daniel de wolf | Ghent University (original) (raw)

Papers by daniel de wolf

Research paper thumbnail of The Pulmonary Autograft After the Ross Operation: Results of 25-Year Follow-Up in a Pediatric Cohort

The Annals of Thoracic Surgery, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of A clinical scoring system for congenital contractural arachnodactyly

Genetics in Medicine, 2019

Purpose: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue ... more Purpose: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested. We designed a clinical scoring system and diagnostic criteria to support the diagnostic process and guide molecular genetic testing. Methods: In this retrospective study, we assessed 167 probands referred for FBN2 analysis and classified them into a FBN2-positive (n = 44) and FBN2-negative group (n = 123) following molecular analysis. We developed a 20-point weighted clinical scoring system based on the prevalence of ten main clinical characteristics of CCA in both groups. Results: The total score was significantly different between the groups (P < 0.001) and was indicative for classifying patients into unlikely CCA (total score <7) and likely CCA (total score ≥7) groups. Conclusions: Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.

Research paper thumbnail of Pulmonale hypertensie bij kinderen en bij patiënten met aangeboren hartafwijkingen

Bloedvaten Hart Longen, 2008

Research paper thumbnail of Exploring the Mutational Landscape of Isolated Congenital Heart Defects: An Exome Sequencing Study Using Cardiac DNA

Genes

Congenital heart defects (CHD) are the most common congenital anomalies in liveborn children. In ... more Congenital heart defects (CHD) are the most common congenital anomalies in liveborn children. In contrast to syndromic CHD (SCHD), the genetic basis of isolated CHD (ICHD) is complex, and the underlying pathogenic mechanisms appear intricate and are incompletely understood. Next to rare Mendelian conditions, somatic mosaicism or a complex multifactorial genetic architecture are assumed for most ICHD. We performed exome sequencing (ES) in 73 parent–offspring ICHD trios using proband DNA extracted from cardiac tissue. We identified six germline de novo variants and 625 germline rare inherited variants with ‘damaging’ in silico predictions in cardiac-relevant genes expressed in the developing human heart. There were no CHD-relevant somatic variants. Transmission disequilibrium testing (TDT) and association testing (AT) yielded no statistically significant results, except for the AT of missense variants in cilia genes. Somatic mutations are not a common cause of ICHD. Rare de novo and i...

Research paper thumbnail of Endocarditis prophylaxis in daily practice of pediatricians and dentists in Flanders

European Journal of Pediatrics, 2020

Endocarditis is a potentially life-threatening disease in children with congenital heart disease ... more Endocarditis is a potentially life-threatening disease in children with congenital heart disease (CHD) and correct prophylaxis (EP) is of utmost importance. We conducted two surveys among pediatricians and dentists in Flanders about their knowledge of EP guidelines. The survey was completed by 910 dentists and 100 pediatricians. Sixty-five percent of the dentists did not know any guideline. They relied for information on the internet or the child's physician. 87% identified low risk treatments correctly, but only 64% identified high risk procedures correctly. Eighty-three percent asked for the presence of CHD and allergy to antibiotics. Dentists asked advice of the patient's physician, but 29% would withhold treatments in high-risk patients and 50% did not know the pediatric antibiotic dosages. Forty-seven percent of the pediatricians did not know EP guidelines and they would preferably contact the child's cardiologist. Pediatricians had difficulties with the identification of low-risk procedures and would give unnecessary antibiotics. They identified most CHD at high risk, but scored lower for the identification of lower risk CHD. Conclusion: The knowledge of Flemish dentists and pediatricians of EP guidelines is low. The knowledge about EP guidelines and the communication between dentists and pediatricians should be improved. Patients should be provided with an individual EP card.

Research paper thumbnail of Body mass index in adults with congenital heart disease

Congenital Heart Disease, 2019

Presently, the majority of children with congenital heart disease (CHD) survive into adulthood, e... more Presently, the majority of children with congenital heart disease (CHD) survive into adulthood, even those with most complex lesions. 1 Therefore, factors that influence long-term cardiac outcomes are of increasing importance. The increasing prevalence of overweight and obesity in the past three decades has become a universal serious public health problem, 2 especially, obesity is an independent risk factor for cardiovascular disease and associated with an increased risk of morbidity and mortality as well as reduced life expectancy. 3 Many cardiologists who treat patients with adult CHD (ACHD) focus on residual lesions, heart failure, arrhythmias and medication, while lifestyle choices such as dietary behavior and physical activity

Research paper thumbnail of Practical recommendations on the use of echocardiography to assess pulmonary arterial hypertension--a Belgian expert consensus endorsed by the Working Group on Non-Invasive Cardiac Imaging

Acta cardiologica

Pulmonary hypertension (PH) is defined by a sustained increase in mean pulmonary arterial pressur... more Pulmonary hypertension (PH) is defined by a sustained increase in mean pulmonary arterial pressure > 25 mmHg. Due to its widespread availability, echocardiography (ECHO) is used as the first-line imaging modality to detect pulmonary PH and assess right ventricular (RV) function in daily routine. As such, ECHO is the key examination to detect the presence of PH, to provide valuable prognostic information and to give an orientation to therapeutic strategies. In addition to detection and screening, ECHO also provides clues for the differential diagnosis of PH. The present document, based on a consensus of experts, provides practical recommendations for the use of ECHO in the evaluation of PH and of its consequences on the right ventricle.

