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The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national cohort of young sudden unexplained death cases.

Introduction: Sudden unexplained death account for one‐third of all sudden natural deaths in the young (1–35 years). Hitherto, the prevalence of genopositive cases has primarily been based on deceased persons referred for postmortem genetic testing. These deaths potentially may represent the worst of cases, thus possibly overestimating the prevalence of potentially disease causing mutations in the 3 major long‐QT syndrome (LQTS) genes in the general population. We therefore wanted to investigate the prevalence of mutations in an unselected population of sudden unexplained deaths in a nationwide setting.

Lack of Evidence for a Causal Relationship Between Hypoxic-Ischemic Encephalopathy and Subdural Hemorrhage in Fetal Life, Infancy, and Early Childhood

It has been asserted that hypoxic-ischemic encephalopathy (HIE) with cerebral swelling in the absence of marked trauma may be responsible for subural hemorrhage in the young. As this may have considerable implications in determining both the mechanism of death and the degree of force required to cause injury in certain cases of inflicted head injury in infancy, clarification is required. A retrospective study of 82 fetuses, infants, and toddlers with proven HIE and no trauma was undertaken from forensic institutes in Australia, the United Kingdom, Germany, Denmark, and the United States. The age range was 35 weeks gestation to 3 years, with a male to female ratio of 2:1. All cases had histologically confirmed HIE. Causes of the hypoxic episodes were temporarily resuscitated sudden infant death syndrome with delayed death (N = 30), drowning (N = 12), accidental asphyxia (N = 10), intrauterine/delivery asphyxia (N = 8), congenital disease (N = 6), aspiration of food/gastric contents (N = 4), inflicted asphyxia (N = 3), epilepsy (N = 1), dehydration (N = 1), drug toxicity (N = 1), complications of prematurity (N = 1), and complications of anesthesia (N = 1). The initiating event was not determined in 4 instances. In no case was there macroscopic evidence of subdural hemorrhage. In this study no support could be given to the hypothesis that HIE in the young in the absence of trauma causes subdural hemorrhage.

Serious Invasive Saffold Virus Infections in Children, 2009

This virus might have caused previously unexplained cerebral infections and deaths in children.

Genetic investigations of sudden unexpected deaths in infancy using next-generation sequencing of 100 genes associated with cardiac diseases

Sudden infant death syndrome (SIDS) is the most frequent manner of post-perinatal death among infants. One of the suggested causes of the syndrome is inherited cardiac diseases, mainly channelopathies, that can trigger arrhythmias and sudden death. The purpose of this study was to investigate cases of sudden unexpected death in infancy (SUDI) for potential causative variants in 100 cardiac-associated genes. We investigated 47 SUDI cases of which 38 had previously been screened for variants in RYR2, KCNQ1, KCNH2 and SCN5A. Using the Haloplex Target Enrichment System (Agilent) and next-generation sequencing (NGS), the coding regions of 100 genes associated with inherited channelopathies and cardiomyopathies were captured and sequenced on the Illumina MiSeq platform. Sixteen (34%) of the SUDI cases had variants with likely functional effects, based on conservation, computational prediction and allele frequency, in one or more of the genes screened. The possible effects of the variants were not verified with family or functional studies. Eight (17%) of the SUDI cases had variants in genes affecting ion channel functions. The remaining eight cases had variants in genes associated with cardiomyopathies. In total, one third of the SUDI victims in a forensic setting had variants with likely functional effect that presumably contributed to the cause of death. The results support the assumption that channelopathies are important causes of SUDI. Thus, analysis of genes associated with cardiac diseases in SUDI victims is important in the forensic setting and a valuable supplement to the clinical investigation in all cases of sudden death.

Testing a Multiple Mediator Model of the Effect of Childhood Sexual Abuse on Adolescent Sexual Victimization

The present study modeled the direct relationship between child sexual abuse (CSA) and adolescent peer-to-peer sexual victimization (APSV) and the mediated effect via variables representing the number of sexual partners, sexual risk behavior, and signaling sexual boundaries. A cross-sectional study on the effect of CSA on APSV was conducted, utilizing a multiple mediator model. Mediated and direct effects in the model were estimated employing Mplus using bootstrapped percentile based confidence intervals to test for significance of mediated effects. The study employed 327 Danish female adolescents with a mean age of 14.9 years (SD = 0.5). The estimates from the mediational model indicated full mediation of the effect of CSA on APSV via number of sexual partners and sexual risk behavior. The current study suggests that the link between CSA and APSV was mediated by sexual behaviors specifically pertaining to situations of social peer interaction, rather than directly on prior experiences of sexual victimization. The present study identifies a modifiable target area for intervention to reduce adolescent sexual revictimization.

