2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Five-Year Retrospective Case Series of Genetic Findings in Patients with Planned Surgical Interventions for Cardiac Left-Right Patterning Differences

Pdf Summary

This study is a five-year retrospective case series that examines the genetic findings in patients with surgical interventions for cardiac left-right patterning differences (LRPD). LRPD refers to a range of congenital anomalies characterized by abnormal lateralization of visceral organs along the right-left axis. It affects a small percentage of live births and a higher percentage of newborns with congenital heart disease. Infants with LRPD-associated congenital heart disease often require high-risk surgical interventions.<br /><br />The study focuses on the relationship between LRPD and primary ciliary dyskinesia (PCD), a condition characterized by impaired mucociliary clearance, chronic sinopulmonary infections, and obstructive airway disease. Proper ciliary motility is important for right-left lateralization in early embryogenesis, and it is suspected that genetic variants in genes related to ciliary structure and function may be associated with both PCD and LRPD.<br /><br />The results of genetic testing in infants with LRPD-associated congenital heart disease who required surgery were evaluated. Variants in ciliary genes were analyzed for their association with PCD, and cardiac anatomy and perioperative respiratory outcomes were reported.<br /><br />The study found that PCD was prevalent among infants with LRPD requiring surgery, and sequencing-based testing was useful in identifying ciliary-related variants. Incorporating early sequencing-based testing in this population may facilitate targeted respiratory care and anticipatory guidance.<br /><br />The case series included 32 individuals who underwent cardiac surgery for LRPD-related congenital heart disease. Twelve out of the 32 individuals had genetic testing, and 10 out of the 12 had variants in ciliary genes. Three individuals had molecular evidence for PCD. There was no clear correlation between cardiac phenotype and the presence of cilia gene variants. The postoperative outcomes were characterized by a high rate of respiratory complications, and individuals with symptoms consistent with PCD benefited from respiratory therapy.<br /><br />In conclusion, this study highlights the prevalence of PCD and ciliary gene variants in infants with LRPD requiring surgery. Early sequencing-based testing can aid in identifying these variants and guide respiratory care for these individuals.

Asset Subtitle

Presenting Author - Jonathan Marquez, MD, PhD; Co-Author - Lauren N. Carlozzi, MD, MPH; Co-Author - Danny E. Miller, MD, PhD; Co-Author - Matthew D. Files, MD; Co-Author - BreAnna Kinghorn, MD, MS; Co-Author - Eyal Sagiv, MD, PhD;

Meta Tag

Cardiac/circulatory disorders

Congenital Anomaly

Identification of Disease Genes

Malformation

Co-Author Lauren N. Carlozzi, MD, MPH

Co-Author Danny E. Miller, MD, PhD

Co-Author Matthew D. Files, MD

Co-Author BreAnna Kinghorn, MD, MS

Co-Author Eyal Sagiv, MD, PhD

Presenting Author Jonathan Marquez, MD, PhD

Keywords

genetic findings

surgical interventions

LRPD

congenital heart disease

primary ciliary dyskinesia

PCD

ciliary genes

respiratory care

sequencing-based testing

case series