Research paper thumbnail of Determinants of Physical Fitness in Children with Repaired Congenital Heart Disease

Pediatric Cardiology, 2021

The aim of this study was to determine factors associated with physical fitness (PF) in children ... more The aim of this study was to determine factors associated with physical fitness (PF) in children who underwent surgery for congenital heart disease (CHD). Sixty-six children (7-14 years) who underwent surgery for ventricular septal defect (n = 19), transposition of great arteries (n = 22), coarctation of aorta (n = 10), and tetralogy of Fallot (n = 15) were included. All children performed PF tests: cardiorespiratory fitness, upper-and lower-limb muscle strength, speed, balance, and flexibility. Cardiac evaluation was done via echocardiography and cardiopulmonary exercise test. Factors related to child's characteristics, child's lifestyle, physical activity motivators/barriers, and parental factors were assessed. Linear regression analyses were conducted. The results showed no significant differences in physical activity (PA) level by CHD type. Boys had better cardiorespiratory fitness (difference = 1.86 ml/kg/min [0.51;3.22]) and were more physically active (difference = 19.40 min/ day [8.14;30.66]), while girls had better flexibility (difference = − 3.60 cm [− 7.07;− 0.14]). Physical activity motivators showed an association with four out of six PF components: cardiorespiratory fitness, coefficient = 0.063 [0.01;0.11]; upperlimb muscle strength, coefficient = 0.076 [0.01;0.14]; lower-limb muscle strength, coefficient = 0.598 [0.07;1.13]; and speed, coefficient = 0.03 [0.01;0.05]. Age, sex, and motivators together reached a maximum adjusted R 2 = 0.707 for upper-limb strength. Adding other possible determinants did not significantly increase the explained variance. Apart from age and sex as non-modifiable determinants, the main target which might improve fitness would be the introduction of an intervention which increases the motivation to be active.

Research paper thumbnail of Paediatric subaortic stenosis: long-term outcome and risk factors for reoperation

Interactive CardioVascular and Thoracic Surgery, 2021

OBJECTIVES Surgical repair of subaortic stenosis (SAS) is associated with a substantial reoperati... more OBJECTIVES Surgical repair of subaortic stenosis (SAS) is associated with a substantial reoperation risk. We aimed to identify risk factors for reintervention in relation to discrete and tunnel-type SAS morphology. METHODS Single-centre retrospective study of paediatric SAS diagnosed between 1992 and 2017. Multivariable Cox regression analysis was performed to identify reintervention risk factors. RESULTS Eighty-five children [median age 2.5 (0.7–6.5) years at diagnosis] with a median follow-up of 10.1 (5.5–16.4) years were included. Surgery was executed in 83% (n = 71). Freedom from reoperation was 88 ± 5% at 5 years and 82 ± 6% at 10 years for discrete SAS, compared to, respectively, 33 ± 16% and 17 ± 14% for tunnel-type SAS (log-rank P < 0.001). Independent risk factors for reintervention were a postoperative gradient >20 mmHg [hazard ratio (HR) 6.56, 95% confidence interval (CI) 1.41–24.1; P = 0.005], tunnel-type SAS (HR 7.46, 95% CI 2.48–22.49; P < 0.001), aortic annul...

Research paper thumbnail of Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe

Circulation, 2021

Background: The aim of the study was to document cardiovascular clinical findings, cardiac imagin... more Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging, and laboratory markers in children presenting with the novel multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) infection. Methods: This real-time internet-based survey has been endorsed by the Association for European Paediatric and Congenital Cardiologists Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Children 0 to 18 years of age admitted to a hospital between February 1 and June 6, 2020, with a diagnosis of an inflammatory syndrome and acute cardiovascular complications were included. Results: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (interquartile range, 3.8–12.4 years) and 67% were boys. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion, and coronary artery dilatation. Reduced left ventricular ejection fra...

