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.

Familial isolated noncompaction of ventricular myocardium

“…The clinical and pathological features are similar to those reported by Chin et al and Bleyl et al Chin et al (1990) first reported four patients of familial occurrence. Later, two patients were presented by Shinozaki et al (1995), four from one family by Hamamichi et al (1996), two from one family by Ritter et al (1997), and six from one family by Bleyl et al (1997a). Within these seven families, including our case, all but one finding occurred in sibs (Table 1).…”

Isolated noncompaction left ventricular myocardium and polymorphic ventricular tachycardia

“…4 Clinical manifestations of the disorder included depressed LV systolic function, ventricular arrhythmias, and systemic embolization. [3][4][5] Both sporadic and familial 4,6,7 forms have been described.…”

New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies

“…In this study, however, the echocardiogram of the younger brother appeared to be normal at 20 weeks of gestation. It is not clear whether these findings were related to limitations of the fetal echocardiography technique or to the postnatal development of the disorder (14). Left ventricular noncompaction has mostly been associated with disorders causing skeletal muscle or cardiac disease, or with chromosomal anomalies (15,16).…”