ABSTRACT
We describe the case of an infant with DiGeorge syndrome born with a right aortic arch and left arterial duct. Despite the remote location of the right aortic arch from the left arterial duct, he developed coarctation of the aorta during treatment with indomethacin. This was relieved by prostaglandin treatment. This case highlights the fact that, even in the absence of an arterial duct, ductal tissue can still be present in the aorta, and cause coarctation when exposed to indomethacin. We also demonstrate the utility of prostaglandin for relief of this type of obstruction.
Subject(s)
Aortic Coarctation/diagnostic imaging , Aortic Coarctation/drug therapy , DiGeorge Syndrome/complications , Indomethacin/adverse effects , Prostaglandins/therapeutic use , Aorta, Thoracic/abnormalities , Aorta, Thoracic/drug effects , Aortic Coarctation/chemically induced , Ductus Arteriosus/abnormalities , Ductus Arteriosus/drug effects , Echocardiography, Doppler, Color , Humans , Infant, Newborn , MaleABSTRACT
PURPOSE: The genetic etiology of atrioventricular septal defect (AVSD) is unknown in 40% cases. Conventional sequencing and arrays have identified the etiology in only a minority of nonsyndromic individuals with AVSD. METHODS: Whole-exome sequencing was performed in 81 unrelated probands with AVSD to identify potentially causal variants in a comprehensive set of 112 genes with strong biological relevance to AVSD. RESULTS: A significant enrichment of rare and rare damaging variants was identified in the gene set, compared with controls (odds ratio (OR): 1.52; 95% confidence interval (CI): 1.35-1.71; P = 4.8 × 10(-11)). The enrichment was specific to AVSD probands, compared with a cohort without AVSD with tetralogy of Fallot (OR: 2.25; 95% CI: 1.84-2.76; P = 2.2 × 10(-16)). Six genes (NIPBL, CHD7, CEP152, BMPR1a, ZFPM2, and MDM4) were enriched for rare variants in AVSD compared with controls, including three syndrome-associated genes (NIPBL, CHD7, and CEP152). The findings were confirmed in a replication cohort of 81 AVSD probands. CONCLUSION: Mutations in genes with strong biological relevance to AVSD, including syndrome-associated genes, can contribute to AVSD, even in those with isolated heart disease. The identification of a gene set associated with AVSD will facilitate targeted genetic screening in this cohort.
Subject(s)
Exome , Genetic Variation , Heart Septal Defects/genetics , Adolescent , Cohort Studies , DNA Mutational Analysis , Female , Genotype , Humans , Male , Mutation , Phenotype , Sequence Analysis, DNAABSTRACT
BACKGROUND: The aim of this study was to assess and quantify the effects of indomethacin on cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) in preterm infants undergoing treatment for a patent ductus arteriosus (PDA). METHODS: CBF and CMRO2 were measured before and after the first dose of a 3-d course of indomethacin to close hemodynamically significant PDA in preterm neonates. Indocyanine-green (ICG) concentration curves were acquired before and after indomethacin injection to quantify CBF and CMRO2. RESULTS: Eight preterm neonates (gestational age, 27.6 ± 0.5 wk; birth weight, 992 ± 109 g; 6 males:2 females) were treated at a median age of 4.5 d (range, 4-21 d). Indomethacin resulted in an average CBF decrease of 18% (pre- and post-CBF = 12.9 ± 1.3 and 10.6 ± 0.8 ml/100 g/min, respectively) and an OEF increase of 11% (pre- and post-OEF = 0.38 ± 0.02 and 0.42 ± 0.02, respectively) but no significant change in CMRO2 (pre- and post-CMRO2 = 0.83 ± 0.07 and 0.76 ± 0.07 ml O2/100 g/min, respectively). Corresponding mean blood pressure (BP), arterial oxygen saturation (SaO2), heart rate, and end-tidal carbon dioxide tension levels remained unchanged. CONCLUSION: Indomethacin resulted in significant reduction in CBF but did not alter CMRO2 because of a compensatory increase in OEF.