Research paper thumbnail of Early outcomes of percutaneous pulmonary valve implantation using the Edwards SAPIEN XT transcatheter heart valve system

International journal of cardiology, Jan 6, 2017

Patients with congenital or acquired heart defects affecting the pulmonary valve and right ventri... more Patients with congenital or acquired heart defects affecting the pulmonary valve and right ventricular outflow tract (RVOT) commonly require multiple surgical interventions, resulting in significant morbidity. A less invasive alternative is percutaneous pulmonary valve implantation (PPVI). Though studies have previously reported the safety and efficacy of the early generation transcatheter heart valves (THVs), data on more recent devices are severely lacking. We performed a multinational, multicentre, retrospective, observational registry analysis of patients who underwent PPVI using the Edwards SAPIEN XT THV. Of the 46 patients that were enrolled, the majority had tetralogy of Fallot as the underlying diagnosis (58.7%), and stentless xenograft as the most common RVOT anatomy (34.8%). Procedural success rate was high (93.5%), with a low frequency of periprocedural complications and adverse events (6.5% and 10.9%, respectively). At 30days post-procedure, NYHA class had improved signi...

Research paper thumbnail of An Alternative Strategy for Bridge-to-Transplant/Recovery in Small Children with Dilated Cardiomyopathy

Pediatric cardiology, Jan 29, 2017

Dilated cardiomyopathy in children still has a poor prognosis with high rates of mortality and ca... more Dilated cardiomyopathy in children still has a poor prognosis with high rates of mortality and cardiac transplantation (resp. around 20 and 25%). Awaiting transplantation or possible recovery, these pediatric patients are mechanically supported with extracorporeal membrane oxygenation or a paracorporeal ventricular assist device, both resulting in higher survival rates but also entailing considerable risks of infection, thrombosis, or bleeding. A new indication for an old technique, i.e., pulmonary artery banding, presents itself as an interesting alternative to mechanical circulatory support in selected infants and small children with dilated LV cardiomyopathy and preserved RV function. Here we present a brief review of literature and report on two patients in whom PAB has been successfully implemented as either bridge-to-recovery or bridge-to-transplant.

Research paper thumbnail of Characterizing cerebral and locomotor muscle oxygenation to incremental ramp exercise in healthy children: relationship with pulmonary gas exchange

European Journal of Applied Physiology, 2016

To characterize the oxygenation responses at cerebral and locomotor muscle level to incremental e... more To characterize the oxygenation responses at cerebral and locomotor muscle level to incremental exercise in children and to assess the interrelationship with the pulmonary gas exchange responses. Eighteen children (9 boys, 9 girls) (mean age 10.9 ± 1.0 years) performed incremental cycle ramp exercise to exhaustion. The concentration of cerebral and muscle oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin (by means of near-infrared spectroscopy) and pulmonary gas exchange was recorded. Cerebral and muscle O2Hb and HHb values were expressed as functions of oxygen uptake (VO2) and breakpoints were detected by means of double linear model analysis. The respiratory compensation point (RCP) was determined. The breakpoints in cerebral and muscle O2Hb and HHb were compared and correlated to RCP. The subjects reached peak power output of 105 ± 18 W and VO2peak of 43.5 ± 7.0 ml min(-1) kg(-1). Cerebral O2Hb increased to an intensity of 89.4 ± 5.5 %VO2peak, where a breakpoint occurred at which cerebral O2Hb started to decrease. Cerebral HHb increased slightly to 88.1 ± 4.8 %VO2peak, at which the increase was accelerated. Muscle HHb increased to 90.5 ± 4.8 %VO2peak where a leveling-off occurred. RCP occurred at 89.3 ± 4.3 %VO2peak. The breakpoints and RCP did not differ significantly (P = 0.13) and were strongly correlated (r &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.70, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). There were no differences between boys and girls (P = 0.43) and there was no significant correlation with VO2peak (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). It was shown that cerebral and muscle oxygenation responses undergo significant changes as work rate increases and show breakpoints in the ongoing response at high intensity (85-95 %VO2peak). These breakpoints are strongly interrelated and associated with changes in pulmonary gas exchange.

Research paper thumbnail of Impact of Oxidative Stress on the Endothelial Dysfunction of Children and Adolescents With Type 1 Diabetes Mellitus: Protection by Superoxide Dismutase?

