy, Myofibrillar, 9, with Early Respiratory Failure:

76
# Symbol AA change Variation ID SNP ID
1 TTN p.Arg279Trp VAR_026634 rs138060032

ClinVar genetic disease variations for Myopathy, Myofibrillar, 9, with Early Respiratory Failure:

6 (show top 50) (show all 2242)
# Gene Variation Type Significance SNP ID Assembly Location
1 TTN NM_133378.4(TTN) indel Pathogenic rs281864927 GRCh37 Chromosome 2, 179391925: 179391935
2 TTN NM_133378.4(TTN) indel Pathogenic rs281864927 GRCh38 Chromosome 2, 178527198: 178527208
3 TTN NM_001256850.1(TTN): c.835C> T (p.Arg279Trp) single nucleotide variant Uncertain significance rs138060032 GRCh37 Chromosome 2, 179664293: 179664293
4 TTN NM_001256850.1(TTN): c.835C> T (p.Arg279Trp) single nucleotide variant Uncertain significance rs138060032 GRCh38 Chromosome 2, 178799566: 178799566
5 TTN NM_001256850.1(TTN): c.102966delA (p.Lys34322Asnfs) deletion Pathogenic rs281864930 GRCh37 Chromosome 2, 179391826: 179391826
6 TTN NM_001256850.1(TTN): c.102966delA (p.Lys34322Asnfs) deletion Pathogenic rs281864930 GRCh38 Chromosome 2, 178527099: 178527099
7 TTN TTN: c.1003G> A (p.Val335Met) single nucleotide variant Benign/Likely benign rs72647846 GRCh37 Chromosome 2, 179659891: 179659891
8 TTN TTN: c.1003G> A (p.Val335Met) single nucleotide variant Benign/Likely benign rs72647846 GRCh38 Chromosome 2, 178795164: 178795164
9 TTN NM_133378.4(TTN): c.10256G> A (p.Ser3419Asn) single nucleotide variant Benign/Likely benign rs2291310 GRCh37 Chromosome 2, 179623758: 179623758
10 TTN NM_133378.4(TTN): c.10256G> A (p.Ser3419Asn) single nucleotide variant Benign/Likely benign rs2291310 GRCh38 Chromosome 2, 178759031: 178759031
11 TTN NM_133378.4(TTN): c.10793G> A (p.Arg3598Lys) single nucleotide variant Benign/Likely benign rs2742347 GRCh37 Chromosome 2, 179600648: 179600648
12 TTN NM_133378.4(TTN): c.10793G> A (p.Arg3598Lys) single nucleotide variant Benign/Likely benign rs2742347 GRCh38 Chromosome 2, 178735921: 178735921
13 TTN NM_133378.4(TTN): c.1079G> C (p.Arg360Thr) single nucleotide variant Benign/Likely benign rs56128843 GRCh37 Chromosome 2, 179659815: 179659815
14 TTN NM_133378.4(TTN): c.1079G> C (p.Arg360Thr) single nucleotide variant Benign/Likely benign rs56128843 GRCh38 Chromosome 2, 178795088: 178795088
15 TTN NM_133378.4(TTN): c.10878C> T (p.Ser3626=) single nucleotide variant Benign/Likely benign rs2742348 GRCh37 Chromosome 2, 179600563: 179600563
16 TTN NM_133378.4(TTN): c.10878C> T (p.Ser3626=) single nucleotide variant Benign/Likely benign rs2742348 GRCh38 Chromosome 2, 178735836: 178735836
17 TTN NM_133378.4(TTN): c.11033G> A (p.Ser3678Asn) single nucleotide variant Benign/Likely benign rs184740744 GRCh37 Chromosome 2, 179600408: 179600408
18 TTN NM_133378.4(TTN): c.11033G> A (p.Ser3678Asn) single nucleotide variant Benign/Likely benign rs184740744 GRCh38 Chromosome 2, 178735681: 178735681
19 TTN NM_133378.4(TTN): c.11252C> G (p.Pro3751Arg) single nucleotide variant Benign/Likely benign rs72648927 GRCh37 Chromosome 2, 179599667: 179599667
20 TTN NM_133378.4(TTN): c.11252C> G (p.Pro3751Arg) single nucleotide variant Benign/Likely benign rs72648927 GRCh38 Chromosome 2, 178734940: 178734940
21 TTN NM_133378.4(TTN): c.11446G> A (p.Val3816Ile) single nucleotide variant Benign/Likely benign rs72648929 GRCh37 Chromosome 2, 179599473: 179599473
22 TTN NM_133378.4(TTN): c.11446G> A (p.Val3816Ile) single nucleotide variant Benign/Likely benign rs72648929 GRCh38 Chromosome 2, 178734746: 178734746
23 TTN NM_133378.4(TTN): c.11446G> C (p.Val3816Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs72648929 GRCh37 Chromosome 2, 179599473: 179599473
24 TTN NM_133378.4(TTN): c.11446G> C (p.Val3816Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs72648929 GRCh38 Chromosome 2, 178734746: 178734746
25 TTN NM_003319.4(TTN): c.13282+4410G> A single nucleotide variant Benign/Likely benign rs72648932 GRCh37 Chromosome 2, 179598399: 179598399
26 TTN NM_003319.4(TTN): c.13282+4410G> A single nucleotide variant Benign/Likely benign rs72648932 GRCh38 Chromosome 2, 178733672: 178733672
