Page 64 - Clinical variability in Noonan syndrome with emphasison ear and eye

CHAPTER 4
The primary outcome of this study was the presence of ocular abnormalities in a NS population and ophthalmological, pediatric, and genetic data were used. The ocular outcomes were linked to the genotypes. In the patients without a known mutation, there were either no genetic analyses done or (until now) no mutations identified after testing (a selection of) the NS genes. Since NS is a clinical diagnosis, and in 15–20% of the patients no causative mutation is known, we included all patients in our study. We included all registered ocular abnormalities in the categories vision and refraction, external ocular features, ocular alignment and motility, anterior ocular segment, and posterior ocular segment. No statistical analyses were used and the results were descriptive.
Results
There were 128 patients who gave permission for the use of their data. In 14 patients, no ophthalmological data were available and 9 of 128 patients (7%) were excluded because they never visited an ophthalmologist. A total of 105 patients were included and 68 of them were younger than 18 years old. The median age of the cohort was 12 years, with a range between 1 and 60 years. Genetic examinations showed a causative mutation for NS in 78 patients. The ocular features and gene mutations of the 105 NS patients are shown in Table 1. Seven patients were visually impaired, defined as binocular best-corrected visual acuity (BCVA) lower than 0.3, mainly attributable to binocular optic nerve abnormalities and manifest nystagmus These patients had a mutation in the RAF1gene (1 patient), SHOC2 gene (2 patients), or KRAS gene (2 patients); in 1 patient, no mutation was identified after genetic testing and another patient had no genetic analysis. These 7 patients are shown comprehensively in Table 2. Amblyopia, defined as visual loss caused by visual deprivation (e.g., by strabismus, refractive errors, cataract, or ptosis) in childhood, was reported in 28 patients.
Refractive errors, defined as spherical equivalent of ametropia (SEA) of one diopter or more, showed myopia (25 patients), hyperopia (39 patients), and astigmatism (35 patients). High refractive errors, defined as 5 diopters or more, were found for myopia in 5 patients, for hyperopia in 2 patients, and for astigmatism in 3 patients, mainly associated with a causative PTPN11 mutation.
In 3 patients with a delay in first presentation to an ophthalmologist, ocular abnormalities were found. All 3 of them were diagnosed with Noonan syndrome early in childhood. They were referred to an ophthalmologist for the first time at the ages of 17 to 20 years.
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