Ebstein anomaly associated with left ventricular noncompaction: An autosomal dominant condition that can be caused by mutations in MYH7

Abstract

Left ventricular noncompaction (LVNC) is a relatively common genetic cardiomyopathy, characterized by prominent trabeculations with deep intertrabecular recesses in mainly the left ventricle. Although LVNC often occurs in an isolated entity, it may also be present in various types of congenital heart disease (CHD). The most prevalent CHD in LVNC is Ebstein anomaly, which is a rare form of CHD characterized by apical displacement and partial fusion of the septal and posterior leaflet of the tricuspid valve with the ventricular septum. Several reports of sporadic as well as familial cases of Ebstein anomaly associated with LVNC have been reported. Recent studies identified mutations in the MYH7 gene, encoding the sarcomeric β-myosin heavy chain protein, in patients harboring this specific phenotype. Here, we will review the association between Ebstein anomaly, LVNC and mutations in MYH7, which seems to represent a subtype of Ebstein anomaly with autosomal dominant inheritance and variable penetrance.

Loss of Function Mutations in NNT Are Associated With Left Ventricular Noncompaction

“…Numerous reports have associated LVNC in humans with depressed LV systolic function; this has been associated independently with increased mortality in both children and adults. Moreover, LVNC is reported increasingly in conjunction with congenital heart disease 45–47 . The implication of NNT in brachycardia may offer future understanding of the mechanisms behind LVNC and concomitant CHD.…”

Genetics and Disease of Ventricular Muscle

“…Moreover, mutations in the same gene can cause different cardiomyopathies. For example, mutations in the MYH7 gene have been associated with HCM (Geisterfer-Lowrance et al 1990), DCM (Kamisago et al 2000), LVNC (Hoedemaekers et al 2007;Vermeer et al 2013), and RCM (Karam et al 2008). These observations raise the question of how distinctive the cardiomyopathies really are, and how the phenotypical differences and commonalities can be reconciled at a mechanistic level.…”

Inherited Cardiomyopathies

“…Multiple genes causing autosomal dominant LVNC have now been identified, including mutations in genes causing CHD with LVNC. In patients with HLHS and LVNC, the cytoskeletal gene α-dystrobrevin was identified while mutations in Nkx-2.5 in children with LVNC and ASD and MYH7 in patients with LVNC and Ebstein's anomaly have also been reported ( Table 3 ) [58, 63-66]. In LVNC without CHD, mutations in the Z-line protein-encoding ZASP/LDB3 gene and the sarcomere-encoding genes (MYH7, ACTC, TNNT2, MYBPC3, TMP1, and TNNI3) appear to account for 20% or more of LVNC [58, 67, 68].…”