Congenital Heart Defect Syndromes GROUP I: ECTOMESENCHYMAL TISSUE MIGRATION ABNORMALITIES Ventricular septal defect, subarterial Trisomy 18 Deletion 22q11.2 (DiGeorge/VCF syndrome) Kabuki syndrome Double-outlet right ventricle Trisomy 18 Deletion 22q11.2 (DiGeorge/VCF syndrome) VACTERL Association Tetralogy of Fallot Down syndrome Trisomy 18 Trisomy 13 Deletion 8p23 Deletion 22q11.2 (DiGeorge/VCF syndrome) Microdeletion 1q21.1 CHARGE syndrome Alagille syndrome VACTERL association Oculo-auriculo-vertebral spectrum (Goldenhar) Tetralogy of Fallot with pulmonary atresia Deletion 22q11.2 (DiGeorge/VCF syndrome) CHARGE syndrome Aortopulmonary window VACTERL association CHARGE syndrome Truncus arteriosus Deletion 22q11.2 (DiGeorge/VCF syndrome) Duplication 8q (interstitial) “Distal” deletion 22q11.2 CHARGE syndrome GROUP II: INTRACARDIAC BLOOD FLOW DEFECTS Ventricular septal defect, perimembranous Trisomy 13 Trisomy 18 Left-sided obstruction defects (bicuspid aortic valve, aortic coarctation, aortic valve Turner syndrome stenosis, interrupted aortic arch type A, hypoplastic left heart, aortic atresia, mitral Deletion 11q (Jacobsen atresia) syndrome) Williams syndrome Noonan syndrome/RASopathies Kabuki syndrome Atrial septal defect, ostium secundum Down syndrome Trisomy 18 Trisomy 13 Holt-Oram syndrome Noonan syndrome/RASopathies Kabuki syndrome Pulmonary valve stenosis Deletion 4p (WolfHirschhorn syndrome) Noonan syndrome/RASopathies Williams syndrome GROUP III: CELL DEATH ABNORMALITIES Ventricular septal defect, muscular Ebstein malformation of the tricuspid valve GROUP IV: EXTRACELLULAR MATRIX ABNORMALITIES Atrial septal defect, ostium primum, Ventricular septal defect, type III (posterior “atrioventricular canal” type) Atrioventricular canal Dysplastic aortic or pulmonary valve GROUP V: ABNORMAL TARGETED GROWTH DEFECTS Anomalous pulmonary venous return (partial) Anomalous pulmonary venous return (total) Cor triatriatum Atrial septal defect, sinus venosus Holt-Oram syndrome Trisomy 18 Trisomy 13 Microdeletion 1p36 Deletion 8p23 Deletion 18q (terminal) Down syndrome Deletion 8p23 Deletion 3p25 Noonan syndrome Ellis-van Creveld syndrome Oral-Facial-Digital syndrome Smith-Lemli-Opitz syndrome CHARGE syndrome Tetrasomy 22 (cat-eye syndrome) Trisomy 22 Turner syndrome Holt-Oram syndrome Townes-Brocks syndrome Oculo-auriculo-vertebral spectrum (Goldenhar syndrome) VACTERL association Genetic Counseling Clinical evaluation of patients with CHD should include reconstruction of family history, phenotypic evaluation, and screening for extracardiac malformations If a specific syndrome is suspected, the related chromosomal testing (karyotype or fluorescence in situ hybridization or array comparative genomic hybridization [CGH] analysis) or the related molecular analysis (sequencing by Sanger testing or next-generation sequencing) should be performed Chromosomal analysis and array CGH are indicated also in syndromic patients without a specific diagnostic suspicion Genetic counseling to families can then be performed according to the recurrence risks related to the specific syndrome Management of Congenital Heart Defects in Genetic Syndromes In the past, treatment of CHD associated with genetic syndromes had been a debated issue from ethical and technical points of view.8,12 Nowadays we know that recognizing the specific cardiovascular and extracardiac risk factors associated with each syndromic condition will facilitate management, early detection of clinical problems, and finally improve the surgical results in this different group of patients.9,18 The multidisciplinary management of these complex children represents the last challenge for pediatric cardiologists and cardiac surgeons The development of syndrome-based diagnostic and perioperative protocols must guide the prophylactic actions and ultimately improve the specific outcomes for the more frequently encountered genetic syndromes.9 The early and accurate cardiac care of these children improves their survival, contributes to the reduction of the handicap, and improves the quality of life of the patients and their families Moreover, the genetic studies and the clinical care of the complex cases with CHD associated with genetic syndromes have also improved our knowledge of pathogenesis and our skills in treating all patients with syndromic and nonsyndromic types of cardiac defects ... different group of patients.9,18 The multidisciplinary management of these complex children represents the last challenge for pediatric cardiologists and cardiac surgeons The development of syndrome-based diagnostic and perioperative protocols must guide the prophylactic actions and ultimately