Background: Left ventricular hypertrabeculation (LVHT), also known as noncompaction or spongy myocardium, is a cardiac abnormality of unknown etiology and pathogenesis frequently associated with genetic cardiac and noncardiac disorders, particularly genetic neuromuscular disease. This study aimed to review the current knowledge about the genetic or pathogenetic background of LVHT.
Methods: A literature review of all human studies dealing with the association of LVHT with genetic cardiac and noncardiac disorders, particularly neuromuscular disorders, was conducted.
Results: Most frequently, LVHT is associated with mitochondrial disorders (mtDNA, nDNA mutations), Barth syndrome (G4.5, TAZ mutations), hypertrophic cardiomyopathy (MYH7, ACTC mutations), zaspopathy (ZASP/LDB3 mutations), myotonic dystrophy 1 (DMPK mutations), and dystrobrevinopathy (DTNA mutations). More rarely, LVHT is associated with mutations in the DMD, SCNA5, MYBPC3, FNLA1, PTPN11, LMNA, ZNF9, AMPD1, PMP22, TNNT2, fibrillin2, SHP2, MMACHC, LMX1B, HCCS, or NR0B1 genes. Additionally, LVHT occurs with a number of chromosomal disorders, polymorphisms, and not yet identified genes, as well in a familial context. The broad heterogeneity of LVHT's genetic background suggests that the uniform morphology of LVHT not only is attributable to embryonic noncompaction but also may result from induction of hypertrabeculation as a compensatory reaction of an impaired myocardium.
Conclusions: Most frequently, LVHT is associated with mutations in genes causing muscle or cardiac disease, or with chromosomal disorders. These associations require comprehensive cardiac, neurologic, and cytogenetic investigations.