**2. Genetic syndromes**

Genetic syndromes are defined as a consistent pattern of malformation caused by a genetic alteration. A malformation syndrome consists of multiple structural defects that are thought to be due to a single cause, even if the suspected cause has not yet been identified [24].

#### **2.1. Noonan's syndrome**

The Noonan phenotype includes characteristic facies (ptosis, hypertelorism, low set ears, and low posterior hairline), short stature, webbed neck and cardiac anomalies. Noonan syndrome occurs in I per 1000 to 1 per 2500 live births diagnosed clinically [25–27]. Cardiac anomalies are present in 80% of individuals [28]. In 70–80% of cases, the lesion is pulmonary stenosis, usually due to dysplastic pulmonary valve leaflets [25]. In 20–30% of affected individuals, the cardiac anomaly is in the form of a cardiomyopathy, which may be present at birth or develop later [25, 29].

Most of the cases of Noonan syndrome are sporadic, although families with a pattern of autosomal dominant inheritance are well known. Mutation in the gene PTPN11 on the chromosome locus 12q24.1 was noted in 45% of cases. Gelb et al. demonstrated a positive association between those with PTPN11 mutations and pulmonary stenosis [30]. Maternal transmission of the gene is three times more common than paternal transmission [28]. Prenatal testing can be established by chorionic villus sampling or amniocentesis, fetal ultrasound can show increased nuchal translucency, increased nuchal thickening, pleural effusions and generalized hydrops [31]. Developmental delays are always present, and intellectual disability is typically in the range of moderate mental retardation [28, 29]. Diagnosis in newborn baby may be difficult unless the cardiac lesion is severe, with either significant pulmonary stenosis or severe cardiomyopathy. The diagnosis can only be confirmed genetically if there is an affected parent with a recognized mutation [25, 27, 30].
