Paul Morrow

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.

Long QT molecular autopsy in sudden unexplained death in the young (1-40 years old): Lessons learnt from an eight year experience in New Zealand

Background To review long QT syndrome molecular autopsy results in sudden unexplained death in young (SUDY) between 2006 and 2013 in New Zealand. Methods Audit of the LQTS molecular autopsy results, cardiac investigations and family screening data from gene-positive families. Results During 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. Conclusion In 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.

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.

Cardiac genetic investigation of sudden cardiac death: advances and remaining limitations

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Autopsy: failed intubation – what was the cause?

Aim and Methods: A 77-year-old man presented to the Emergency Department with profound shortness of breath. The intubation failed due to upper airway obstruction and subsequently he underwent cricothyroidotomy. He had a cardiac arrest for up to 20 minutes in the Emergency Department. He was transferred to the Intensive Care Unit. He showed evidence of global ischaemia of the brain and his life support equipment was stopped after 3 days. His past medical history included beta thalassaemia and C3 to C7 laminectomy for severe cervical myelopathy 4 months prior to his death. Results: The autopsy revealed a polypoid laryngeal tumour 3.2 cm in maximum dimension arising from the right vocal cord. The tumour extended to the glottic and supraglottic spaces. The superior aspect of the tumour was visible behind the epiglottis. Histologically, the tumour was a carcinosarcoma with squamous cell carcinoma and osteosarcoma component with sarcomatous component overgrowth. Discussion: Carcinosarcoma of the larynx is a very rare tumour predominantly occurring in elderly males. They are rapidly growing polypoid tumours which often present with acute airway obstruction. In this case, the retrospective review of the MRI performed 4 months ago for the cervical laminectomy showed a 0.7 cm nodule on the vocal cord.