MPD4
MCID: MYP095
MIFTS: 33

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 56 73 29 13 6 71
Mpd4 56 12 73
Distal Myopathy with Posterior Leg and Anterior Hand Involvement 12 58
Williams Distal Myopathy 56 73
Distal Abd-Filaminopathy 12 58
Distal Muscular Dystrophy 4 12
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:

56
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 56 614065
MeSH 43 D049310
ICD10 via Orphanet 33 G71.0
Orphanet 58 ORPHA63273
MedGen 41 C3279722
UMLS 71 C3279722

Summaries for Myopathy, Distal, 4

OMIM : 56 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)

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

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

UniProtKB/Swiss-Prot : 73 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

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 inability to walk 58 31 hallmark (90%) Very frequent (99-80%) HP:0002540
2 difficulty walking 58 31 hallmark (90%) Very frequent (99-80%) HP:0002355
3 exercise-induced myalgia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003738
4 intrinsic hand muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008954
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 foot dorsiflexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009027
8 distal lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009053
9 difficulty running 58 31 frequent (33%) Frequent (79-30%) HP:0009046
10 finger flexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0031177
11 hip flexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0012515
12 limited knee flexion 58 31 frequent (33%) Frequent (79-30%) HP:0006389
13 fatiguable weakness of proximal limb muscles 58 31 occasional (7.5%) Occasional (29-5%) HP:0030200
14 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
15 proximal muscle weakness in lower limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0008994
16 distal upper limb muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0008959
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 proximal muscle weakness 31 HP:0003701
26 sensory impairment 58 Excluded (0%)
27 abnormality of the calf musculature 31 HP:0001430
28 distal lower limb amyotrophy 31 HP:0008944
29 distal upper limb amyotrophy 31 HP:0007149
30 mildly elevated creatine kinase 31 HP:0008180

Symptoms via clinical synopsis from OMIM:

56
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

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

MalaCards organs/tissues related to Myopathy, Distal, 4:

40
Bone

Publications for Myopathy, Distal, 4

Articles related to Myopathy, Distal, 4:

# Title Authors PMID Year
1
Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy. 56 6
21620354 2011
2
A new dominant distal myopathy affecting posterior leg and anterior upper limb muscles. 56 6
15824355 2005

Variations for Myopathy, Distal, 4

ClinVar genetic disease variations for Myopathy, Distal, 4:

6 (show top 50) (show all 687) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FLNC NM_001458.4(FLNC):c.752T>C (p.Met251Thr)SNV Pathogenic 29591 rs387906586 7:128477504-128477504 7:128837450-128837450
2 FLNC NM_001458.4(FLNC):c.1948C>T (p.Arg650Ter)SNV Pathogenic 421215 rs770606675 7:128481358-128481358 7:128841304-128841304
3 FLNC NM_001458.4(FLNC):c.4716del (p.Leu1573fs)deletion Pathogenic 478127 rs1554400021 7:128488747-128488747 7:128848693-128848693
4 FLNC NM_001458.4(FLNC):c.7294C>T (p.Gln2432Ter)SNV Pathogenic 478131 rs1554401756 7:128496614-128496614 7:128856560-128856560
5 FLNC NM_001458.4(FLNC):c.1519_1525del (p.Gly507fs)deletion Pathogenic 478121 rs1554398092 7:128480181-128480187 7:128840127-128840133
6 FLNC NM_001458.4(FLNC):c.2390-10_2406deldeletion Pathogenic 478125 rs1554398674 7:128482836-128482862 7:128842782-128842808
7 FLNC NM_001458.4(FLNC):c.4926_4927insACGTCACA (p.Val1643fs)insertion Pathogenic 478128 rs1402879259 7:128489028-128489029 7:128848974-128848975
8 FLNC NM_001458.4(FLNC):c.7371del (p.Glu2458fs)deletion Pathogenic 478132 rs1554401780 7:128496691-128496691 7:128856637-128856637
9 FLNC NM_001458.4(FLNC):c.3934_3937dup (p.Arg1313fs)duplication Pathogenic 478126 rs1554399513 7:128486183-128486184 7:128846129-128846130
10 FLNC NM_001458.4(FLNC):c.6976C>T (p.Arg2326Ter)SNV Pathogenic 478129 rs748416758 7:128494715-128494715 7:128854661-128854661
11 FLNC NM_001458.4(FLNC):c.7496_7497insTGCT (p.Gln2499fs)insertion Pathogenic 539334 rs1554401830 7:128496910-128496911 7:128856856-128856857
12 FLNC NM_001458.4(FLNC):c.444G>A (p.Trp148Ter)SNV Pathogenic 539439 rs1554397197 7:128475471-128475471 7:128835417-128835417
13 FLNC NM_001458.4(FLNC):c.805C>T (p.Arg269Ter)SNV Pathogenic 539411 rs755583250 7:128477557-128477557 7:128837503-128837503
14 FLNC NM_001458.4(FLNC):c.5165del (p.Gly1722fs)deletion Pathogenic 539390 rs1554400242 7:128489594-128489594 7:128849540-128849540
15 FLNC NM_001458.4(FLNC):c.5697dup (p.Ser1900fs)duplication Pathogenic 539446 rs1554400700 7:128491536-128491537 7:128851482-128851483
16 FLNC NM_001458.4(FLNC):c.1605C>A (p.Cys535Ter)SNV Pathogenic 539354 rs199976790 7:128480657-128480657 7:128840603-128840603
17 FLNC NM_001458.4(FLNC):c.2065G>T (p.Glu689Ter)SNV Pathogenic 539448 rs1446694237 7:128481565-128481565 7:128841511-128841511
18 FLNC NM_001458.4(FLNC):c.7251+1G>ASNV Pathogenic 539340 rs1554401581 7:128495369-128495369 7:128855315-128855315
19 FLNC NM_001458.4(FLNC):c.7536_7548del (p.Pro2513fs)deletion Pathogenic 539437 rs1554401837 7:128496949-128496961 7:128856895-128856907
20 FLNC NM_001458.4(FLNC):c.4621A>T (p.Lys1541Ter)SNV Pathogenic 577928 rs1562999451 7:128488655-128488655 7:128848601-128848601
21 FLNC NM_001458.4(FLNC):c.4333_4336del (p.Gly1444_Lys1445insTer)deletion Pathogenic 571885 rs1562998858 7:128487793-128487796 7:128847739-128847742
22 FLNC NM_001458.4(FLNC):c.5653A>T (p.Lys1885Ter)SNV Pathogenic 567717 rs1563001456 7:128491399-128491399 7:128851345-128851345
23 FLNC NM_001458.4(FLNC):c.6447del (p.Ile2150fs)deletion Pathogenic 574095 rs1563003153 7:128493853-128493853 7:128853799-128853799
24 FLNC NC_000007.13:g.(?_128470672)_(128498597_?)deldeletion Pathogenic 584412 7:128470672-128498597 7:128830618-128858543
25 FLNC NM_001458.4(FLNC):c.5672delGdeletion Pathogenic 567017 rs1563001548 7:128491508-128491508 7:128851454-128851454
