Ocular Manifestations of Noonan Syndrome: A Prospective Clinical and Genetic Study of 25 Patients

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• 作者：Dorothé ; e C. van Trier ; MD¹ ; Anna M.C. Vos ; MD² ; ³ ; Renske W. Draaijer ; CO² ; Ineke van der Burgt ; MD ; PhD⁴ ; Jos M.Th. Draaisma ; MD ; PhD¹ ; Johannes R.M. Cruysberg ; MD ; PhD² ; ^{j.cruysberg@ru.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：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
• 刊名：Ophthalmology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：123
• 期：10
• 页码：2137-2146
• 全文大小：1562 K

文摘

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.