Progressive familial heart block, type 1A(PFHB1A)

MedGen UID:: 406301
•Concept ID:: C1879286
•: Disease or Syndrome

Synonyms:	Cardiac conduction defect progressive; Heart block progressive familial type 1; HEART BLOCK, PROGRESSIVE FAMILIAL, TYPE I; Heart block, progressive, type IA; Hereditary bundle branch system defect; PFHB1A; PROGRESSIVE FAMILIAL HEART BLOCK, TYPE IA
SNOMED CT:	Lev syndrome (283645003); Progressive familial heart block, type IA (283645003); Lev-Lenègre disease (283645003); Progressive familial heart block (698249005); Progressive cardiac conduction defect (283645003); Lenegre-Lev syndrome (283645003); Lenegre syndrome (283645003); Lev's disease (283645003); Lev's syndrome (283645003)

Gene (location): Gene(s) directly associated with this condition or phenotype.	SCN5A (3p22.2)

Monarch Initiative:	MONDO:0007240
OMIM®:	113900

Definition

Progressive familial heart block type I (PFHBI, PFHB1) is an autosomal dominant cardiac bundle branch disorder that may progress to complete heart block (Brink and Torrington, 1977; van der Merwe et al., 1986; van der Merwe et al., 1988). It is defined on electrocardiogram by evidence of bundle branch disease, i.e., right bundle branch block, left anterior or posterior hemiblock, or complete heart block, with broad QRS complexes. Progression has been shown from a normal electrocardiogram to right bundle branch block and from the latter to complete heart block. These electrocardiographic features differentiate PFHB type I from progressive familial heart block type II (PFHBII, PFHB2; 140400), in which the onset of complete heart block is associated with narrow complexes. Electrocardiographically the changes represent, respectively, bundle branch disease (PFHB1) and atrioventricular nodal disease with an atrioventricular block and an idionodal escape rhythm (PFHB2). PFHBI is manifested symptomatically when complete heart block supervenes, either with dyspnea, syncopal episodes, or sudden death. Treatment, which is best managed by regular electrocardiographic follow-up, is by the timely implantation of a pacemaker (Brink et al., 1995). Genetic Heterogeneity of Progressive Familial Heart Block Type I Progressive familial heart block type IB (PFHB1B; 604559) is caused by mutation in the TRPM4 gene (606936) on chromosome 19q13.32. [from OMIM]

Additional description

From MedlinePlus Genetics
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. https://medlineplus.gov/genetics/condition/progressive-familial-heart-block

Clinical features

From HPO

Sudden death

MedGen UID:: 8257
•Concept ID:: C0011071
•: Pathologic Function

Rapid and unexpected death.

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Sudden cardiac death

MedGen UID:: 38841
•Concept ID:: C0085298
•: Pathologic Function

The heart suddenly and unexpectedly stops beating resulting in death within a short time period (generally within 1 h of symptom onset).

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Syncope

MedGen UID:: 21443
•Concept ID:: C0039070
•: Sign or Symptom

Syncope is a syndrome in which loss of consciousness is of relatively sudden onset, temporary (usually less than 1 to 2 minutes), self-terminating, and of usually rapid recovery. Syncope leads to a generalized weakness of muscles with loss of postural tone, inability to stand upright, and loss of consciousness. Once the patient is in a horizontal position, blood flow to the brain is no longer hindered by gravitation and consciousness is regained. Unconsciousness usually lasts for seconds to minutes. Headache and drowsiness (which usually follow seizures) do not follow a syncopal attack. Syncope results from a sudden impairment of brain metabolism usually due to a reduction in cerebral blood flow.

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Right bundle branch block

MedGen UID:: 88445
•Concept ID:: C0085615
•: Disease or Syndrome

A conduction block of the right branch of the bundle of His. This manifests as a prolongation of the QRS complex (greater than 0.12 s) with delayed activation of the right ventricle and terminal delay on the EKG.

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Left anterior fascicular block

MedGen UID:: 75547
•Concept ID:: C0264912
•: Disease or Syndrome

Conduction block in the anterior division of the left bundle branch of the bundle of His.

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Left posterior fascicular block

MedGen UID:: 78115
•Concept ID:: C0264913
•: Disease or Syndrome

Conduction block in the posterior division of the left bundle branch of the bundle of His.

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Prolonged PR interval

MedGen UID:: 154645
•Concept ID:: C0600125
•: Finding

Increased time for the PR interval (beginning of the P wave to the beginning of the QRS complex).

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Complete heart block with broad QRS complexes

MedGen UID:: 1391206
•Concept ID:: C4476543
•: Disease or Syndrome

A type of third degree heart block in which the escape rhythm arises at a relatively low part of the conduction system (below the atrioventricular node), which produces a wide QRS complex.

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Dyspnea