ObjectiveTo describe experience of long QT (LQT) molecular autopsy in sudden infant death syndrome (SIDS).DesignDescriptive audit from two distinct periods: (1) A prospective, population-based series between 2006 and 2008 (‘unselected’). (2) Before and after 2006–2008, with testing guided by a cardiac genetic service (‘selected’). LQT genes 1, 2, 3, 5, 6 and 7 were sequenced. Next of kin were offered cardiac evaluation.SettingNew Zealand.Patients102 SIDS cases.InterventionsNil.Main outcome measuresDetection of genetic variants.ResultsMaori 49 (47%), and Pacific island 24 (23%), infants were over-represented. Risk factors were common; bed sharing was reported in 49%. Rare genetic variants were commoner within the selected than unselected populations (5 of 31 infants (16%) vs 3 of 71 infants (4%) p < 0.05). In the selected population two infants had variants of definite or probable pathogenicity (KCNQ1, E146K; KCNH2, R1047L), two had novel variants of possible pathogenicity in SCN5A (I795F, F1522Y) and one had R1193Q in SCN5A, of doubtful pathogenicity. R1193Q was also the only variant in the three cases from the unselected population and occurred as a second variant with R1047L. Engaging families proved challenging. Only 3 of 8 (38%) variant-positive cases and 18 of 94 (19%) of variant-negative families participated in cardiac/genetic screening.ConclusionsLQT molecular autopsy has a very low diagnostic yield among unselected SIDS cases where risk factors are common. Diagnostic yield can be higher with case selection. Engagement of the family prior to genetic testing is essential to counsel for the possible uncertainty of the results and to permit family genotype-phenotype cosegregation studies.

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We conclude that PTE may result in right ventricular myocardial inflammation and necrosis, distinct from that seen in typical myocardial infarction due to atherosclerotic coronary artery disease, or myocarditis. This observation may be explained, in part, by local stretch and strain of the right ventricle due to increased afterload, possibly compounded by diminished diastolic blood flow to the right ventricular myocardium and the effects of global myocardial hypoxia.

BackgroundTo review long QT syndrome molecular autopsy results in sudden unexplained death in young (SUDY) between 2006 and 2013 in New Zealand.MethodsAudit of the LQTS molecular autopsy results, cardiac investigations and family screening data from gene-positive families.ResultsDuring the study period, 365 SUDY cases were referred for molecular autopsy. 128 cases (35%) underwent LQTS genetic testing. 31 likely pathogenic variants were identified in 27 cases (21%); SCN5A (14/31, 45%), KCNH2 (7/31, 22%), KCNQ1 (4/31, 13%), KCNE2 (3/31, 10%), KCNE1 (2/31, 7%), KCNJ2 (1/31, 3%). Thirteen variants (13/128, 10%) were ultimately classified as pathogenic. Most deaths (63%) occurred during sleep. Gene variant carriage was more likely with a positive medical history (mostly seizures, 63% vs 36%, p = 0.01), amongst females (36% vs 12%, p = 0.001) and whites more than Maori (31% vs 0, p = 0.0009). Children 1–12 years were more likely to be gene-positive (33% vs 14%, p = 0.02). Family screening identified 42 gene-positive relatives, 18 with definitive phenotypic expression of LQTS/Brugada. 76% of the variants were maternally inherited (p = 0.007). Further family investigations and research now support pathogenicity of the variant in 13/27 (48%) of gene-positive cases.ConclusionIn New Zealand, variants in SCN5A and KCNH2, with maternal inheritance, predominate. A rare variant in LQTS genes is more likely in whites rather than Maori, females, children 1–12 years and those with a positive personal and family history of seizures, syncope or SUDY. Family screening supported the diagnosis in a third of the cases. The changing classification of variants creates a significant challenge.

Postmortem tryptase is a useful biochemical test to aid the diagnosis of anaphylaxis. Multiple perimortem and postmortem factors have been documented to cause an elevation in postmortem tryptase level. One factor that was recently recognized to have an impact on postmortem tryptase level is correct sampling technique. A recent study recommended aspirating blood samples from a clamped femoral/external iliac vein to be used for reliable postmortem tryptase analysis. This study sampled 120 consecutive nonanaphylactic deaths in which all the peripheral bloods were sampled as recommended. Postmortem interval, resuscitation, different nonanaphylactic causes of death, sex, and age did not show any statistical significant relation to postmortem tryptase level in Student t test, Pearson correlation, and univariate and multivariate analyses. The mean (SD) postmortem tryptase level was 8.4 (5.2) μg/L (minimum, 1.0 μg/L; maximum, 36.1 μg/L; median, 7.3 μg/L). Using nonparametric methods, the postmortem tryptase reference range in nonanaphylactic death was established as <23 μg/L (97.5th percentile).