Pediatric and Developmental Pathology 18, 71-75, 2015 DOI: 10.2350/14-07-1532-CR.1 © 2015 Society fo r Pediatric Pathology
A Novel Association of Biventricular Cardiac Noncompaction and Diabetic Embryopathy: Case Report and Review of the Literature Jennifer S. W o o , 1* M ari P erez-R osendahl , 1 D a na H aydel , 1 G regory P erens, 2 and M ichael C. Fishbein 1 'Departm ent of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, USA d iv is io n o f Pediatric Cardiology, David Geffen School o f Medicine at UCLA, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, USA
Received July 30, 2014; accepted October 26, 2014; published online November 11, 2014.
ABSTRACT
Diabetic embryopathy refers to a constellation of congen ital malformations arising in the setting of poorly controlled maternal diabetes mellitus. Cardiac abnormal ities are the most frequently observed findings, with a 5fold risk over normal pregnancies. Although a diverse spectrum of cardiac defects has been documented, cardiac noncompaction morphology has not been associated with this syndrome. In this report, we describe a novel case of biventricular cardiac noncompaction in a neonate of a diabetic mother. The patient was a late preterm female with right anotia, caudal dysgenesis, multiple cardiac septal and aortic arch defects, and biventricular cardiac noncompaction. Examination of both ventricles demon strated spongy myocardium with increased myocardial trabeculation greater than 50% left ventricular thickness and greater than 75% right ventricular thickness, with hypoplasia of the bilateral papillary muscles, consistent with noncompaction morphology. Review of the literature highlights the importance of gene expression and epigenomic regulation in cardiac embryogenesis. Key words: cardiac noncompaction, congenital heart
disease, diabetic embryopathy, embryogenesis
INTRODUCTION
During early embryogenesis, fetal myocardium is com posed of a trabecular network of spongy myocardium separated by deep recesses that allows blood to supply the developing myocardium. During weeks 3-8 of embryonic development, the ventricular myocardium progressively loses its immature, noncompacted trabeculae along and across decreasing gradients from the epicardium to the endocardium, from the base to the apex, and from left to *Corresponding author, e-mail: [email protected]
right [1], Cardiac noncompaction refers to the abnormal embryogenesis of the endocardium and myocardium, resulting in the lack of compaction of the early myocardial network [2]. Noncompaction was first de scribed in 1932 from an autopsy performed on a newborn infant with aortic atresia/coronary-ventricular fistula [3]. The first case of isolated left ventricular cardiac noncompaction (LVNC) was published in 1984 by Engberding and Bender [2], Noncompaction morphology is characterized by ventricular myocardium with a spongiform appearance. It is defined by the absence of well-formed left ventricular papillary muscles with myocardial trabeculation occupying at least 50% of the total thickness with hypoplasia of the left ventricular papillary muscles. Right ventricular (RV) involvement is defined by trabeculation occupying at least 75% of the total RV thickness [4], Currently, the American Heart Association classifies isolated LVNC as a primary genetic cardiomyopathy [5], Cardiac noncompaction morphology has also been implicated in a number of clinical syndromes including Barth syndrome [6], DiGeorge syndrome [7], myopathic changes with inclusions in skeletal muscle fibers [7], and Melnick-Needles syn drome [8]. The noncompaction phenotype, including the aforementioned syndromes, is usually limited to the left ventricle, although rare cases of RV or biventricular involvement have been documented [9-11]. In this case report, we describe the autopsy findings of a late preterm female neonate with biventricular cardiac noncompaction as well as features consistent with diabetic embryopathy (DE). Diabetic embryopathy is a syndrome characterized by a constellation of congenital abnormalities, including cardiac defects, arising in the setting of poorly controlled maternal diabetes. Although a diverse range of cardiac malformations has been docu mented in DE, cardiac noncompaction morphology has not been associated with this syndrome. In this report,
Figure 1. T ransthoracic echo cardio gram on day o f life 0, A pical 4-cham ber v ie w o f th e le ft ve n tricle d e m o n stra tin g re la tiv e ly non com pa cte d le ft v e n tric u la r apical muscle, co m p le te a trio v e n tric u la r canal, and an apical m uscular v e n tric u la r septal defect. The rig h t ve n tricle is n o t show n.
unifying pathogenetic mechanisms of cardiovascular malformations arising within in a diabetic environment are discussed. CASE REPORT The patient was a late preterm female with prenatally diagnosed congenital heart disease, bom at 36 weeks and 4 days to a 28-year-old G3P0111 woman with a pregnancy complicated by polyhydramnios and pregestational diabe tes. No record of the mother’s glucose control was documented during the current pregnancy secondary to poor antenatal care, but HbAlc at time of delivery was 7.3 g/dL (normal range
A Novel Association of Biventricular Cardiac Noncompaction and Diabetic Embryopathy: Case Report and Review of the Literature Jennifer S. W o o , 1* M ari P erez-R osendahl , 1 D a na H aydel , 1 G regory P erens, 2 and M ichael C. Fishbein 1 'Departm ent of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, USA d iv is io n o f Pediatric Cardiology, David Geffen School o f Medicine at UCLA, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, USA
Received July 30, 2014; accepted October 26, 2014; published online November 11, 2014.
