i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) s 4 9 es 5 7
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ihj
Review Article
Inherited arrhythmia syndromes leading to sudden cardiac death in the young: A global update and an Indian perspective Priya Chockalingam a,*, Arthur A. Wilde a,b a
Department of Clinical and Experimental Cardiology, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands b Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia
article info
abstract
Article history:
Inherited primary arrhythmias, namely congenital long QT syndrome, Brugada syndrome
Received 31 October 2013
and catecholaminergic polymorphic ventricular tachycardia, account for a significant
Accepted 7 November 2013
proportion of sudden cardiac deaths in young and apparently healthy individuals. Genetic
Available online 17 December 2013
testing plays an integral role in the diagnosis, risk-stratification and treatment of probands and family members. It is increasingly obvious that collaborative efforts are required to
Keywords:
understand and manage these relatively rare but potentially lethal diseases. This article
Cardiac channelopathies
aims to update readers on the recent developments in our knowledge of inherited ar-
Family screening
rhythmias and to lay the foundation for a national synergistic effort to characterize them
Genetic testing
in the Indian population.
Inherited arrhythmias
Copyright ª 2013, Cardiological Society of India. All rights reserved.
Sudden cardiac death
Inherited primary arrhythmia syndromes are electrical abnormalities of the heart caused by derangements in the structure and function of the cardiac ion channels. Since a majority of the primary arrhythmias are due to mutations in the genes encoding the ion channels of the heart, namely Naþ, Kþ and Caþþ channels, they are referred to as “cardiac ion channelopathies”.1 These are typically monogenic disorders, that is, disorders that follow a clear Mendelian pattern of inheritance, although for some of them a more complex pattern emerges.2 They are most often inherited in an autosomal dominant pattern, which explains the strong role for family screening in the management of affected patients.3
Autosomal recessive inheritance and the occurrence of de novo mutations are also seen but less frequently. Sudden cardiac death (SCD), defined as death from a cardiac cause occurring shortly after the onset of symptoms, is most often due to an organic cardiac abnormality, such as coronary artery disease or structural heart disease. However, death in young, active and previously healthy individuals with no identifiable cause on autopsy, termed sudden arrhythmic death syndrome (SADS), constitutes up to 5% of SCD in the general population aged 16e64 years and almost 25e35% of sudden deaths in the
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ihj
Review Article
Inherited arrhythmia syndromes leading to sudden cardiac death in the young: A global update and an Indian perspective Priya Chockalingam a,*, Arthur A. Wilde a,b a
Department of Clinical and Experimental Cardiology, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands b Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia
article info
abstract
Article history:
Inherited primary arrhythmias, namely congenital long QT syndrome, Brugada syndrome
Received 31 October 2013
and catecholaminergic polymorphic ventricular tachycardia, account for a significant
Accepted 7 November 2013
proportion of sudden cardiac deaths in young and apparently healthy individuals. Genetic
Available online 17 December 2013
testing plays an integral role in the diagnosis, risk-stratification and treatment of probands and family members. It is increasingly obvious that collaborative efforts are required to
Keywords:
understand and manage these relatively rare but potentially lethal diseases. This article
Cardiac channelopathies
aims to update readers on the recent developments in our knowledge of inherited ar-
Family screening
rhythmias and to lay the foundation for a national synergistic effort to characterize them
Genetic testing
in the Indian population.
Inherited arrhythmias
Copyright ª 2013, Cardiological Society of India. All rights reserved.
Sudden cardiac death
Inherited primary arrhythmia syndromes are electrical abnormalities of the heart caused by derangements in the structure and function of the cardiac ion channels. Since a majority of the primary arrhythmias are due to mutations in the genes encoding the ion channels of the heart, namely Naþ, Kþ and Caþþ channels, they are referred to as “cardiac ion channelopathies”.1 These are typically monogenic disorders, that is, disorders that follow a clear Mendelian pattern of inheritance, although for some of them a more complex pattern emerges.2 They are most often inherited in an autosomal dominant pattern, which explains the strong role for family screening in the management of affected patients.3
Autosomal recessive inheritance and the occurrence of de novo mutations are also seen but less frequently. Sudden cardiac death (SCD), defined as death from a cardiac cause occurring shortly after the onset of symptoms, is most often due to an organic cardiac abnormality, such as coronary artery disease or structural heart disease. However, death in young, active and previously healthy individuals with no identifiable cause on autopsy, termed sudden arrhythmic death syndrome (SADS), constitutes up to 5% of SCD in the general population aged 16e64 years and almost 25e35% of sudden deaths in the
