MPD4
MCID: MYP095
MIFTS: 37

Myopathy, Distal, 4 (MPD4)

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

Aliases & Classifications for Myopathy, Distal, 4

MalaCards integrated aliases for Myopathy, Distal, 4:

Name: Myopathy, Distal, 4 57 72 29 13 6 70
Mpd4 57 12 72
Distal Myopathy with Posterior Leg and Anterior Hand Involvement 12 58
Distal Muscular Dystrophy 4 12 15
Williams Distal Myopathy 57 72
Distal Abd-Filaminopathy 12 58
Myopathy, Distal, Type 4 39
Distal Myopathy 4 12

Characteristics:

Orphanet epidemiological data:

58
distal myopathy with posterior leg and anterior hand involvement
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
patients remain ambulatory
variable age at onset, mostly in third decade (range teenage years to fourth decade)
two families have been reported (as of 6/2011)


HPO:

31
myopathy, distal, 4:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0111190
OMIM® 57 614065
MeSH 44 D049310
ICD10 via Orphanet 33 G71.0
Orphanet 58 ORPHA63273
MedGen 41 C3279722
UMLS 70 C3279722

Summaries for Myopathy, Distal, 4

OMIM® : 57 Williams distal myopathy is an autosomal dominant slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows nonspecific changes with no evidence of rods, necrosis, or inflammation (summary by Duff et al., 2011). Mutation in the FLNC gene can also cause myofibrillar myopathy-5 (MFM5; 609524), which shows a different pattern of muscle involvement and different histologic changes. (614065) (Updated 05-Apr-2021)

MalaCards based summary : Myopathy, Distal, 4, also known as mpd4, is related to hemifacial hyperplasia and cardiomyopathy, familial hypertrophic, 26, and has symptoms including calf muscle weakness An important gene associated with Myopathy, Distal, 4 is FLNC (Filamin C). Related phenotypes are difficulty walking and inability to walk

Disease Ontology : 12 A distal muscular dystrophy that has material basis in heterozygous mutation in FLNC on 7q32.

UniProtKB/Swiss-Prot : 72 Myopathy, distal, 4: A slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non- specific changes with no evidence of rods, necrosis, or inflammation.

Related Diseases for Myopathy, Distal, 4

Graphical network of the top 20 diseases related to Myopathy, Distal, 4:



Diseases related to Myopathy, Distal, 4

Symptoms & Phenotypes for Myopathy, Distal, 4

Human phenotypes related to Myopathy, Distal, 4:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 difficulty walking 58 31 hallmark (90%) Very frequent (99-80%) HP:0002355
2 inability to walk 58 31 hallmark (90%) Very frequent (99-80%) HP:0002540
3 intrinsic hand muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008954
4 exercise-induced myalgia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003738
5 hyporeflexia of lower limbs 58 31 hallmark (90%) Very frequent (99-80%) HP:0002600
6 gait imbalance 58 31 frequent (33%) Frequent (79-30%) HP:0002141
7 distal lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009053
8 foot dorsiflexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009027
9 hip flexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0012515
10 difficulty running 58 31 frequent (33%) Frequent (79-30%) HP:0009046
11 finger flexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0031177
12 limited knee flexion 58 31 frequent (33%) Frequent (79-30%) HP:0006389
13 proximal muscle weakness in lower limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0008994
14 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
15 distal upper limb muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0008959
16 fatiguable weakness of proximal limb muscles 58 31 occasional (7.5%) Occasional (29-5%) HP:0030200
17 weakness of facial musculature 58 31 occasional (7.5%) Occasional (29-5%) HP:0030319
18 decreased finger mobility 58 31 occasional (7.5%) Occasional (29-5%) HP:0006135
19 dysphagia 58 Excluded (0%)
20 muscle weakness 31 HP:0001324
21 myopathy 31 HP:0003198
22 abnormality of the cardiovascular system 58 Occasional (29-5%)
23 respiratory insufficiency due to muscle weakness 58 Excluded (0%)
24 hyporeflexia 31 HP:0001265
25 mildly elevated creatine kinase 31 HP:0008180
26 sensory impairment 58 Excluded (0%)
27 proximal muscle weakness 31 HP:0003701
28 abnormality of the calf musculature 31 HP:0001430
29 distal upper limb amyotrophy 31 HP:0007149
30 distal lower limb amyotrophy 31 HP:0008944

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Muscle Soft Tissue:
calf muscle weakness
type 1 fiber predominance
muscle weakness, distal upper and lower limbs
muscle atrophy, distal upper and lower limbs
sparing of the anterior tibial compartment
more
Cardiovascular Heart:
cardiomyopathy (in 2 of 4 patients from 1 family)