ABSTRACT
Diabetic embryopathy refers to a constellation of congen ital malformations arising in the setting of poorly controlled maternal diabetes mellitus. Cardiac abnormal ities are the most frequently observed findings, with a 5fold risk over normal pregnancies. Although a diverse spectrum of cardiac defects has been documented, cardiac noncompaction morphology has not been associated with this syndrome. In this report, we describe a novel case of biventricular cardiac noncompaction in a neonate of a diabetic mother. The patient was a late preterm female with right anotia, caudal dysgenesis, multiple cardiac septal and aortic arch defects, and biventricular cardiac noncompaction. Examination of both ventricles demon strated spongy myocardium with increased myocardial trabeculation greater than 50% left ventricular thickness and greater than 75% right ventricular thickness, with hypoplasia of the bilateral papillary muscles, consistent with noncompaction morphology. Review of the literature highlights the importance of gene expression and epigenomic regulation in cardiac embryogenesis. Key words: cardiac noncompaction, congenital heart
disease, diabetic embryopathy, embryogenesis
INTRODUCTION
During early embryogenesis, fetal myocardium is com posed of a trabecular network of spongy myocardium separated by deep recesses that allows blood to supply the developing myocardium. During weeks 3-8 of embryonic development, the ventricular myocardium progressively loses its immature, noncompacted trabeculae along and across decreasing gradients from the epicardium to the endocardium, from the base to the apex, and from left to *Corresponding author, e-mail: [email protected]
right [1], Cardiac noncompaction refers to the abnormal embryogenesis of the endocardium and myocardium, resulting in the lack of compaction of the early myocardial network [2]. Noncompaction was first de scribed in 1932 from an autopsy performed on a newborn infant with aortic atresia/coronary-ventricular fistula [3]. The first case of isolated left ventricular cardiac noncompaction (LVNC) was published in 1984 by Engberding and Bender [2], Noncompaction morphology is characterized by ventricular myocardium with a spongiform appearance. It is defined by the absence of well-formed left ventricular papillary muscles with myocardial trabeculation occupying at least 50% of the total thickness with hypoplasia of the left ventricular papillary muscles. Right ventricular (RV) involvement is defined by trabeculation occupying at least 75% of the total RV thickness [4], Currently, the American Heart Association classifies isolated LVNC as a primary genetic cardiomyopathy [5], Cardiac noncompaction morphology has also been implicated in a number of clinical syndromes including Barth syndrome [6], DiGeorge syndrome [7], myopathic changes with inclusions in skeletal muscle fibers [7], and Melnick-Needles syn drome [8]. The noncompaction phenotype, including the aforementioned syndromes, is usually limited to the left ventricle, although rare cases of RV or biventricular involvement have been documented [9-11]. In this case report, we describe the autopsy findings of a late preterm female neonate with biventricular cardiac noncompaction as well as features consistent with diabetic embryopathy (DE). Diabetic embryopathy is a syndrome characterized by a constellation of congenital abnormalities, including cardiac defects, arising in the setting of poorly controlled maternal diabetes. Although a diverse range of cardiac malformations has been docu mented in DE, cardiac noncompaction morphology has not been associated with this syndrome. In this report,
Figure 1. T ransthoracic echo cardio gram on day o f life 0, A pical 4-cham ber v ie w o f th e le ft ve n tricle d e m o n stra tin g re la tiv e ly non com pa cte d le ft v e n tric u la r apical muscle, co m p le te a trio v e n tric u la r canal, and an apical m uscular v e n tric u la r septal defect. The rig h t ve n tricle is n o t show n.
unifying pathogenetic mechanisms of cardiovascular malformations arising within in a diabetic environment are discussed. CASE REPORT The patient was a late preterm female with prenatally diagnosed congenital heart disease, bom at 36 weeks and 4 days to a 28-year-old G3P0111 woman with a pregnancy complicated by polyhydramnios and pregestational diabe tes. No record of the mother’s glucose control was documented during the current pregnancy secondary to poor antenatal care, but HbAlc at time of delivery was 7.3 g/dL (normal range
