CVD1
MCID: CRD017
MIFTS: 37

Cardiac Valvular Dysplasia, X-Linked (CVD1)

Categories: Blood diseases, Cardiovascular diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Cardiac Valvular Dysplasia, X-Linked

MalaCards integrated aliases for Cardiac Valvular Dysplasia, X-Linked:

Name: Cardiac Valvular Dysplasia, X-Linked 57 72 29 13 6
X-Linked Cardiac Valvular Dysplasia 12 20 43 36 15
Cvd1 57 12 20 43 72
Xmvd 57 12 20 43 72
Filamin a-Related X-Linked Myxomatous Valvular Dysplasia 12 20 58
Flna-Related X-Linked Myxomatous Valvular Dysplasia 12 20 58
Flna-Related Valvular Dystrophy 12 20 58
Myxomatous Valvular Dystrophy, X-Linked 57 20
X-Linked Myxomatous Valvular Dystrophy 43 72
Dystrophie Valvulaire Associee a Flna 12 58
Valvular Heart Disease, Congenital 57 20
Congenital Valvular Heart Disease 43 72
Ehlers-Danlos Syndrome, Type V, Formerly; Eds5, Formerly 57
Filamin-a-Associated Myxomatous Mitral Valve Disease 43
Filamin-a-Related Myxomatous Mitral Valve Dystrophy 43
Myxomatous Valvular Dystrophy, X-Linked; Xmvd 57
Ehlers-Danlos Syndrome, Type V, Formerly 57
Dystrophie Valvulaire Associée À Flna 20
Ehlers-Danlos Syndrome, Type 5 12
Ehlers-Danlos Syndrome Type 5 44
Congenital Valvular Dysplasia 72
Eds5, Formerly 57
Eds 5 12
Cvdx 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
phenotypic variability
male patients more severely affected than female patients

Inheritance:
x-linked


HPO:

31
cardiac valvular dysplasia, x-linked:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare cardiac malformations
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0111765
OMIM® 57 314400
KEGG 36 H02230
NCIt 50 C141423
SNOMED-CT 67 67202007
ICD10 via Orphanet 33 Q23.8
Orphanet 58 ORPHA555877
MedGen 41 C0262436
UMLS 70 C0268341

Summaries for Cardiac Valvular Dysplasia, X-Linked

MedlinePlus Genetics : 43 X-linked cardiac valvular dysplasia is a condition characterized by the abnormal development (dysplasia) of heart (cardiac) valves. The normal heart has four valves, two on the left side of the heart and two on the right side, that allow blood to move through the heart and prevent blood from flowing backward. In X-linked cardiac valvular dysplasia, one or more of the four heart valves is thickened and cannot open and close completely when the heart beats and pumps blood. These malformed valves can cause abnormal blood flow and an irregular heart sound during a heartbeat (heart murmur).The signs and symptoms of X-linked cardiac valvular dysplasia vary greatly among affected individuals. Some people have no health problems, while in others blood can leak through the thickened and partially closed valves. This valve leakage (regurgitation) typically affects the mitral valve, which connects the two left chambers of the heart, or the aortic valve, which regulates blood flow from the heart into the large artery called the aorta. Valve regurgitation forces the heart to pump harder to move blood through the heart. As a result, affected individuals may develop chest pains, shortness of breath, or lightheadedness.In X-linked cardiac valvular dysplasia, the mitral or aortic valve can also be prolapsed, which means that the valve is weak or floppy. Valve prolapse further prevents the thickened valve from closing properly and can lead to valve regurgitation. Other rare complications of X-linked cardiac valvular dysplasia include inflammation of the inner lining of the heart (endocarditis), abnormal blood clots, or sudden death.X-linked cardiac valvular dysplasia can be diagnosed anytime from birth (in some cases prenatally) to late adulthood but is typically diagnosed in early to mid-adulthood because valve malformation is often a slow process. This condition affects males more often and more severely than females.

