Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging.

BACKGROUND: The lack of dystrophin in cardiomyocytes in Duchenne muscular dystrophy (DMD) is associated with progressive decline in cardiac function eventually leading to death by 20-40 years of age. The aim of this prospective study was to determine rate of progressive decline in left ventricular (LV) function in Duchenne muscular dystrophy (DMD) over 5 years. METHODS: Short axis cine and grid tagged images of the LV were acquired in individuals with DMD (n = 59; age = 5.3-18.0 years) yearly, and healthy controls at baseline (n = 16, age = 6.0-18.3 years) on a 3 T MRI scanner. Grid-tagged images were analyzed for composite circumferential strain (ℇcc%) and ℇcc% in six mid LV segments. Cine images were analyzed for left ventricular ejection fraction (LVEF), LV mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), LV atrioventricular plane displacement (LVAPD), and circumferential uniformity ratio estimate (CURE). LVM, EDV, and ESV were normalized to body surface area for a normalized index of LVM (LVMI), EDV (EDVI) and ESV (ESVI). RESULTS: At baseline, LV ℇcc% was significantly worse in DMD compared to controls and five of the six mid LV segments demonstrated abnormal strain in DMD. Longitudinal measurements revealed that ℇcc% consistently declined in individuals with DMD with the inferior segments being more affected. LVEF progressively declined between 3 to 5 years post baseline visit. In a multivariate analysis, the use of cardioprotective drugs trended towards positively impacting cardiac measures while loss of ambulation and baseline age were associated with negative impact. Eight out of 17 cardiac parameters reached a minimal clinically important difference with a threshold of 1/3 standard deviation. CONCLUSION: The study shows a worsening of circumferential strain in dystrophic myocardium. The findings emphasize the significance of early and longitudinal assessment of cardiac function in DMD and identify early biomarkers of cardiac dysfunction to help design clinical trials to mitigate cardiac pathology. This study provides valuable non-invasive and non-contrast based natural history data of cardiac changes which can be used to design clinical trials or interpret the results of current trials aimed at mitigating the effects of decreased cardiac function in DMD.

In Utero Diagnoses of Strikingly Similar Presentations of Complete Atrioventricular Septal Defects in a Pair of Dizygotic Twins Concordant for Trisomy 21.

Trisomy 21, or Down syndrome (DS), is a genetic disorder affecting approximately 1 in 500-750 live births. The prevalence of DS has increased over the past two decades, correlating with a rise in the proportion of pregnancies complicated by advanced maternal age. There is also a correlation between advanced maternal age and dizygotic twinning rates. There is an increased risk of at least one twin being affected in dizygotic pregnancies compared to singletons. However, despite this greater relative risk, reports of concordance of DS in both dizygotic twins are very rare. Congenital heart disease (CHD) occurs in roughly 40% of individuals with DS, but there can be considerable phenotypic variation. The most common, atrioventricular septal defect accounts for only 40% of CHD seen in DS. There is also a higher incidence of CHD in twins, but also with a low incidence of concordance. There have been only five reported cases of concordant DS in dizygotic twins with confirmed chromosomal analyses; none of which describe concordant congenital heart disease. Here, we describe an unusual case of dizygotic twins of differing genders concordant for both Down syndrome and congenital heart disease of a strikingly similar presentation.