ACMG recommendations on incidental findings: a commentary

By Ron Zimmern

2 April 2013


American College of Medical Genetics and Genomics Recommendations 
(link to PDF of full recommendations)

We read with some dismay the recommendations issued by the American College of Medical Genetics and Genomics for the Reporting of Incidental Findings in Clinical Exome and Genome Sequencing. The recommendations require laboratories, regardless of the indication for which the clinical sequencing was ordered, to explicitly seek and report on a minimum list of variants set out in the paper. They do not allow patients to decide on whether or not they would wish to receive such information, recommending instead that patients who decline to receive information about these incidental (secondary) variants should not be allowed to have their genome or exomes sequenced. Reports are to be sent to the referring clinician who must take the responsibility for whether or how to communicate this information to their patient, if necessary after consulting a clinical geneticist. These variants are to be reported regardless of the age of the patient.

It is quite extraordinary that a professional institution such as the American College should make recommendations that are so contrary to international ethical standards regarding consent, and put forward so coercive a regime as to deny patients what might prove to be an essential clinical investigation were they not to assent to receiving information about incidental (secondary) variants. The placing of total responsibility on the referring clinician by the laboratory geneticist is in our view an unacceptable burden. We appreciate and support the idea that the appropriate place for discussion with the patient is at the clinician-patient interface, but believe that the laboratory should be more explicitly involved in helping to interpret the findings with the referring clinician. From this side of the Atlantic we can only surmise that these recommendations have, at least to some extent, been influenced by medico-legal considerations.

Unlike imaging and other modalities of investigation where incidental findings are truly incidental in that the clinician interpreting the primary or pertinent findings cannot but help noticing the secondary findings, most secondary genetic variants have to be explicitly sought. Indeed the recommendations require the laboratory to make explicit attempts to seek such findings at the time the primary findings are reported. The paper makes little attempt to discuss in any detail the alternative strategy where explicit interrogation and analysis of such incidental (secondary) findings, although sequenced, is not carried out unless explicitly consented to by the patient. The authors make the analogy with opportunistic screening but decline to discuss the fact that opportunistic screening should require the explicit consent of the patient.The failure to discuss the issues of consent and merely to assert that patients who do not consent to the return of secondary findings should not be offered WGS or exome sequencing is in our view totally unacceptable.

Although the paper recognises the implication of low prior probability and its effect on the positive predictive value of the result, the implications of this fact were not discussed in any detail. Nor was mention made of reports, where in some instances known pathogenic variants of high penetrance inherited disorders have been found in patients with no symptoms or signs of such disorders. The implications of reduced penetrance or of expressivity of variants were also not mentioned. Their recommendations about incidental findings in children are also contrary to international standards about how and in what circumstances there should be feedback of genetic test results to minors.

There is little to commend in the set of recommendations except the fact that it will generate much discussion about the return of findings, both pertinent and incidental, in WGS. The strategy that has been recommended is an acceptable and possible option that certain patients may wish to consider; but not to give patients the choice of other options, or to deny them the test if they decline to receive information about secondary variants is a coercive strategy that should have no place in the modern practice of medicine.

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