Sudden Infant Death Syndrome: The Role of Cardiac Ion Channel Mutations

Abstract

The sudden infant death syndrome (SIDS) causes the sudden and unexplained death of an apparently healthy infant. Primary electrical diseases of the heart, with lethal arrhythmogenic events as a result of dysfunctioning cardiac ion channels (‘ion channelopathies’), may underlie such death. Genetic analysis in cohorts of SIDS victims (‘molecular autopsy’) has revealed a large number of mutations in ion channel‐related genes linked to inheritable arrhythmogenic syndromes, in particular the long QT syndrome, the short QT syndrome, the Brugada syndrome and cathecholaminergic polymorphic ventricular tachycardia. Combining data from population‐based cohort studies, it can be concluded that one out of five SIDS victims carries a mutation in a cardiac ion channel‐related gene and that the majority of these mutations are of a known malignant phenotype.

Key Concepts:

  • The sudden infant death syndrome (SIDS) is defined as “the sudden unexpected death of an infant <1 year of age, with onset of the fatal episode apparently occurring during sleep, that remains unexplained after a thorough investigation, including performance of a complete autopsy and review of the circumstances of death and the clinical history”.

  • The pathophysiology of SIDS is still poorly understood, and SIDS remains a diagnosis of exclusion.

  • SIDS is a multifactorial disorder, with multiple factors contributing or predisposing to its development.

  • Long QT syndrome, short QT syndrome, Brugada syndrome and cathecholaminergic polymorphic ventricular tachycardia are inheritable cardiac disorders, with arrhythmogenic and possibly lethal events as a result of mutations in cardiac ion channel‐related genes.

  • As primary electrical diseases these ion channelopathies are not detectable during a standard post‐mortem examination.

  • The role of cardiac ion channel mutations as contributors to SIDS is currently well established.

  • At least one out of five SIDS victims carries a mutation in a cardiac ion channel‐related gene and the majority of these mutations are of a known malignant phenotype.

Keywords: sudden infant death; cardiac arrhythmias; ion channelopathies; long QT syndrome; short QT syndrome; Brugada syndrome; cathecholaminergic polymorphic ventricular tachycardia

Figure 1.

Triple risk hypothesis in the sudden infant death syndrome (SIDS). Genetic predisposition and risks during development create a vulnerable infant. If this vulnerable infant encounters environmental triggers during a critical developmental period, it may become a SIDS victim. Reproduced from Courts and Madea .

Figure 2.

Cardiac ion channel‐related mutations in the SIDS. (a) All 13 genes in which mutations have been identified in population‐based cohort studies and their relative occurrence. No mutations were found in three remaining genes (KCNJ2, SCN1B and SCN2B; see Table ). (b) All 12 genes in which these mutations have been designated as functionally significant and the relative occurrence of these functionally significant mutations. Mutations specified in Table .

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Further Reading

Cerrone M and Priori SG (2011) Genetics of sudden death: focus on inherited channelopathies. European Heart Journal 32: 2109–2118.

Chopra N and Knollmann BC (2011) Genetics of sudden cardiac death syndromes. Current Opinion in Cardiology 26: 196–203.

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How to Cite close
Wilders, Ronald(Oct 2012) Sudden Infant Death Syndrome: The Role of Cardiac Ion Channel Mutations. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024378]