First described in 1983, Barth syndrome (BTHS) is widely regarded as a rare X-linked genetic disease characterised by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA). Fewer than 200 living males are known worldwide, but evidence is accumulating that the disorder is substantially under-diagnosed. Clinical features include variable combinations of the following wide spectrum: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC), ventricular arrhythmia, sudden cardiac death, prolonged QTc interval, delayed motor milestones, proximal myopathy, lethargy and fatigue, neutropenia (absent to severe; persistent, intermittent or perfectly cyclical), compensatory monocytosis, recurrent bacterial infection, hypoglycaemia, lactic acidosis, growth and pubertal delay, feeding problems, failure to thrive, episodic diarrhoea, characteristic facies, and X-linked family history. Historically regarded as a cardiac disease, BTHS is now considered a multi-system disorder which may be first seen by many different specialists or generalists. Phenotypic breadth and variability present a major challenge to the diagnostician: some children with BTHS have never been neutropenic, whereas others lack increased 3-MGCA and a minority has occult or absent CM. Furthermore, BTHS was first described in 2010 as an unrecognised cause of fetal death. Disabling mutations or deletions of the tafazzin (TAZ) gene, located at Xq28, cause the disorder by reducing remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane. A definitive biochemical test, based on detecting abnormal ratios of different cardiolipin species, was first described in 2008. Key areas of differential diagnosis include metabolic and viral cardiomyopathies, mitochondrial diseases, and many causes of neutropenia and recurrent male miscarriage and stillbirth. Cardiolipin testing and TAZ sequencing now provide relatively rapid diagnostic testing, both prospectively and retrospectively, from a range of fresh or stored tissues, blood or neonatal bloodspots. TAZ sequencing also allows female carrier detection and antenatal screening. Management of BTHS includes medical therapy of CM, cardiac transplantation (in 14% of patients), antibiotic prophylaxis and granulocyte colony-stimulating factor (G-CSF) therapy. Multidisciplinary teams/clinics are essential for minimising hospital attendances and allowing many more individuals with BTHS to live into adulthood.

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.

The commonest autosomal deletion, 22q11.2 deletion syndrome (22q11DS) is a multisystem disorder varying greatly in severity and age of identification between affected individuals. Holistic care is best served by a multidisciplinary team, with an anticipatory approach. Priorities tend to change with age, from feeding difficulties, infections and surgery of congenital abnormalities particularly of the heart and velopharynx in infancy and early childhood to longer-term communication, learning, behavioural and mental health difficulties best served by evaluation at intervals to consider and initiate management. Regular monitoring of growth, endocrine status, haematological and immune function to enable early intervention helps in maintaining health. Conclusion: Guidelines to best practice management of 22q11DS based on a literature review and consensus have been developed by a national group of professionals with consideration of the limitations of available medical and educational resources.

Our experience demonstrates that general anaesthesia for cardiac MRI can be provided safely in infants and small children with CHD, despite the complexity and pathophysiology of many defects, the frequent breath-holding for image acquisitions and the MRI environment.

Barth syndrome (BTHS) is an X-linked disorder characterised by cardiomyopathy, neutropenia, skeletal myopathy and growth delay. This study describes the UK national clinical experience and outcome of cardiomyopathy in BTHS. The clinical course and echocardiographic changes of all patients with BTHS in the UK were reviewed from 2004 to 2014. In addition, strain analysis using 2D speckle tracking echocardiography was performed to further assess left ventricular function in the most recent follow-up. At last follow-up, 22 of 27 patients were alive with a median age of 12.6 (2.0-23.8) years; seven underwent cardiac transplantation at a median age of 2 (0.33-3.6) years, and five died (18.5%) at a median age of 1.8 (0.02-4.22) years. All deaths were related to cardiomyopathy or its management. Left ventricular diastolic dimension and systolic function measured by fractional shortening tended to normalise and stabilise after the first 3 years of life in the majority of patients. However, patients with BTHS (n = 16) had statistically significant reduction in global longitudinal and circumferential strain compared to controls (n = 18), (p < 0.001), despite apparent normal conventional measures of function. There was also reduced or reversed apical rotation and reduced left ventricular twist. Sustained ventricular arrhythmia was not seen at follow-up. Cardiac phenotype in BTHS is variable; however, longer-term outcome in our cohort suggests good prognosis after the first 5 years of life. Most patients appeared to have recovered near normal cardiac function by conventional echocardiographic measures, but strain analysis showed abnormal myocardial deformation and rotational mechanics.

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Measuring the diameter of the pulmonary trunk at the base of the valvar hinge points was most repeatable. Repeatability of right ventricular output was similar to that of left, with absolute values similar to those published by other workers.