Purpose
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–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 nonglaucomatous optic disc excavation (20%),
relatively low (<10 mmHg) intraocular pressure (22%), and optic nerve hypoplasia (4%).
Mutations were established in 22 patients: 19
PTPN11 mutations (76%), 1
SOS1 mutation, 1
BRAF mutation, and 1
KRAS mutation. The patient with the highest number of prominent corneal nerves had an
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 3 ocular features (range, 3–13; mean, 7),
including at least 1 external ocular feature in more than 95% of the patients.
Conclusions
Noonan syndrome is a clinical diagnosis with multiple genetic bases associated with
an extensive variety of congenital ocular abnormalities. Ocular features of NS are
characterized by 1 or more developmental anomalies of the eyelids (involving the position,
opening, and closure) associated with various other ocular abnormalities in childhood,
including amblyopia, myopia, astigmatism, strabismus, limited ocular motility, prominent
corneal nerves, and posterior embryotoxon.
Abbreviations and Acronyms:
C/D ( cup-to-disc ratio), D ( diopters), F ( female), IOP ( intraocular pressure), LE ( left eye), M ( male), NR ( feature not recorded), NS ( Noonan syndrome), NVC ( normal visual contact), ONH ( optic nerve head), ONHH ( optic nerve head hypoplasia), Ras/MAPK ( Ras/mitogen-activated protein kinase pathway), RE ( right eye), SD OCT ( spectral-domain optical coherence tomography), SEA ( spherical equivalent of ametropia), TRV ( tortuous retinal vessels)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: August 09, 2016
Accepted:
June 24,
2016
Received in revised form:
June 16,
2016
Received:
January 17,
2016
Footnotes
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Author Contributions:
Conception and design: van Trier, Vos, Draaijer, van der Burgt, Draaisma, Cruysberg
Analysis and interpretation: van Trier, Vos, Draaijer, van der Burgt, Draaisma, Cruysberg
Data collection: van Trier, Vos, Draaijer, van der Burgt, Draaisma, Cruysberg
Obtained funding: none
Overall responsibility: van Trier, Vos, Draaijer, van der Burgt, Draaisma, Cruysberg
Identification
Copyright
© 2016 by the American Academy of Ophthalmology
