Page 14 - Clinical variability in Noonan syndrome with emphasison ear and eye

CHAPTER 1
Craniofacial features
Characteristic facial dysmorphisms play an important role in diagnosing Noonan syndrome and have a dominant function in the scoring system. Changes in phenotype are described when the patients get older (32). The facial appearance is most characteristic during infancy with a large head and forehead, wide-spaced eyes, downslanting palpebral fissures, epicanthic folds, low-set posteriorly rotated ears, high arched palate, micrognathia and short neck with excess nuchal skin and low posterior hairline. With the age the shape of the face becomes more triangular and during childhood the face can lack expression and looks myopathic with prominent eyes and ptosis. By adolescence, the neck is less short, eyes are less prominent, and the face is in the shape of an inverted triangle. Adults can have unremarkable faces but other adult Noonan syndrome patients can present with typical features including ptosis, hypertelorism, low-set ears and webbed neck (14,16,31-33).
Cardiovascular features
Cardiovascular abnormalities in Noonan syndrome occur in up to more than 80% (31,34, 35). The most common congenital heart anomaly is the pulmonary valve stenosis and the valve is often dysplastic. Furthermore, a variety of cardiac abnormalities are described including the atrial septal defect, ventricular septal defect and hypertrophic cardiomyopathy (13,14,26,36). Less frequent heart defects include coarctatio aortae, tetralogy of Fallot, atrioventricular canal, aortic stenosis, patent ductus arteriosus, coronary artery anomaly and mitral valve anomaly (14,34,36,37). The electrocardiogram (ECG) in Noonan syndrome is characterized by left axis deviation, wide QRS complexes and small R waves in the left precordial lead (14,34,35,37,38).
Psychological health and cognitive issues
There is a wide range in the level of intelligence. The average level of the mean full-scale intelligence quotient (IQ) is 85 and this is 10 points less than unaffected family members. Intellectual disability and learning disabilities are usually mild and described in 15-35% of the patients (39,40). Delay in language development and articulation abnormalities are found frequently (39-41). Behavioral issues described in Noonan syndrome are attention deficits, social problems, irritability, anxiety, fidgety, poor coordination and eating problems. Most Noonan patients are raised by parental support alone without other interventions, finish high school and have paying jobs (26,41,42,43). Cognitive problems and difficulties in processing affective information are found in Noonan syndrome including alexithymia and deficiencies in social and emotional recognition (44,45). Limited literature is available on psychological and psychiatric problems in Noonan syndrome. In one study with NS adults, depression is described in 49% (46).
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