Tuesday, 15 March 2016

Should doctors advise molecular autopsy in every sudden unexplained death?

Should doctors advise molecular autopsy in every sudden unexplained death? Yes. Personally, I feel the answer to this question should be a ‘yes’. I recall my college days when our head of the Pathology, Dr Arora, used to insist on a mini post mortem in every death for the purpose of learning. Sudden death can be explained or unexplained. For example, a person may come with VT/VF and die; we know the cause. On the other hand, a person may be brought in as cardiac arrest with failed CPR. If a person is brought in cardiac arrest and CPR fails then we need to inform the police as the primary cause of cardiac arrest is not known and an autopsy is usually done. But what about sudden death in the young due to arrhythmia or acute MI. All such cases should be advised molecular autopsy to go to the root cause of sudden death to avoid similar deaths in other members of the family. Medscape recently reported a case of 29-year-old man who died unexpectedly, his mother refused to accept sudden cardiac death as the cause, and went searching for answers. As per the mother Dardanel Robinson, she grew up surrounded by relatives who died in their 40s and 50s. Her grandmother "dropped dead of cardiac death at an early age,” the same happened to her uncles — one at age 42 and the other at age 57 — and to her 52-year-old father. In September 2014, Robinson got a call from her son's roommate in Birmingham, Alabama, who had found Daniel blue and unresponsive and called the paramedics, who could not save him. The medical examiner in Birmingham reported that Daniel likely experienced sudden dysrhythmia that produced a blood clot. She insisted for a molecular autopsy. She needed an answer “before any more of my children died”. She asked her children, her brother, and her cousins — 69 relatives in all — to create a multigenerational family tree and urged them to get genetic testing. And she found the cause, a high occurrence of mutations in the TRPM4 gene in the family, which are known to cause progressive familial heart block. We, the doctors, should get tissue preservation is all such sudden deaths. And if there is an unexplained death in the same family and somebody gets sequenced, please look back at the family history and match with earlier preserved samples. Molecular autopsy or post-mortem molecular testing is a set of molecular techniques used in forensic medicine to attempt to determine the cause of death in unexplained cases, in particular sudden unexplained deaths (for example sudden cardiac death). About 30% of sudden cardiac deaths in young people are not explained after full conventional autopsy, and are classified as sudden unexplained deaths. The use of a panel of genetic markers for long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and cardiac channel myopathies elucidated around 40 to 45% of the cases. One may expect that 10–15% of samples from victims of sudden unexplained death carry a mutation in KCNQ1, KCNH2, or SCN5A. The addition of the screening of the RyR2 gene for mutations that cause catecholaminergic polymorphic ventricular tachycardia may increase the yield of molecular autopsy by an additional 5–10%, thus bringing the expected yield of molecular autopsy to 15–25%. Where no cause of death is identified, genetic testing of deoxyribonucleic acid (DNA) extracted from postmortem blood (the molecular autopsy) may identify a cause of death in up to 30% of sudden unexplained deaths.

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