(1092) Identification of maternal Alzheimer’s disease risk after an atypical finding on SNP-based prenatal cfDNA screening

A patient was referred for GC due to an AF on cfDNA suggestive of a copy number variant (CNV) on chr 21 of unknown origin. Maternal microarray identified a 3 Mb duplication at 21q21.2q21.3, encompassing the APP gene, which, when duplicated, is associated with autosomal dominant early-onset Alzheimer’s disease (ADEOAD). The patient reported no known prior genetic testing; however, family history was notable for early-onset Alzheimer’s disease. In a subsequent pregnancy, cfDNA screening again identified an AF on chr 21, this time of maternal origin, consistent with a duplication involving the APP gene.

Her sister had previously been referred for GC after an AF on cfDNA suggestive of a CNV on chr 21 of unknown origin. No follow-up testing was performed at that time. During a subsequent pregnancy, she was referred again, and maternal microarray identified the same CNV that had previously been identified in her sister.

Conclusion:
This case series highlights how delayed diagnoses, such as maternal APP duplication associated with ADEOAD, may stem from limitations in early recognition and follow-up. As chr21 is routinely assessed in prenatal cfDNA screening, the incidental detection of AFs may reveal clinically relevant information for both mother and fetus. To facilitate timely diagnosis and informed reproductive decision-making, pre-test counseling should address the possibility of AFs, with prompt referral for GC and appropriate clinical follow-up when they are identified.