MalaCards based summary : Cardiac Valvular Dysplasia, X-Linked, also known as x-linked cardiac valvular dysplasia, is related to x-linked ehlers-danlos syndrome and marfan syndrome. An important gene associated with Cardiac Valvular Dysplasia, X-Linked is FLNA (Filamin A). Affiliated tissues include heart, and related phenotypes are ptosis and hypertelorism

Disease Ontology : 12 A heart valve disease characterized by multivalvular dysplasia and regurgitation with more severe phenotypes in hemizygous males compared to heterozygous females that has material basis in mutation in FLNA on chromosome Xq28.

OMIM® : 57 X-linked cardiac valvular dysplasia is a rare form of heart disease characterized by multivalvular dysplasia and regurgitation, which can lead to lethal heart failure in some patients. Heterozygous females are more mildly affected than hemizygous males. Some patients also exhibit features of Ehler-Danlos syndrome (EDS; see 130000), with hyperextensible skin and joint hypermobility, whereas others have stiffening of joints from early childhood (Kyndt et al., 2007; Ritelli et al., 2017; Mercer et al., 2017). (314400) (Updated 20-May-2021)

KEGG : 36 X-linked cardiac valvular dysplasia is characterized by mitral valve dystrophy frequently associated with degeneration of the aortic valves affecting males and, to a lower severity, females. It has been reported that mutations in FLNA encoding filamin A cause this disease.

UniProtKB/Swiss-Prot : 72 Cardiac valvular dysplasia, X-linked: A rare X-linked heart disease characterized by mitral and/or aortic valve regurgitation. The histologic features include fragmentation of collagenous bundles within the valve fibrosa and accumulation of proteoglycans, which produces excessive valve tissue leading to billowing of the valve leaflets.

Related Diseases for Cardiac Valvular Dysplasia, X-Linked

Graphical network of the top 20 diseases related to Cardiac Valvular Dysplasia, X-Linked:



Diseases related to Cardiac Valvular Dysplasia, X-Linked

Symptoms & Phenotypes for Cardiac Valvular Dysplasia, X-Linked

Human phenotypes related to Cardiac Valvular Dysplasia, X-Linked:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 ptosis 31 very rare (1%) HP:0000508
2 hypertelorism 31 very rare (1%) HP:0000316
3 prominent supraorbital ridges 31 very rare (1%) HP:0000336
4 joint stiffness 31 very rare (1%) HP:0001387
5 thick vermilion border 31 very rare (1%) HP:0012471
6 bicuspid aortic valve 31 very rare (1%) HP:0001647
7 joint laxity 31 very rare (1%) HP:0001388
8 cutis laxa 31 very rare (1%) HP:0000973
9 congestive heart failure 31 HP:0001635
10 mitral valve prolapse 31 HP:0001634
11 mitral regurgitation 31 HP:0001653
12 abnormality of metabolism/homeostasis 31 HP:0001939
13 tricuspid regurgitation 31 HP:0005180
14 aortic regurgitation 31 HP:0001659
15 short chordae tendineae of the tricuspid valve 31 HP:0006692
16 short chordae tendineae of the mitral valve 31 HP:0011580

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Cardiovascular Heart:
congestive heart failure
mitral valve prolapse
mitral regurgitation
tricuspid regurgitation
aortic regurgitation
more
Head And Neck Face:
prominent supraorbital ridges (in some patients)

Skeletal:
joint laxity, mild (in some patients)
joint stiffness (in some patients)

Skeletal Feet:
proximally placed and externally rotated fifth toe (in some patients)

Muscle Soft Tissue:
reduced limb musculature (in some patients)

Head And Neck Eyes:
hypertelorism (in some patients)
ptosis (in some patients)

Head And Neck Mouth:
thick lips (in some patients)

Skeletal Limbs:
limited supination of elbows
fixed flexion of knees
fixed flexion of ankles

Skin Nails Hair Skin:
skin laxity (in some patients)
keloid scarring (in some patients)

