MCID: FML250
MIFTS: 33

Familial Progressive Cardiac Conduction Defect

Categories: Rare diseases, Genetic diseases

Aliases & Classifications for Familial Progressive Cardiac Conduction Defect

MalaCards integrated aliases for Familial Progressive Cardiac Conduction Defect:

Name: Familial Progressive Cardiac Conduction Defect 53 59
Familial Progressive Heart Block 53 59
Hereditary Bundle Branch Defect 53 59
Familial Lev-Lenègre Disease 53 59
Familial Lenègre Disease 53 59
Familial Lev Disease 53 59
Familial Pccd 53 59
Hereditary Bundle Branch System Defect 73
Progressive Familial Heart Block 53

Characteristics:

Orphanet epidemiological data:

59
familial progressive cardiac conduction defect
Inheritance: Autosomal dominant; Age of onset: Adult; Age of death: elderly;

Classifications:



External Ids:

Orphanet 59 ORPHA871
UMLS via Orphanet 74 C1879286
ICD10 via Orphanet 34 I45.8
SNOMED-CT via HPO 69 102594003 44808001 698247007
UMLS 73 C1879286

Summaries for Familial Progressive Cardiac Conduction Defect

NIH Rare Diseases : 53 Familial progressive cardiac conduction defect (PCCD) is a is a cardiac (heart) conduction disorder that may progress to complete heart block. Affected people may not have any symptoms, or the condition may cause shortness of breath, dizziness, fainting, abdominal pain, heart failure, or sudden death. Mutations in several genes, including the SCN5A, SCN1B and TRPM4 genes, can cause PCCD. Several other genes may be the cause when PCCD occurs with congenital heart disease. Familial PCCD is usually inherited in an autosomal dominant manner. However, not all people that have the mutated gene will have the condition; in those that do, symptoms and severity can vary (known as reduced penetrance and variable expressivity). Autosomal recessive inheritance and sporadic cases have been reported, but are rare. Treatment includes implantation of a pacemaker.

MalaCards based summary : Familial Progressive Cardiac Conduction Defect, also known as familial progressive heart block, is related to progressive familial heart block and progressive familial heart block, type ii, and has symptoms including dyspnea and syncopal episode. An important gene associated with Familial Progressive Cardiac Conduction Defect is SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5), and among its related pathways/superpathways are Aldosterone synthesis and secretion and Cardiac conduction. Affiliated tissues include heart, and related phenotypes are arrhythmia and no phenotypic analysis

Related Diseases for Familial Progressive Cardiac Conduction Defect

Graphical network of the top 20 diseases related to Familial Progressive Cardiac Conduction Defect:



Diseases related to Familial Progressive Cardiac Conduction Defect

Symptoms & Phenotypes for Familial Progressive Cardiac Conduction Defect

Human phenotypes related to Familial Progressive Cardiac Conduction Defect:

59 32
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 arrhythmia 59 32 frequent (33%) Frequent (79-30%) HP:0011675

UMLS symptoms related to Familial Progressive Cardiac Conduction Defect:


dyspnea, syncopal episode

MGI Mouse Phenotypes related to Familial Progressive Cardiac Conduction Defect:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 no phenotypic analysis MP:0003012 8.8 NKX2-5 SCN1B TRPM4

Drugs & Therapeutics for Familial Progressive Cardiac Conduction Defect

Search Clinical Trials , NIH Clinical Center for Familial Progressive Cardiac Conduction Defect

Genetic Tests for Familial Progressive Cardiac Conduction Defect

Anatomical Context for Familial Progressive Cardiac Conduction Defect

MalaCards organs/tissues related to Familial Progressive Cardiac Conduction Defect:

41
Heart

Publications for Familial Progressive Cardiac Conduction Defect

Articles related to Familial Progressive Cardiac Conduction Defect:

(show all 13)
# Title Authors Year
1
Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I. ( 26820365 )
2016
2
A connexin40 mutation associated with a malignant variant of progressive familial heart block type I. ( 22247482 )
2012
3
Progressive familial heart block type I in a korean patient. ( 21731570 )
2011
4
Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I. ( 19726882 )
2009
5
A gene locus for progressive familial heart block type II (PFHBII) maps to chromosome 1q32.2-q32.3. ( 16086176 )
2005
6
Progressive familial heart block type II (PFHBII): a clinical profile from 1977 to 2003. ( 15258623 )
2004
7
Characterisation of the human voltage-gated potassium channel gene, KCNA7, a candidate gene for inherited cardiac disorders, and its exclusion as cause of progressive familial heart block I (PFHBI). ( 11896454 )
2002
8
Gene for progressive familial heart block type I maps to chromosome 19q13. ( 7882468 )
1995
9
Progressive familial heart block type I. Clinical and pathological observations. ( 2063242 )
1991
10
Progressive familial heart block (type I). A follow-up study after 10 years. ( 3347879 )
1988
11
Progressive familial heart block. Part II. Clinical and ECG confirmation of progression--report on 4 cases. ( 3750143 )
1986
12
Progressive familial heart block. Part I. Extent of the disease. ( 3750142 )
1986
13
Progressive familial heart block--two types. ( 897853 )
1977

