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Sudden cardiac death in young Danes


Bo Gregers Winkel


Sudden Cardiac Death (SCD) in the young (aged 1-35 years), although presumably rare, is alwaysa tragic and devastating event often occurring in apparently healthy persons. Through the lastdecades, research have been undertaken to estimate the incidence rate and underlying causes ofthese deaths. However, because autopsy is not always conducted, the true incidence of SCDmight be underestimated.The incidence of sudden infant death syndrome (SIDS) has previously been thoroughlyinvestigated, also in Denmark. However, data has not been precise in sudden unexpected death ininfancy (SUDI) estimates. SIDS is a diagnosis of exclusion and an ICD-10 diagnosis (R95.9), but towhat 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 causeof (inherited) death. It would be of great clinical interest if DNA derived from the Danish NeonatalScreening 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 highestpossible incidence rate of SCD in the young. We elaborate on regional differences in post-morteminvestigations of sudden death cases in Denmark and validate a method for whole-genomeamplification of DNA from Guthrie cards to be used in genetic screening for disease causingmutations.We found 7% of all deaths in the young could be attributed to SCD. A total of 25% of suddenunexpected death in the 1-35 years old were not autopsied. The incidence of SCD of 2.8 per 100000 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. Wefound that regional differences exist in the investigation of sudden unexpected deaths. Fewerdeaths were medico-legally investigated by external examinations (retslægeligt ligsyn) in someparts 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 duringtheir 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 ofunexplained deaths (including SIDS). Due to the limited amount of DNA available from the driedblood spots, we performed whole-genome amplification on the DNA (wgaDNA). We investigatedthe 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, wewill investigate the causes of death in the 36-49 years old, as these may also suffer from cardiacdisease that can be predisposed in the family.