Clinical features from OMIM®:

314400 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Cardiac Valvular Dysplasia, X-Linked according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased viability GR00386-A-1 8.62 GDPGP1 H2AC18

Drugs & Therapeutics for Cardiac Valvular Dysplasia, X-Linked

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 An Open-label, Single-arm, Post-authorization Pragmatic Clinical Trial On The Safety And Efficacy Of Benefix (Nonacog Alfa, Recombinant Factor Ix) In Subjects With Hemophilia B In Usual Care Settings In China Completed NCT02336178 Phase 4 Benefix

Search NIH Clinical Center for Cardiac Valvular Dysplasia, X-Linked

Cochrane evidence based reviews: ehlers-danlos syndrome type 5

Genetic Tests for Cardiac Valvular Dysplasia, X-Linked

Genetic tests related to Cardiac Valvular Dysplasia, X-Linked:

# Genetic test Affiliating Genes
1 Cardiac Valvular Dysplasia, X-Linked 29 FLNA

Anatomical Context for Cardiac Valvular Dysplasia, X-Linked

MalaCards organs/tissues related to Cardiac Valvular Dysplasia, X-Linked:

40
Heart

Publications for Cardiac Valvular Dysplasia, X-Linked

Articles related to Cardiac Valvular Dysplasia, X-Linked:

(show all 15)
# Title Authors PMID Year
1
Familial Ebstein Anomaly: Whole Exome Sequencing Identifies Novel Phenotype Associated With FLNA. 57 6
29237676 2017
2
Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA. 57 6
27739212 2017
3
Mutations in the gene encoding filamin A as a cause for familial cardiac valvular dystrophy. 57 6
17190868 2007
4
Mapping of X-linked myxomatous valvular dystrophy to chromosome Xq28. 6 57
9497244 1998
5
Sex linked valvular dysplasia. 57 6
8230166 1993
6
Familial Ebstein's anomaly: a report of six cases in two generations associated with mild skeletal abnormalities. 57 6
1854572 1991
7
Lysyl oxidase deficiency in Ehlers-Danlos syndrome type V. 6 57
240645 1975
8
The 2017 international classification of the Ehlers-Danlos syndromes. 57
28306229 2017
9
Molecular diagnostic experience of whole-exome sequencing in adult patients. 6
26633545 2016
10
X-linked Ehlers-Danlos syndrome type V; the next generation. 57
4006272 1985
11
Cross-linking of collagen in the X-linked Ehlers-Danlos Type V. 57
36897 1979
12
Possible X-linked congenital heart disease. 57
5787314 1969
13
Symptomatic valvular myxomatous transformation (the floppy valve syndrome). A possible forme fruste of the Marfan syndrome. 57
5845248 1965
14
Coincident linkage of type 2 diabetes, metabolic syndrome, and measures of cardiovascular disease in a genome scan of the diabetes heart study. 61
16804067 2006
15
Plasmodium falciparum: in vitro characterization and human infectivity of a cloned line. 61
1346766 1992

Variations for Cardiac Valvular Dysplasia, X-Linked

ClinVar genetic disease variations for Cardiac Valvular Dysplasia, X-Linked:

