HBBD
MCID: PRG126
MIFTS: 59

Progressive Familial Heart Block (HBBD)

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

Aliases & Classifications for Progressive Familial Heart Block

MalaCards integrated aliases for Progressive Familial Heart Block:

Name: Progressive Familial Heart Block 12 20 43 29 6 15
Hereditary Bundle Branch Defect 12 20 43 58
Familial Progressive Heart Block 12 20 58
Familial Lev Disease 12 20 58
Familial Pccd 12 20 58
Familial Progressive Cardiac Conduction Defect 20 58
Hereditary Bundle Branch System Defect 43 70
Familial Lev-Lenegre Disease 12 58
Familial Lenegre Disease 12 58
Progressive Cardiac Conduction Defect 43
Familial Lev-Lenègre Disease 20
Familial Lenègre Disease 20
Bundle Branch Block 43
Lenegre Lev Disease 43
Lev-Lenègre Disease 43
Bundle-Branch Block 70
Lev's Disease 43
Lev Syndrome 43
Pccd 43
Hbbd 43
Pfhb 12

Characteristics:

Orphanet epidemiological data:

58
familial progressive cardiac conduction defect
Inheritance: Autosomal dominant; Age of onset: Adult; Age of death: elderly;

Classifications:



External Ids:

Disease Ontology 12 DOID:0111073
ICD10 via Orphanet 33 I45.8
UMLS via Orphanet 71 C1879286
Orphanet 58 ORPHA871
UMLS 70 C0006384 C1879286

Summaries for Progressive Familial Heart Block

MedlinePlus Genetics : 43 Progressive familial heart block is a genetic condition that alters the normal beating of the heart. A normal heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. These signals begin in a specialized cluster of cells called the sinoatrial node (the heart's natural pacemaker) located in the heart's upper chambers (the atria). From there, a group of cells called the atrioventricular node carries the electrical signals to another cluster of cells called the bundle of His. This bundle separates into multiple thin spindles called bundle branches, which carry electrical signals into the heart's lower chambers (the ventricles). Electrical impulses move from the sinoatrial node down to the bundle branches, stimulating a normal heartbeat in which the ventricles contract slightly later than the atria.Heart block occurs when the electrical signaling is obstructed anywhere from the atria to the ventricles. In people with progressive familial heart block, the condition worsens over time: early in the disorder, the electrical signals are partially blocked, but the block eventually becomes complete, preventing any signals from passing through the heart. Partial heart block causes a slow or irregular heartbeat (bradycardia or arrhythmia, respectively), and can lead to the buildup of scar tissue (fibrosis) in the cells that carry electrical impulses. Fibrosis contributes to the development of complete heart block, resulting in uncoordinated electrical signaling between the atria and the ventricles and inefficient pumping of blood in the heart. Complete heart block can cause a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, fainting (syncope), or sudden cardiac arrest and death.Progressive familial heart block can be divided into type I and type II, with type I being further divided into types IA and IB. These types differ in where in the heart signaling is interrupted and the genetic cause. In types IA and IB, the heart block originates in the bundle branch, and in type II, the heart block originates in the atrioventricular node. The different types of progressive familial heart block have similar signs and symptoms.Most cases of heart block are not genetic and are not considered progressive familial heart block. The most common cause of heart block is fibrosis of the heart, which occurs as a normal process of aging. Other causes of heart block can include the use of certain medications or an infection of the heart tissue.

MalaCards based summary : Progressive Familial Heart Block, also known as hereditary bundle branch defect, is related to progressive familial heart block, type ib and progressive familial heart block, type ia, and has symptoms including dyspnea and syncopal episode. An important gene associated with Progressive Familial Heart Block is SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5), and among its related pathways/superpathways are Cardiac conduction and cGMP-PKG signaling pathway. The drugs tannic acid and Benzocaine have been mentioned in the context of this disorder. Affiliated tissues include heart, atrioventricular node and skeletal muscle, and related phenotypes are congestive heart failure and abdominal pain

Disease Ontology : 12 A heart conduction disease characterized by autosomal dominant inheritance of a cardiac conduction defect that may progress to complete atrioventricular (AV) block and maybe asymptomatic of manifest as shortness of breath, dizziness, syncope, abdominal pain, heart failure or sudden death.

GARD : 20 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.

Related Diseases for Progressive Familial Heart Block

Diseases in the Heart Block, Congenital family:

Progressive Familial Heart Block, Type Ia Progressive Familial Heart Block, Type Ii
Progressive Familial Heart Block, Type Ib Progressive Familial Heart Block