Laboratory Abnormalities:
normal or mildly increased serum creatine kinase

Neurologic Peripheral Nervous System:
hyporeflexia in the lower limbs

Clinical features from OMIM®:

614065 (Updated 05-Apr-2021)

UMLS symptoms related to Myopathy, Distal, 4:


calf muscle weakness

Drugs & Therapeutics for Myopathy, Distal, 4

Search Clinical Trials , NIH Clinical Center for Myopathy, Distal, 4

Genetic Tests for Myopathy, Distal, 4

Genetic tests related to Myopathy, Distal, 4:

# Genetic test Affiliating Genes
1 Myopathy, Distal, 4 29 FLNC

Anatomical Context for Myopathy, Distal, 4

Publications for Myopathy, Distal, 4

Articles related to Myopathy, Distal, 4:

(show all 14)
# Title Authors PMID Year
1
Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy. 6 57
21620354 2011
2
A new dominant distal myopathy affecting posterior leg and anterior upper limb muscles. 6 57
15824355 2005
3
Filamin C Truncation Mutations Are Associated With Arrhythmogenic Dilated Cardiomyopathy and Changes in the Cell-Cell Adhesion Structures. 6
30067491 2018
4
Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy. 6
28436997 2017
5
Congenital dilated cardiomyopathy caused by biallelic mutations in Filamin C. 6
27601210 2016
6
Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies. 6
27908349 2016
7
FLNC Gene Splice Mutations Cause Dilated Cardiomyopathy. 6
28008423 2016
8
FLNC myofibrillar myopathy results from impaired autophagy and protein insufficiency. 6
26969713 2016
9
Myofibrillar instability exacerbated by acute exercise in filaminopathy. 6
26472074 2015
10
Use of Whole-Exome Sequencing for Diagnosis of Limb-Girdle Muscular Dystrophy: Outcomes and Lessons Learned. 6
26436962 2015
11
Prioritizing causal disease genes using unbiased genomic features. 6
25633252 2014
12
Pathophysiology of protein aggregation and extended phenotyping in filaminopathy. 6
22961544 2012
13
LOVD v.2.0: the next generation in gene variant databases. 6
21520333 2011
14
A mutation in the dimerization domain of filamin c causes a novel type of autosomal dominant myofibrillar myopathy. 6
15929027 2005

Variations for Myopathy, Distal, 4

ClinVar genetic disease variations for Myopathy, Distal, 4:

