Page 12 - Clinical variability in Noonan syndrome with emphasison ear and eye

CHAPTER 1
History
In 1883, Kobylinkski described the first patient with clinical features compatible with Noonan syndrome (1). In his report ‘Ueber eine flughautahnliche Ausbreiting am Halse’ he reported a 20-year old male with marked webbing of the neck, which was a defining characteristic in early reports. In 1930, Ullrich described patients with webbed neck and short stature (2). In retrospect they represented patients with both Turner syndrome and Noonan syndrome. Henry Turner presented older patients with sexual infantilism, short stature, webbed neck and cubitus valgus (3). Turner syndrome was later recognized as a sex-linked disease. Ullrich recognized both females and males with a similar phenotype, which he named ‘Bonnevie-Ullrich’ (after Bonnevie’s work on mice) (4). As a result of these publications, the term ‘Ullrich-Turner syndrome’ was born. Furthermore the terms ‘male Turner syndrome’ or ‘Turner syndrome with normal chromosomes’ were introduced (5,6,7,8).
In 1963, Jacqueline Noonan (pediatric cardiologist) performed a clinical study on associated non-cardiac anomalies in children with congenital heart disease (9). In nine patients characteristic facial features, including hypertelorism, low-set posteriorly rotated ears, downslanting palpebral fissures and ptosis, were identified. Furthermore pulmonary stenosis, short stature, chest deformity and undescended testes in males were described. Chromosome studies were normal. Five years later she supplemented an additional ten patients to the earlier described group of nine. The group was named ‘Hypertelorism with Turner phenotype’ (10). As Jacqueline Noonan was the first to describe this group, John Opitz suggested the eponym Noonan syndrome and in 1968 this eponym was used for the first time (11,12).
Clinical characteristics
Noonan syndrome has a variable phenotype and it is diagnosed clinically by a combination of features. Facial features play an important role in diagnosing Noonan syndrome. Other characteristics include congenital heart defect, short stature, chest wall deformity, cryptorchidism, skeletal abnormality, lymphatic dysplasia and developmental delay (13-16). Different mutations are described but Noonan syndrome still is a clinical diagnosis. Van der Burgt developed a scoring system, which was updated in 2007 (16). These criteria help in the diagnosing process but are also of value in the research domain. The scoring system is embedded in the clinical guideline for Noonan syndrome that was published in 2010 (14, 17).
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