Letter to the Editor
The Use by Medical Examiners of Genetic Testing for Long QT Syndrome in Suspected Sudden Cardiac Death To the Editor.—Long QT syndrome (LQTS) is one of several inherited genetically heterogeneous cardiac channelopathies (CCs) that are the cause for as many as 35% of sudden unexplained cardiac death (SUD) cases1 and 7% of cases of sudden infant death syndrome.2 Postmortem genetic testing in SUD can identify a CC mutation in 35% of cases. While this makes no difference to the patient, it has major significance to biologic relatives, as each first-degree relative is at increased risk for carrying a mutation, and therefore for SUD. Genetic testing is the only definitive method to determine if they are at risk.3 In practice, genetic testing in SUD has been shown to have substantial benefit in 1 study1 in which 28% of asymptomatic first-degree relatives tested were found to have the LQTS mutation. It has been suggested that genetic testing for CCs become standard of care.4 However, barriers exist. One is cost, but just as significant is the ability of the medical examiner (ME) to order the right test and communicate the results to the family of the deceased person. To explore this we surveyed the ME community by using the National Medical Examiners’ listserv through the National Association of Medical Examiners to determine their knowledge of LQTS and
Arch Pathol Lab Med—Vol 138, November 2014
other CCs, their perceived utility and availability of genetic testing, and their protocol for counseling of families. The study was approved by the Institutional Review Board of the University of Alabama at Birmingham. Of the 48 respondents to the 23question survey, 79% identified themselves as MEs and 46% as MDs. Most (87%) had no additional training in genetics and those that did report genetics training received this during residency rotations. The vast majority knew of genetic testing for CCs (97%) from a variety of sources: journals (85%), conferences (83%), colleagues (62%), medical school education (17%), and other sources (24%) including advertisements from commercial genetic testing companies. Almost all (98%) consider LQTS and other genetic CCs in SUD. Many reported that they investigated this possibility further by eliciting a family history (73%), genetic testing (29%), or through other methods such as referring patient’s families to geneticists or cardiologists, saving pathology specimens, consulting local geneticists, or reviewing past medical records. However, 60% reported never ordering the genetic test, with cost being the barrier (98%). Most (72%) reported personally counseling families about LQTS, but only 18% knew that these conditions are overwhelmingly inherited (as opposed to de novo mutations), and only 29% knew that they are autosomal dominant. More importantly, only 9% knew that a mutation will be identified in 35% of SUD cases; 55% believed it was less than 5%. Only 39% knew the risk to first-degree family members. This study has obvious limitations, with a small number of respondents.
However, the results do indicate that the MEs surveyed are aware of these inherited CCs and do consider them in their evaluation of SUD. However, most did not know important facts about these conditions, including their inheritance pattern, the new mutation rate, and the value of genetic testing for at-risk relatives. Further studies seek to devise educational strategies to close medical knowledge gaps for genetic disorders that account for SUD. REBEKAH WEIL, MD Department of Medicine University of Alabama at Birmingham School of Medicine C. BRUCE ALEXANDER, MD Department of Pathology NATHANIEL H. ROBIN, MD Departments of Genetics, Pediatrics, Otolaryngology University of Alabama at Birmingham Birmingham, AL 35294 1. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. J Am Coll Cardiol. 2007;49(2): 247–249. 2. Tester DJ, Ackerman MJ. The role of molecular autopsy in unexplained sudden cardiac death. Curr Opin Cardiol. 2006;21(3):166–172. 3. Alders M, Mannens MMAM. Romano-Ward syndrome. In: Pagon RA, Adam MP, Bird TD, et al, eds. GeneReviews [online]. Seattle, WA: University of Washington, Seattle; 1993–2014. http://www. ncbi.nlm.nih.gov/books/NBK1129/. Posted February 20, 2003. Updated May 31, 2012. Accessed May 10, 2013. 4. Di Paolo M, Luchini D, Bloise R, Priori SG. Postmortem molecular analysis in victims of sudden unexplained death. Am J Forensic Med Pathol. 2004;25(2):182–184.