6 (show all 36)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FLNA NM_001110556.2(FLNA):c.1910C>A (p.Pro637Gln) SNV Pathogenic 11776 rs267606815 GRCh37: X:153593006-153593006
GRCh38: X:154364638-154364638
2 FLNA NM_001110556.2(FLNA):c.862G>A (p.Gly288Arg) SNV Pathogenic 11777 rs267606816 GRCh37: X:153595771-153595771
GRCh38: X:154367403-154367403
3 FLNA NM_001110556.2(FLNA):c.2132T>A (p.Val711Asp) SNV Pathogenic 11778 rs267606817 GRCh37: X:153592631-153592631
GRCh38: X:154364263-154364263
4 FLNA NM_001110556.2(FLNA):c.2280+266_2827-25delinsTG Indel Pathogenic 11779 GRCh37: X:153590180-153592124
GRCh38: X:154361812-154363756
5 FLNA NM_001110556.2(FLNA):c.1923C>T (p.Gly641=) SNV Pathogenic 11770 rs80338841 GRCh37: X:153592993-153592993
GRCh38: X:154364625-154364625
6 FLNA NM_001110556.2(FLNA):c.1829-1G>C SNV Pathogenic 635974 rs1603362402 GRCh37: X:153593088-153593088
GRCh38: X:154364720-154364720
7 FLNA NM_001110556.2(FLNA):c.1910C>T (p.Pro637Leu) SNV Pathogenic 931568 GRCh37: X:153593006-153593006
GRCh38: X:154364638-154364638
8 FLNA NM_001110556.2(FLNA):c.1924G>T (p.Glu642Ter) SNV Likely pathogenic 931351 GRCh37: X:153592992-153592992
GRCh38: X:154364624-154364624
9 FLNA NM_001110556.2(FLNA):c.4750_4755+18del Deletion Likely pathogenic 871720 GRCh37: X:153586549-153586572
GRCh38: X:154358181-154358204
10 FLNA NM_001110556.2(FLNA):c.4660G>A (p.Gly1554Arg) SNV Likely pathogenic 635975 rs1603360542 GRCh37: X:153586662-153586662
GRCh38: X:154358294-154358294
11 FLNA NM_001110556.2(FLNA):c.622+5G>C SNV Likely pathogenic 930545 GRCh37: X:153596205-153596205
GRCh38: X:154367837-154367837
12 FLNA NM_001110556.2(FLNA):c.4726G>A (p.Gly1576Arg) SNV Likely pathogenic 209154 rs797045044 GRCh37: X:153586596-153586596
GRCh38: X:154358228-154358228
13 FLNA NM_001110556.2(FLNA):c.461T>C (p.Met154Thr) SNV Uncertain significance 435209 rs782240483 GRCh37: X:153596371-153596371
GRCh38: X:154368003-154368003
14 FLNA NM_001110556.2(FLNA):c.2467G>A (p.Asp823Asn) SNV Uncertain significance 930326 GRCh37: X:153590884-153590884
GRCh38: X:154362516-154362516
15 FLNA NM_001110556.2(FLNA):c.546G>C (p.Gln182His) SNV Uncertain significance 548502 rs1557179648 GRCh37: X:153596286-153596286
GRCh38: X:154367918-154367918
16 LOC107988032 , FLNA NM_001110556.2(FLNA):c.7628G>A (p.Cys2543Tyr) SNV Uncertain significance 392335 GRCh37: X:153577858-153577858
GRCh38: X:154349490-154349490
17 FLNA NM_001110556.2(FLNA):c.6863G>A (p.Arg2288His) SNV Uncertain significance 465015 rs782275601 GRCh37: X:153580296-153580296
GRCh38: X:154351928-154351928
18 FLNA NM_001110556.2(FLNA):c.6725G>A (p.Arg2242Gln) SNV Uncertain significance 435203 rs781984274 GRCh37: X:153580593-153580593
GRCh38: X:154352225-154352225
19 FLNA NM_001110556.2(FLNA):c.6719A>G (p.Lys2240Arg) SNV Uncertain significance 211024 rs797045581 GRCh37: X:153580599-153580599
GRCh38: X:154352231-154352231
20 FLNA NM_001110556.2(FLNA):c.6376C>T (p.Pro2126Ser) SNV Uncertain significance 533577 rs782400832 GRCh37: X:153581143-153581143
GRCh38: X:154352775-154352775
