Page 19 - Clinical variability in Noonan syndrome with emphasison ear and eye

Thesis outline
The aim of this thesis is to study different clinical aspects of Noonan syndrome. Although the diagnosis of Noonan syndrome can be confirmed with genetic analysis in 70-80% of the cases, it remains predominantly a clinical diagnosis. However, the great variety of features and phenotypes can make it difficult to diagnose Noonan syndrome. Not all features described in Noonan syndrome are included in the scoring systems. Additionally, there are different phenotypes described within the same family and a changing phenotype in the older patient is mentioned.
In Chapter 2 we focus on the variable phenotypic expressions within a single large Noonan syndrome family. In this family a new pathogenic SOS1 mutation was found. Clinical data were collected in three different generations. This was the first time that phenotypic findings within a single large Noonan syndrome family due to SOS1 mutation were published.
Furthermore, studies were focused on the ocular features in Noonan syndrome. Ocular features are less frequently described, but they occur very common. The external ocular abnormalities, including hypertelorism, ptosis, and epicanthic folds, are part of the facial characteristics. Facial features are used in the clinical scoring system, facial characteristics are scored as typical of suggestive for Noonan syndrome. Other ocular abnormalities described in literature include refractive errors, strabismus, amblyopia and abnormalities in the anterior and posterior segment of the eye. In Chapter 3 we describe a prospective clinical and genetic study in 25 Noonan syndrome patients on ocular abnormalities. All patients underwent extensive ocular examinations and genotypes were correlated with phenotypes. Ocular abnormalities were classified in ‘vision and refraction’, ‘external ocular features’, ‘strabismus and ocular motility’, ‘anterior segment’, ‘posterior segment’, and ‘intraocular pressure’. In Chapter 4 we describe a large retrospective cohort of ocular features. In total 103 patients were included, which is the largest cohort of ocular features in Noonan syndrome. The primary outcome measures were vision and refraction. For the secondary outcome measures all ocular abnormalities were included and we looked at delay between diagnosis and the initial ocular examinations. The aim of the study was to show the frequency of ocular manifestations and importance of early ocular examinations in Noonan syndrome patients.
In Chapter 5 external ear anomalies and hearing impairment in Noonan syndrome were studied. In this cohort 97 patients were included and both data on facial features
INTRODUCTION
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