Variations for Familial Progressive Cardiac Conduction Defect

ClinVar genetic disease variations for Familial Progressive Cardiac Conduction Defect:

6
(show top 50) (show all 268)
# Gene Variation Type Significance SNP ID Assembly Location
1 SCN5A NM_198056.2(SCN5A): c.3308C> A (p.Ser1103Tyr) single nucleotide variant risk factor rs7626962 GRCh37 Chromosome 3, 38620907: 38620907
2 SCN5A NM_198056.2(SCN5A): c.3308C> A (p.Ser1103Tyr) single nucleotide variant risk factor rs7626962 GRCh38 Chromosome 3, 38579416: 38579416
3 SCN5A NM_198056.2(SCN5A): c.1569T> A (p.Arg523=) single nucleotide variant Conflicting interpretations of pathogenicity rs41313693 GRCh37 Chromosome 3, 38645524: 38645524
4 SCN5A NM_198056.2(SCN5A): c.1569T> A (p.Arg523=) single nucleotide variant Conflicting interpretations of pathogenicity rs41313693 GRCh38 Chromosome 3, 38604033: 38604033
5 SCN5A NM_198056.2(SCN5A): c.6003C> T (p.Leu2001=) single nucleotide variant Conflicting interpretations of pathogenicity rs538707712 GRCh37 Chromosome 3, 38591860: 38591860
6 SCN5A NM_198056.2(SCN5A): c.6003C> T (p.Leu2001=) single nucleotide variant Conflicting interpretations of pathogenicity rs538707712 GRCh38 Chromosome 3, 38550369: 38550369
7 SCN5A NM_198056.2(SCN5A): c.4824C> T (p.Leu1608=) single nucleotide variant Conflicting interpretations of pathogenicity rs45437099 GRCh37 Chromosome 3, 38593039: 38593039
8 SCN5A NM_198056.2(SCN5A): c.4824C> T (p.Leu1608=) single nucleotide variant Conflicting interpretations of pathogenicity rs45437099 GRCh38 Chromosome 3, 38551548: 38551548
9 SCN5A NM_198056.2(SCN5A): c.1068T> C (p.Asp356=) single nucleotide variant Conflicting interpretations of pathogenicity rs41313703 GRCh37 Chromosome 3, 38648232: 38648232
10 SCN5A NM_198056.2(SCN5A): c.1068T> C (p.Asp356=) single nucleotide variant Conflicting interpretations of pathogenicity rs41313703 GRCh38 Chromosome 3, 38606741: 38606741
11 SCN5A NM_001099404.1(SCN5A): c.1598G> A (p.Arg533His) single nucleotide variant Uncertain significance rs146848219 GRCh37 Chromosome 3, 38645495: 38645495
12 SCN5A NM_001099404.1(SCN5A): c.1598G> A (p.Arg533His) single nucleotide variant Uncertain significance rs146848219 GRCh38 Chromosome 3, 38604004: 38604004
13 SCN5A NM_198056.2(SCN5A): c.4109A> G (p.Asp1370Gly) single nucleotide variant Uncertain significance rs775485359 GRCh37 Chromosome 3, 38601774: 38601774
14 SCN5A NM_198056.2(SCN5A): c.4109A> G (p.Asp1370Gly) single nucleotide variant Uncertain significance rs775485359 GRCh38 Chromosome 3, 38560283: 38560283
15 SCN5A NM_198056.2(SCN5A): c.2956C> T (p.Arg986Trp) single nucleotide variant Uncertain significance rs561547165 GRCh37 Chromosome 3, 38622694: 38622694
16 SCN5A NM_198056.2(SCN5A): c.2956C> T (p.Arg986Trp) single nucleotide variant Uncertain significance rs561547165 GRCh38 Chromosome 3, 38581203: 38581203
17 SCN5A NM_198056.2(SCN5A): c.787G> A (p.Val263Ile) single nucleotide variant Uncertain significance rs752824646 GRCh37 Chromosome 3, 38651372: 38651372
18 SCN5A NM_198056.2(SCN5A): c.787G> A (p.Val263Ile) single nucleotide variant Uncertain significance rs752824646 GRCh38 Chromosome 3, 38609881: 38609881
19 TRPM4 NM_017636.3(TRPM4): c.322C> T (p.Arg108Cys) single nucleotide variant Benign/Likely benign rs115335683 GRCh37 Chromosome 19, 49671228: 49671228
20 TRPM4 NM_017636.3(TRPM4): c.322C> T (p.Arg108Cys) single nucleotide variant Benign/Likely benign rs115335683 GRCh38 Chromosome 19, 49167971: 49167971
21 TRPM4 NM_017636.3(TRPM4): c.783G> A (p.Lys261=) single nucleotide variant Benign/Likely benign rs111930830 GRCh38 Chromosome 19, 49168723: 49168723
22 TRPM4 NM_017636.3(TRPM4): c.783G> A (p.Lys261=) single nucleotide variant Benign/Likely benign rs111930830 GRCh37 Chromosome 19, 49671980: 49671980
23 SCN5A NM_001099404.1(SCN5A): c.4267G> A (p.Asp1423Asn) single nucleotide variant Uncertain significance rs746291609 GRCh37 Chromosome 3, 38598754: 38598754