Pediatric Research, 2007

Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). We invest... more Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). We investigated whether these abnormalities are interrelated in children and adolescents with type 1 diabetes mellitus (T1DM) and if early OS markers predictive of vascular dysfunction can be identified. Thirty-five T1DM patients were matched for sex, age, height, and weight with nondiabetic subjects as healthy controls (CO). Flow-mediated dilatation (FMD), carotid intima media thickness (IMT), and OS status in fasting blood were measured. Diabetic children had impaired FMD (6.68 Ϯ 1.98 versus 7.92 Ϯ 1.60% in CO, p ϭ 0.004), which was more pronounced in boys. The degree of FMD impairment was not related to the lower plasma levels of antioxidants or to the higher glucose, glycation, lipids, and peroxidation products. Erythrocyte superoxide dismutase activity, copper/zinc superoxide dismutase (Cu/Zn SOD), was higher in diabetic subjects (1008 Ϯ 224 versus 845 Ϯ 195 U/g Hb in CO, p ϭ 0.003) and was positively associated with FMD. After correcting for diabetes and gender, the subgroup of children with high Cu/Zn SOD (Ͼ955 U/g Hb) had a significantly better FMD (p ϭ 0.035). These results suggest that higher circulating Cu/Zn SOD could protect T1DM children and adolescents against endothelial dysfunction. Low Cu/Zn SOD is a potential early marker of susceptibility to diabetic vascular disease.

Research paper thumbnail of The influence of low afterload on the nature of the stress-velocity relationship

Journal of the American College of Cardiology, 1999

Research paper thumbnail of Use of an event recorder in the decision for pacemaker implantation in a child with syncope

European Journal of Pediatrics, 2002

The use of a patient-triggered and automatic event recorder is documented in a 17 month old girl ... more The use of a patient-triggered and automatic event recorder is documented in a 17 month old girl presenting with paroxysmal episodes of loss of consciousness. After pacemaker implant the paroxysmal attacks disappeared.We recommend a more frequent use of the event recorder in the investigation of syncope, even in small children.

Research paper thumbnail of Surgical repair of atrioventricular septal defect with common atrioventricular valve in early infancy

Cardiology in the Young, 2006

The repair of atrioventricular septal defect with a common atrioventricular valve is reconstructi... more The repair of atrioventricular septal defect with a common atrioventricular valve is reconstructive surgery at its best, and hence one of the favourite operations performed by paediatric cardiac surgeons. In the past, the post-operative course from such patients was dominated by the occurrence of pulmonary hypertension crises, which were responsible for significant morbidity and mortality. Nowadays, repair is generally undertaken early in infancy, and this approach has mitigated the problems emanating from pulmonary hypertension. Coupled with a better understanding of the anatomy, and adaptation of the surgical techniques, repair can now be achieved safely at around 2 to 4 months of life, without increasing the risk of postoperative regurgitation across the reconstructed left atrioventricular valve. In this review, we discuss the surgical techniques required for, and clinical results of, such early repair.

Research paper thumbnail of Do parental ratings on cognition reflect neuropsychological outcome in congenital heart disease?

Acta Paediatrica, 2007

To describe the parental view of the cognitive skills of their child with a surgically corrected ... more To describe the parental view of the cognitive skills of their child with a surgically corrected congenital heart disease (CHD) and compare it to objectified cognitive measures in children with CHD 6-12 years postoperatively. Parents completed a questionnaire on several cognitive functions of their child. Children with CHD and healthy controls (n=86, aged 8 years 8 months +/- 1 year 6 months) underwent an abbreviated IQ-testing and a neurodevelopmental assessment. Parents of the children with CHD more frequently indicated lower sustained attention (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), lower divided attention (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), more problems with memory and learning skills (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), and deficient gross motor functioning (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) compared to the parents of healthy controls. Intellectual and neuropsychological assessment revealed a lower estimated full-scale IQ (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), worse sensorimotor functioning (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), and lower performances on language (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), attention/executive functioning (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), and memory…

Research paper thumbnail of A Reassessment of Copy Number Variations in Congenital Heart Defects: Picturing the Whole Genome

Genes

Copy number variations (CNVs) can modulate phenotypes by affecting protein-coding sequences direc... more Copy number variations (CNVs) can modulate phenotypes by affecting protein-coding sequences directly or through interference of gene expression. Recent studies in cancer and limb defects pinpointed the relevance of non-coding gene regulatory elements such as long non-coding RNAs (lncRNAs) and topologically associated domain (TAD)-related gene-enhancer interactions. The contribution of such non-coding elements is largely unexplored in congenital heart defects (CHD). We performed a retrospective analysis of CNVs reported in a cohort of 270 CHD patients. We reviewed the diagnostic yield of pathogenic CNVs, and performed a comprehensive reassessment of 138 CNVs of unknown significance (CNV-US), evaluating protein-coding genes, lncRNA genes, and potential interferences with TAD-related gene-enhancer interactions. Fifty-two of the 138 CNV-US may relate to CHD, revealing three candidate CHD regions, 19 candidate CHD genes, 80 lncRNA genes of interest, and six potentially CHD-related TAD in...