Diseases related to Progressive Familial Heart Block via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 301)
# Related Disease Score Top Affiliating Genes
1 progressive familial heart block, type ib 33.7 TRPM4 HRC
2 progressive familial heart block, type ia 33.7 SCN5A GJA5 DSP
3 left bundle branch hemiblock 33.5 TNNT2 SCN5A RYR2 DSP
4 progressive familial heart block, type ii 33.5 TNNT2 PFHB2 FICD
5 wolff-parkinson-white syndrome 32.5 TNNT2 SCN5A NKX2-5 MYH7 MYBPC3 KCNQ1
6 brugada syndrome 4 32.5 SCN5A KCNQ1 CACNA1C
7 arrhythmogenic right ventricular dysplasia, familial, 1 32.5 RYR2 MYBPC3 DSP
8 ventricular fibrillation, paroxysmal familial, 1 32.3 TNNT2 SCN5A RYR2 NKX2-5 KCNQ1 DSP
9 brugada syndrome 5 32.3 SCN5A SCN1B
10 heart septal defect 31.9 TNNT2 NKX2-5 GJA5
11 congestive heart failure 31.8 TNNT2 SCN5A RYR2 MYH7 KCNQ1 CACNA1C
12 third-degree atrioventricular block 31.7 SCN5A SCN1B GJA5
13 mitral valve insufficiency 31.6 TNNT2 MYH7 MYBPC3
14 atrial standstill 1 31.6 TNNT2 SCN5A SCN1B RYR2 MYH7 MYBPC3
15 lipoprotein quantitative trait locus 31.5 TNNT2 SCN5A RYR2 NKX2-5 MYH7 MYBPC3
16 tetralogy of fallot 31.5 TNNT2 SCN5A RYR2 NKX2-5 GJA5
17 atrial heart septal defect 31.3 TNNT2 SCN5A NKX2-5 MYH7 GJA5
18 heart disease 31.3 TNNT2 SCN5A RYR2 NKX2-5 MYH7 MYBPC3
19 sick sinus syndrome 31.3 SCN5A SCN1B LOC110121269 GJA5 CACNA1C
20 atrial fibrillation 31.2 SCN5A SCN1B RYR2 MYH7 MYBPC3 KCNQ1
21 cardiac arrest 31.1 TNNT2 SCN5A RYR2 MYH7 MYBPC3 KCNQ1
22 cardiac conduction defect 31.1 TRPM4 SCN5A SCN1B RYR2 MYH7 MYBPC3
23 arrhythmogenic right ventricular cardiomyopathy 31.1 TRPM4 SCN5A RYR2 MYH7 HRC FLNC
24 cardiac arrhythmia 30.9 SCN5A SCN1B RYR2 LOC110121269 KCNQ1 DSP
25 familial long qt syndrome 30.8 SCN5A LOC110121269 KCNQ1 DSP
26 right bundle branch block 30.8 TRPM4 SCN5A SCN1B CACNA1C
27 aortic valve disease 2 30.7 TNNT2 NKX2-5 MYH7 MYBPC3
28 lateral myocardial infarction 30.7 TRPM4 SCN5A SCN1B
29 mobitz type ii atrioventricular block 30.7 TNNT2 MYH7
30 sinoatrial node disease 30.6 SCN5A SCN1B RYR2 NKX2-5 KCNQ1 GJA5
31 first-degree atrioventricular block 30.6 SCN5A MYH7
32 patent foramen ovale 30.6 TRPM4 TNNT2 NKX2-5 GJA5 FLNC-AS1 FLNC
33 long qt syndrome 30.6 TRPM4 SCN5A SCN1B RYR2 MYH7 MYBPC3
34 brugada syndrome 1 30.5 SCN5A RYR2 MYBPC3 LOC110121269
35 syncope 30.5 TNNT2 SCN5A RYR2 KCNQ1
36 hypertrophic cardiomyopathy 30.5 TRPM4 TNNT2 SCN5A RYR2 NKX2-5 MYH7
37 atrioventricular block 30.4 TRPM4 SCN5A RYR2 NKX2-5 MYH7 KCNQ1
38 left ventricular noncompaction 30.2 TNNT2 SCN5A SCN1B RYR2 NKX2-5 MYH7
39 restrictive cardiomyopathy 30.1 TRPM4 TNNT2 MYH7 MYBPC3 FLNC-AS1 FLNC
40 dilated cardiomyopathy 29.9 TNNT2 SCN5A RYR2 NKX2-5 MYH7 MYBPC3
41 brugada syndrome 29.8 TRPM4 TNNT2 SCN5A SCN1B RYR2 NKX2-5
42 bundle branch block, familial isolated complete right 11.4
43 heart-hand syndrome, spanish type 11.3
44 brugada syndrome 2 11.3
45 brugada syndrome 3 11.3
46 brugada syndrome 6 11.3
47 brugada syndrome 7 11.3
48 brugada syndrome 8 11.3
49 brugada syndrome 9 11.3
50 arrhythmogenic right ventricular dysplasia, familial, 14 11.3

Graphical network of the top 20 diseases related to Progressive Familial Heart Block:



Diseases related to Progressive Familial Heart Block

Symptoms & Phenotypes for Progressive Familial Heart Block

Human phenotypes related to Progressive Familial Heart Block:

58 31 (show all 8)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 congestive heart failure 58 31 frequent (33%) Frequent (79-30%) HP:0001635
2 abdominal pain 58 31 frequent (33%) Frequent (79-30%) HP:0002027
3 dyspnea 58 31 frequent (33%) Frequent (79-30%) HP:0002094
4 vertigo 58 31 frequent (33%) Frequent (79-30%) HP:0002321
5 arrhythmia 58 31 frequent (33%) Frequent (79-30%) HP:0011675
6 bundle branch block 58 31 frequent (33%) Frequent (79-30%) HP:0011710
7 syncope 58 31 frequent (33%) Frequent (79-30%) HP:0001279
8 heart block 58 Frequent (79-30%)

UMLS symptoms related to Progressive Familial Heart Block:


dyspnea; syncopal episode

MGI Mouse Phenotypes related to Progressive Familial Heart Block:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.93 CACNA1C DSP FLNC GJA5 KCNQ1 MYBPC3
2 muscle MP:0005369 9.7 CACNA1C DSP FLNC GJA5 KCNQ1 MYBPC3
3 normal MP:0002873 9.23 GJA5 KCNQ1 MYH7 NKX2-5 RYR2 SCN1B

