Incidental Findings Identified by Prenatal Microarray Analysis and Consensus Reporting Criteria of the Catalan Public Health Network XIGENICS.

Abstract

Objective: The study aimed to evaluate the frequency of pathogenic copy number variants (CNVs) classified as incidental findings (IFs) in prenatal diagnosis and to develop consensus recommendations for standardizing their reporting across six centers within the Catalan public health system (XIGENICS network).

Method: A retrospective review of 4219 consecutive prenatal microarrays performed within the network from 2018 to 2023 was conducted, including all referral reasons. To develop consensus recommendations, several discussion meetings were held along with an extensive review of the existing literature.

Results: A total of 69 IFs were identified in 68 samples, revealing a detection rate of 1.6%. They included: 5 CNVs associated with neurodevelopmental disorders and/or congenital defects with complete penetrance, 41 CNVs for neurodevelopmental disorders and/or congenital defects with incomplete penetrance, 4 disorders that can potentially be prevented or treated, 5 non-childhood onset neurological disorders, 13 X-linked disorders (mainly STS and DMD deletions), and 1 deletion of the SHOX gene. Long-term follow-up revealed that newborns with high penetrance neurosusceptibility CNVs exhibited clinical manifestations more frequently than those with low penetrance CNVs. At the time of reporting, 52 IFs were disclosed, while 17 were not. According to the new consensus criteria, 43 IFs would now be reported, 17 would not, and 9 would depend on parental decision. CNVs consistent with the referral reason were identified in 4% of cases.

Conclusion: This study represents the largest series rigorously documenting all identified IFs in consecutive pregnancies evaluated by microarray, including both reported and unreported findings. IFs were found at a higher frequency than previously recognized, underscoring the need for specific clinical attention. Comprehensive consensus reporting recommendations were developed to ensure uniformity of criteria, and an ad hoc committee was established to manage complex cases.