6 (show top 50) (show all 1558)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FLNC NM_001458.4(FLNC):c.752T>C (p.Met251Thr) SNV Pathogenic 29591 rs387906586 GRCh37: 7:128477504-128477504
GRCh38: 7:128837450-128837450
2 FLNC NM_001458.4(FLNC):c.4716del (p.Leu1573fs) Deletion Pathogenic 478127 rs1554400021 GRCh37: 7:128488747-128488747
GRCh38: 7:128848693-128848693
3 FLNC NM_001458.4(FLNC):c.774del (p.Lys259fs) Deletion Pathogenic 478133 rs1554397506 GRCh37: 7:128477523-128477523
GRCh38: 7:128837469-128837469
4 FLNC NM_001458.4(FLNC):c.3557C>T (p.Ala1186Val) SNV Pathogenic 427928 rs1114167361 GRCh37: 7:128485076-128485076
GRCh38: 7:128845022-128845022
5 FLNC NM_001458.4(FLNC):c.2390-10_2406del Deletion Pathogenic 478125 rs1554398674 GRCh37: 7:128482836-128482862
GRCh38: 7:128842782-128842808
6 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.7294C>T (p.Gln2432Ter) SNV Pathogenic 478131 rs1554401756 GRCh37: 7:128496614-128496614
GRCh38: 7:128856560-128856560
7 FLNC NM_001458.4(FLNC):c.4926_4927insACGTCACA (p.Val1643fs) Insertion Pathogenic 478128 rs1402879259 GRCh37: 7:128489028-128489029
GRCh38: 7:128848974-128848975
8 FLNC NM_001458.4(FLNC):c.1519_1525del (p.Gly507fs) Deletion Pathogenic 478121 rs1554398092 GRCh37: 7:128480181-128480187
GRCh38: 7:128840127-128840133
9 FLNC NM_001458.4(FLNC):c.3934_3937dup (p.Arg1313fs) Duplication Pathogenic 478126 rs1554399513 GRCh37: 7:128486183-128486184
GRCh38: 7:128846129-128846130
10 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.6976C>T (p.Arg2326Ter) SNV Pathogenic 478129 rs748416758 GRCh37: 7:128494715-128494715
GRCh38: 7:128854661-128854661
11 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.7371del (p.Glu2458fs) Deletion Pathogenic 478132 rs1554401780 GRCh37: 7:128496691-128496691
GRCh38: 7:128856637-128856637
12 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.7251+1G>A SNV Pathogenic 539340 rs1554401581 GRCh37: 7:128495369-128495369
GRCh38: 7:128855315-128855315
13 FLNC NM_001458.4(FLNC):c.5165del (p.Gly1722fs) Deletion Pathogenic 539390 rs1554400242 GRCh37: 7:128489594-128489594
GRCh38: 7:128849540-128849540
14 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.7496_7497insTGCT (p.Gln2499fs) Insertion Pathogenic 539334 rs1554401830 GRCh37: 7:128496910-128496911
GRCh38: 7:128856856-128856857
15 FLNC NM_001458.4(FLNC):c.805C>T (p.Arg269Ter) SNV Pathogenic 539411 rs755583250 GRCh37: 7:128477557-128477557
GRCh38: 7:128837503-128837503
16 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.5672delG Deletion Pathogenic 567017 rs1563001548 GRCh37: 7:128491508-128491508
GRCh38: 7:128851454-128851454
17 FLNC NM_001127487.2(FLNC):c.147delinsTCT (p.Lys51fs) Indel Pathogenic 567163 rs1562988883 GRCh37: 7:128470838-128470838
GRCh38: 7:128830784-128830784
18 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.5653A>T (p.Lys1885Ter) SNV Pathogenic 567717 rs1563001456 GRCh37: 7:128491399-128491399
GRCh38: 7:128851345-128851345
19 FLNC NM_001458.4(FLNC):c.4333_4336del (p.Gly1444_Lys1445insTer) Deletion Pathogenic 571885 rs1562998858 GRCh37: 7:128487793-128487796
GRCh38: 7:128847739-128847742
20 FLNC NM_001458.4(FLNC):c.1605C>A (p.Cys535Ter) SNV Pathogenic 539354 rs199976790 GRCh37: 7:128480657-128480657
GRCh38: 7:128840603-128840603
21 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.6447del (p.Ile2150fs) Deletion Pathogenic 574095 rs1563003153 GRCh37: 7:128493853-128493853
GRCh38: 7:128853799-128853799
22 FLNC NM_001458.4(FLNC):c.3937C>T (p.Arg1313Ter) SNV Pathogenic 579589 rs766330686 GRCh37: 7:128486190-128486190
GRCh38: 7:128846136-128846136
23 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.7536_7548del (p.Pro2513fs) Deletion Pathogenic 539437 rs1554401837 GRCh37: 7:128496949-128496961
GRCh38: 7:128856895-128856907
24 FLNC NM_001458.4(FLNC):c.1444C>T (p.Arg482Ter) SNV Pathogenic 517207 rs1420159591 GRCh37: 7:128480109-128480109
GRCh38: 7:128840055-128840055
25 FLNC NM_001458.4(FLNC):c.4621A>T (p.Lys1541Ter) SNV Pathogenic 577928 rs1562999451 GRCh37: 7:128488655-128488655
GRCh38: 7:128848601-128848601
26 FLNC NM_001458.4(FLNC):c.2065G>T (p.Glu689Ter) SNV Pathogenic 539448 rs1446694237 GRCh37: 7:128481565-128481565
GRCh38: 7:128841511-128841511