Drugs & Therapeutics for Progressive Familial Heart Block

Drugs for Progressive Familial Heart Block (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 31)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
tannic acid Approved Phase 1, Phase 2 1401-55-4
2
Benzocaine Approved, Investigational Phase 1, Phase 2 1994-09-7, 94-09-7 2337
3
Lidocaine Approved, Vet_approved Phase 2 137-58-6 3676
4
Clonidine Approved Phase 2 4205-90-7 2803
5 Anesthetics Phase 2
6 Anesthetics, Local Phase 2
7 Neurotransmitter Agents Phase 2
8 Anti-Arrhythmia Agents Phase 2
9 Adrenergic Agonists Phase 2
10 Adrenergic alpha-Agonists Phase 2
11 Sodium Channel Blockers Phase 2
12 Adrenergic Agents Phase 2
13 Antihypertensive Agents Phase 2
14 Sympatholytics Phase 2
15 Diuretics, Potassium Sparing Phase 2
16 Analgesics Phase 2
17 Vasodilator Agents Phase 1, Phase 2
18 Pharmaceutical Solutions Phase 1, Phase 2
19 Vasoconstrictor Agents Phase 1, Phase 2
20 Calcium, Dietary Phase 1, Phase 2
21
Calcium Nutraceutical Phase 1, Phase 2 7440-70-2 271
22
Prednisolone Approved, Vet_approved 50-24-8 5755
23
Methylprednisolone Approved, Vet_approved 83-43-2 6741
24
Prednisolone acetate Approved, Vet_approved 52-21-1
25
Methylprednisolone hemisuccinate Approved 2921-57-5
26
Prednisolone phosphate Approved, Vet_approved 302-25-0
27
Chlorhexidine Approved, Vet_approved 55-56-1 2713 9552079
28
Nimodipine Approved, Investigational 66085-59-4 4497
29
Prednisolone hemisuccinate Experimental 2920-86-7
30 Chlorhexidine gluconate
31 Methylprednisolone Acetate

Interventional clinical trials:

