The genetic landscape of cardiovascular left–right patterning defects

Heterotaxy is a disorder with complex congenital heart defects and diverse left–right (LR) patterning defects in other organ systems. Despite evidence suggesting a strong genetic component in heterotaxy, the majority of molecular causes remain unknown. Established genes often involve a ciliated, embryonic structure known as the left-right organizer (LRO). Herein, we focus on genetic discoveries in heterotaxy in the past two years. These include complex genetic architecture, novel mechanisms regulating cilia formation, and evidence for conservation of LR patterning between distant species. We feature new insights regarding established LR signaling pathways, bring attention to heterotaxy candidate genes in novel pathways, and provide an extensive overview of genes previously associated with laterality phenotypes in humans. •Heterotaxy is a disorder of abnormal left–right (LR) patterning during development.•Established and new genetic pathways controlling LR patterning are reviewed.•Potential mechanisms underlying phenotypic pleiotropy are highlighted.•Evidence of multigenic or post-transcriptional mechanisms of disease is discussed.•Supplemental tables provide comprehensive human and model organism evidence.