Progressive Cardiac Conduction Disease

Genetic MONDO:0019490 Pathograph 6 Show in embeddings browser Cardiovascular Disease Genetic Disorder

Progressive cardiac conduction disease (PCCD), historically Lenègre-Lev disease, is the inherited, progressive impairment of impulse propagation through the cardiac conduction system (His-Purkinje network and atrioventricular node) in the absence of a primary structural cardiomyopathy. Its prototypical Mendelian cause is a loss-of-function variant in SCN5A, the gene encoding the main pore-forming subunit of the cardiac voltage-gated sodium channel Nav1.5; reduced sodium current slows conduction, and the deficit worsens with age as the conduction system fibroses, producing progressive PR and QRS prolongation, bundle-branch and atrioventricular block, syncope, pacemaker dependence, and a risk of sudden death. PCCD is one phenotype of the SCN5A "sodium channel disease" spectrum and overlaps allelically with Brugada syndrome (which shares SCN5A loss of function); other genes include TRPM4 and, in overlap syndromes, SCN1B and TRPM4. Inheritance is autosomal dominant.

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1
Inheritance
5
Pathophys.
4
Phenotypes
6
Pathograph
1
Genes
1
Medical Actions
🏷

Classifications

Harrison's Part
CARDIOVASCULAR GENETICS ENVIRONMENT DISEASE
👪

Inheritance

1
Autosomal dominant HP:0000006
PCCD is inherited as an autosomal dominant trait; a single loss-of-function SCN5A allele produces disease in affected families, with conduction impairment that progresses with age. Allelic overlap with Brugada syndrome means the same SCN5A variant can produce either or both phenotypes within a family.
Autosomal dominant inheritance Penetrance: INCOMPLETE
Show evidence (1 reference)
PMID:16643399 SUPPORT Human Clinical
"Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease)"
Establishes SCN5A loss of function as the Mendelian cause of PCCD (inherited Lenègre disease) and its allelic overlap with Brugada syndrome, in a family carrier cohort.
⚙