Research paper thumbnail of Sleep apnea and the impact on cardiovascular risk in patients with Marfan syndrome

Molecular Genetics & Genomic Medicine

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmer... more This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Research paper thumbnail of The Pulmonary Autograft After the Ross Operation: Results of 25-Year Follow-Up in a Pediatric Cohort

The Annals of Thoracic Surgery, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of A clinical scoring system for congenital contractural arachnodactyly

Genetics in Medicine, 2019

Purpose: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue ... more Purpose: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested. We designed a clinical scoring system and diagnostic criteria to support the diagnostic process and guide molecular genetic testing. Methods: In this retrospective study, we assessed 167 probands referred for FBN2 analysis and classified them into a FBN2-positive (n = 44) and FBN2-negative group (n = 123) following molecular analysis. We developed a 20-point weighted clinical scoring system based on the prevalence of ten main clinical characteristics of CCA in both groups. Results: The total score was significantly different between the groups (P < 0.001) and was indicative for classifying patients into unlikely CCA (total score <7) and likely CCA (total score ≥7) groups. Conclusions: Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.

Research paper thumbnail of Pulmonale hypertensie bij kinderen en bij patiënten met aangeboren hartafwijkingen

Bloedvaten Hart Longen, 2008

Research paper thumbnail of Exploring the Mutational Landscape of Isolated Congenital Heart Defects: An Exome Sequencing Study Using Cardiac DNA

Genes

Congenital heart defects (CHD) are the most common congenital anomalies in liveborn children. In ... more Congenital heart defects (CHD) are the most common congenital anomalies in liveborn children. In contrast to syndromic CHD (SCHD), the genetic basis of isolated CHD (ICHD) is complex, and the underlying pathogenic mechanisms appear intricate and are incompletely understood. Next to rare Mendelian conditions, somatic mosaicism or a complex multifactorial genetic architecture are assumed for most ICHD. We performed exome sequencing (ES) in 73 parent–offspring ICHD trios using proband DNA extracted from cardiac tissue. We identified six germline de novo variants and 625 germline rare inherited variants with ‘damaging’ in silico predictions in cardiac-relevant genes expressed in the developing human heart. There were no CHD-relevant somatic variants. Transmission disequilibrium testing (TDT) and association testing (AT) yielded no statistically significant results, except for the AT of missense variants in cilia genes. Somatic mutations are not a common cause of ICHD. Rare de novo and i...

Research paper thumbnail of Endocarditis prophylaxis in daily practice of pediatricians and dentists in Flanders

European Journal of Pediatrics, 2020

Endocarditis is a potentially life-threatening disease in children with congenital heart disease ... more Endocarditis is a potentially life-threatening disease in children with congenital heart disease (CHD) and correct prophylaxis (EP) is of utmost importance. We conducted two surveys among pediatricians and dentists in Flanders about their knowledge of EP guidelines. The survey was completed by 910 dentists and 100 pediatricians. Sixty-five percent of the dentists did not know any guideline. They relied for information on the internet or the child's physician. 87% identified low risk treatments correctly, but only 64% identified high risk procedures correctly. Eighty-three percent asked for the presence of CHD and allergy to antibiotics. Dentists asked advice of the patient's physician, but 29% would withhold treatments in high-risk patients and 50% did not know the pediatric antibiotic dosages. Forty-seven percent of the pediatricians did not know EP guidelines and they would preferably contact the child's cardiologist. Pediatricians had difficulties with the identification of low-risk procedures and would give unnecessary antibiotics. They identified most CHD at high risk, but scored lower for the identification of lower risk CHD. Conclusion: The knowledge of Flemish dentists and pediatricians of EP guidelines is low. The knowledge about EP guidelines and the communication between dentists and pediatricians should be improved. Patients should be provided with an individual EP card.

Research paper thumbnail of Body mass index in adults with congenital heart disease

Congenital Heart Disease, 2019

Presently, the majority of children with congenital heart disease (CHD) survive into adulthood, e... more Presently, the majority of children with congenital heart disease (CHD) survive into adulthood, even those with most complex lesions. 1 Therefore, factors that influence long-term cardiac outcomes are of increasing importance. The increasing prevalence of overweight and obesity in the past three decades has become a universal serious public health problem, 2 especially, obesity is an independent risk factor for cardiovascular disease and associated with an increased risk of morbidity and mortality as well as reduced life expectancy. 3 Many cardiologists who treat patients with adult CHD (ACHD) focus on residual lesions, heart failure, arrhythmias and medication, while lifestyle choices such as dietary behavior and physical activity

Research paper thumbnail of Practical recommendations on the use of echocardiography to assess pulmonary arterial hypertension--a Belgian expert consensus endorsed by the Working Group on Non-Invasive Cardiac Imaging

Acta cardiologica

Pulmonary hypertension (PH) is defined by a sustained increase in mean pulmonary arterial pressur... more Pulmonary hypertension (PH) is defined by a sustained increase in mean pulmonary arterial pressure > 25 mmHg. Due to its widespread availability, echocardiography (ECHO) is used as the first-line imaging modality to detect pulmonary PH and assess right ventricular (RV) function in daily routine. As such, ECHO is the key examination to detect the presence of PH, to provide valuable prognostic information and to give an orientation to therapeutic strategies. In addition to detection and screening, ECHO also provides clues for the differential diagnosis of PH. The present document, based on a consensus of experts, provides practical recommendations for the use of ECHO in the evaluation of PH and of its consequences on the right ventricle.

