Noonan Syndrome

• Highly variable but most have short stature, mild intellectual disability or developmental delay and
• Characteristic faces
  • High forehead
  • depressed nasal bridge
  • low-set posteriorly rotated ears with fleshy helices

Photos from J Med Genet. 1987;24(1):9-13.

• Refractive Errors: Myopia, hyperopia and astigmatism
• Ptosis
• Hypertelorism
• Downslanting palpebral fissures
• Epicanthal folds
• Keratoconus
• vivid blue or blue-green iris
• Posterior embryotoxin
• Cataract
• Strabismus
• Nystagmus
• Optic nerve hypoplasia
• Optic nerve coloboma

• Webbed or broad neck
• Chiari Malformation
• Hydrocephalus
• Macrocephaly
• Craniosynostosis
• Sensorineural deafness
• Conductive hearing loss
• Giant cell tumors of the jaw
• Sternal deformities
  • pectus carinatum of the superior sternum
  • pectus excavated of the inferior sternum
• Cardiovascular defects
  • Pulmonic stenosis
  • hypertrophic cardiomyopathy
  • ASD
  • VSD
  • lymphatic dysplasia
• Chyptorchidism
• Infertility
• Hematologic abnormalities
  • elevation in PT/PTT
  • abnormal platelets, count and function

• Genetic disorder of the genes in the RAS-MAPK pathway
  • PTPN11 (50%)
  • SOS1 (13%)
  • RAF1 (5%)
  • RIT1 (5%)
  • others
    • KRAS, BRAF, LZTR1, NRAS
• This pathway is important in cellular differentiation and proliferation
• Autosomal dominant inheritance most commonly with 2/3 denovo
• Associated with advanced paternal age

• van Trier, et al. Ocular findings in NS: a retrospective cohort study of 105 patients. European Journal of Pediatrics. 2018;177(8):1293–1298
• van Trier et al. Ocular Manifestations of Noonan Syndrome: A Prospective Clinical and Genetic Study of 25 Patients. Ophthalmology.2016;123(10):2134-2146
• Allanson, JE. Noonan Syndrome. J Med Genet. 1987;24(1):9-13.
• eyeWiki