**2.9. Trisomy 21 (Down's syndrome)**

The most familiar syndrome to cardiologists is Down's syndrome is trisomy 21 in which there is a complete extra copy of chromosome 21 in 94% of cases. Less commonly, partial trisomy of chromosome 21(6% overall), is present owing to a chromosomal translocation or mosaicism. Common findings include: hypotonia, global developmental delays and moderate intellectual disability, microbrachycephaly, small ears, mouth and nose, protruding tongue, up-slanting eyes with epicanthal folds, transverse palmar creases, and sparse hair. Skeletal anomalies include fifth finger clinodactyly, brachydactyly, a gap between first and second toes, atlantoaxial instability, hypoplastic pelvis, and joint laxity. Additional problems involve the visual, auditory, endocrine, hematologic, reproductive, and gastrointestinal systems. Almost half of live born Down's syndrome individuals have a CHD, approximately 40% of whom have a complete atrioventricular septal defect (also known as atrioventricular canal defect or endocardial cushion defect) [75]. The association of Down syndrome and atrioventricular septal defects is underscored by the fact that approximately 75% of patients with a complete atrioventricular septal defect have Down syndrome. Other common CHDs include secundum atrial septal defect, conoventricular and muscular ventricular septal defect, tetralogy of Fallot (with and without atrioventricular septal defect), and hemodynamically significant patent ductus arteriosus [75]. The overall prevalence of Down syndrome is 1 in 700 live births [76].

The risk of conceiving a child with aneuploidy (an extra chromosome), including Down's syndrome increases with maternal age. Overall survival has improved, although prenatally diagnosed CHDs and/or growth retardation may predict a poorer outcome [77]. The largest survey study to date reported that the frequency of CHDs in patients with Down syndrome mosaicism was similar to the complete trisomy 21 comparison group (∼42 and 50%) [78]. Prenatal screening programs providing risk figures for Down's syndrome in individual pregnancies are widely available. Definitive testing involves an invasive procedure, either chorionic villus sampling or amniocentesis, and a rapid result can be obtained by FISH. The diagnosis is suspected clinically and confirmed by karyotyping. The risk of recurrence is about 1% for women aged 39 or less [61].

### **2.10. Trisomy 18 (Edward's syndrome)**

It is a rare syndrome with a prevalence of 1 in 6000, and a male to female ratio of 1:4. Majority of this syndrome is caused by maternal meiotic non-disjunction. Greater than 90% of cases have trisomy 18, the remainder having trisomy 18-mosaicism or partial trisomy of 18q. All cases have cardiac anomalies: mal-aligned VSD is the most common finding; ASD and patent ductus arteriosus are also common findings in these patients. Polyvalvular dysplasia, usually without stenosis or regurgitation, is usually present [79, 80]. Karyotyping is indicated if prenatal screening detected structural anomalies on ultrasound. The risk of recurrence is low, at around 1 in 200 [61].
