Xq28-linked noncompaction of the left ventricular myocardium: Prenatal diagnosis and pathologic analysis of affected individuals

Abstract

Isolated noncompaction of the left ventricular myocardium (INVM) is characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses within the left ventricle, sometimes also affecting the right ventricle and interventricular septum. Familial occurrence of this disorder was described previously. We present a family in which 6 affected individuals demonstrated X-linked recessive inheritance of this trait. Affected relatives presented postnatally with left ventricular failure and arrhythmias, associated with the pathognomonic echocardiographic findings of INVM. The usual findings of Barth syndrome (neutropenia, growth retardation, elevated urinary organic acids, low carnitine levels, and mitochondrial abnormalities) were either absent or found inconsistently. Fetal echocardiograms obtained between 24-30 weeks of gestation in 3 of the affected males showed a dilated left ventricle in one heart, but were not otherwise diagnostic of INVM in any of the cases. Four of the affected individuals died during infancy, one is in cardiac failure at age 8 months, and one is alive following cardiac transplant at age 9 months. The hearts from infants who died or underwent transplantation appeared, on gross examination, to be enlarged, with coarse, deep ventricular trabeculations and prominent endocardial fibroelastosis. Histologically, there were loosely organized fascicles of myocytes in subepicardial and midmyocardial zones of both ventricles, and the myocytes showed thin, often angulated fibers with prominent central clearing and reduced numbers of filaments. Markedly elongated mitochondria were present in some ventricular myocytes from one specimen, but this finding was not reproducible. Genetic linkage analysis has localized INVM to the Xq28 region, where other myopathies with cardiac involvement have been located.

Spontaneous Left Ventricular Hypertrabeculation in Dystrophin Duplication Based Becker's Muscular Dystrophy

“…The trabeculations are surrounded by intertrabecular spaces which are perfused from the ventricular cavity, have the same echogenicity as the myocardium, move synchronously with the myocardium, and are not connected to the papillary muscles or the left ventricular wall [2,5,12]. Trabeculations can be delineated from false tendons and aberrant bands by taking atypical views [5,12].…”

“…Left ventricular hypertrabeculation has been shown to be associated with neuromuscular disorders in the majority of the cases so far described [1][2][3][4][5][6][7][8]. Whether left ventricular hypertrabeculation develops during life or is present already at birth is yet unknown.…”

Left Ventricular Hypertrabeculation in Myotonic Dystrophy Type 1

“…The trabeculations are surrounded by intertrabecular spaces which are perfused from the ventricular cavity, have the same echogenicity as the myocardium, move synchronously with the myocardium, and are not connected to the papillary muscles or the left ventricular wall [1,2,17]. Trabeculations can be delineated from false tendons and aberrant bands by taking atypical views [2,17].…”

“…Besides echocardiography, LVHT can be visualized by cardiac MRI and ventriculography [6]. LVHT may be associated with congenital cardiac malformations, thickening of the left ventricular myocardium, decreased left ventricular systolic function, and dilated left ventricle [1]. LVHT is assumed due to a disturbed endomyocardial morphogenesis, particularly an arrest in the compaction process of the myocardium [1].…”

“…Presumably, LVHT does not change over time. LVHT is commonly associated with neuromuscular disorders, particularly Becker's muscular dystrophy [19], Barth's syndrome (neutropenia, growth retardation, elevated urine organic acids, low carnitine levels, and mitochondrial abnormalities) [1], and defects of the oxidative phosphorylation [6,17]. In MD1 LVHT has not been described before.…”