Pathophysiology

5
SCN5A Loss-of-Function Variant in the Cardiac Sodium Channel
The prototypical initiating lesion in PCCD is a loss-of-function variant in SCN5A, encoding the alpha subunit of the cardiac voltage-gated sodium channel Nav1.5 that carries the depolarizing sodium current (INa) responsible for rapid impulse conduction. The same loss-of-function SCN5A alleles underlie Brugada syndrome, so PCCD sits within the sodium-channel-disease spectrum; other PCCD genes include TRPM4.
Cardiac pacemaker/conduction cardiomyocyte CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiac pacemaker/conduction cardiomyocyte, annotated with cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology.
SCN5A hgnc:10593 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves SCN5A (hgnc:10593). hgnc:10593 is a gene from the HUGO Gene Nomenclature Committee.
Voltage-gated sodium channel activity GO:0005248 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased Voltage-gated sodium channel activity (GO:0005248). GO:0005248 is a molecular function from the Gene Ontology. ↓ DECREASED
Downstream
Reduced Sodium Current and Conduction Slowing Reduced Nav1.5 current slows the upstroke of the action potential and thereby impulse conduction through the His-Purkinje and AV conduction tissue.
Show evidence (2 references)
PMID:16643399 SUPPORT Human Clinical
"Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease)"
Identifies SCN5A loss of function as the causal lesion of PCCD.
PMID:12747584 SUPPORT Other
"It is now appropriate to consider the "sodium channel syndrome" as a unique clinical entity that may manifest itself with a spectrum of possible phenotypes."
Places PCCD (Lev-Lenègre) within the SCN5A sodium-channel-disease spectrum alongside Brugada syndrome and LQT3. Evidence source is OTHER because this is a review.
Reduced Sodium Current and Conduction Slowing
Reduced Nav1.5 sodium current slows the rate of rise of the cardiac action potential, which slows impulse propagation through the His-Purkinje system and atrioventricular node. On the surface ECG this manifests as progressive lengthening of the P-wave and the PR and QRS intervals, the electrocardiographic signature of conduction slowing.
Cardiac muscle cell CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology.
Cardiac Conduction GO:0061337 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased Cardiac Conduction (GO:0061337). GO:0061337 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Age-Related Conduction-System Fibrosis The chronic sodium-channel deficit is accompanied by progressive fibrotic remodeling of the conduction system and myocardium with aging.
Progressive Atrioventricular and Bundle-Branch Block Conduction slowing progresses to frank block in the AV node and bundle branches.
Show evidence (1 reference)
PMID:15809371 SUPPORT Model Organism
"Scn5a+/- mice showed extensive fibrosis of their ventricular myocardium"
The Scn5a heterozygous-knockout Lenègre model, which recapitulates age-related conduction slowing (P/PR/QRS lengthening) and myocardial fibrosis driven by the sodium-channel deficit.
Progressive Atrioventricular and Bundle-Branch Block
Conduction slowing, amplified by fibrosis, progresses over years to higher-grade block: right or left bundle-branch block, hemiblock, and increasing degrees of atrioventricular block up to complete heart block. The hallmark of the disease is that this block aggravates with aging, often culminating in the need for a permanent pacemaker.
Cardiac muscle cell CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology.
Cardiac Conduction GO:0061337 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Cardiac Conduction (GO:0061337). GO:0061337 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Syncope, Pacemaker Dependence and Sudden Death Risk
Show evidence (1 reference)
PMID:16643399 SUPPORT Human Clinical
"conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations"
Documents the defining age-related progression of conduction block to pacemaker requirement in SCN5A carriers.
Syncope, Pacemaker Dependence and Sudden Death Risk
High-grade atrioventricular block and bradyarrhythmia reduce cerebral and systemic perfusion, producing syncope (Stokes-Adams attacks) and, if untreated, a risk of sudden death from asystole. Definitive treatment of symptomatic high-grade block is permanent pacemaker implantation, on which affected individuals become dependent.
Cardiac muscle cell CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology.
Cardiac Conduction GO:0061337 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Cardiac Conduction (GO:0061337). GO:0061337 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Show evidence (1 reference)
PMID:16643399 SUPPORT Human Clinical
"conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations"
Ties the progressive block to its clinical endpoint — pacemaker implantation.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Progressive Cardiac Conduction Disease Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

4
Cardiovascular 2
Atrioventricular Block HP:0001678 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Atrioventricular block (HP:0001678). HP:0001678 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:15809371 SUPPORT Model Organism
"Scn5a+/- mice showed extensive fibrosis of their ventricular myocardium"
The Lenègre model recapitulates the age-related atrial and ventricular conduction impairment underlying AV block.
Syncope HP:0001279 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Syncope (HP:0001279). HP:0001279 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:16643399 SUPPORT Human Clinical
"conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations"
The progression to symptomatic high-grade block requiring pacing is the substrate for syncope in PCCD.
Other 2
Heart Block OBLIGATE HP:0012722 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Heart block (HP:0012722). HP:0012722 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:16643399 SUPPORT Human Clinical
"conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations"
Documents progressive conduction block as the defining, pacemaker-requiring feature.
Right Bundle Branch Block Complete right bundle branch block HP:0011712 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Complete right bundle branch block (HP:0011712). HP:0011712 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:16643399 SUPPORT Human Clinical
"Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease)"
Anchors the intraventricular conduction block phenotype to the SCN5A PCCD cohort in which right bundle-branch block was a common finding.
🧬

Genetic Associations

1
SCN5A
Gene: SCN5A hgnc:10593 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is SCN5A (hgnc:10593). hgnc:10593 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE
Show evidence (1 reference)
PMID:16643399 SUPPORT Human Clinical
"Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease)"
Assigns progressive cardiac conduction disease to SCN5A loss-of-function alleles and, by naming Brugada syndrome in the same sentence, is also the basis for treating the two as allelic disorders of one gene rather than one entity.
💊