26 FLNC NM_001458.4(FLNC):c.1861_1885dup (p.Arg629fs)duplication Pathogenic 663736 7:128481269-128481270 7:128841215-128841216
27 FLNC NM_001458.4(FLNC):c.554G>A (p.Trp185Ter)SNV Pathogenic 643595 7:128475581-128475581 7:128835527-128835527
28 FLNC NM_001458.4(FLNC):c.4729C>T (p.Gln1577Ter)SNV Pathogenic 645256 7:128488763-128488763 7:128848709-128848709
29 FLNC NM_001458.4(FLNC):c.3937C>T (p.Arg1313Ter)SNV Pathogenic 579589 rs766330686 7:128486190-128486190 7:128846136-128846136
30 FLNC NM_001458.4(FLNC):c.5675_5678del (p.Leu1892fs)deletion Pathogenic 660879 7:128491512-128491515 7:128851458-128851461
31 FLNC NM_001458.4(FLNC):c.6242dup (p.Ser2082fs)duplication Pathogenic 661219 7:128493553-128493554 7:128853499-128853500
32 FLNC NM_001458.4(FLNC):c.6883C>T (p.Gln2295Ter)SNV Pathogenic 642313 7:128494622-128494622 7:128854568-128854568
33 FLNC NM_001458.4(FLNC):c.5904dup (p.Ile1969fs)duplication Pathogenic 640320 7:128492705-128492706 7:128852651-128852652
34 FLNC NM_001127487.2(FLNC):c.147delinsTCT (p.Lys51fs)indel Pathogenic 567163 rs1562988883 7:128470838-128470838 7:128830784-128830784
35 FLNC NM_001127487.2(FLNC):c.7235_7236AC[2] (p.Pro2414fs)short repeat Pathogenic 659634 7:128496653-128496654 7:128856599-128856600
36 FLNC NM_001458.4(FLNC):c.7365C>A (p.Tyr2455Ter)SNV Pathogenic 651699 7:128496685-128496685 7:128856631-128856631
37 FLNC NM_001458.4(FLNC):c.4127+1G>TSNV Pathogenic 643473 7:128486518-128486518 7:128846464-128846464
38 FLNC NM_001458.4(FLNC):c.4969C>T (p.Arg1657Ter)SNV Pathogenic/Likely pathogenic 620418 rs1563000044 7:128489402-128489402 7:128849348-128849348
39 FLNC NM_001458.4(FLNC):c.3180del (p.Asp1061fs)deletion Pathogenic/Likely pathogenic 421585 rs1064795229 7:128484308-128484308 7:128844254-128844254
40 FLNC NM_001458.4(FLNC):c.3791-1G>CSNV Pathogenic/Likely pathogenic 420146 rs781135153 7:128486043-128486043 7:128845989-128845989
41 FLNC NM_001458.4(FLNC):c.3557C>T (p.Ala1186Val)SNV Pathogenic/Likely pathogenic 427928 rs1114167361 7:128485076-128485076 7:128845022-128845022
42 FLNC NM_001458.4(FLNC):c.6997+1G>TSNV Likely pathogenic 642447 7:128494737-128494737 7:128854683-128854683
43 FLNC NM_001458.4(FLNC):c.2550+2T>CSNV Likely pathogenic 641368 7:128483010-128483010 7:128842956-128842956
44 FLNC NM_001458.4(FLNC):c.2265+1G>ASNV Likely pathogenic 642799 7:128482429-128482429 7:128842375-128842375
45 FLNC NM_001458.4(FLNC):c.699+1G>ASNV Likely pathogenic 567368 rs1562991776 7:128477312-128477312 7:128837258-128837258
46 FLNC NM_001458.4(FLNC):c.7780+1G>ASNV Likely pathogenic 582258 rs1563005607 7:128497391-128497391 7:128857337-128857337
47 FLNC NM_001458.4(FLNC):c.4952-2A>TSNV Likely pathogenic 570065 rs774945928 7:128489383-128489383 7:128849329-128849329
48 FLNC NM_001458.4(FLNC):c.3193-2A>GSNV Likely pathogenic 573818 rs749889670 7:128484710-128484710 7:128844656-128844656
49 FLNC NM_001458.4(FLNC):c.1548_1549+2deldeletion Likely pathogenic 580786 rs763330423 7:128480213-128480216 7:128840159-128840162
50 FLNC NM_001458.4(FLNC):c.2389+2T>CSNV Likely pathogenic 569372 rs112903432 7:128482754-128482754 7:128842700-128842700

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

73
# 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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