Research paper thumbnail of Determinants of Physical Fitness in Children with Repaired Congenital Heart Disease

Pediatric Cardiology, 2021

The aim of this study was to determine factors associated with physical fitness (PF) in children ... more The aim of this study was to determine factors associated with physical fitness (PF) in children who underwent surgery for congenital heart disease (CHD). Sixty-six children (7-14 years) who underwent surgery for ventricular septal defect (n = 19), transposition of great arteries (n = 22), coarctation of aorta (n = 10), and tetralogy of Fallot (n = 15) were included. All children performed PF tests: cardiorespiratory fitness, upper-and lower-limb muscle strength, speed, balance, and flexibility. Cardiac evaluation was done via echocardiography and cardiopulmonary exercise test. Factors related to child's characteristics, child's lifestyle, physical activity motivators/barriers, and parental factors were assessed. Linear regression analyses were conducted. The results showed no significant differences in physical activity (PA) level by CHD type. Boys had better cardiorespiratory fitness (difference = 1.86 ml/kg/min [0.51;3.22]) and were more physically active (difference = 19.40 min/ day [8.14;30.66]), while girls had better flexibility (difference = − 3.60 cm [− 7.07;− 0.14]). Physical activity motivators showed an association with four out of six PF components: cardiorespiratory fitness, coefficient = 0.063 [0.01;0.11]; upperlimb muscle strength, coefficient = 0.076 [0.01;0.14]; lower-limb muscle strength, coefficient = 0.598 [0.07;1.13]; and speed, coefficient = 0.03 [0.01;0.05]. Age, sex, and motivators together reached a maximum adjusted R 2 = 0.707 for upper-limb strength. Adding other possible determinants did not significantly increase the explained variance. Apart from age and sex as non-modifiable determinants, the main target which might improve fitness would be the introduction of an intervention which increases the motivation to be active.

Research paper thumbnail of Paediatric subaortic stenosis: long-term outcome and risk factors for reoperation

Interactive CardioVascular and Thoracic Surgery, 2021

OBJECTIVES Surgical repair of subaortic stenosis (SAS) is associated with a substantial reoperati... more OBJECTIVES Surgical repair of subaortic stenosis (SAS) is associated with a substantial reoperation risk. We aimed to identify risk factors for reintervention in relation to discrete and tunnel-type SAS morphology. METHODS Single-centre retrospective study of paediatric SAS diagnosed between 1992 and 2017. Multivariable Cox regression analysis was performed to identify reintervention risk factors. RESULTS Eighty-five children [median age 2.5 (0.7–6.5) years at diagnosis] with a median follow-up of 10.1 (5.5–16.4) years were included. Surgery was executed in 83% (n = 71). Freedom from reoperation was 88 ± 5% at 5 years and 82 ± 6% at 10 years for discrete SAS, compared to, respectively, 33 ± 16% and 17 ± 14% for tunnel-type SAS (log-rank P < 0.001). Independent risk factors for reintervention were a postoperative gradient >20 mmHg [hazard ratio (HR) 6.56, 95% confidence interval (CI) 1.41–24.1; P = 0.005], tunnel-type SAS (HR 7.46, 95% CI 2.48–22.49; P < 0.001), aortic annul...

Research paper thumbnail of Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe

Circulation, 2021

Background: The aim of the study was to document cardiovascular clinical findings, cardiac imagin... more Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging, and laboratory markers in children presenting with the novel multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) infection. Methods: This real-time internet-based survey has been endorsed by the Association for European Paediatric and Congenital Cardiologists Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Children 0 to 18 years of age admitted to a hospital between February 1 and June 6, 2020, with a diagnosis of an inflammatory syndrome and acute cardiovascular complications were included. Results: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (interquartile range, 3.8–12.4 years) and 67% were boys. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion, and coronary artery dilatation. Reduced left ventricular ejection fra...