(show top 50) (show all 56)
# Name Status NCT ID Phase Drugs
1 Assessment of the Prognosis of Persistent Left Bundle Branch Block (LBBB) After Transcatheter Aortic Valve Implantation (TAVI ) by an Electrophysiological and Remote Monitoring Risk-adapted Algorithm Unknown status NCT02482844 Phase 4
2 Resynchronization in Paced Heart Failure Patients With ICD Indication Unknown status NCT01415024 Phase 4
3 Effect of Cardiac Resynchronization Therapy on Skeletal Muscle Histology, Neuroendocrine Activation and Inflammatory Response Completed NCT01019915 Phase 4
4 MADIT ASIA Cardiac Resynchronization Trial (MADIT-ASIA) Terminated NCT01872234 Phase 3
5 The Effects of Different Clonidine Concentrations on Axillary Brachial Plexus Block With 1,5% Lidocaine for Upper Limb Surgery: a Prospective Randomized Study Completed NCT01620112 Phase 2 high Clonidine concentration;low clonidine concentration;Lidocaine;Lidocaine 40 ml
6 Washington Study of Hemofiltration After Out-of-Hospital Cardiac Arrest Completed NCT01509040 Phase 1, Phase 2
7 Congenital or Idiopathic Complete Right Bundle Branch Block: Physiological Significance and Molecular Characterization Unknown status NCT00173342
8 HV Electrophysiology Study In Transcatheter Aortic Valve Implantation Patients Unknown status NCT02659137
9 Management of Acute Myocardial Infarction in the Presence of Left Bundle Branch Block Unknown status NCT01494870
10 Cohort Description of Younger With AV-block Unknown status NCT03024047
11 Left Ventricular Septal Pacing: Potential Application for Cardiac Resynchronization Therapy Unknown status NCT03415945
12 Postoperative Right Bundle Branch Block - Long-term Effect on the Right Ventricle in Children Operated for Ventricular Septal Defect Completed NCT01480908
13 Cardiac Resynchronization Therapy (CRT) Implant Strategy Using the Longest Electrical Delay for Non-left Bundle Branch Block Patients (ENHANCE CRT). A Prospective, Randomized, Postmarket, Pilot Study. Completed NCT01983293
14 Direct HIS-pacing as an Alternative to Biventricular Pacing in Symptomatic Heart Failure Patients With Severely Reduced LVEF and a True Left Bundle Branch Block Completed NCT03614169
15 Pacemaker Utilization and Ventricular Pacing in Patients Undergoing Trans-catheter Aortic Valve Replacement (TAVR) Completed NCT02994667
16 Tailor-CRT: Better Application of Cardiac Resynchronization Therapy by Automated and Improved Selection of Location and Timing of Stimulation Completed NCT02326493
17 Conventional Versus EP-Catheter Guided Implantation of Coronary Sinus Lead in Patients Undergoing Cardiac Resynchronization Therapy Completed NCT01922544
18 Serial Evaluation of Left Bundle Branch Block; Role of New Imaging Techniques. Three-Dimensional Echocardiography, Tissue Doppler Imaging, and Magnetic Resonance Imaging Completed NCT00269659
19 Real-Time Intracardiac Impedograms of Left Ventricular Leads to Locate Sites of Latest Mechanical Delay in Cardiac Resynchronization Therapy Completed NCT01129635
20 Corrected QT Interval in Patients With Pacemaker Dependency (QT-TENDENCY-Study) Completed NCT01694550
21 Edwards SAPIEN 3 PPI Registry - A Retrospective Survey and Prospective Identification of Procedure Related Variables Associated With Permanent Pacemaker Implantation in Patients Receiving an Edwards SAPIEN 3 Valve Completed NCT03497611
22 AV Optimisation Delivered With Direct His Bundle Pacing, in Patients With Heart Failure, Long PR Without Left Bundle Branch Block: Randomised Multi-centre Clinical Outcome Study. Completed NCT02671903
23 Bifocal Right Ventricular PAcing in Right Bundle Branch blocK and Heart Failure With Reduced Ejection Fraction Recruiting NCT03524001
24 Morphological and Functional Changes, Risk Stratification and Prognosis of Patients With Compete Left Bundle Branch Block Recruiting NCT03096678
25 Prediction of Heart-failure and Mortality by Echocardiographic Parameters and Machine Learning in Individuals With Left Bundle Branch Block Recruiting NCT04293471
26 Non-invasive Mapping Using Ultra-high Frequency Electrocardiography Recruiting NCT04537455
27 Comparison of a Clinical Monitoring Strategy Versus Electrophysiology-guided Algorithmic Approach in Patients With a New Left Bundle Branch Block After Transcatheter Aortic Valve Implantation (TAVI) a Bayesian Randomized Trial (COME-TAVI) Recruiting NCT03303612
28 Right Ventricular Septal Pacing in Patients With Right Bundle Branch Block and Heart Failure, a Pilot Clinical Trial (The SPARK Trial) Recruiting NCT02441101
29 Pacing for Cardiac Resynchronisation Using the Intrinsic Conduction System to Maintain Physiologic Ventricular Activation Recruiting NCT04416958
30 Registry of His Bundle, Bachmann Bundle and Left Bundle Branch Area Pacing for Various Pacing Indications Recruiting NCT04749836
31 Comparison of the Effectiveness of Ultrasound-guided Versus Radioguided Medial Lumbar Bundle Branch Block Recruiting NCT04658953
32 Direct HIS/LBB Pacing as an Alternative to Biventricular Pacing in Patients With Symptomatic Heart Failure Despite Optimal Medical Treatment and an ECG With a Typical Left Bundle Branch Block Pattern. Recruiting NCT04409119
33 Mapping and Pacing of the His Bundle for Heart Failure Patients With Left Bundle Branch Block Recruiting NCT03803995
34 Edwards SAPIEN 3 PPI Registry - A Retrospective Survey and Prospective Identification of Procedure Related Variables Associated With Permanent Pacemaker Implantation in Patients Receiving an Edwards SAPIEN 3 Valve Recruiting NCT03715894
35 Mid-Q Response Study Recruiting NCT04180696
36 Does Targeted LV Lead Positioning Towards Latest Local Electric Activation at CRT Implantation Reduce Incidence of the Combined Endpoint "Death or Non-planned Hospitalisation for Heart Failure (HF)" in Patients With HF and Prolonged QRS Recruiting NCT03280862
37 Ambulatory Electrocardiographic Monitoring for the Detection of High-Degree Atrio-Ventricular Block in Patients With New-onset PeRsistent LEft Bundle Branch Block After Transcatheter Aortic Valve Implantation. The "MARE" Study Recruiting NCT02153307
38 A Single-Arm Prospective, Multi-Centered Study to Assess the SHERLOCK 3CG™ Diamond Tip Confirmation System Recruiting NCT03288766
39 Evaluation of Mechanisms and Innovations in Cardiac Resynchronization Therapy Recruiting NCT04221763
40 Changes in Infranodal Conduction Times and New Onset Left Bundle Branch Block: Possible Predictors for High-grade AV Block Following Transcatheter Aortic Valve Replacement Recruiting NCT04128384
41 Permanent Left Bundle Branch Area Pacing for Atrioventricular Block Recruiting NCT03851315
42 AdaptResponse Clinical Trial Active, not recruiting NCT02205359
43 Adaptive CRT Effect on Electrical Dyssynchrony Active, not recruiting NCT02543281
44 Investigating Inhomogeneities of Regional Myocardial WORKload and Metabolism in a Cardiac Resynchronisation Therapy Patient Population Active, not recruiting NCT02537782
45 Characterization of Acute and Long Term Response to Left Ventricle Only Pacing Combined With MultiPoint Pacing and SyncAV Enrolling by invitation NCT03567096
46 Clinical, Structural and Mechanical Features in Patients With Left Bundle Branch Block: an Observational and Prospective Study. Not yet recruiting NCT04328649
47 Acute Hemodynamic Effects of His-bundle Pacing in Bi-Ventricular Pacing Non-responders (The HEPA-His Trial) Not yet recruiting NCT04701112
48 Multimodality Assessment of Acute and Long Term Response to Optimised MultiSite Pacing Cardiac Resynchronisation (MSP CRT) Devices Compared to Biventricular (BiV) CRT, in Patients With Heart Failure Not yet recruiting NCT03938090
49 Correlation of Clinical Outcomes With ECG Findings in Patients With Left Bundle Branch Block Being Evaluated for Acute Coronary Syndrome - a Prospective Cohort Study Terminated NCT02283619
50 Pacing Affects Cardiovascular Endpoints in Patients With Right Bundle-Branch Block (The PACE-RBBB Trial) Terminated NCT01169493

Search NIH Clinical Center for Progressive Familial Heart Block

Genetic Tests for Progressive Familial Heart Block

Genetic tests related to Progressive Familial Heart Block:

# Genetic test Affiliating Genes
1 Progressive Familial Heart Block 29

Anatomical Context for Progressive Familial Heart Block

MalaCards organs/tissues related to Progressive Familial Heart Block:

40
Heart, Atrioventricular Node, Skeletal Muscle, Temporal Lobe

Publications for Progressive Familial Heart Block

Articles related to Progressive Familial Heart Block:

(show all 41)
# Title Authors PMID Year
1
Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I. 61 6
19726882 2009
2
Progressive familial heart block--two types. 6 61
897853 1977
3
Aberrant Deactivation-Induced Gain of Function in TRPM4 Mutant Is Associated with Human Cardiac Conduction Block. 6
30021168 2018
4
Sodium Channel β Subunits in Epilepsy: Location, Location, Location. 6
28331474 2017
5
β1-C121W Is Down But Not Out: Epilepsy-Associated Scn1b-C121W Results in a Deleterious Gain-of-Function. 6
27277800 2016
6
Mutational spectrum in the Ca(2+)--activated cation channel gene TRPM4 in patients with cardiac conductance disturbances. 6
21887725 2012
7
Gain-of-function mutations in TRPM4 cause autosomal dominant isolated cardiac conduction disease. 6
20562447 2010
8
Mutations in sodium channel β1- and β2-subunits associated with atrial fibrillation. 6
19808477 2009
9
Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. 6
18464934 2008
10
Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. 6
18378609 2008
11
Generalized epilepsy with febrile seizures plus-associated sodium channel beta1 subunit mutations severely reduce beta subunit-mediated modulation of sodium channel function. 6
17629415 2007
12
Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. 6
17020904 2007
13
A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. 6
12569159 2003
14
Generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN1B. 6
12011299 2002
15
Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. 6
11997281 2002
16
Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. 6
11804990 2002
17
Cardiac conduction defects associate with mutations in SCN5A. 6
10471492 1999
18
Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. 6
9697698 1998
19
Hereditary bundle branch system defect: survey of a family with four affected generations. 6
619595 1978
20
Arthroplasty of the temporomandibular joint. 6
5421039 1970
21
Structure of full-length human TRPM4. 61
29463718 2018
22
Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I. 61
26820365 2016
23
Reduced Penetrance and Variable Expression of SCN5A Mutations and the Importance of Co-inherited Genetic Variants: Case Report and Review of the Literature. 61
24948852 2014
24
TRPM4 channels in the cardiovascular system. 61
24721656 2014
25
Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction, and repolarization. 61
23734001 2013
26
A connexin40 mutation associated with a malignant variant of progressive familial heart block type I. 61
22247482 2012
27
Progressive familial heart block type I in a korean patient. 61
21731570 2011
28
Transient receptor potential genes and human inherited disease. 61
21290338 2011
29
Endocytic control of ion channel density as a target for cardiovascular disease. 61
19726880 2009
30
Mendelian-inherited heart disease: a gateway to understanding mechanisms in heart disease Update on work done at the University of Stellenbosch. 61
19287818 2009
31
A gene locus for progressive familial heart block type II (PFHBII) maps to chromosome 1q32.2-q32.3. 61
16086176 2005
32
Progressive familial heart block type II (PFHBII): a clinical profile from 1977 to 2003. 61
15258623 2004
33
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). 61
11896454 2002
34
Hereditary bundle branch defect: right bundle branch blocks of different causes have different morphologic characteristics. 61
9023172 1997
35
[Progressive familial heart block (PFHB)]. 61
9047471 1996
36
Gene for progressive familial heart block type I maps to chromosome 19q13. 61
7882468 1995
37
Progressive familial heart block type I. Clinical and pathological observations. 61
2063242 1991
38
Progressive familial heart block (type I). A follow-up study after 10 years. 61
3347879 1988
39
Progressive familial heart block. Part II. Clinical and ECG confirmation of progression--report on 4 cases. 61
3750143 1986
40
Progressive familial heart block. Part I. Extent of the disease. 61
3750142 1986
41
Inherited disorders in the Afrikaner population of southern Africa. Part I. Historical and demographic background, cardiovascular, neurological, metabolic and intestinal conditions. 61
6226121 1983

Variations for Progressive Familial Heart Block

ClinVar genetic disease variations for Progressive Familial Heart Block:

6 (show top 50) (show all 791)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TRPM4 NM_017636.4(TRPM4):c.19G>A (p.Glu7Lys) SNV Pathogenic 3770 rs267607142 GRCh37: 19:49661142-49661142
GRCh38: 19:49157885-49157885
2 SCN5A NM_000335.4(SCN5A):c.3960+2T>C SNV Pathogenic 9378 rs397514447 GRCh37: 3:38603904-38603904
GRCh38: 3:38562413-38562413
3 TRPM4 NM_017636.4(TRPM4):c.490C>T (p.Arg164Trp) SNV Pathogenic 35488 rs387907216 GRCh37: 19:49671558-49671558
GRCh38: 19:49168301-49168301
4 TRPM4 NM_017636.4(TRPM4):c.2741A>G (p.Lys914Arg) SNV Pathogenic 35490 rs172151858 GRCh37: 19:49703652-49703652
GRCh38: 19:49200395-49200395
5 SCN1B NM_001037.5(SCN1B):c.363C>G (p.Cys121Trp) SNV Pathogenic 9252 rs104894718 GRCh37: 19:35524558-35524558
GRCh38: 19:35033654-35033654
6 SCN5A NM_198056.2(SCN5A):c.1099C>T (p.Arg367Cys) SNV Pathogenic 67633 rs199473097 GRCh37: 3:38648201-38648201
GRCh38: 3:38606710-38606710
7 SCN5A NM_000335.5(SCN5A):c.665G>A (p.Arg222Gln) SNV Pathogenic 39444 rs45546039 GRCh37: 3:38655272-38655272
GRCh38: 3:38613781-38613781
8 SCN1B NM_001037.5(SCN1B):c.254G>A (p.Arg85His) SNV Pathogenic 60767 rs16969925 GRCh37: 19:35524449-35524449
GRCh38: 19:35033545-35033545
9 SCN1B NM_001037.5(SCN1B):c.254G>A (p.Arg85His) SNV Pathogenic 60767 rs16969925 GRCh37: 19:35524449-35524449
GRCh38: 19:35033545-35033545
10 KCNQ1 NM_000218.3(KCNQ1):c.1552C>T (p.Arg518Ter) SNV Pathogenic 3131 rs17215500 GRCh37: 11:2790111-2790111
GRCh38: 11:2768881-2768881
11 DSP NM_004415.4(DSP):c.1054_1059delinsCA (p.Asp352fs) Indel Pathogenic 418788 rs1064793435 GRCh37: 6:7567596-7567601
GRCh38: 6:7567363-7567368
12 TRPM4 NM_017636.4(TRPM4):c.3031dup (p.Cys1011fs) Duplication Pathogenic 997516 GRCh37: 19:49705297-49705298
GRCh38: 19:49202040-49202041
13 MYBPC3 NM_000256.3(MYBPC3):c.2308G>A (p.Asp770Asn) SNV Pathogenic 36604 rs36211723 GRCh37: 11:47360071-47360071
GRCh38: 11:47338520-47338520
14 SCN5A NM_198056.2(SCN5A):c.5872C>T (p.Arg1958Ter) SNV Pathogenic 201546 rs757532106 GRCh37: 3:38591991-38591991
GRCh38: 3:38550500-38550500
15 TRPM4 NM_017636.4(TRPM4):c.2849_2850insACAC (p.Leu951fs) Insertion Pathogenic 1033847 GRCh37: 19:49703938-49703939
GRCh38: 19:49200681-49200682
16 TRPM4 NM_017636.4(TRPM4):c.2857del (p.Arg953fs) Deletion Pathogenic 1033848 GRCh37: 19:49703946-49703946
GRCh38: 19:49200689-49200689
17 TRPM4 NM_017636.4(TRPM4):c.2860_2861del (p.Pro954fs) Deletion Pathogenic 1033849 GRCh37: 19:49703949-49703950
GRCh38: 19:49200692-49200693
18 SCN5A NM_198056.2(SCN5A):c.4783G>A (p.Asp1595Asn) SNV Pathogenic 9385 rs137854607 GRCh37: 3:38595800-38595800
GRCh38: 3:38554309-38554309
19 SCN5A NM_198056.2(SCN5A):c.1535C>T (p.Thr512Ile) SNV Pathogenic 440849 rs199473118 GRCh37: 3:38645558-38645558
GRCh38: 3:38604067-38604067
20 MYH7 NM_000257.4(MYH7):c.345+1G>A SNV Likely pathogenic 862006 GRCh37: 14:23902292-23902292
GRCh38: 14:23433083-23433083
21 SCN1B NM_001037.5(SCN1B):c.363C>G (p.Cys121Trp) SNV Likely pathogenic 9252 rs104894718 GRCh37: 19:35524558-35524558
GRCh38: 19:35033654-35033654
22 SCN5A NM_198056.2(SCN5A):c.1567C>T (p.Arg523Cys) SNV Likely pathogenic 67667 rs199473119 GRCh37: 3:38645526-38645526
GRCh38: 3:38604035-38604035
23 RYR2 NM_001035.3(RYR2):c.243G>A (p.Met81Ile) SNV Likely pathogenic 684806 rs1572627115 GRCh37: 1:237494252-237494252
GRCh38: 1:237330952-237330952
24 SCN5A NM_000335.5(SCN5A):c.5894C>G (p.Ser1965Cys) SNV Likely pathogenic 684784 rs1575703249 GRCh37: 3:38591966-38591966
GRCh38: 3:38550475-38550475
25 FLNC-AS1 , FLNC NM_001458.5(FLNC):c.5685del (p.Val1896fs) Deletion Likely pathogenic 978274 GRCh37: 7:128491524-128491524
GRCh38: 7:128851470-128851470
26 CACNA1C NM_000719.7(CACNA1C):c.32del (p.Pro11fs) Deletion Likely pathogenic 978276 GRCh37: 12:2162759-2162759
GRCh38: 12:2053593-2053593
27 RYR2 NM_001035.3(RYR2):c.9848T>A (p.Ile3283Asn) SNV Likely pathogenic 978366 GRCh37: 1:237870516-237870516
GRCh38: 1:237707216-237707216
28 DSP NM_004415.4(DSP):c.5051A>G (p.His1684Arg) SNV Likely pathogenic 431487 rs1135401735 GRCh37: 6:7581474-7581474
