**2.7. Alagille syndrome**

Alagille syndrome was originally defined as the presence of bile duct paucity on liver biopsy in conjunction with three of the following five findings: cholestasis, congenital heart disease, skeletal or ocular abnormalities or typical facial features which give the face an inverted triangle appearance (broad forehead, deep set eyes, rounded tip and pear like shape of the nose and pointed chin) [63, 64]. Alagille syndrome is an autosomal dominant condition with high penetrance (94%) and variable expressivity, which is the result of mutations or deletions in the JAG-1 gene (locus 20p11.2). De novo mutations occur in 50–60% of cases [65, 66]. Alagille syndrome is now recognized to be a genetically heterogeneous disorder. Approximately 5% of the patients with a chromosomal deletion involving one copy of the entire JAG1 gene, whereas most will have various intragenic JAG1 mutations [67].

The prevalence is 1 in 70,000 to 100,000 live births [68]. Cardiovascular anomalies are present 90% of the cases [68]. The most common cardiac lesion is pulmonary artery branch stenosis (PABS), tetralogy of Fallot (in up to 10% of cases), pulmonary stenosis and coarctation of the aorta [69]. If the mutation or deletion is identified in a parent, prenatal diagnosis is available on samples from chorionic villus sampling or amniocentesis. It is, however, not possible to predict the severity of the phenotype in an identified fetus [69]. The diagnosis needs to be considered in a baby with a cardiac defect and prolonged jaundice, and with at least three of the recognized features [61]. Alagille syndrome has a mortality rate around 10–20%. The risk of recurrence is low in the absence of a positive family history, but it is 50% if there is an affected parent [61, 68].

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

Congenital Heart Disease: Genetic Aspect and Prenatal and Postnatal Counseling

http://dx.doi.org/10.5772/intechopen.72486

419

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,

The process of prenatal counseling and its recommendations, should be based on the best available current evidenced-based practice. This process may require more than one consultation due to its emotional nature of the situation and complexity of information being delivered. Any prenatal counseling should include the suspected cardiac diagnosis in detail based on the fetal ultrasound findings. The purpose of this is to give the most accurate and up to date information about the prognosis and outcome of the pregnancy and fetus. This will allow

In regards to the screening ultrasound, all relevant information available needs to be given prior to the examination. Ideally, all prescreening information should be made available to the referring hospital. It needs to be emphasized that not all cardiac defects can be detected in the initial ultrasound examination [81, 82]. Whenever a cardiac abnormalities is detected this will require prompt referral for specialist examination. The general screening detection rates for congenital heart disease (CHD) vary between 14–45% [83]. A standard 4-chamber view can detect 40–50% of major CHD [84], while a 4-chamber view and outflow tract detects 70–80% of major CHD [85]. In dedicated fetal cardiac centers the diagnostic accuracy is close to 100% [86, 87]. Thereafter a referral for specialized echocardiography and cardiology consultation should be done. If there are suspected cardiac abnormalities on the screening fetal ultrasound, there should be minimal time delay in referring the mother for a fetal echocardiogram

the parents to make the best-informed decision for them and the fetus.

about 1% for women aged 39 or less [61].

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

at around 1 in 200 [61].

**3. Counseling**

**3.1. Prenatal**
