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

Prenat Diagn. 2010 Oct;30(10):970-6. doi: 10.1002/pd.2599.

Abstract

Objective: Barth 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.

Method: Case note review on 19 families originating from the UK and known to the Barth Syndrome Service of the Bristol Royal Hospital for Children.

Results: Details 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.

Conclusion: These 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases
  • Barth Syndrome / epidemiology
  • Barth Syndrome / genetics*
  • Barth Syndrome / pathology
  • Biomarkers / blood
  • Cardiolipins / blood
  • Cardiomyopathy, Dilated / epidemiology
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / pathology
  • Chromosomes, Human, X / genetics*
  • Cohort Studies
  • Endocardial Fibroelastosis / epidemiology
  • Endocardial Fibroelastosis / genetics
  • Endocardial Fibroelastosis / pathology
  • Female
  • Fetal Death / epidemiology
  • Fetal Death / genetics*
  • Fetal Diseases / epidemiology
  • Fetal Diseases / genetics*
  • Fetal Diseases / pathology
  • Humans
  • Isolated Noncompaction of the Ventricular Myocardium / epidemiology
  • Isolated Noncompaction of the Ventricular Myocardium / genetics
  • Isolated Noncompaction of the Ventricular Myocardium / pathology
  • Lysophospholipids / blood
  • Male
  • Pedigree
  • Sequence Analysis, DNA
  • Sex Factors
  • Stillbirth / epidemiology
  • Stillbirth / genetics*
  • Transcription Factors / genetics
  • United Kingdom / epidemiology

Substances

  • Biomarkers
  • Cardiolipins
  • Lysophospholipids
  • Transcription Factors
  • monolysocardiolipin
  • Acyltransferases
  • TAFAZZIN protein, human