Medical Actions

1
Permanent Pacemaker Implantation
Action: pacemaker placementNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is pacemaker placement (NCIT:C80434). NCIT:C80434 is a clinical intervention from the NCI Thesaurus. Ontology label: Pacemaker Placement NCIT:C80434
Permanent pacemaker implantation is the definitive treatment for symptomatic high-grade atrioventricular or bundle-branch block, restoring adequate ventricular rate and preventing syncope and asystolic death.
📊

Prevalence

1
Worldwide
Unknown Unknown
No precise population rate is established for the inherited (SCN5A) form of progressive cardiac conduction disease; acquired age-related conduction disease is common, but the monogenic form is rare.
{ }

Source YAML

click to show 
name: Progressive Cardiac Conduction Disease
creation_date: "2026-08-22T00:00:00Z"
synonyms:
- PCCD
- progressive familial heart block
- hereditary Lenegre disease
- Lenegre-Lev disease
- progressive cardiac conduction defect
- hereditary bundle branch system defect
description: >-
  Progressive cardiac conduction disease (PCCD), historically Lenègre-Lev disease,
  is the inherited, progressive impairment of impulse propagation through the
  cardiac conduction system (His-Purkinje network and atrioventricular node) in the
  absence of a primary structural cardiomyopathy. Its prototypical Mendelian cause
  is a loss-of-function variant in SCN5A, the gene encoding the main pore-forming
  subunit of the cardiac voltage-gated sodium channel Nav1.5; reduced sodium current
  slows conduction, and the deficit worsens with age as the conduction system
  fibroses, producing progressive PR and QRS prolongation, bundle-branch and
  atrioventricular block, syncope, pacemaker dependence, and a risk of sudden death.
  PCCD is one phenotype of the SCN5A "sodium channel disease" spectrum and overlaps
  allelically with Brugada syndrome (which shares SCN5A loss of function); other
  genes include TRPM4 and, in overlap syndromes, SCN1B and TRPM4. Inheritance is
  autosomal dominant.
category: Genetic
classifications:
  harrisons_chapter:
  - classification_value: CARDIOVASCULAR
  - classification_value: GENETICS_ENVIRONMENT_DISEASE
disease_term:
  preferred_term: progressive familial heart block
  term:
    id: MONDO:0019490
    label: progressive familial heart block
parents:
- Cardiovascular Disease
- Genetic Disorder
inheritance:
- name: Autosomal dominant
  description: >-
    PCCD is inherited as an autosomal dominant trait; a single loss-of-function
    SCN5A allele produces disease in affected families, with conduction impairment
    that progresses with age. Allelic overlap with Brugada syndrome means the same
    SCN5A variant can produce either or both phenotypes within a family.
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  penetrance: INCOMPLETE
  evidence:
  - reference: PMID:16643399
    reference_title: "Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease)"
    explanation: >-
      Establishes SCN5A loss of function as the Mendelian cause of PCCD (inherited
      Lenègre disease) and its allelic overlap with Brugada syndrome, in a family
      carrier cohort.
prevalence:
- population: Worldwide
  measure_type: UNKNOWN
  prevalence_class: UNKNOWN
  notes: >-
    No precise population rate is established for the inherited (SCN5A) form of
    progressive cardiac conduction disease; acquired age-related conduction disease
    is common, but the monogenic form is rare.
pathophysiology:
- name: SCN5A Loss-of-Function Variant in the Cardiac Sodium Channel
  biological_scale: MOLECULAR
  role: trigger
  conforms_to: "cardiac_ion_channel_repolarization#Cardiac Ion-Channel or Calcium-Handling Variant"
  description: >-
    The prototypical initiating lesion in PCCD is a loss-of-function variant in
    SCN5A, encoding the alpha subunit of the cardiac voltage-gated sodium channel
    Nav1.5 that carries the depolarizing sodium current (INa) responsible for rapid
    impulse conduction. The same loss-of-function SCN5A alleles underlie Brugada
    syndrome, so PCCD sits within the sodium-channel-disease spectrum; other PCCD
