The genetic message of a sudden, unexpected death due to thoracic aortic dissection.
Thoracic aortic aneurysms are associated with sudden, unexpected death due to dissection and/or rupture. In such cases, the latent, preceding state of aortic dilatation has often gone undiagnosed. As a consequence of the sudden unresolved death, medico-legal autopsy requested by a public prosecutor will be the consequence to establish the cause and manner of death. Usually, autopsy records do not include relevant information for differential diagnosis of heritable syndromic and non-syndromic diseases associated with thoracic aortic aneurysms/dissections (TAAD), including e.g. Marfan syndrome, Loeys-Dietz syndrome, and isolated thoracic aortic aneurysms/dissection. However, for at-risk relatives of the deceased, it could be of great benefit to be alerted to the potential heritable aetiology, because early diagnosis of the latent stage of the disease would allow preventive management. Such attempts, including recommendations to seek genetic counselling, are nevertheless rarely made in the context of medico-legal autopsies, in which primarily the legal aspects are considered. We report here on three cases to underline the practical relevance of (i) documentation of relevant information for differential diagnosis of TAAD-associated disorders, (ii) storage of unfixed tissue samples for subsequent molecular genetic testing, and most importantly (iii) the information of relatives at risk. In view of the general ethical principal of nonmaleficience, direct or indirect contact with family members of victims of possible heritable forms of TAAD should be established as a standard of care, also in the medico-legal setting.
Ripperger
Tim
T
Institute of Cell and Molecular Pathology, Hannover Medical School, Carl Neuberg Street 1, 30625 Hannover, Germany.
Tröger
Hans Dieter
HD
Schmidtke
Jörg
J
D000328:Adult; D000784:Aortic Dissection / Q000175:diagnosis* / Q000235:genetics*; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis* / Q000235:genetics*; D003645:Death, Sudden / Q000209:etiology*; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D000071837:Fibrillins; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics; D008840:Microfilament Proteins / Q000032:analysis; D008967:Molecular Biology; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis
D000071837:Fibrillins; D008840:Microfilament Proteins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II