Research paper thumbnail of Early outcomes of percutaneous pulmonary valve implantation using the Edwards SAPIEN XT transcatheter heart valve system

International journal of cardiology, Jan 6, 2017

Patients with congenital or acquired heart defects affecting the pulmonary valve and right ventri... more Patients with congenital or acquired heart defects affecting the pulmonary valve and right ventricular outflow tract (RVOT) commonly require multiple surgical interventions, resulting in significant morbidity. A less invasive alternative is percutaneous pulmonary valve implantation (PPVI). Though studies have previously reported the safety and efficacy of the early generation transcatheter heart valves (THVs), data on more recent devices are severely lacking. We performed a multinational, multicentre, retrospective, observational registry analysis of patients who underwent PPVI using the Edwards SAPIEN XT THV. Of the 46 patients that were enrolled, the majority had tetralogy of Fallot as the underlying diagnosis (58.7%), and stentless xenograft as the most common RVOT anatomy (34.8%). Procedural success rate was high (93.5%), with a low frequency of periprocedural complications and adverse events (6.5% and 10.9%, respectively). At 30days post-procedure, NYHA class had improved signi...

Research paper thumbnail of An Alternative Strategy for Bridge-to-Transplant/Recovery in Small Children with Dilated Cardiomyopathy

Pediatric cardiology, Jan 29, 2017

Dilated cardiomyopathy in children still has a poor prognosis with high rates of mortality and ca... more Dilated cardiomyopathy in children still has a poor prognosis with high rates of mortality and cardiac transplantation (resp. around 20 and 25%). Awaiting transplantation or possible recovery, these pediatric patients are mechanically supported with extracorporeal membrane oxygenation or a paracorporeal ventricular assist device, both resulting in higher survival rates but also entailing considerable risks of infection, thrombosis, or bleeding. A new indication for an old technique, i.e., pulmonary artery banding, presents itself as an interesting alternative to mechanical circulatory support in selected infants and small children with dilated LV cardiomyopathy and preserved RV function. Here we present a brief review of literature and report on two patients in whom PAB has been successfully implemented as either bridge-to-recovery or bridge-to-transplant.

Research paper thumbnail of Characterizing cerebral and locomotor muscle oxygenation to incremental ramp exercise in healthy children: relationship with pulmonary gas exchange

European Journal of Applied Physiology, 2016

To characterize the oxygenation responses at cerebral and locomotor muscle level to incremental e... more To characterize the oxygenation responses at cerebral and locomotor muscle level to incremental exercise in children and to assess the interrelationship with the pulmonary gas exchange responses. Eighteen children (9 boys, 9 girls) (mean age 10.9 ± 1.0 years) performed incremental cycle ramp exercise to exhaustion. The concentration of cerebral and muscle oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin (by means of near-infrared spectroscopy) and pulmonary gas exchange was recorded. Cerebral and muscle O2Hb and HHb values were expressed as functions of oxygen uptake (VO2) and breakpoints were detected by means of double linear model analysis. The respiratory compensation point (RCP) was determined. The breakpoints in cerebral and muscle O2Hb and HHb were compared and correlated to RCP. The subjects reached peak power output of 105 ± 18 W and VO2peak of 43.5 ± 7.0 ml min(-1) kg(-1). Cerebral O2Hb increased to an intensity of 89.4 ± 5.5 %VO2peak, where a breakpoint occurred at which cerebral O2Hb started to decrease. Cerebral HHb increased slightly to 88.1 ± 4.8 %VO2peak, at which the increase was accelerated. Muscle HHb increased to 90.5 ± 4.8 %VO2peak where a leveling-off occurred. RCP occurred at 89.3 ± 4.3 %VO2peak. The breakpoints and RCP did not differ significantly (P = 0.13) and were strongly correlated (r &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.70, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). There were no differences between boys and girls (P = 0.43) and there was no significant correlation with VO2peak (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). It was shown that cerebral and muscle oxygenation responses undergo significant changes as work rate increases and show breakpoints in the ongoing response at high intensity (85-95 %VO2peak). These breakpoints are strongly interrelated and associated with changes in pulmonary gas exchange.

Research paper thumbnail of Impact of Oxidative Stress on the Endothelial Dysfunction of Children and Adolescents With Type 1 Diabetes Mellitus: Protection by Superoxide Dismutase?

