Simon Stables

Prospective, population-based long QT molecular autopsy study of postmortem negative sudden death in 1 to 40 year olds

BACKGROUND Retrospective investigation of sudden unexplained death in the young (SUDY) reveals that a high proportion is due to inherited heart disease. OBJECTIVE The purpose of this study was to ascertain the diagnostic value of postmortem long QT (LQT) genetic analysis in a prospective study of SUDY victims 1-40 years old. METHODS Denaturing high-performance liquid chromatography or direct sequencing of LQT genes 1, 2, 3, 5, and 6 was performed, in a National New Zealand protocol, in SUDY victims aged 1-40 years. RESULTS Over 26 months (2006-2008), DNA was stored at autopsy from 52 victims of sudden unexpected death. Further testing revealed a diagnosis in 19 cases (poisoning 4, dilated cardiomyopathy 3, myocarditis 3, other 9). The remaining 33 cases underwent genetic testing (age at death 18 months-40 years, median 25 years). Eighteen (55%) died during sleep or at rest, and 7 (21%) died during light activity. Rare missense variants in LQT genes were found in 5 (15%) cases (confidence interval 3%-27%): T96R in KCNQ1 (11-year-old male), P968L in KCNH2 (32-year-old female), P2006A in SCN5A (34-year-old female), and R67H and R98W in KCNE1 (17- and 38-year-old females, respectively). Evidence of pathogenicity was provided by in vitro evidence (T96R), family phenotype-genotype co-segregation (R98W, P2006A), and/or previous reports (R67H, P968L, P2006A, R98W). Family cardiac investigation was possible in 23 (70%) families and revealed probable cause of death for 5 (15%) other victims (confidence interval 3%-27%). CONCLUSION Most community SUDY occurs at rest or during light activity. A diagnostic rate of 15% supports the transition of LQT genetic autopsy, combined with family investigation, into routine medical practice.

Anaphylactic deaths in Auckland, New Zealand: a review of coronial autopsies from 1985 to 2005

Aims: To determine the frequency of anaphylactic deaths amongst coronial autopsy cases performed in the greater Auckland region from 1985 to 2005, and review the circumstances of death and autopsy findings. Methods: A computerised search for anaphylactic deaths was performed using the Forensic Pathology Department database at Auckland City Hospital. Postmortem reports and police reports were reviewed to determine the circumstances of death. Details recorded included basic demographic data, medical history, agent responsible for the allergic reaction, and pathologic findings at autopsy. Results: A total of 18 cases of anaphylactic deaths were identified for the study period, including nine males and nine females, age range 33–76 years, mean 51.9 years. There were 10 reactions to drugs or contrast media (4 anaesthetic agents, 3 antibiotic, 2 IV contrast media, 1 streptokinase), four to bee/wasp venom, two to seafood, and two undetermined. Death occurred within 1 hour of onset of anaphylaxis in 12 cases. Findings at autopsy included non‐specific pulmonary oedema and congestion (n = 13), laryngeal oedema (n = 5), cerebral hypoxia (n = 4) and cutaneous oedema (n = 1). Serum tryptase levels were measured in 15 cases, and were significantly elevated (>20 µg/L) in eight cases. Conclusion: Anaphylactic reaction is an uncommon cause of sudden death. In many cases, no specific macroscopic or microscopic findings were detected at autopsy. In the presence of a typical clinical history, postmortem measurement of serum tryptase levels can be a useful diagnostic aid.

Long QT molecular autopsy in sudden infant death syndrome

Objective To describe experience of long QT (LQT) molecular autopsy in sudden infant death syndrome (SIDS). Design Descriptive 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. Setting New Zealand. Patients 102 SIDS cases. Interventions Nil. Main outcome measures Detection of genetic variants. Results Maori 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. Conclusions LQT 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.

Sink or Swim: The Advantages of Full Postmortem Examination in Cases of Drowning

Background There is current debate whether full postmortems should be carried out on drowning victims. Objective To document the value of full postmortem examinations of drowning victims. Methods Retrospective data gathered from 42 postmortem reports of drowning cases over a two-year period. Results Forty-two drowning cases were included, 34 of which were adult internal examinations. Excluding fluid analysis, 38.2% of drowning cases were found to have diagnoses other than drowning thought to have contributed significantly to death. This figure rose to 50% when fluid analysis was included in the postmortem examination. Eighty-eight point two percent of adult internal examination cases found incidental diagnoses other than drowning at postmortem. Conclusion There is advantage to routinely conducting full postmortem examinations on suspected drowning cases, including the extraction of fluid samples.

Post mortem vitreous magnesium in adult population.

BACKGROUND The study of post mortem vitreous magnesium (Mg) is less common than sodium (Na), chloride (Cl) and potassium (K) in the forensic literature. There is no accepted normal range for post mortem vitreous Mg and the relationship between post mortem vitreous Mg levels and post mortem interval (PMI), other electrolyte levels, disease conditions, age and sex have not been fully established. AIM To investigate the relationship of post mortem vitreous Mg with age, sex, PMI, vitreous electrolyte levels and diabetic status. METHODS A retrospective study of 20 consecutive cases of diabetics and 20 non-diabetic adult deaths was performed. Spearman correlation and the permutation test were used to explore the relationship between post mortem vitreous Mg and continuous and categorical variables respectively. RESULTS The mean post mortem vitreous Mg was 1.03mmol/L (95%CI: 0.98-1.08mmol/L). The absolute Spearman correlation coefficients (rho) between post mortem vitreous Mg with PMI, age, and other vitreous electrolytes (Na, Cl, and K) ranged between 0.04-0.21 (p>0.19). Post mortem vitreous Mg was statistically higher in diabetics (mean difference: 0.08mmol/L; area-under-the-curve=0.65 on receiver-operator-characteristic curve). No statistical difference was demonstrated between sexes (p=0.92). CONCLUSIONS In our adult population, post mortem vitreous Mg did not correlate with age, PMI, other vitreous electrolytes (sodium, chloride and potassium) or sex. It was higher in diabetics, however had limited utility as a surrogate marker. Overall, post mortem Mg is steady in the early post mortem period with a mean of 1.03mmol/L.

Coronial deaths in auckland due to atherosclerotic coronary artery disease in persons ≤40 years: a retrospective study 2000–2007

Aims To identify the demographic distribution, frequency and circumstances of coronial deaths in Auckland due to coronary artery atherosclerotic disease (CAD) in persons ≤40 years. To review the associated autopsy findings and cardiovascular risk factors (CVRF). Method A computerised search for coronial deaths due to CAD in persons ≤40 years from 2000 to 2007 was conducted using the Forensic Pathology Department database at Auckland City Hospital. The police reports and autopsy reports were reviewed to record the demographic detail, to determine the circumstances preceding death and to summarise the pathological findings. The main CVRF were analysed. Results A total of 89 coronial deaths due to CAD in persons ≤40 years were identified. There were Caucasian 23 (25.8%), Maori 33 (37.1%), Polynesian 26 (29.2%), Indian descent 3 (3.4%), Asian except Indian 1 (1.1%). Maori was the predominant ethnic group represented in this study and combined with the Polynesian group, made up 66.3% of cases. Conclusion This autopsy-based study revealed that in Auckland, Maori and Pacific people require an early screening (≤40 years of age) for CVRF assessment and management.