    genes include TRPM4.
  genes:
  - preferred_term: SCN5A
    term:
      id: hgnc:10593
      label: SCN5A
  cell_types:
  - preferred_term: Cardiac pacemaker/conduction cardiomyocyte
    term:
      id: CL:0000746
      label: cardiac muscle cell
  molecular_functions:
  - preferred_term: Voltage-gated sodium channel activity
    term:
      id: GO:0005248
      label: voltage-gated sodium channel activity
    modifier: DECREASED
  evidence:
  - reference: PMID:16643399
    reference_title: "Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease)"
    explanation: >-
      Identifies SCN5A loss of function as the causal lesion of PCCD.
  - reference: PMID:12747584
    reference_title: "Cardiac sodium channel diseases."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is now appropriate to consider the "sodium channel syndrome" as a unique
      clinical entity that may manifest itself with a spectrum of possible
      phenotypes.
    explanation: >-
      Places PCCD (Lev-Lenègre) within the SCN5A sodium-channel-disease spectrum
      alongside Brugada syndrome and LQT3. Evidence source is OTHER because this is
      a review.
  downstream:
  - target: Reduced Sodium Current and Conduction Slowing
    causal_link_type: DIRECT
    description: >-
      Reduced Nav1.5 current slows the upstroke of the action potential and thereby
      impulse conduction through the His-Purkinje and AV conduction tissue.
- name: Reduced Sodium Current and Conduction Slowing
  biological_scale: CELLULAR
  role: effector
  description: >-
    Reduced Nav1.5 sodium current slows the rate of rise of the cardiac action
    potential, which slows impulse propagation through the His-Purkinje system and
    atrioventricular node. On the surface ECG this manifests as progressive
    lengthening of the P-wave and the PR and QRS intervals, the electrocardiographic
    signature of conduction slowing.
  cell_types:
  - preferred_term: Cardiac muscle cell
    term:
      id: CL:0000746
      label: cardiac muscle cell
  biological_processes:
  - preferred_term: Cardiac Conduction
    term:
      id: GO:0061337
      label: cardiac conduction
    modifier: DECREASED
  evidence:
  - reference: PMID:15809371
    reference_title: "Mouse model of SCN5A-linked hereditary Lenègre's disease: age-related conduction slowing and myocardial fibrosis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Scn5a+/- mice showed extensive fibrosis of their ventricular myocardium"
    explanation: >-
      The Scn5a heterozygous-knockout Lenègre model, which recapitulates
      age-related conduction slowing (P/PR/QRS lengthening) and myocardial fibrosis
      driven by the sodium-channel deficit.
  downstream:
  - target: Age-Related Conduction-System Fibrosis
    causal_link_type: DIRECT
    description: >-
      The chronic sodium-channel deficit is accompanied by progressive fibrotic
      remodeling of the conduction system and myocardium with aging.
  - target: Progressive Atrioventricular and Bundle-Branch Block
    causal_link_type: DIRECT
    description: >-
      Conduction slowing progresses to frank block in the AV node and bundle
      branches.
- name: Age-Related Conduction-System Fibrosis
  biological_scale: TISSUE
  role: amplifier
  description: >-
    A distinctive feature of SCN5A-linked PCCD is that a monogenic ion-channel
    defect progressively produces structural change: with aging the ventricular
    myocardium and conduction system develop extensive fibrosis, which further
    degrades conduction and accounts for the relentless, age-dependent progression
    of block. This was the first demonstration that a primary channelopathy can
    drive myocardial structural anomalies.
  cell_types:
  - preferred_term: Cardiac Fibroblast
    term:
      id: CL:0002548
      label: fibroblast of cardiac tissue
  biological_processes:
  - preferred_term: Extracellular Matrix Organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
    modifier: INCREASED
  evidence:
  - reference: PMID:15809371
