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noonan [2022/09/25 23:47] – created Scott Larsonnoonan [2025/06/14 04:17] (current) – [Resources] Scott Larson
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 ====== Noonan Syndrome ====== ====== Noonan Syndrome ======
 +====Main Features====
 +  * 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
 +<WRAP round box>
 +{{::noonan_syndrome.jpg?|}}
 +{{::noonan_syndrome_child.jpg?|}}
 +Photos from [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1049850/pdf/jmedgene00075-0018.pdf|J Med Genet. 1987;24(1):9-13.]]
 +</WRAP>
  
 +====Eye Findings====
 +  * 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
 +====Other Findings====
 +  * 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 
 +====Etiology====
 +  * 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 
 +====Resources====
 +  - [[https://doi.org/10.1007/s00431-018-3183-1| van Trier, et al. Ocular findings in NS: a retrospective cohort study of 105 patients. European Journal of Pediatrics. 2018;177(8):1293–1298]]
 +  - [[https://www.aaojournal.org/article/S0161-6420(16)30594-2/fulltext|van Trier et al. Ocular Manifestations of Noonan Syndrome: A Prospective Clinical and Genetic Study of 25 Patients. Ophthalmology.2016;123(10):2134-2146]]
 +  - [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1049850/pdf/jmedgene00075-0018.pdf|Allanson, JE. Noonan Syndrome. J Med Genet. 1987;24(1):9-13.]]
 +  - [[https://eyewiki.aao.org/Noonan_Syndrome#Ophthalmic_presentation|eyeWiki]]
 +
 +{{tag>syndrome}}