GRCh38: 6:7581241-7581241
29 TRPM4 NM_017636.4(TRPM4):c.2674C>T (p.Arg892Cys) SNV Conflicting interpretations of pathogenicity 329866 rs147854826 GRCh37: 19:49703585-49703585
GRCh38: 19:49200328-49200328
30 TRPM4 NM_017636.4(TRPM4):c.3489A>G (p.Gly1163=) SNV Conflicting interpretations of pathogenicity 415726 rs760190293 GRCh37: 19:49714299-49714299
GRCh38: 19:49211042-49211042
31 TRPM4 NM_017636.4(TRPM4):c.3377C>G (p.Ser1126Trp) SNV Conflicting interpretations of pathogenicity 697632 rs567938424 GRCh37: 19:49714015-49714015
GRCh38: 19:49210758-49210758
32 TRPM4 NM_017636.4(TRPM4):c.748C>T (p.Arg250Cys) SNV Conflicting interpretations of pathogenicity 329849 rs144208673 GRCh37: 19:49671945-49671945
GRCh38: 19:49168688-49168688
33 TRPM4 NM_017636.4(TRPM4):c.657C>T (p.Asp219=) SNV Conflicting interpretations of pathogenicity 468942 rs373953725 GRCh37: 19:49671854-49671854
GRCh38: 19:49168597-49168597
34 SCN1B NM_001037.5(SCN1B):c.253C>T (p.Arg85Cys) SNV Conflicting interpretations of pathogenicity 190859 rs786205830 GRCh37: 19:35524448-35524448
GRCh38: 19:35033544-35033544
35 TRPM4 NM_017636.4(TRPM4):c.1874-9C>T SNV Conflicting interpretations of pathogenicity 698453 rs199805560 GRCh37: 19:49692194-49692194
GRCh38: 19:49188937-49188937
36 TRPM4 NM_017636.4(TRPM4):c.755G>A (p.Arg252His) SNV Conflicting interpretations of pathogenicity 241182 rs146564314 GRCh37: 19:49671952-49671952
GRCh38: 19:49168695-49168695
37 TRPM4 NM_017636.4(TRPM4):c.2531G>A (p.Gly844Asp) SNV Conflicting interpretations of pathogenicity 35489 rs200038418 GRCh37: 19:49700017-49700017
GRCh38: 19:49196760-49196760
38 TRPM4 NM_017636.4(TRPM4):c.2254C>T (p.Gln752Ter) SNV Conflicting interpretations of pathogenicity 373748 rs769917929 GRCh37: 19:49699740-49699740
GRCh38: 19:49196483-49196483
39 TRPM4 NM_017636.4(TRPM4):c.1242T>C (p.Phe414=) SNV Conflicting interpretations of pathogenicity 329854 rs200633475 GRCh37: 19:49684697-49684697
GRCh38: 19:49181440-49181440
40 TRPM4 NM_017636.4(TRPM4):c.3611C>T (p.Pro1204Leu) SNV Conflicting interpretations of pathogenicity 381692 rs150391806 GRCh37: 19:49714497-49714497
GRCh38: 19:49211240-49211240
41 TRPM4 NM_017636.4(TRPM4):c.2561A>G (p.Gln854Arg) SNV Conflicting interpretations of pathogenicity 381691 rs172155862 GRCh37: 19:49700047-49700047
GRCh38: 19:49196790-49196790
42 TRPM4 NM_017636.4(TRPM4):c.2209G>A (p.Gly737Arg) SNV Conflicting interpretations of pathogenicity 468934 rs145847114 GRCh37: 19:49694029-49694029
GRCh38: 19:49190772-49190772
43 TRPM4 NM_017636.4(TRPM4):c.988G>A (p.Glu330Lys) SNV Conflicting interpretations of pathogenicity 329851 rs145771389 GRCh37: 19:49674964-49674964
GRCh38: 19:49171707-49171707
44 SCN1B NM_001037.5(SCN1B):c.448+189C>A SNV Conflicting interpretations of pathogenicity 190846 rs766373298 GRCh37: 19:35524832-35524832
GRCh38: 19:35033928-35033928
45 TRPM4 NM_017636.4(TRPM4):c.1368C>G (p.Thr456=) SNV Conflicting interpretations of pathogenicity 241173 rs56118173 GRCh37: 19:49685939-49685939
GRCh38: 19:49182682-49182682
46 TRPM4 NM_017636.4(TRPM4):c.870C>T (p.Asn290=) SNV Conflicting interpretations of pathogenicity 386319 rs141997826 GRCh37: 19:49674846-49674846
GRCh38: 19:49171589-49171589
47 TRPM4 NM_017636.4(TRPM4):c.2231A>T (p.Lys744Met) SNV Conflicting interpretations of pathogenicity 329862 rs569301210 GRCh37: 19:49699717-49699717
GRCh38: 19:49196460-49196460
48 HRC , TRPM4 NM_017636.4(TRPM4):c.1744G>A (p.Gly582Ser) SNV Conflicting interpretations of pathogenicity 35486 rs172149856 GRCh37: 19:49691898-49691898
GRCh38: 19:49188641-49188641
49 HRC , TRPM4 NM_017636.4(TRPM4):c.1294G>A (p.Ala432Thr) SNV Conflicting interpretations of pathogenicity 35487 rs201907325 GRCh37: 19:49685865-49685865
GRCh38: 19:49182608-49182608
50 SCN1B NM_001037.5(SCN1B):c.448+193G>A SNV Conflicting interpretations of pathogenicity 190847 rs66876876 GRCh37: 19:35524836-35524836
GRCh38: 19:35033932-35033932

