Any test that produces visual images or digital or genetic sequences will tend to produce incidental findings because more will be visible than what was originally sought. We conducted a systematic review of the ethical reasons presented in the literature for and against the disclosure of incidental findings arising in clinical and research genetics contexts. A search of electronic databases resulted in 13 articles included for systematic review. Articles presented reasons for and against disclosure, and reasons for proceeding with caution when making decisions about disclosure. One major recommendation of the reviewed articles is in favor of qualified disclosure: incidental findings with confirmed clinical utility where there is the possibility of treatment or prevention should be disclosed, with exceptions. A second type of recommendation is that disclosure should proceed with caution, especially in the context of new genetic technologies and genetic testing involving minors. It is also recommended that the number of possible incidental findings be limited even before genetic testing is carried out. Such a policy, which we advocate, would show preference for non-disclosure.

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Original research article INTRODUCTIONConventional karyotyping has been considered the gold standard for routine prenatal genetic diagnosis for many decades now, allowing for microscopic visualization and inspection of chromosomes and thus detection of numerical and structural chromosomal rearrangements. The main limitations are the resolution achieved by G-banding, which is limited to 5-10 Mb at best, and the requirement for cultured cells, needing a minimum of 8-10 days. The introduction of targeted methods of analysis such as fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) overcome the time constraints and resolution limitations inherent to karyotyping but do not provide a genome-wide analysis.1 More recently, molecular karyotyping using genomic microarrays has reached mainstream use in the postnatal diagnostic setting, providing a genome-wide screen for genomic imbalances at a far superior resolution to karyotyping.2 A number of studies have demonstrated the feasibility of prenatal diagnosis by genomic arrays using a variety of platforms, 3-7 but challenges remain in applying high-resolution genomic arrays to prenatal diagnosis. 6,8,9 One of the major ethical issues often raised is how to deal with variants of uncertain significance (VOUS) or risk loci, the detection of which leads to additional challenges for genetic counseling of parents. Furthermore, array analysis may reveal an imbalance for known "risk loci" where the future penetrance is uncertain or may be associated with variable expression. The penetrance risks for a number of recurrent copy-number variations (CNVs) have been estimated based on the frequencies in patients and controls. [10][11][12] However, although it is possible to calculate a populationbased risk, it is impossible in the prenatal setting to predict the phenotypic outcome in the child. Purpose:To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound. Methods: Patients referred for prenatal diagnosis due to ultrasound anomalies underwent analysis by array comparative genomic hybridization as the first-tier diagnostic test.Results: A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization. Array analysis revealed causal imbalances in a total of 9.6% of patients (n = 37). Submicroscopic copy-number variations were detected in 2.6% of patients (n = 10/37), and arrays added valuable information over conventional karyotyping in 3.9% of patients (n = 15/37). We highlight a novel advantage of arrays; a 500-kb paternal insertional translocation is the likely driver of a de novo unbalanced translocation, thus improving recurrence risk calculation in this family. Variants of uncertain significance were revealed in 1.6% of patients (n = 6/383). Conclusion:We demonstrate the added value of chromosomal microarrays for prenatal diagnosis in the presence of ultrasound anomalies. We advocate reporting back on...

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The disclosure of incidental findings, also called unsolicited findings, unexpected results, and secondary variants, is increasingly recognised as an issue in clinical and research genetics contexts. The rise of next generation sequencing methods has only intensified the issue, increasing the likelihood of incidental findings appearing. This review focuses on empirical research on the ethical issues involved. Electronic databases were searched for articles covering quantitative and qualitative research on the ethical issues involved in the disclosure of incidental findings in clinical and research genetics contexts. 16 articles were ultimately accepted for review. Data was extracted and synthesised on the factors that should be taken into account during the decision-making process surrounding the disclosure of an incidental finding in a genetics context. These factors include the possibility of disclosure, various practical and technical factors, and various ethical factors. We suggest the development of a decision-making tree, involving an exploration of the practical and ethical concerns raised by the studies. This is in our view the best way of handling the wide variety of both possible incidental findings and parties interested in the disclosure of incidental findings.