Expectations, needs and mid-term outcomes in people accessing to secondary findings from ES: 1st French mixed study (FIND Study).

Generation and subsequently accessibility of secondary findings (SF) in diagnostic practice is a subject of debate around the world and particularly in Europe. The French FIND study has been set up to assess patient/parent expectations regarding SF from exome sequencing (ES) and to collect their real-life experience until 1 year after the delivery of results. 340 patients who had ES for undiagnosed developmental disorders were included in this multicenter mixed study (quantitative N = 340; qualitative N = 26). Three groups of actionable SF were rendered: predisposition to late-onset actionable diseases; genetic counseling; pharmacogenomics. Participants expressed strong interest in obtaining SF and a high satisfaction level when a SF is reported. The medical actionability of the SF reinforced parents' sense of taking action for their child and was seen as an opportunity. While we observed no serious psychological concerns, we showed that these results could have psychological consequences, in particular for late-onset actionable diseases SF, within families already dealing with rare diseases. This study shows that participants remain in favor of accessing SF despite the potential psychological, care, and lifestyle impacts, which are difficult to anticipate. The establishment of a management protocol, including the support of a multidisciplinary team, would be necessary if national policy allows the reporting of these data.

Exome sequencing in clinical settings: preferences and experiences of parents of children with rare diseases (SEQUAPRE study).

Exome sequencing (ES) has revolutionized diagnostic procedures in medical genetics, particularly for developmental diseases. The variety and complexity of the information produced has raised issues regarding its use in a clinical setting. Of particular interest are patients' expectations regarding the information disclosed, the accompaniment provided, and the value patients place on these. To explore these issues in parents of children with developmental disorders and no diagnosis with known etiology, a multidisciplinary group of researchers from social and behavioral sciences and patient organizations conducted a mixed-methodology study (quantitative and qualitative) in two centers of expertise for rare diseases in France. The quantitative study aimed to determine the preferences of 513 parents regarding the disclosure of ES results. It showed that parents wished to have exhaustive information, including variants of unknown significance possibly linked to their child's disorder and secondary findings. This desire for information could be a strategy to maximize the chances of obtaining a diagnosis. The qualitative study aimed to understand the expectations and reactions of 57 parents interviewed just after the return of ES results. In-depth analysis showed that parents had ambivalent feelings about the findings whatever the results returned. The contrasting results from these studies raise questions about the value of the information provided and parents' high expectations regarding the results. The nature of parental expectations has emerged as an important topic in efforts to optimize accompaniment and support for families during the informed decision-making process and after disclosure of the results in an overall context of uncertainty.