The Trouble with Trabeculation: How Genetics Can Help to Unravel a Complex and Controversial Phenotype

Abstract

Excessive trabeculation of the cardiac left ventricular wall is a complex phenotypic substrate associated with various physiological and pathological processes. There has been considerable conjecture as to whether hypertrabeculation contributes to disease and whether left ventricular non-compaction (LVNC) cardiomyopathy is a distinct pathology. Building on recent insights into the genetic basis of LVNC cardiomyopathy, in particular three meta-analysis studies exploring genotype–phenotype associations using different methodologies, this review examines how genetic research can advance our understanding of trabeculation. Three groups of genes implicated in LVNC are described—those associated with other cardiomyopathies, other cardiac/syndromic conditions and putatively with isolated LVNC cardiomyopathy—demonstrating how these findings can inform the underlying pathologies in LVNC patients and aid differential diagnosis and management in clinical practice despite the limited utility suggested for LVNC genetic testing in recent guidelines. The outstanding questions and future research priorities for exploring the genetics of hypertrabeculation are discussed. Graphical Abstract: [Figure not available: see fulltext.].