    reference_title: "Mouse model of SCN5A-linked hereditary Lenègre's disease: age-related conduction slowing and myocardial fibrosis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "a monogenic ion channel defect can progressively lead to myocardial structural anomalies"
    explanation: >-
      Establishes that the SCN5A channel defect drives progressive myocardial
      fibrosis/structural remodeling, the amplifier of age-related conduction
      failure.
  downstream:
  - target: Progressive Atrioventricular and Bundle-Branch Block
    causal_link_type: DIRECT
- name: Progressive Atrioventricular and Bundle-Branch Block
  biological_scale: ORGANISM
  role: effector
  description: >-
    Conduction slowing, amplified by fibrosis, progresses over years to
    higher-grade block: right or left bundle-branch block, hemiblock, and
    increasing degrees of atrioventricular block up to complete heart block. The
    hallmark of the disease is that this block aggravates with aging, often
    culminating in the need for a permanent pacemaker.
  cell_types:
  - preferred_term: Cardiac muscle cell
    term:
      id: CL:0000746
      label: cardiac muscle cell
  biological_processes:
  - preferred_term: Cardiac Conduction
    term:
      id: GO:0061337
      label: cardiac conduction
    modifier: ABNORMAL
  evidence:
  - reference: PMID:16643399
    reference_title: "Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations"
    explanation: >-
      Documents the defining age-related progression of conduction block to
      pacemaker requirement in SCN5A carriers.
  downstream:
  - target: Syncope, Pacemaker Dependence and Sudden Death Risk
    causal_link_type: DIRECT
- name: Syncope, Pacemaker Dependence and Sudden Death Risk
  biological_scale: ORGANISM
  role: consequence
  description: >-
    High-grade atrioventricular block and bradyarrhythmia reduce cerebral and
    systemic perfusion, producing syncope (Stokes-Adams attacks) and, if untreated,
    a risk of sudden death from asystole. Definitive treatment of symptomatic
    high-grade block is permanent pacemaker implantation, on which affected
    individuals become dependent.
  cell_types:
  - preferred_term: Cardiac muscle cell
    term:
      id: CL:0000746
      label: cardiac muscle cell
  biological_processes:
  - preferred_term: Cardiac Conduction
    term:
      id: GO:0061337
      label: cardiac conduction
    modifier: ABNORMAL
  evidence:
  - reference: PMID:16643399
    reference_title: "Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations"
    explanation: >-
      Ties the progressive block to its clinical endpoint — pacemaker implantation.
phenotypes:
- name: Heart Block
  category: Cardiovascular
  description: >-
    Progressive impairment of atrioventricular and intraventricular conduction is
    the defining feature, ranging from bundle-branch block to complete heart block.
  phenotype_term:
    preferred_term: Heart block
    term:
      id: HP:0012722
      label: Heart block
  frequency: OBLIGATE
  evidence:
  - reference: PMID:16643399
    reference_title: "Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations"
    explanation: >-
      Documents progressive conduction block as the defining, pacemaker-requiring
      feature.
- name: Atrioventricular Block
  category: Cardiovascular
  description: >-
    Increasing degrees of atrioventricular block, up to complete heart block, are a
    characteristic manifestation.
  phenotype_term:
    preferred_term: Atrioventricular block
    term:
      id: HP:0001678
      label: Atrioventricular block
  evidence:
  - reference: PMID:15809371
    reference_title: "Mouse model of SCN5A-linked hereditary Lenègre's disease: age-related conduction slowing and myocardial fibrosis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Scn5a+/- mice showed extensive fibrosis of their ventricular myocardium"
    explanation: >-
      The Lenègre model recapitulates the age-related atrial and ventricular
      conduction impairment underlying AV block.
- name: Right Bundle Branch Block
  category: Cardiovascular
  description: >-
    Right bundle-branch block is among the intraventricular conduction anomalies
    seen in SCN5A conduction disease.
  phenotype_term:
    preferred_term: Complete right bundle branch block
    term:
      id: HP:0011712
      label: Complete right bundle branch block
  evidence:
  - reference: PMID:16643399
    reference_title: "Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease)"
    explanation: >-
      Anchors the intraventricular conduction block phenotype to the SCN5A PCCD
      cohort in which right bundle-branch block was a common finding.
- name: Syncope
  category: Cardiovascular
  description: >-
    Transient loss of consciousness (Stokes-Adams attacks) from bradyarrhythmia and
    high-grade block.
  phenotype_term:
    preferred_term: Syncope
    term:
      id: HP:0001279
      label: Syncope
  evidence:
  - reference: PMID:16643399
    reference_title: "Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations"
    explanation: >-
      The progression to symptomatic high-grade block requiring pacing is the
      substrate for syncope in PCCD.
genetic:
- name: SCN5A
  gene_term:
    preferred_term: SCN5A
    term:
      id: hgnc:10593
      label: SCN5A
  relationship_type: CAUSATIVE
  frequency: >-
    The principal gene of the monogenic form, which is itself rare against the
    common acquired age-related conduction disease; no case fraction has been
    reported in a screened cohort.
  evidence:
  - reference: PMID:16643399
    reference_title: "Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium
      channel are responsible for Brugada syndrome (BS) and also for
      progressive cardiac conduction disease (inherited Lenègre disease)
    explanation: >-
      Assigns progressive cardiac conduction disease to SCN5A loss-of-function
      alleles and, by naming Brugada syndrome in the same sentence, is also
      the basis for treating the two as allelic disorders of one gene rather
      than one entity.
  notes: >-
    No ClinGen Gene-Disease Validity assertion is cited here because none is
    cached in this repository for the SCN5A-progressive cardiac conduction
    disease pair specifically; the cached SCN5A assertions are against dilated
    cardiomyopathy and Brugada syndrome. That absence is recorded rather than
    substituted with a neighbouring assertion.
treatments:
- name: Permanent Pacemaker Implantation
  description: >-
    Permanent pacemaker implantation is the definitive treatment for symptomatic
    high-grade atrioventricular or bundle-branch block, restoring adequate
    ventricular rate and preventing syncope and asystolic death.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: pacemaker placement
    term:
      id: NCIT:C80434
      label: Pacemaker Placement
notes: >-
  Scope. This entry fills the gap of a dedicated progressive cardiac conduction
  disease (Lenègre-Lev) entity; previously the KB represented conduction disease
  only piecemeal (Mobitz type I AV block, sinoatrial block, atrial standstill, and
  secondarily via LMNA/Emery-Dreifuss). It is curated as the SCN5A-prototypical
  inherited form. Only the trigger node conforms to the
  cardiac_ion_channel_repolarization module (at its "Cardiac Ion-Channel or
  Calcium-Handling Variant" node): PCCD is a bona fide cardiac sodium channelopathy,
  but its downstream phenotype is His-Purkinje/AV conduction block rather than the
  module's sinoatrial-automaticity or ventricular-tachyarrhythmia branches, so the
  disease-specific conduction chain is modeled here rather than mapped onto those
  branches. Allelic overlap with Brugada syndrome (shared SCN5A loss of function) is
  recorded; TRPM4 and, in overlap syndromes, SCN1B are additional genes.

  GeneReviews scope. GeneReviews has no chapter for progressive cardiac
  conduction disease itself, and none is tagged in `references`. The nearest
  cached SCN5A resource is the Brugada Syndrome chapter (PMID:20301690), which
  covers a distinct allelic entity rather than this one and is content_type
  abstract_only in any case, so no clinical section could be mined from it. The
  clinical-characteristics baseline for this entry is therefore built entirely
  from the primary literature cited throughout, principally PMID:16643399,
  PMID:15809371.