Page 65 - Clinical variability in Noonan syndrome with emphasison ear and eye

OCULAR FINDINGS IN NOONAN SYNDROME: A RETROSPECTIVE STUDY OF 105 PATIENTS
One of them was diagnosed with visual impairment due to congenital optic nerve hypoplasia and the other 2 were diagnosed with high corneal astigmatism resulting in keratoconus. In retrospect, visual complaints were noticed earlier in childhood.
External ocular features were frequently found without ophthalmological examination, mostly described by pediatricians and clinical geneticists. The findings included hypertelorism (63 patients), ptosis (55 patients), and downslanting palpebral fissures (39 patients). Other ophthalmological abnormalities included strabismus (40 patients) and nystagmus (16 patients). Anterior segment abnormalities included keratoconus (4 patients), different types and densities of cataract (3 patients), and posterior embryotoxon (2 patients). The posterior ocular segment showed abnormalities of the optic nerve head (ONH), including ONH excavation (8 patients), ONH coloboma (1 patient), ONH hypoplasia (1 patient), and ANH paleness (8 patients) diagnosed as optic nerve atrophy in 5 of them.
In 50 patients, a PTPN11 mutation was found with genetic testing. These patients were diagnosed with ocular manifestations in the different categories including refractive errors, external ocular features, ocular alignment and motility, and abnormalities in the anterior and posterior ocular segment. No visual impairment was found in the patients with a PTPN11 mutation. In the NS patients due to a SOS1 mutation, the most frequent ocular findings were hypertelorism and ptosis. We also found prominent corneal nerves. In the group with NS due to a RAF1 mutation, we found 1 patient with a unilateral exudative retinopathy (Coats disease).
Discussion
In 2016, we published our prospective study of ocular manifestations in 25 Noonan syndrome patients (20). The present retrospective cohort shows a larger group, with more heterogeneity in the patients and more information on the causative molecular findings. This is a retrospective cohort, and therefore we have missing data and there might be a response bias. Nevertheless, it is important to show a larger group of Noonan syndrome patients including their genetic results, and we hypothesized that we could confirm the ocular findings from our prospective cohort.
Visual impairment (binocular BCVA < 0.3) was seen in 7 patients. The cause of the visual impairment is probably a developmental disorder of the optic nerves, presenting with optic nerve atrophy and optic nerve hypoplasia, associated with nystagmus and
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