27 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.5697dup (p.Ser1900fs) Duplication Pathogenic 539446 rs1554400700 GRCh37: 7:128491536-128491537
GRCh38: 7:128851482-128851483
28 FLNC NM_001458.4(FLNC):c.444G>A (p.Trp148Ter) SNV Pathogenic 539439 rs1554397197 GRCh37: 7:128475471-128475471
GRCh38: 7:128835417-128835417
29 FLNC NM_001458.4(FLNC):c.3557C>T (p.Ala1186Val) SNV Pathogenic 427928 rs1114167361 GRCh37: 7:128485076-128485076
GRCh38: 7:128845022-128845022
30 FLNC and overlap with 1 gene(s) NC_000007.14:g.(?_128830618)_(128858543_?)del Deletion Pathogenic 584412 GRCh37: 7:128470672-128498597
GRCh38: 7:128830618-128858543
31 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.5904dup (p.Ile1969fs) Duplication Pathogenic 640320 rs1585167678 GRCh37: 7:128492705-128492706
GRCh38: 7:128852651-128852652
32 FLNC NM_001458.4(FLNC):c.4729C>T (p.Gln1577Ter) SNV Pathogenic 645256 rs1585163755 GRCh37: 7:128488763-128488763
GRCh38: 7:128848709-128848709
33 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.7365C>A (p.Tyr2455Ter) SNV Pathogenic 651699 rs540386120 GRCh37: 7:128496685-128496685
GRCh38: 7:128856631-128856631
34 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.6883C>T (p.Gln2295Ter) SNV Pathogenic 642313 rs1585169831 GRCh37: 7:128494622-128494622
GRCh38: 7:128854568-128854568
35 FLNC NM_001458.4(FLNC):c.4127+1G>T SNV Pathogenic 643473 rs1346981294 GRCh37: 7:128486518-128486518
GRCh38: 7:128846464-128846464
36 FLNC NM_001458.4(FLNC):c.554G>A (p.Trp185Ter) SNV Pathogenic 643595 rs1585151331 GRCh37: 7:128475581-128475581
GRCh38: 7:128835527-128835527
37 FLNC-AS1 , FLNC NM_001127487.2(FLNC):c.7235_7236AC[2] (p.Pro2414fs) Microsatellite Pathogenic 659634 rs1585171628 GRCh37: 7:128496653-128496654
GRCh38: 7:128856599-128856600
38 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.6242dup (p.Ser2082fs) Duplication Pathogenic 661219 rs1585168573 GRCh37: 7:128493553-128493554
GRCh38: 7:128853499-128853500
39 FLNC NM_001458.4(FLNC):c.1861_1885dup (p.Arg629fs) Duplication Pathogenic 663736 rs1585156327 GRCh37: 7:128481269-128481270
GRCh38: 7:128841215-128841216
40 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.5675_5678del (p.Leu1892fs) Deletion Pathogenic 660879 rs1585166614 GRCh37: 7:128491512-128491515
GRCh38: 7:128851458-128851461
41 FLNC NC_000007.14:g.(?_128848551)_(128848992_?)del Deletion Pathogenic 830847 GRCh37: 7:128488605-128489046
GRCh38:
42 FLNC NM_001458.4(FLNC):c.3699del (p.Val1235fs) Deletion Pathogenic 834916 GRCh37: 7:128485218-128485218
GRCh38: 7:128845164-128845164
43 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.6753dup (p.Ala2252fs) Duplication Pathogenic 837501 GRCh37: 7:128494491-128494492
GRCh38: 7:128854437-128854438
44 FLNC NM_001458.4(FLNC):c.3084C>A (p.Tyr1028Ter) SNV Pathogenic 841507 GRCh37: 7:128484212-128484212
GRCh38: 7:128844158-128844158
45 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.6190dup (p.Val2064fs) Duplication Pathogenic 843365 GRCh37: 7:128493066-128493067
GRCh38: 7:128853012-128853013
46 FLNC NM_001458.4(FLNC):c.3854del (p.Gly1285fs) Deletion Pathogenic 843605 GRCh37: 7:128486106-128486106
GRCh38: 7:128846052-128846052
47 FLNC-AS1 , FLNC NM_001458.4(FLNC):c.5469_5482del (p.Val1824fs) Deletion Pathogenic 845598 GRCh37: 7:128490924-128490937
GRCh38: 7:128850870-128850883
48 FLNC NM_001458.4(FLNC):c.4108C>T (p.Arg1370Ter) SNV Pathogenic 842060 GRCh37: 7:128486498-128486498
GRCh38: 7:128846444-128846444
49 FLNC NM_001458.4(FLNC):c.2119C>T (p.Gln707Ter) SNV Pathogenic 849024 GRCh37: 7:128481619-128481619
GRCh38: 7:128841565-128841565
50 FLNC NM_001458.4(FLNC):c.4984C>T (p.Gln1662Ter) SNV Pathogenic 852214 GRCh37: 7:128489417-128489417
GRCh38: 7:128849363-128849363

UniProtKB/Swiss-Prot genetic disease variations for Myopathy, Distal, 4:

72
# Symbol AA change Variation ID SNP ID
1 FLNC p.Ala193Thr VAR_066212 rs387906587
2 FLNC p.Met251Thr VAR_066213 rs387906586

Expression for Myopathy, Distal, 4

Search GEO for disease gene expression data for Myopathy, Distal, 4.

Pathways for Myopathy, Distal, 4

GO Terms for Myopathy, Distal, 4

Sources for Myopathy, Distal, 4

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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