27 TTN TTN: c.15792T> C (p.Ile5264=) single nucleotide variant Benign/Likely benign rs12993099 GRCh37 Chromosome 2, 179598228: 179598228
28 TTN TTN: c.15792T> C (p.Ile5264=) single nucleotide variant Benign/Likely benign rs12993099 GRCh38 Chromosome 2, 178733501: 178733501
29 TTN NM_133378.4(TTN): c.12363C> T (p.Asn4121=) single nucleotide variant Benign/Likely benign rs72648935 GRCh37 Chromosome 2, 179597808: 179597808
30 TTN NM_133378.4(TTN): c.12363C> T (p.Asn4121=) single nucleotide variant Benign/Likely benign rs72648935 GRCh38 Chromosome 2, 178733081: 178733081
31 TTN NM_133378.4(TTN): c.12381T> C (p.Asn4127=) single nucleotide variant Conflicting interpretations of pathogenicity rs143845692 GRCh37 Chromosome 2, 179597790: 179597790
32 TTN NM_133378.4(TTN): c.12381T> C (p.Asn4127=) single nucleotide variant Conflicting interpretations of pathogenicity rs143845692 GRCh38 Chromosome 2, 178733063: 178733063
33 TTN NM_133378.4(TTN): c.12571G> A (p.Val4191Met) single nucleotide variant Conflicting interpretations of pathogenicity rs72648937 GRCh37 Chromosome 2, 179597600: 179597600
34 TTN NM_133378.4(TTN): c.12571G> A (p.Val4191Met) single nucleotide variant Conflicting interpretations of pathogenicity rs72648937 GRCh38 Chromosome 2, 178732873: 178732873
35 TTN NM_133378.4(TTN): c.12797A> G (p.Tyr4266Cys) single nucleotide variant Benign/Likely benign rs72648939 GRCh37 Chromosome 2, 179597259: 179597259
36 TTN NM_133378.4(TTN): c.12797A> G (p.Tyr4266Cys) single nucleotide variant Benign/Likely benign rs72648939 GRCh38 Chromosome 2, 178732532: 178732532
37 TTN NM_133378.4(TTN): c.13316A> G (p.Tyr4439Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs72648942 GRCh37 Chromosome 2, 179596554: 179596554
38 TTN NM_133378.4(TTN): c.13316A> G (p.Tyr4439Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs72648942 GRCh38 Chromosome 2, 178731827: 178731827
39 TTN NM_133378.4(TTN): c.13451-7C> T single nucleotide variant Conflicting interpretations of pathogenicity rs371785683 GRCh37 Chromosome 2, 179596317: 179596317
40 TTN NM_133378.4(TTN): c.13451-7C> T single nucleotide variant Conflicting interpretations of pathogenicity rs371785683 GRCh38 Chromosome 2, 178731590: 178731590
41 TTN NM_133378.4(TTN): c.1365G> A (p.Thr455=) single nucleotide variant Conflicting interpretations of pathogenicity rs145211131 GRCh37 Chromosome 2, 179659159: 179659159
42 TTN NM_133378.4(TTN): c.1365G> A (p.Thr455=) single nucleotide variant Conflicting interpretations of pathogenicity rs145211131 GRCh38 Chromosome 2, 178794432: 178794432
43 TTN NM_133378.4(TTN): c.1398+8C> T single nucleotide variant Benign/Likely benign rs72647848 GRCh37 Chromosome 2, 179659118: 179659118
44 TTN NM_133378.4(TTN): c.1398+8C> T single nucleotide variant Benign/Likely benign rs72647848 GRCh38 Chromosome 2, 178794391: 178794391
45 TTN NM_001267550.2(TTN): c.17741-9A> G single nucleotide variant Benign/Likely benign rs72648944 GRCh37 Chromosome 2, 179595528: 179595528
46 TTN NM_001267550.2(TTN): c.17741-9A> G single nucleotide variant Benign/Likely benign rs72648944 GRCh38 Chromosome 2, 178730801: 178730801
47 TTN NM_133378.4(TTN): c.14156A> G (p.Glu4719Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs146983095 GRCh37 Chromosome 2, 179595372: 179595372
48 TTN NM_133378.4(TTN): c.14156A> G (p.Glu4719Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs146983095 GRCh38 Chromosome 2, 178730645: 178730645
49 TTN NM_001256850.1(TTN): c.17038G> A (p.Ala5680Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs72648946 GRCh37 Chromosome 2, 179595271: 179595271
50 TTN NM_001256850.1(TTN): c.17038G> A (p.Ala5680Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs72648946 GRCh38 Chromosome 2, 178730544: 178730544

Expression for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

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Pathways for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

GO Terms for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

Sources for Myopathy, Myofibrillar, 9, with Early Respiratory Failure

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