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Browsing by Subject "Hypoplastic left heart syndrome"
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Item Cognitive and Attentional Function in Children with Hypoplastic Left Heart Syndrome: A Pilot Study(Springer Nature, 2021) Siciliano, Rachel E.; Murphy, Lexa K.; Prussien, Kemar V.; Henry, Lauren M.; Watson, Kelly H.; Patel, Niral J.; Lee, Chelsea A.; McNally, Colleen M.; Markham, Larry W.; Compas, Bruce E.; Jordan, Lori C.; Pediatrics, School of MedicineWhile survival for children with hypoplastic left heart syndrome (HLHS) has improved, compromised cardiac output and oxygen delivery persist, and children show cognitive deficits. Most research has assessed young children on broad cognitive indices; less is known about specific indices in older youth. In this pilot study, cognitive function and attention in youth ages 8 to 16 years with HLHS (n = 20) was assessed with the Wechsler Intelligence Scale for Children – Fifth Edition (WISC-V) and NIH Toolbox Cognition Battery (NTCB); parents completed the Child Behavior Checklist. Children scored significantly lower than normative means on the WISC-V Full Scale IQ, Verbal Comprehension, Visual Spatial, Working Memory, and Processing Speed indices, and the NTCB Fluid Cognition Composite; effect sizes ranged from medium to large. Attention problems had a large significant effect. Child age corresponded to lower visual spatial scores. Findings highlight the importance of assessing multiple cognitive indices for targeted intervention and investigating age and disease factors as potential correlates in larger samples.Item The HAND1 frameshift A126FS mutation does not cause hypoplastic left heart syndrome in mice(Oxford University Press, 2017-12-01) Firulli, Beth A.; Toolan, Kevin P.; Harkin, Jade; Millar, Hannah; Pineda, Santiago; Firulli, Anthony B.; Pediatrics, School of MedicineAims: To test if a human Hand1 frame shift mutation identified in human samples is causative of hypoplastic left heart syndrome (HLHS). Methods and results: HLHS is a poorly understood single ventricle congenital heart defect that affects two to three infants in every 10 000 live births. The aetiologies of HLHS are largely unknown. The basic helix-loop-helix transcription factor HAND1 is required for normal heart development. Interrogation of HAND1 sequence from fixed HLHS tissues identified a somatic frame-shift mutation at Alanine 126 (NP_004812.1 p.Ala126Profs13X defined as Hand1A126fs). Hand1A126fs creates a truncated HAND1 protein that predictively functions as dominant negative. To determine if this mutation is causative of HLHS, we engineered a conditional Hand1A126fs mouse allele. Activation of this allele with Nkx2.5Cre results in E14.5 lethality accompanied by cardiac outflow tract and intraventricular septum abnormalities. Using αMHC-Cre or Mef2CAHF-Cre to activate Hand1A126fs results in reduced phenotype and limited viability. Left ventricles of Hand1A126FS mutant mice are not hypoplastic. Conclusions: Somatically acquired Hand1A126FS mutation is not causative of HLHS. Hand1A126FS mutation does exhibit embryonic lethal cardiac defects that reflect a dominant negative function supporting the critical role of Hand1 in cardiogenesis.Item Hypoplastic Left Heart Syndrome(StatPearls Publishing, 2021) Kritzmire, Stacy M.; Cossu, Anne E.; Anesthesia, School of MedicineHypoplastic left heart syndrome (HLHS) is a type of congenital heart disease that results in the underdevelopment of the left-sided structures of the heart, including the mitral valve, left ventricle, aortic valve, ascending aorta, and aortic arch. HLHS was first described as a syndrome in 1958 by Nadas and NoonanFontanwho referred to it as combined aortic and mitral atresia.[1] HLHS affects 1 in 5,000 neonates or 3% of all infants born with congenital heart disease.[2][3] Thirty years ago, there were no treatment options for these neonates, and mortality was 100% within the first week of life.[4] Neonates born with HLHS are dependent on a patent ductus arteriosus and an interatrial communication for survival until surgical intervention. A continuous infusion of prostaglandin E1 (PGE1) is needed to maintain ductal patency. Today, several treatment options are available in the prenatal or neonatal period, including the Norwood procedure, hybrid stage 1, heart transplantation, palliative care, and fetal intervention. A series of three palliative surgical operations (Norwood/Hybrid, Hemi-Fontan/Bidirectional Glenn, and Fontan) are typically necessary for survival beyond the neonatal period and infancy. Though rare, a diagnosis of HLHS is responsible for 23% of all cardiac deaths in the first week of life.[1]Item Hypoplastic Left Heart Syndrome Sequencing Reveals a Novel NOTCH1 Mutation in a Family with Single Ventricle Defects(Springer Nature, 2017-08) Durbin, Matthew D.; Cadar, Adrian G.; Williams, Charles H.; Guo, Yan; Bichell, David P.; Su, Yan Ru; Hong, Charles C.; Pediatrics, School of MedicineHypoplastic left heart syndrome (HLHS) has been associated with germline mutations in 12 candidate genes and a recurrent somatic mutation in HAND1 gene. Using targeted and whole exome sequencing (WES) of heart tissue samples from HLHS patients, we sought to estimate the prevalence of somatic and germline mutations associated with HLHS. We performed Sanger sequencing of the HAND1 gene on 14 ventricular (9 LV and 5 RV) samples obtained from HLHS patients, and WES of 4 LV, 2 aortic, and 4 matched PBMC samples, analyzing for sequence discrepancy. We also screened for mutations in the 12 candidate genes implicated in HLHS. We found no somatic mutations in our HLHS cohort. However, we detected a novel germline frameshift/stop-gain mutation in NOTCH1 in a HLHS patient with a family history of both HLHS and hypoplastic right heart syndrome (HRHS). Our study, involving one of the first familial cases of single ventricle defects linked to a specific mutation, strengthens the association of NOTCH1 mutations with HLHS and suggests that the two morphologically distinct single ventricle conditions, HLHS and HRHS, may share a common molecular and cellular etiology. Finally, somatic mutations in the LV are an unlikely contributor to HLHS.Item KMT2D-NOTCH Mediates Coronary Abnormalities in Hypoplastic Left Heart Syndrome(American Heart Association, 2022) Yu, Zhiyun; Zhou, Xin; Liu, Ziyi; Pastrana-Gomez, Victor; Liu, Yu; Guo, Minzhe; Tian, Lei; Nelson, Timothy J.; Wang, Nian; Mital, Seema; Chitayat, David; Wu, Joseph C.; Rabinovitch, Marlene; Wu, Sean M.; Snyder, Michael P.; Miao, Yifei; Gu, Mingxia; Radiology and Imaging Sciences, School of MedicineItem Spinal Anesthesia for Open Gastrostomy in an Infant after Stage I Norwood for Hypoplastic Left Heart(Wolters Kluwer, 2022) Acquaviva, Michael A.; Hardacker, Doris M.; Packiasabapathy, Senthil; Burns, Robert C.; Anesthesia, School of MedicineInfants with hypoplastic left heart are at increased risk of adverse events including mortality when they undergo procedures with general anesthesia in the inter-stage period after stage I Norwood. This is primarily caused by an imbalance between pulmonary and systemic blood flows augmented by decreased function of the single ventricle. These factors can be aggravated by general anesthesia, hence the increased risk. Many of these infants experience feeding dysfunction and require a gastrostomy to optimize nutrition. We report a case of open gastrostomy in an infant with Norwood physiology under spinal anesthesia with an excellent outcome.