24 SCN5A NM_001099404.1(SCN5A): c.4267G> A (p.Asp1423Asn) single nucleotide variant Uncertain significance rs746291609 GRCh38 Chromosome 3, 38557263: 38557263
25 SCN5A NM_198056.2(SCN5A): c.5607C> T (p.Asp1869=) single nucleotide variant Conflicting interpretations of pathogenicity rs560476223 GRCh38 Chromosome 3, 38550765: 38550765
26 SCN5A NM_198056.2(SCN5A): c.5607C> T (p.Asp1869=) single nucleotide variant Conflicting interpretations of pathogenicity rs560476223 GRCh37 Chromosome 3, 38592256: 38592256
27 SCN5A NM_198056.2(SCN5A): c.5454C> T (p.Ala1818=) single nucleotide variant Conflicting interpretations of pathogenicity rs370114378 GRCh38 Chromosome 3, 38550918: 38550918
28 SCN5A NM_198056.2(SCN5A): c.5454C> T (p.Ala1818=) single nucleotide variant Conflicting interpretations of pathogenicity rs370114378 GRCh37 Chromosome 3, 38592409: 38592409
29 SCN5A NM_198056.2(SCN5A): c.3542T> C (p.Val1181Ala) single nucleotide variant Uncertain significance rs376965389 GRCh37 Chromosome 3, 38616912: 38616912
30 SCN5A NM_198056.2(SCN5A): c.3542T> C (p.Val1181Ala) single nucleotide variant Uncertain significance rs376965389 GRCh38 Chromosome 3, 38575421: 38575421
31 TRPM4 NM_017636.3(TRPM4): c.448+6C> T single nucleotide variant Benign/Likely benign rs78051297 GRCh38 Chromosome 19, 49168103: 49168103
32 TRPM4 NM_017636.3(TRPM4): c.448+6C> T single nucleotide variant Benign/Likely benign rs78051297 GRCh37 Chromosome 19, 49671360: 49671360
33 TRPM4 NM_017636.3(TRPM4): c.449-10G> A single nucleotide variant Benign/Likely benign rs78444754 GRCh38 Chromosome 19, 49168250: 49168250
34 TRPM4 NM_017636.3(TRPM4): c.449-10G> A single nucleotide variant Benign/Likely benign rs78444754 GRCh37 Chromosome 19, 49671507: 49671507
35 TRPM4 NM_017636.3(TRPM4): c.1368C> G (p.Thr456=) single nucleotide variant Conflicting interpretations of pathogenicity rs56118173 GRCh38 Chromosome 19, 49182682: 49182682
36 TRPM4 NM_017636.3(TRPM4): c.1368C> G (p.Thr456=) single nucleotide variant Conflicting interpretations of pathogenicity rs56118173 GRCh37 Chromosome 19, 49685939: 49685939
37 TRPM4 NM_017636.3(TRPM4): c.-12G> A single nucleotide variant Benign/Likely benign rs3760663 GRCh37 Chromosome 19, 49661112: 49661112
38 TRPM4 NM_017636.3(TRPM4): c.-12G> A single nucleotide variant Benign/Likely benign rs3760663 GRCh38 Chromosome 19, 49157855: 49157855
39 TRPM4 NM_017636.3(TRPM4): c.2934T> C (p.Ile978=) single nucleotide variant Benign/Likely benign rs35516880 GRCh37 Chromosome 19, 49704023: 49704023
40 TRPM4 NM_017636.3(TRPM4): c.2934T> C (p.Ile978=) single nucleotide variant Benign/Likely benign rs35516880 GRCh38 Chromosome 19, 49200766: 49200766
41 SCN5A NM_198056.2(SCN5A) insertion Likely benign rs45592631 GRCh38 Chromosome 3, 38548175: 38548176
42 SCN5A NM_198056.2(SCN5A) insertion Likely benign rs45592631 GRCh37 Chromosome 3, 38589666: 38589667
43 SCN5A NM_198056.2(SCN5A): c.*1701G> T single nucleotide variant Uncertain significance rs886058441 GRCh38 Chromosome 3, 38548620: 38548620
44 SCN5A NM_198056.2(SCN5A): c.*1701G> T single nucleotide variant Uncertain significance rs886058441 GRCh37 Chromosome 3, 38590111: 38590111
45 SCN5A NM_198056.2(SCN5A): c.*1602G> T single nucleotide variant Uncertain significance rs886058444 GRCh38 Chromosome 3, 38548719: 38548719
46 SCN5A NM_198056.2(SCN5A): c.*1602G> T single nucleotide variant Uncertain significance rs886058444 GRCh37 Chromosome 3, 38590210: 38590210
47 SCN5A NM_198056.2(SCN5A): c.*1537T> C single nucleotide variant Likely benign rs41315485 GRCh38 Chromosome 3, 38548784: 38548784
48 SCN5A NM_198056.2(SCN5A): c.*1537T> C single nucleotide variant Likely benign rs41315485 GRCh37 Chromosome 3, 38590275: 38590275
49 SCN5A NM_198056.2(SCN5A): c.*1165C> T single nucleotide variant Likely benign rs41313017 GRCh38 Chromosome 3, 38549156: 38549156
50 SCN5A NM_198056.2(SCN5A): c.*1165C> T single nucleotide variant Likely benign rs41313017 GRCh37 Chromosome 3, 38590647: 38590647

