Ciliopathy gene variants and perioperative respiratory outcomes in infants with heterotaxy syndrome and congenital heart disease

Abstract

BACKGROUND: Ciliary dysfunction underlies the pathogenesis of both heterotaxy syndrome and primary ciliary dyskinesia (PCD), often with overlapping genetic variants. OBJECTIVE: This case series aims to describe genetic testing and postoperative outcomes for infants with heterotaxy-associated congenital heart disease (H-CHD) with pathogenic variants in genes associated with ciliary structure or function. METHODS: Infants who underwent surgery for H-CHD between 2017 and 2022 were included in this single-center review. The results of genetic testing, microarray or sequencing-based tests, were reviewed. Baseline clinical data and postoperative outcomes are summarized for individuals with variants in ciliary genes. RESULTS: Of 32 infants who underwent surgery, 12 had sequencing-based testing. A genetic variant associated with ciliopathy was reported in 10 of 12 infants (83%), 3 (25%) were diagnostic of PCD and 2 (17%) were considered possibly diagnostic. Infants with variants in ciliary genes had high prevalence of postoperative respiratory complications, however a relationship between genetic test results and respiratory complications could not be proven. All infants with a genetic diagnosis of PCD showed clinical symptoms of PCD on follow-up. CONCLUSIONS: Sequencing-based testing has high detection rate for PCD in infants with H-CHD and may be valuable given their increased risk of respiratory complications after surgery.