Molecular autopsy in young sudden cardiac death victims with suspected cardiomyopathy

The aim of this investigation was to identify and characterise pathogenic mutations in a sudden cardiac death (SCD) cohort suspected of cardiomyopathy in persons aged 0-40 years. The study material for the genetic screening of cardiomyopathies consisted of 41 cases and was selected from the case database at the Institute of Forensic Medicine. Mutational screening by DNA sequencing was performed to detect mutations in DNA samples from deceased persons suspected of suffering from hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricle cardiomyopathy (ARVC). A total of 9 of the examined 41 cases had a rare sequence variant in the MYBPC3, MYH7, LMNA, PKP2 or TMEM43 genes, of which 4 cases (9.8%) were presumed to be pathogenic mutations. The presumed pathogenic mutations were distributed with one case of suspected HCM and DCM (MYH7; p.R442H), one case of suspected DCM (LMNA; p.R471H), and two cases of suspected ARVC (PKP2; p.R79X and LMNA; p.R644C). The presented data adds important information on the genetic elements of SCD in the young, and calls for expert pathological evaluation and molecular autopsy in the post-mortem examination of SCD victims with structural anomalies of the heart.

Surveillance of HIV and viral hepatitis by analysis of samples from drug related deaths

Objectives:To determine the prevalence of antibodies against HIV, hepatitis B (HBV) and hepatitis C (HCV) in postmortem samples from drug related deaths (DRDs) in Denmark.Design:Prospective cohort study. Postmortem samples tested for anti-HIV, anti-HCV anti-HBc and anti-HBs. Comparison to pre-mortem testing when possible. DRDs were searched for in the national register of drug treatment, national prison registers, and the national infectious disease register.Setting:National level.Participants:Drug related deaths admitted to Danish Institutes of Forensic Medicine during 2004.Main outcome measures:Prevalence of antibodies, injection drug use, drug treatment experience and prevalence of cirrhosis.Results:Samples for analysis were obtained from 78% (233/299) of DRDs. The prevalences of anti-HIV, anti-HCV and anti-HBc were 4% (9/214), 51% (110/215), and 35% (74/209), indicating a persisting low prevalence of HIV and a declining prevalence of HCV and HBV. Injecting ever was detected among 45% of DRDs and this was associated with a significantly higher prevalence of hepatitis B and C. Among the DRDs 56% received drug treatment and 12% had cirrhosis at autopsy. Evidence of vaccination against HBV was found among 16% (21/128).Conclusions:Monitoring of viral hepatitis and HIV among DRDs is feasible, and our survey indicates a falling prevalence among Danish drug users. Surveillance based on drug users in treatment may overestimate the true prevalence.

Congenital Lesions Associated With Airway Narrowing, Respiratory Distress, and Unexpected Infant and Early Childhood Death

A review was undertaken of the range of possible congenital lesions of the major airways and adjacent tissues that may cause critical compromise of luminal diameter with resultant respiratory arrest from airway occlusion. Lesions included micrognathic syndromes, macroglossia, choanal atresia and stenosis, tumors and choristomas, posterior lingual masses, laryngeal atresia and stenosis, laryngeal webs, laryngeal cysts and laryngoceles, laryngomalacia, tracheomalacia, and bronchomalacia. An autopsy approach to possible congenital obstructive lesions of the upper airway requires: (1) review of the clinical and family histories looking specifically at the nature of the terminal episode; (2) external examination looking for dysmorphic syndromes with mandibular or mid-facial hypoplasia; and (3) internal examination with layer dissection of the soft tissues of the neck and en bloc removal of the upper aerodigestive tract, with photographic recording and histological sampling.

Sudden cardiac death in young adults: environmental risk factors and genetic aspects of premature atherosclerosis.

Abstract:  Familial hypercholesterolemia (FH) is a genetic disorder that may lead to premature coronary heart disease (CHD) and sudden cardiac death (SCD). Mutations in the LDLR or APOB genes cause FH. We have screened the LDLR and the ligand‐binding region of APOB genes in 52 cases of SCD. Deceased patients were younger than 40 years of age and were suspected of having FH. The LDLR and APOB genes were examined via PCR, high‐resolution melting, and DNA sequencing. Therein, it was observed that 7.7% of the screened patients exhibited a rare sequence variant in the LDLR gene, with 5.7% suspected of being pathogenic mutations. Lipid profiles and genetic testing for FH could be considered when autopsy reveals significant atherosclerosis of the coronary arteries in young adults. First‐degree family members are advised to seek medical advice and testing to determine their own risks of atherosclerosis to prevent premature CHD and SCD.

Adolescent sexual victimization: A prospective study on risk factors for first time sexual assault

The present study set out to investigate predictors of first time adolescent peer-on-peer sexual victimization (APSV) among 238 female Grade 9 students from 30 schools in Denmark. A prospective research design was utilized to examine the relationship among five potential predictors as measured at baseline and first time APSV during a 6-month period. Data analysis was a binary logistic regression analysis. Number of sexual partners and displaying sexual risk behaviors significantly predicted subsequent first time peer-on-peer sexual victimization, whereas a history of child sexual abuse, early sexual onset and failing to signal sexual boundaries did not. The present study identifies specific risk factors for first time sexual victimization that are potentially changeable. Thus, the results may inform prevention initiatives targeting initial experiences of APSV.