Expression for Familial Progressive Cardiac Conduction Defect

Search GEO for disease gene expression data for Familial Progressive Cardiac Conduction Defect.

Pathways for Familial Progressive Cardiac Conduction Defect

Pathways related to Familial Progressive Cardiac Conduction Defect according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.41 SCN1B SCN5A TRPM4
2
Show member pathways
12.16 NKX2-5 SCN1B SCN5A
3
Show member pathways
11.5 SCN1B SCN5A
4
Show member pathways
11.2 SCN1B SCN5A
5 10.9 SCN1B SCN5A
6 10.68 NKX2-5 SCN5A
7 10.1 SCN1B SCN5A

GO Terms for Familial Progressive Cardiac Conduction Defect

Cellular components related to Familial Progressive Cardiac Conduction Defect according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intercalated disc GO:0014704 9.26 SCN1B SCN5A
2 T-tubule GO:0030315 9.16 SCN1B SCN5A
3 voltage-gated sodium channel complex GO:0001518 8.96 SCN1B SCN5A
4 sodium channel complex GO:0034706 8.62 SCN1B TRPM4

Biological processes related to Familial Progressive Cardiac Conduction Defect according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.71 SCN1B SCN5A TRPM4
2 regulation of ion transmembrane transport GO:0034765 9.56 SCN1B SCN5A
3 sodium ion transport GO:0006814 9.55 SCN1B SCN5A
4 sodium ion transmembrane transport GO:0035725 9.52 SCN1B SCN5A
5 membrane depolarization GO:0051899 9.51 SCN1B SCN5A
6 cardiac conduction GO:0061337 9.5 SCN1B SCN5A TRPM4
7 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.49 SCN1B SCN5A
8 cardiac muscle cell action potential involved in contraction GO:0086002 9.48 SCN1B SCN5A
9 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.46 SCN1B SCN5A
10 regulation of atrial cardiac muscle cell membrane depolarization GO:0060371 9.43 SCN1B SCN5A
11 cardiac muscle contraction GO:0060048 9.43 NKX2-5 SCN1B SCN5A
12 membrane depolarization during AV node cell action potential GO:0086045 9.4 SCN5A TRPM4
13 membrane depolarization during bundle of His cell action potential GO:0086048 9.37 SCN5A TRPM4
14 regulation of heart rate by cardiac conduction GO:0086091 9.33 SCN1B SCN5A TRPM4
15 positive regulation of sodium ion transport GO:0010765 9.13 NKX2-5 SCN1B SCN5A
16 membrane depolarization during Purkinje myocyte cell action potential GO:0086047 8.8 SCN1B SCN5A TRPM4

Molecular functions related to Familial Progressive Cardiac Conduction Defect according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 calmodulin binding GO:0005516 9.4 SCN5A TRPM4
2 ion channel activity GO:0005216 9.37 SCN5A TRPM4
3 voltage-gated ion channel activity GO:0005244 9.32 SCN1B SCN5A
4 voltage-gated sodium channel activity GO:0005248 9.26 SCN1B SCN5A
5 voltage-gated sodium channel activity involved in cardiac muscle cell action potential GO:0086006 9.16 SCN1B SCN5A
6 voltage-gated sodium channel activity involved in Purkinje myocyte action potential GO:0086062 8.96 SCN1B SCN5A
7 sodium channel activity GO:0005272 8.8 SCN1B SCN5A TRPM4

Sources for Familial Progressive Cardiac Conduction Defect

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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