Incidental Identification of Potentially Affected Individuals Through Expanded Carrier Screening During Preconception or Early Pregnancy.

Abstract

Objective: Expanded carrier screening (ECS) is used to assess the reproductive probability of having an offspring affected by an autosomal recessive or X-linked recessive genetic disorder. Rarely, a presumably healthy individual may be identified to carry variants that could influence their health. This study aimed to investigate the incidence of potentially affected individuals, with the objective of improving counseling for ECS.

Methods: A retrospective study of a cohort of 3001 individuals who sought ECS during early pregnancy or preconception was conducted. Potentially affected individuals carrying biallelic pathogenic variants for autosomal recessive diseases, as well as females carrying a heterozygous pathogenic variant for X-linked disease, were identified.

Results: A total of 13 potentially affected individuals (0.43%) were identified; 5 patients were homozygous or compound heterozygous for autosomal recessive diseases, and 8 were heterozygous for X-linked diseases. The majority of the potentially affected individuals were asymptomatic (85%, 11/13) at the time of assessment. Only two patients exhibited mild clinical manifestations.

Conclusion: People who intend to undergo ECS should be informed that they themselves may be identified as potentially affected individuals for whom clinical evaluation and surveillance are recommended.