Page 42 - Clinical variability in Noonan syndrome with emphasison ear and eye

CHAPTER 3
Abstract
Objective
To determine the full spectrum of ocular manifestations in patients with Noonan syndrome (NS).
Design
Prospective cross-sectional clinical and genetic study in a tertiary referral center.
Participants
Twenty-five patients with NS (mean age, 14 years; range, 8 months to 25 years), clinically diagnosed by validated criteria.
Methods
All patients were examined by the same team following a detailed study protocol. Genetic analyses were performed in 23 patients.
Main Outcome Measures
Ocular abnormalities of vision and refraction, external ocular features, ocular position and motility, anterior segment, posterior segment, and intraocular pressure.
Results
Ocular features of vision and refraction were amblyopia (32%), myopia (40%), and astigmatism (52%). External ocular features were epicanthic folds (84%), hypertelorism (68%), ptosis (56%), high upper eyelid crease (64%), lower eyelid retraction (60%), abnormal upward slanting palpebral fissures (36%), downward slanting palpebral fissures (32%), and lagophthalmos (28%). Orthoptic abnormalities included strabismus (40%), abnormal stereopsis (44%), and limited ocular motility (40%). Anterior segment abnormalities included prominent corneal nerves (72%) and posterior embryotoxon (32%). Additional ocular features were found, including non-glaucomatous optic disc excavation (20%), relatively low (< 10 mm Hg) intraocular pressure (22%), and optic nerve hypoplasia (4%). Mutations were established in 22 patients: 19 PTPN11 mutations (76%), one SOS1 mutation, one BRAF mutation and one KRAS mutation. The patient with the highest number of prominent corneal nerves had a SOS1 mutation. The patient with the lowest visual acuity, associated with bilateral optic nerve hypoplasia, had a BRAF mutation. Patients with severe ptosis and nearly total absence of levator muscle function had PTPN11 mutations. All patients showed at least three (range, 3-13; mean, 7) ocular features, including at least one external ocular feature in more than 95 percent of the patients
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