Cordula M Wolf1, Martin Zenker2, Emma Burkitt-Wright3, Thomas Edouard4, Sixto García-Miñaúr5, Jan Lebl6, Guftar Shaikh7, Marco Tartaglia8, Alain Verloes9, Ingegerd Östman-Smith10. 1. Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. 2. Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany. 3. Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust and University of Manchester, Manchester, UK. 4. Endocrine, Bone Diseases, And Genetics Unit, Children's Hospital, Toulouse University Hospital, RESTORE INSERM UMR1301, Toulouse, France. 5. Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz Research Institute (IdiPAZ), Hospital Universitario La Paz, Madrid, Spain. 6. Department of Pediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic. 7. Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, United Kingdom. 8. Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy. 9. Department of Genetics, APHP-Robert Debré University Hospital and Université de Paris Medical School, Paris, France. 10. Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. Electronic address: ingegerd.ostman-smith@pediat.gu.se.
Abstract
BACKGROUND: The majority of children with Noonan syndrome (NS) or other diseases from the RASopathy spectrum suffer from congenital heart disease. This study aims to survey cardiac care of this patient cohort within Europe. METHODS: A cross-sectional exploratory survey assessing the treatment and management of patients with NS by paediatric endocrinologists, cardiologists and clinical geneticists was developed. This report details responses of 110 participating paediatric cardiologists from multiple countries. RESULTS: Most paediatric cardiologists responding to the questionnaire were associated with university hospitals, and most treated <10 patients/year with congenital heart disease associated with the NS spectrum. Molecular genetic testing for diagnosis confirmation was initiated by 81%. Half of the respondents reported that patients with NS and congenital heart disease typically present <1y of age, and that a large percentage of affected patients require interventions and pharmacotherapy early in life. A higher proportion of infant presentation and need for pharmacotherapy was reported by respondents from Germany and Sweden than from France and Spain (p = 0.031; p = 0.014; Fisher's exact test). Older age at first presentation was reported more from general hospitals and independent practices than from university hospitals (p = 0.031). The majority of NS patients were followed at specialist centres, but only 37% reported that their institution offered dedicated transition clinic to adult services. Very few NS patients with hypertrophic cardiomyopathy (HCM) were reported to carry implantable cardioverter defibrillators for sudden cardiac death prevention. Uncertainty was evident in regard to growth hormone treatment in patients with NS and co-existing HCM, where 13% considered it not a contra-indication, 24% stated they did not know, but 63% considered HCM either a possible (20%) or definite (15%) contraindication, or a cause for frequent monitoring (28%). Regarding adverse reactions for patients with NS on growth hormone therapy, 5/19 paediatric cardiology respondents reported a total of 12 adverse cardiac events. CONCLUSIONS: Congenital heart disease in patients with NS or other RASopathies is associated with significant morbidity during early life, and specialty centre care is appropriate. More research is needed regarding the use of growth hormone in patients with NS with congenital heart disease, and unmet medical needs have been identified.
BACKGROUND: The majority of children with Noonan syndrome (NS) or other diseases from the RASopathy spectrum suffer from congenital heart disease. This study aims to survey cardiac care of this patient cohort within Europe. METHODS: A cross-sectional exploratory survey assessing the treatment and management of patients with NS by paediatric endocrinologists, cardiologists and clinical geneticists was developed. This report details responses of 110 participating paediatric cardiologists from multiple countries. RESULTS: Most paediatric cardiologists responding to the questionnaire were associated with university hospitals, and most treated <10 patients/year with congenital heart disease associated with the NS spectrum. Molecular genetic testing for diagnosis confirmation was initiated by 81%. Half of the respondents reported that patients with NS and congenital heart disease typically present <1y of age, and that a large percentage of affected patients require interventions and pharmacotherapy early in life. A higher proportion of infant presentation and need for pharmacotherapy was reported by respondents from Germany and Sweden than from France and Spain (p = 0.031; p = 0.014; Fisher's exact test). Older age at first presentation was reported more from general hospitals and independent practices than from university hospitals (p = 0.031). The majority of NS patients were followed at specialist centres, but only 37% reported that their institution offered dedicated transition clinic to adult services. Very few NS patients with hypertrophic cardiomyopathy (HCM) were reported to carry implantable cardioverter defibrillators for sudden cardiac death prevention. Uncertainty was evident in regard to growth hormone treatment in patients with NS and co-existing HCM, where 13% considered it not a contra-indication, 24% stated they did not know, but 63% considered HCM either a possible (20%) or definite (15%) contraindication, or a cause for frequent monitoring (28%). Regarding adverse reactions for patients with NS on growth hormone therapy, 5/19 paediatric cardiology respondents reported a total of 12 adverse cardiac events. CONCLUSIONS: Congenital heart disease in patients with NS or other RASopathies is associated with significant morbidity during early life, and specialty centre care is appropriate. More research is needed regarding the use of growth hormone in patients with NS with congenital heart disease, and unmet medical needs have been identified.
Authors: Kirsten M Farncombe; Emily Thain; Carolina Barnett-Tapia; Hamid Sadeghian; Raymond H Kim Journal: BMC Med Genomics Date: 2022-07-15 Impact factor: 3.622