Molecular Genetics of Sudden Infant Death Syndrome

Abstract

The sudden infant death syndrome (SIDS) is currently defined as the sudden unexpected death of an infant less than 1 year of age with onset of the fatal episode apparently occurring during sleep, which remains unexplained after a thorough investigation. SIDS, whose aetiology remains rather vague, is still the major cause of death among infants between 1 month and 1 year of age in industrialised countries with varying incidences in different subpopulations.

After touching on definitory approaches and several current hypotheses concerning SIDS aetiology, the triple risk hypothesis as an explanatory model for SIDS is introduced, followed by the discussion of associated genetic risk factors potentially contributing to or predisposing for the generation of a vulnerable infant that, when encountering an environmental trigger, may succumb to SIDS. An overview of current animal models for SIDS is presented and future prospects are briefly discussed.

Key Concepts:

  • A proper definition and strict adherence to diagnostic criteria is critical to valid SIDS research.

  • SIDS is multifactorial disease probably with a genetic predisposition.

  • The triple risk areas model is an explanatory approach that may be fitted to most hypotheses concerning SIDS aetiology.

  • Numerous and very different genetic variants are potentially predisposing for SIDS.

  • Current animal models for SIDS may be useful but can each only represent a subgroup of SIDS.

  • Functional studies of SIDS pathomechanisms are required.

Keywords: sudden infant death syndrome; triple risk model; genetic predisposition; brainstem hypothesis; SIDS animal model

Figure 1.

(a) ‘Three risk areas model’ SIDS may occur, when at least but not limited to one factor from each area (Genetic, Individual and Environment) is present in the same infant. (b) TRAM: three risk areas model as an explicatory funnel. The pathomechanisms postulated in the various hypotheses (H1 to Hn) each account for a subgroup of SIDS cases. The ‘three risk areas model’ also allows for a combination of the effects of different and/or combined hypotheses (Hn+Hm), for example, immunologic and central nervous system hypotheses.

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Further Reading

Byard RW (2011) Sudden infant death syndrome. In: Sudden Death in the Young, 3rd edn, pp. 555–630. Cambridge: Cambridge University Press.

Courts C and Madea B (2010) Genetics of the sudden infant death syndrome. Forensic Science International 203(1–3): 25–33.

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Hauck FR (2001) Changing epidemiology. In: Sudden Infant Death Syndrome: Problems, Progress and Possibilities, pp. 31–57. London: Arnold.

Hauck FR and Tanabe KO (2008) International trends in sudden infant death syndrome: stabilization of rates requires further action. Pediatrics 122(3): 660–666.

Kinney HC and Thach BT (2009) The sudden infant death syndrome. New England Journal of Medicine 361(8): 795–805.

Leach CE, Blair PS, Fleming PJ et al. (1999) Epidemiology of SIDS and explained sudden infant deaths. CESDI SUDI Research Group. Pediatrics 104(4): e43.

Opdal SH and Rognum TO (2011) Gene variants predisposing to SIDS: current knowledge. Forensic Science, Medicine and Pathology 7(1): 26–36.

Weese‐Mayer DE, Ackerman MJ, Marazita ML and Berry‐Kravis EM (2007) Sudden Infant Death Syndrome: review of implicated genetic factors. American Journal of Medical Genetics Part A 143A(8): 771–788.

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Courts, Cornelius(Apr 2013) Molecular Genetics of Sudden Infant Death Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022424]