21 FLNA NM_001110556.2(FLNA):c.2254G>A (p.Val752Ile) SNV Uncertain significance 432226 rs1297013254 GRCh37: X:153592416-153592416
GRCh38: X:154364048-154364048
22 FLNA NM_001110556.2(FLNA):c.901C>T (p.Arg301Trp) SNV Uncertain significance 198133 rs192609440 GRCh37: X:153595186-153595186
GRCh38: X:154366818-154366818
23 FLNA NM_001110556.2(FLNA):c.569G>A (p.Arg190Gln) SNV Uncertain significance 213491 rs782447567 GRCh37: X:153596263-153596263
GRCh38: X:154367895-154367895
24 FLNA NM_001110556.2(FLNA):c.4314C>G (p.Phe1438Leu) SNV Uncertain significance 625948 rs1557177412 GRCh37: X:153587512-153587512
GRCh38: X:154359144-154359144
25 FLNA NM_001110556.2(FLNA):c.2974A>G (p.Thr992Ala) SNV Uncertain significance 588552 rs782445995 GRCh37: X:153589909-153589909
GRCh38: X:154361541-154361541
26 FLNA NM_001110556.2(FLNA):c.2364G>A (p.Glu788=) SNV Uncertain significance 625949 rs1448428046 GRCh37: X:153591069-153591069
GRCh38: X:154362701-154362701
27 FLNA NM_001110556.2(FLNA):c.1204A>G (p.Thr402Ala) SNV Uncertain significance 625950 rs1569551838 GRCh37: X:153594700-153594700
GRCh38: X:154366332-154366332
28 FLNA NM_001110556.2(FLNA):c.494A>G (p.Lys165Arg) SNV Uncertain significance 625951 rs1569551874 GRCh37: X:153596338-153596338
GRCh38: X:154367970-154367970
29 FLNA NM_001110556.2(FLNA):c.4403C>T (p.Pro1468Leu) SNV Uncertain significance 996894 GRCh37: X:153587423-153587423
GRCh38: X:154359055-154359055
30 FLNA NM_001110556.2(FLNA):c.1349T>C (p.Met450Thr) SNV Uncertain significance 1030401 GRCh37: X:153594472-153594472
GRCh38: X:154366104-154366104
31 FLNA NM_001110556.2(FLNA):c.3323G>A (p.Cys1108Tyr) SNV Uncertain significance 93756 rs371677498 GRCh37: X:153588840-153588840
GRCh38: X:154360472-154360472
32 FLNA NM_001110556.2(FLNA):c.3691G>A (p.Val1231Ile) SNV Uncertain significance 931380 GRCh37: X:153588472-153588472
GRCh38: X:154360104-154360104
33 FLNA NM_001110556.2(FLNA):c.4265A>G (p.Tyr1422Cys) SNV Uncertain significance 931632 GRCh37: X:153587652-153587652
GRCh38: X:154359284-154359284
34 FLNA NM_001110556.2(FLNA):c.5021T>C (p.Val1674Ala) SNV Uncertain significance 1033846 GRCh37: X:153583389-153583389
GRCh38: X:154355021-154355021
35 FLNA NM_001110556.2(FLNA):c.3886C>T (p.Arg1296Cys) SNV Uncertain significance 1033845 GRCh37: X:153588193-153588193
GRCh38: X:154359825-154359825
36 FLNA NM_001110556.2(FLNA):c.1571G>A (p.Gly524Glu) SNV not provided 440936 rs1557178957 GRCh37: X:153593624-153593624
GRCh38: X:154365256-154365256

UniProtKB/Swiss-Prot genetic disease variations for Cardiac Valvular Dysplasia, X-Linked:

72
# Symbol AA change Variation ID SNP ID
1 FLNA p.Gly288Arg VAR_064156 rs267606816
2 FLNA p.Pro637Gln VAR_064157 rs267606815
3 FLNA p.Val711Asp VAR_064158 rs267606817

Expression for Cardiac Valvular Dysplasia, X-Linked

Search GEO for disease gene expression data for Cardiac Valvular Dysplasia, X-Linked.

Pathways for Cardiac Valvular Dysplasia, X-Linked

GO Terms for Cardiac Valvular Dysplasia, X-Linked

Sources for Cardiac Valvular Dysplasia, X-Linked

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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