Expression for Progressive Familial Heart Block

Search GEO for disease gene expression data for Progressive Familial Heart Block.

Pathways for Progressive Familial Heart Block

GO Terms for Progressive Familial Heart Block

Cellular components related to Progressive Familial Heart Block according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sarcolemma GO:0042383 9.56 SCN5A RYR2 FLNC CACNA1C
2 T-tubule GO:0030315 9.5 SCN5A SCN1B CACNA1C
3 myosin filament GO:0032982 9.46 MYH7 MYBPC3
4 sarcomere GO:0030017 9.46 TNNT2 RYR2 MYH7 MYBPC3
5 voltage-gated sodium channel complex GO:0001518 9.43 SCN5A SCN1B
6 sodium channel complex GO:0034706 9.4 TRPM4 SCN1B
7 cardiac myofibril GO:0097512 9.37 TNNT2 MYBPC3
8 intercalated disc GO:0014704 9.26 SCN5A SCN1B GJA5 DSP
9 Z disc GO:0030018 9.1 SCN5A RYR2 MYH7 HRC FLNC CACNA1C

Biological processes related to Progressive Familial Heart Block according to GeneCards Suite gene sharing:

(show all 36)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 10.11 TRPM4 SCN5A SCN1B RYR2 KCNQ1 KCNA7
2 transmembrane transport GO:0055085 10.1 TRPM4 SCN5A RYR2 KCNQ1 KCNA7 GJA5
3 ion transmembrane transport GO:0034220 9.96 TRPM4 SCN5A SCN1B RYR2
4 regulation of ion transmembrane transport GO:0034765 9.88 SCN5A SCN1B KCNQ1 KCNA7 CACNA1C
5 muscle contraction GO:0006936 9.84 TNNT2 MYH7 HRC
6 muscle filament sliding GO:0030049 9.81 TNNT2 MYH7 MYBPC3
7 regulation of heart contraction GO:0008016 9.8 TNNT2 KCNQ1 HRC
8 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion GO:0010881 9.77 RYR2 HRC CACNA1C
9 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.77 TNNT2 MYH7 MYBPC3
10 regulation of cardiac muscle contraction GO:0055117 9.76 RYR2 NKX2-5 GJA5
11 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.75 SCN5A SCN1B KCNQ1
12 regulation of heart rate GO:0002027 9.73 SCN5A RYR2 MYH7 HRC
13 ventricular cardiac muscle cell action potential GO:0086005 9.72 SCN5A RYR2 KCNQ1
14 cardiac muscle cell action potential involved in contraction GO:0086002 9.71 SCN5A SCN1B CACNA1C
15 positive regulation of sodium ion transport GO:0010765 9.7 SCN5A SCN1B NKX2-5
16 cell communication by electrical coupling involved in cardiac conduction GO:0086064 9.69 RYR2 GJA5 CACNA1C
17 membrane depolarization GO:0051899 9.67 SCN5A SCN1B
18 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.67 SCN5A SCN1B CACNA1C
19 positive regulation of heart rate GO:0010460 9.67 TRPM4 RYR2 KCNQ1 HRC
20 calcium ion transport into cytosol GO:0060402 9.66 RYR2 CACNA1C
21 cellular response to epinephrine stimulus GO:0071872 9.65 RYR2 KCNQ1
22 adult heart development GO:0007512 9.65 NKX2-5 MYH7
23 atrial cardiac muscle cell action potential GO:0086014 9.65 SCN5A KCNQ1
24 cardiac conduction GO:0061337 9.65 TRPM4 SCN5A SCN1B KCNQ1 CACNA1C
25 positive regulation of heart contraction GO:0045823 9.64 NKX2-5 HRC
26 regulation of atrial cardiac muscle cell membrane repolarization GO:0060372 9.64 SCN5A KCNQ1
27 regulation of atrial cardiac muscle cell membrane depolarization GO:0060371 9.63 SCN5A SCN1B GJA5
28 membrane depolarization during atrial cardiac muscle cell action potential GO:0098912 9.62 SCN5A CACNA1C
29 regulation of atrial cardiac muscle cell action potential GO:0098910 9.62 RYR2 GJA5
30 regulation of AV node cell action potential GO:0098904 9.61 RYR2 GJA5
31 membrane depolarization during bundle of His cell action potential GO:0086048 9.61 TRPM4 SCN5A
32 membrane depolarization during AV node cell action potential GO:0086045 9.58 TRPM4 SCN5A CACNA1C
33 membrane depolarization during Purkinje myocyte cell action potential GO:0086047 9.5 TRPM4 SCN5A SCN1B
34 regulation of ventricular cardiac muscle cell action potential GO:0098911 9.46 TRPM4 RYR2 DSP CACNA1C
35 regulation of heart rate by cardiac conduction GO:0086091 9.43 TRPM4 SCN5A SCN1B KCNQ1 DSP CACNA1C
36 cardiac muscle contraction GO:0060048 9.23 TNNT2 SCN5A SCN1B RYR2 NKX2-5 MYH7

Molecular functions related to Progressive Familial Heart Block according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 voltage-gated ion channel activity GO:0005244 9.65 SCN5A SCN1B KCNQ1 KCNA7 CACNA1C
2 calcium channel activity GO:0005262 9.63 TRPM4 RYR2 CACNA1C
3 scaffold protein binding GO:0097110 9.58 SCN5A KCNQ1 DSP
4 ion channel binding GO:0044325 9.55 SCN5A SCN1B RYR2 KCNQ1 HRC
5 voltage-gated sodium channel activity GO:0005248 9.49 SCN5A SCN1B
6 ankyrin binding GO:0030506 9.48 SCN5A FLNC
7 protein kinase A catalytic subunit binding GO:0034236 9.43 RYR2 KCNQ1
8 calmodulin binding GO:0005516 9.43 TRPM4 SCN5A RYR2 MYH7 KCNQ1 CACNA1C
9 voltage-gated sodium channel activity involved in cardiac muscle cell action potential GO:0086006 9.37 SCN5A SCN1B
10 voltage-gated sodium channel activity involved in Purkinje myocyte action potential GO:0086062 9.32 SCN5A SCN1B
11 ion channel activity GO:0005216 9.1 TRPM4 SCN5A RYR2 KCNQ1 KCNA7 CACNA1C

Sources for Progressive Familial Heart Block

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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