ACMG recommendations on incidental findings are flawed scientifically and ethically

Konzepte zur Mitteilung genetischer Zusatzbefunde in der medizinischen Diagnostik und Forschung

“…Genen, die als medizinisch relevant eingestuft werden, blieb in Folge keineswegs unkritisch kommentiert [45,46]. Als Kriterien für die medizinische Relevanz -den klinischen Nutzen und die klinische Validität -benannte das ACMG die bekannte oder erwartete ("with a very high probability of being deleterious" [36]) Pathogenizität einer genetischen Variante, die Behandelbarkeit oder Präventionsmöglichkeit der assoziierten Erkrankung und, sofern vorhanden, die Möglichkeit einer diagnostischen Konfirmation.…”

“…Als Kriterien für die medizinische Relevanz -den klinischen Nutzen und die klinische Validität -benannte das ACMG die bekannte oder erwartete ("with a very high probability of being deleterious" [36]) Pathogenizität einer genetischen Variante, die Behandelbarkeit oder Präventionsmöglichkeit der assoziierten Erkrankung und, sofern vorhanden, die Möglichkeit einer diagnostischen Konfirmation. Ein großes Problem stellt die Zuordnung neuer Varianten der benannten Gene in eine der drei Kategorien "gesichert pathogen", "höchstwahr-scheinlich pathogen" oder "unbedenklich" dar [46] …”

Genetic Testing of Children for Diseases That Have Onset in Adulthood: The Limits of Family Interests

“…With regard to the ACMG claim of a professional obligation to inform parents and children of incidental findings that have significant implications for the family, critics argue that this misses the point and have noted that the mandatory nature of these tests violates patient (and parent) autonomy. With regard to the third justification, the claim of a net benefit to patients and families of testing (note that critics disagree that there is net benefit 15,17,18 ), it would be erroneous to conclude that this claim shows respect for the interests of the family as a social unit. Instead, the benefits to the "family" accrue to them because they happen to be the individuals (other than the patient) likely to benefit most from the testing by virtue of being genetically related to the patient.…”

Clinical Tumor Sequencing: An Incidental Casualty of the American College of Medical Genetics and Genomics Recommendations for Reporting of Incidental Findings

“…Unsurprisingly, they have provoked vigorous discussion and debate regarding issues of patient autonomy and the ethics of returning results for pediatric patients. [2][3][4][5][6] Although there has been comparatively little discussion of the impact of these recommendations on testing of tumor specimens, 7 the scope of these recommendations does extend beyond germline genetic testing into the realm of tumor-focused testing with the statement that "incidental variants should be reported for the normal sample of a tumor-normal sequenced dyad. "…”