doi: 10.5858/arpa.2014-0099-LE
Letter to the Editor 1425
Copyright of Archives of Pathology & Laboratory Medicine is the property of College of American Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
The Use by Medical Examiners of Genetic Testing for Long QT Syndrome in Suspected Sudden Cardiac Death To the Editor.—Long QT syndrome (LQTS) is one of several inherited genetically heterogeneous cardiac channelopathies (CCs) that are the cause for as many as 35% of sudden unexplained cardiac death (SUD) cases1 and 7% of cases of sudden infant death syndrome.2 Postmortem genetic testing in SUD can identify a CC mutation in 35% of cases. While this makes no difference to the patient, it has major significance to biologic relatives, as each first-degree relative is at increased risk for carrying a mutation, and therefore for SUD. Genetic testing is the only definitive method to determine if they are at risk.3 In practice, genetic testing in SUD has been shown to have substantial benefit in 1 study1 in which 28% of asymptomatic first-degree relatives tested were found to have the LQTS mutation. It has been suggested that genetic testing for CCs become standard of care.4 However, barriers exist. One is cost, but just as significant is the ability of the medical examiner (ME) to order the right test and communicate the results to the family of the deceased person. To explore this we surveyed the ME community by using the National Medical Examiners’ listserv through the National Association of Medical Examiners to determine their knowledge of LQTS and
Arch Pathol Lab Med—Vol 138, November 2014
other CCs, their perceived utility and availability of genetic testing, and their protocol for counseling of families. The study was approved by the Institutional Review Board of the University of Alabama at Birmingham. Of the 48 respondents to the 23question survey, 79% identified themselves as MEs and 46% as MDs. Most (87%) had no additional training in genetics and those that did report genetics training received this during residency rotations. The vast majority knew of genetic testing for CCs (97%) from a variety of sources: journals (85%), conferences (83%), colleagues (62%), medical school education (17%), and other sources (24%) including advertisements from commercial genetic testing companies. Almost all (98%) consider LQTS and other genetic CCs in SUD. Many reported that they investigated this possibility further by eliciting a family history (73%), genetic testing (29%), or through other methods such as referring patient’s families to geneticists or cardiologists, saving pathology specimens, consulting local geneticists, or reviewing past medical records. However, 60% reported never ordering the genetic test, with cost being the barrier (98%). Most (72%) reported personally counseling families about LQTS, but only 18% knew that these conditions are overwhelmingly inherited (as opposed to de novo mutations), and only 29% knew that they are autosomal dominant. More importantly, only 9% knew that a mutation will be identified in 35% of SUD cases; 55% believed it was less than 5%. Only 39% knew the risk to first-degree family members. This study has obvious limitations, with a small number of respondents.
However, the results do indicate that the MEs surveyed are aware of these inherited CCs and do consider them in their evaluation of SUD. However, most did not know important facts about these conditions, including their inheritance pattern, the new mutation rate, and the value of genetic testing for at-risk relatives. Further studies seek to devise educational strategies to close medical knowledge gaps for genetic disorders that account for SUD. REBEKAH WEIL, MD Department of Medicine University of Alabama at Birmingham School of Medicine C. BRUCE ALEXANDER, MD Department of Pathology NATHANIEL H. ROBIN, MD Departments of Genetics, Pediatrics, Otolaryngology University of Alabama at Birmingham Birmingham, AL 35294 1. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. J Am Coll Cardiol. 2007;49(2): 247–249. 2. Tester DJ, Ackerman MJ. The role of molecular autopsy in unexplained sudden cardiac death. Curr Opin Cardiol. 2006;21(3):166–172. 3. Alders M, Mannens MMAM. Romano-Ward syndrome. In: Pagon RA, Adam MP, Bird TD, et al, eds. GeneReviews [online]. Seattle, WA: University of Washington, Seattle; 1993–2014. http://www. ncbi.nlm.nih.gov/books/NBK1129/. Posted February 20, 2003. Updated May 31, 2012. Accessed May 10, 2013. 4. Di Paolo M, Luchini D, Bloise R, Priori SG. Postmortem molecular analysis in victims of sudden unexplained death. Am J Forensic Med Pathol. 2004;25(2):182–184.
doi: 10.5858/arpa.2014-0099-LE
Letter to the Editor 1425
Copyright of Archives of Pathology & Laboratory Medicine is the property of College of American Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
