Festschrift for Dr. John M. Opitz: Pathogenesis of cardiac conduction disorders in children genetic and histopathologic aspects

Abstract

Fetal dysrhythmias are usually transient. Abnormal fetal rates and rhythms during labor are “functional.” Fetal dysrhythmias may be associated with congenital heart disease and fetal hydrops. Bradycardia is usually related to fetal distress; supraventricular tachycardia, atrial flutter, and atrial fibrillation may be associated with severe congestive heart failure. Ventricular fibrillation is rare in the fetus and infant and is usually associated with myocardial necrosis with perimembranous septal defect; the nonbranching atrioventricular (AV) bundle may have an aberrant position and result in cardiac arrhythmia. Wolff–Parkinson–White syndrome with conduction abnormalities and left ventricular hypertrophy (LVH) is due to an accessory pathway that bypasses the AV sulcus and results in faster conduction. Carnitine deficiency may be primary or secondary and may result in cardiac arrhythmia. Histiocytoid cardiomyopathy is characterized by cardiomegaly, incessant ventricular tachycardia, and frequently sudden death. Arrhythmogenic right ventricular dysplasia (ARVD) results in ventricular tachycardia and left bundle branch block. Noncompaction of the left ventricle predisposes to potentially fatal arrhythmias. Long Q‐T syndromes (LQTS) are a heterogeneous group of disorders with many genetic mutations. Brugada syndrome is an autosomal dominant trait with right bundle branch block and ST elevation. Barth syndrome is an X‐linked disorder with dilated cardiomyopathy, cyclic neutropenia and skeletal myopathy. Hypertrophic cardiomyopathy in infancy may be related to metabolic diseases, particularly glycogen storage diseases; the familial form predisposes to sudden death. Arrhythmias following cardiac surgery may occur after closure of a ventricular septal defect (VSD) or damage to the conduction system. © 2006 Wiley‐Liss, Inc.

Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

“…Seventy five percent of cases of histiocytoid CM present in female infants (Shehata et al 2015), often below 2 yr of age (Gilbert-Barness and Barness 2006), and the identification of NDUFB11 , found on Xp11.23, as an underlying cause explains the large excess of affected females. There have been no molecular reports yet to confirm this as a cause of embryonic male lethality, although Shehata and coworkers comment it is “tempting to speculate that similar mutations occurring in males are embryonic lethal and cause miscarriage, since there would be no residual protein activity” (Shehata et al 2015).…”

“…Histiocytoid CM is a rare, distinctive form of cardiomyopathy with approximately 150 cases reported worldwide, it has numerous synonyms including oncocytic cardiomyopathy (Shehata et al 2011). Predominantly affecting females early in life, it is characterized by arrhythmias and associated sudden death (Gilbert-Barness and Barness 2006). Associated cardiac abnormalities include ventricular and atrial septal defects, endocardial fibroelastosis, and hypoplastic left heart syndrome (Shehata et al 1998).…”

Atrial Fibrillation in Children

“…Intrathoracic procedures may add to this risk, with incidental mechanical contact with the neonatal atria triggering an arrhythmia. (Estlin et al, 1998;Gilbert-Barness & Barness 2006;Texter et al, 2006). The increased risk with neonates is not just limited to their small size and relative fragility, however.…”

An approach to the diagnosis of inherited metabolic disease

“…The arrhythmias may be episodic such as occurs in fat oxidation defects or persistent such as heart block seen in Kearns–Sayre syndrome, a mitochondrial disorder 10. Cardiomyopathy may present with the features of heart failure including sweatiness and shortness of breath when feeding.…”