Pediatric Research, 2007

Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). We invest... more Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). We investigated whether these abnormalities are interrelated in children and adolescents with type 1 diabetes mellitus (T1DM) and if early OS markers predictive of vascular dysfunction can be identified. Thirty-five T1DM patients were matched for sex, age, height, and weight with nondiabetic subjects as healthy controls (CO). Flow-mediated dilatation (FMD), carotid intima media thickness (IMT), and OS status in fasting blood were measured. Diabetic children had impaired FMD (6.68 Ϯ 1.98 versus 7.92 Ϯ 1.60% in CO, p ϭ 0.004), which was more pronounced in boys. The degree of FMD impairment was not related to the lower plasma levels of antioxidants or to the higher glucose, glycation, lipids, and peroxidation products. Erythrocyte superoxide dismutase activity, copper/zinc superoxide dismutase (Cu/Zn SOD), was higher in diabetic subjects (1008 Ϯ 224 versus 845 Ϯ 195 U/g Hb in CO, p ϭ 0.003) and was positively associated with FMD. After correcting for diabetes and gender, the subgroup of children with high Cu/Zn SOD (Ͼ955 U/g Hb) had a significantly better FMD (p ϭ 0.035). These results suggest that higher circulating Cu/Zn SOD could protect T1DM children and adolescents against endothelial dysfunction. Low Cu/Zn SOD is a potential early marker of susceptibility to diabetic vascular disease.

Research paper thumbnail of The influence of low afterload on the nature of the stress-velocity relationship

Journal of the American College of Cardiology, 1999

Research paper thumbnail of Use of an event recorder in the decision for pacemaker implantation in a child with syncope

European Journal of Pediatrics, 2002

The use of a patient-triggered and automatic event recorder is documented in a 17 month old girl ... more The use of a patient-triggered and automatic event recorder is documented in a 17 month old girl presenting with paroxysmal episodes of loss of consciousness. After pacemaker implant the paroxysmal attacks disappeared.We recommend a more frequent use of the event recorder in the investigation of syncope, even in small children.

Research paper thumbnail of Surgical repair of atrioventricular septal defect with common atrioventricular valve in early infancy

Cardiology in the Young, 2006

The repair of atrioventricular septal defect with a common atrioventricular valve is reconstructi... more The repair of atrioventricular septal defect with a common atrioventricular valve is reconstructive surgery at its best, and hence one of the favourite operations performed by paediatric cardiac surgeons. In the past, the post-operative course from such patients was dominated by the occurrence of pulmonary hypertension crises, which were responsible for significant morbidity and mortality. Nowadays, repair is generally undertaken early in infancy, and this approach has mitigated the problems emanating from pulmonary hypertension. Coupled with a better understanding of the anatomy, and adaptation of the surgical techniques, repair can now be achieved safely at around 2 to 4 months of life, without increasing the risk of postoperative regurgitation across the reconstructed left atrioventricular valve. In this review, we discuss the surgical techniques required for, and clinical results of, such early repair.

Research paper thumbnail of Do parental ratings on cognition reflect neuropsychological outcome in congenital heart disease?

Acta Paediatrica, 2007

To describe the parental view of the cognitive skills of their child with a surgically corrected ... more To describe the parental view of the cognitive skills of their child with a surgically corrected congenital heart disease (CHD) and compare it to objectified cognitive measures in children with CHD 6-12 years postoperatively. Parents completed a questionnaire on several cognitive functions of their child. Children with CHD and healthy controls (n=86, aged 8 years 8 months +/- 1 year 6 months) underwent an abbreviated IQ-testing and a neurodevelopmental assessment. Parents of the children with CHD more frequently indicated lower sustained attention (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), lower divided attention (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), more problems with memory and learning skills (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), and deficient gross motor functioning (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) compared to the parents of healthy controls. Intellectual and neuropsychological assessment revealed a lower estimated full-scale IQ (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), worse sensorimotor functioning (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), and lower performances on language (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), attention/executive functioning (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), and memory…

Research paper thumbnail of A Reassessment of Copy Number Variations in Congenital Heart Defects: Picturing the Whole Genome

Genes

Copy number variations (CNVs) can modulate phenotypes by affecting protein-coding sequences direc... more Copy number variations (CNVs) can modulate phenotypes by affecting protein-coding sequences directly or through interference of gene expression. Recent studies in cancer and limb defects pinpointed the relevance of non-coding gene regulatory elements such as long non-coding RNAs (lncRNAs) and topologically associated domain (TAD)-related gene-enhancer interactions. The contribution of such non-coding elements is largely unexplored in congenital heart defects (CHD). We performed a retrospective analysis of CNVs reported in a cohort of 270 CHD patients. We reviewed the diagnostic yield of pathogenic CNVs, and performed a comprehensive reassessment of 138 CNVs of unknown significance (CNV-US), evaluating protein-coding genes, lncRNA genes, and potential interferences with TAD-related gene-enhancer interactions. Fifty-two of the 138 CNV-US may relate to CHD, revealing three candidate CHD regions, 19 candidate CHD genes, 80 lncRNA genes of interest, and six potentially CHD-related TAD in...

Research paper thumbnail of Sleep apnea and the impact on cardiovascular risk in patients with Marfan syndrome

Molecular Genetics & Genomic Medicine

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmer... more This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.