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Sudden Cardiac Death (SCD) in the young (aged 1-35 years), although presumably rare, is always a tragic and devastating event often occurring in apparently healthy persons. Through the last decades, research have been undertaken to estimate the incidence rate and underlying causes of these deaths. However, because autopsy is not always conducted, the true incidence of SCD might be underestimated. The incidence of sudden infant death syndrome (SIDS) has previously been thoroughly investigated, also in Denmark. However, data has not been precise in sudden unexpected death in infancy (SUDI) estimates. SIDS is a diagnosis of exclusion and an ICD-10 diagnosis (R95.9), but to what extent this diagnosis is being accurately applied has not been investigated in Denmark. A genetic screening for mutations in an otherwise unexplained death, might identify a likely cause of (inherited) death. It would be of great clinical interest if DNA derived from the Danish Neonatal Screening Biobank, containing DNA from all Danes born after 1981, could be used in this respect. In this thesis we provide nationwide data on SCD, SUDI and SIDS in Denmark for the period 2000-2006 by reading death certificates, autopsy reports, and registry data. We report the highest possible incidence rate of SCD in the young. We elaborate on regional differences in post-mortem investigations of sudden death cases in Denmark and validate a method for whole-genome amplification of DNA from Guthrie cards to be used in genetic screening for disease causing mutations. We found 7% of all deaths in the young could be attributed to SCD. A total of 25% of sudden unexpected death in the 1-35 years old were not autopsied. The incidence of SCD of 2.8 per 100 000 person-years - when including non-autopsied cases - was higher than previously reported. Unexplained deaths were abundant and accounted for 22% of all sudden unexpected deaths. Sudden deaths occurring during competitive sports, however, were only seen in few cases. We found that regional differences exist in the investigation of sudden unexpected deaths. Fewer deaths were medico-legally investigated by external examinations ("retslægeligt ligsyn") in some parts of Denmark compared to other parts. The same was the case in autopsy ratios. In infant deaths we found that almost 1 in 2000 live-borns died suddenly and unexpectedly during their first year of life. The R95.9 diagnosis did not reflect the SIDS cases we identified. We were able to get DNA from the Danish Neonatal Screening Biobank on 93 cases of unexplained deaths (including SIDS). Due to the limited amount of DNA available from the dried blood spots, we performed whole-genome amplification on the DNA (wgaDNA). We investigated the use of wgaDNA for genetic screening and it completely resembled genomic DNA (gDNA). Future research will focus on the genetics substrate of sudden unexplained death. In addition, we will investigate the causes of death in the 36-49 years old, as these may also suffer from cardiac disease that can be predisposed in the family.
University Hospital Copenhagen, Rigshospitalet, Department of Cardiology, Laboratory for Molecular Cardiology, 9312, Juliane Maries Vej 20, 2100 Copenhagen Ø, Denmark. firstname.lastname@example.org.
This article was published in the following journal.
Name: Danish medical journal
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