Mainstreaming genomic testing for children with undiagnosed inborn errors of immunity

Abstract

Background/Objectives: Genetic diagnosis of paediatric of inborn errors of immunity (IEI) influences management decisions, and can alter clinical outcomes through hematopoietic stem cell transplantation (HSCT).1,2 Historically, children with undiagnosed IEI in Queensland, Australia were referred to a state-wide clinical genetic service, delaying access to genomic testing and increasing the burden on the genetic clinic. To address this issue, we developed and evaluated a mainstreamed model of care for genomic testing for paediatric IEI. Methods: This state-wide program included a genetic counsellor embedded within the paediatric immunology service, fortnightly multidisciplinary team meetings (MDT), and variant prioritisation meetings. Informed by the literature, 21 different virtual gene lists were developed for whole-exome sequencing. Additionally, parents completed pre-and post-testing survey assessing understanding of, and impact of genomic testing. Recruitment occurred between Nov 2020-Sep 2021. Results: Of the 34 children with results, nine received a genetic diagnosis, and four accessed HSCT. Five children were also referred for further investigations of suspicious VUS. On average, 14 healthcare providers attended the state-wide MDT, including adult and paediatric immunologists, genomic pathologists, genetic healthcare professionals, and other non-genetic-healthcare providers. Parents demonstrated understanding of the implications of testing and reported minimal decisional regret. Conclusion: Genomic testing can be mainstreamed for paediatric IEI. Our program improved access to genomic testing, facilitated treatment decision-making, and was acceptable to parents and clinicians alike.