Progressive Familial Heart Block

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1		Rita Xu	+ 721 word(s)	721	2020-12-15 07:35:55

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/progressive-familial-heart-block

Progressive familial heart block is a genetic condition that alters the normal beating of the heart.

genetic conditions

1. Introduction

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.

2. Frequency

The prevalence of progressive familial heart block is unknown. In the United States, about 1 in 5,000 individuals have complete heart block from any cause; worldwide, about 1 in 2,500 individuals have complete heart block.

3. Causes

Mutations in the SCN5A and TRPM4 genes cause most cases of progressive familial heart block types IA and IB, respectively. The proteins produced from these genes are channels that allow positively charged atoms (cations) into and out of cells. Both channels are abundant in heart (cardiac) cells and play key roles in these cells' ability to generate and transmit electrical signals. These channels play a major role in signaling the start of each heartbeat, coordinating the contractions of the atria and ventricles, and maintaining a normal heart rhythm.

The SCN5A and TRPM4 gene mutations that cause progressive familial heart block alter the normal function of the channels. As a result of these channel alterations, cardiac cells have difficulty producing and transmitting the electrical signals that are necessary to coordinate normal heartbeats, leading to heart block. Death of these impaired cardiac cells over time can lead to fibrosis, worsening the heart block.

Mutations in other genes, some of which are unknown, account for the remaining cases of progressive familial heart block.

4. Inheritance

Progressive familial heart block types I and II are inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Some people with TRPM4 gene mutations never develop the condition, a situation known as reduced penetrance.

In most cases, an affected person has one parent with progressive familial heart block.

5. Other Names for This Condition

bundle branch block
HBBD
hereditary bundle branch defect
hereditary bundle branch system defect
Lenegre Lev disease
Lev syndrome
Lev's disease
Lev-Lenègre disease
PCCD
progressive cardiac conduction defect

References

Barra SN, Providência R, Paiva L, Nascimento J, Marques AL. A review onadvanced atrioventricular block in young or middle-aged adults. Pacing ClinElectrophysiol. 2012 Nov;35(11):1395-405. doi: 10.1111/j.1540-8159.2012.03489.x.
Fernandez P, Corfield VA, Brink PA. Progressive familial heart block type II(PFHBII): a clinical profile from 1977 to 2003. Cardiovasc J S Afr. 2004May-Jun;15(3):129-32.
Fernandez P, Moolman-Smook J, Brink P, Corfield V. A gene locus forprogressive familial heart block type II (PFHBII) maps to chromosome1q32.2-q32.3. Hum Genet. 2005 Oct;118(1):133-7.
Kruse M, Schulze-Bahr E, Corfield V, Beckmann A, Stallmeyer B, Kurtbay G,Ohmert I, Schulze-Bahr E, Brink P, Pongs O. Impaired endocytosis of the ionchannel TRPM4 is associated with human progressive familial heart block type I. JClin Invest. 2009 Sep;119(9):2737-44. doi: 10.1172/JCI38292.
Lee CK, Shin DH, Jang JK, Jang KH, Kim EK, Cheong SS, Yoo SY. Progressivefamilial heart block type I in a korean patient. Korean Circ J. 2011May;41(5):276-9. doi: 10.4070/kcj.2011.41.5.276.
Makita N, Seki A, Sumitomo N, Chkourko H, Fukuhara S, Watanabe H, Shimizu W,Bezzina CR, Hasdemir C, Mugishima H, Makiyama T, Baruteau A, Baron E, Horie M,Hagiwara N, Wilde AA, Probst V, Le Marec H, Roden DM, Mochizuki N, Schott JJ,Delmar M. A connexin40 mutation associated with a malignant variant ofprogressive familial heart block type I. Circ Arrhythm Electrophysiol. 2012Feb;5(1):163-72. doi: 10.1161/CIRCEP.111.967604.
Probst V, Allouis M, Sacher F, Pattier S, Babuty D, Mabo P, Mansourati J,Victor J, Nguyen JM, Schott JJ, Boisseau P, Escande D, Le Marec H. Progressivecardiac conduction defect is the prevailing phenotype in carriers of a Brugadasyndrome SCN5A mutation. J Cardiovasc Electrophysiol. 2006 Mar;17(3):270-5.
Schott JJ, Alshinawi C, Kyndt F, Probst V, Hoorntje TM, Hulsbeek M, Wilde AA, Escande D, Mannens MM, Le Marec H. Cardiac conduction defects associate withmutations in SCN5A. Nat Genet. 1999 Sep;23(1):20-1.
Van der Merwe PL, Weymar HW, Torrington M, Brink AJ. Progressive familialheart block (type I). A follow-up study after 10 years. S Afr Med J. 1988 Mar5;73(5):275-6.
Watanabe H, Koopmann TT, Le Scouarnec S, Yang T, Ingram CR, Schott JJ,Demolombe S, Probst V, Anselme F, Escande D, Wiesfeld AC, Pfeufer A, Kääb S,Wichmann HE, Hasdemir C, Aizawa Y, Wilde AA, Roden DM, Bezzina CR. Sodium channelβ1 subunit mutations associated with Brugada syndrome and cardiac conductiondisease in humans. J Clin Invest. 2008 Jun;118(6):2260-8. doi: 10.1172/JCI33891.

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Subjects: Genetics & Heredity

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Rita Xu

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Entry Collection: MedlinePlus

Update Date: 24 Dec 2020

Table of Contents

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1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

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1. Introduction

2. Frequency

3. Causes

3.1. The Genes Associated with Progressive Familial Heart Block

3.1.1. Additional Information from NCBI Gene

4. Inheritance

5. Other Names for This Condition

References