Barth syndrome: an X‐linked cause of fetal cardiomyopathy and stillbirth

Abstract

ObjectiveBarth Syndrome (BTHS) is an X-linked multisystem disorder (OMIM 302060) usually diagnosed in infancy and characterized by cardiac problems [dilated cardiomyopathy (DCM) ± endocardial fibroelastosis (EFE) ± left ventricular non-compaction (LVNC)], proximal myopathy, feeding problems, growth retardation, neutropenia, organic aciduria and variable respiratory chain abnormalities. We wished to determine whether BTHS had a significant impact on fetal and perinatal health in a large cohort of family groups originating from a defined region.MethodCase note review on 19 families originating from the UK and known to the Barth Syndrome Service of the Bristol Royal Hospital for Children.ResultsDetails are presented on six kindreds (32%) with genetically and biochemically proven BTHS that demonstrate a wider phenotype including male fetal loss, stillbirth and severe neonatal illness or death. In these families, 9 males were stillborn and 14 died as neonates or infants but there were no losses of females. BTHS was definitively proven in five males with fetal onset of DCM ± hydrops/EFE/LVNC.ConclusionThese findings stress the importance of considering BTHS in the differential diagnosis of unexplained male hydrops, DCM, EFE, LVNC or pregnancy loss, as well as in neonates with hypoglycemia, lactic acidosis and idiopathic mitochondrial disease. Copyright © 2010 John Wiley & Sons, Ltd.

Cardiolipin metabolism and its causal role in the etiology of the inherited cardiomyopathy Barth syndrome

“…If Barth syndrome goes undiagnosed, sudden cardiac arrest due to ventricular arrhythmia or bacterial septicaemia due to neutropenia leads to fatalities in most infants within the initial few years after birth. A high rate of fetal loss or stillborn birth in males, but not females, in families known to the Barth Syndrome Service (Steward et al, 2010) has also been observed. Barth syndrome is a life-limiting cardiovascular developmental disorder with additional and various multisystem phenotypes that can contribute to altered patient outcomes.…”

Differing clinical courses and outcomes in two siblings with Barth syndrome and left ventricular noncompaction

“…Because fetal cardiomyopathy associated with Barth syndrome has been documented [23], prenatal echocardiographic diagnosis may be useful as a means of early detection. In our study, however, the echocardiogram of the younger brother revealed normal left ventricular wall motion at 24 weeks of gestation.…”

Barth syndrome diagnosed in the subclinical stage of heart failure based on the presence of lipid storage myopathy and isolated noncompaction of the ventricular myocardium

“…The most severe form is infantile BTHS, in which severe cardiac failure and serious bacterial infection lead to death [14]. However, some patients have limited clinical features of BTHS.…”