title: Ocular Manifestations of Noonan Syndrome: A Prospective Clinical and Genetic Study of 25 Patients.
abstract: To determine the full spectrum of ocular manifestations in patients with Noonan syndrome (NS).
  
  
  
  Prospective cross-sectional clinical and genetic study in a tertiary referral center.
  
  
  
  Twenty-five patients with NS (mean age, 14 years; range, 8 months-25 years) clinically diagnosed by validated criteria.
  
  
  
  All patients were examined by the same team following a detailed study protocol. Genetic analyses were performed in 23 patients.
  
  
  
  Ocular abnormalities of vision and refraction, external ocular features, ocular position and motility, anterior segment, posterior segment, and intraocular pressure.
  
  
  
  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.
  
  
  
  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.
authors: Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Dorothée C
authors: DC
authors: van Trier
authors: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Ophthalmology, Rijnstate Hospital, Arnhem, The Netherlands.
authors: Anna M C
authors: AM
authors: Vos
authors: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Renske W
authors: RW
authors: Draaijer
authors: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Ineke
authors: I
authors: van der Burgt
authors: Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Jos M Th
authors: JM
authors: Draaisma
authors: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: j.cruysberg@ru.nl.
authors: Johannes R M
authors: JR
authors: Cruysberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003941:Diagnostic Techniques, Ophthalmological; D005128:Eye Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009634:Noonan Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D011446:Prospective Studies; D055815:Young Adult