The estimated incidence is at ~1 in 1000-2500 10. As individuals have normal number of chromosomes, both males and females can be affected.
An immense number of clinical features have been described which can be present at varying degrees. These include:
- generalized musculoskeletal
- renal anomalies
- dilated renal pelvices 6,9
The inheritance is autosomal dominant although a significant proportion of cases are sporadic 8. Many genes have been implicated, the most common being the PTPN11 gene which encodes for SHP2, which results in an inability to inactivate SHP2 causing increased signaling of the Ras/MAPK pathway. However. other genes that may be less commonly implicated including SOS1, KRAS, RAF1, NRAS, and SHOC2 10. Because of its effect in amplifying the Ras/MAPK pathway, it is considered to be a RASopathy 10.
Early 1st trimester ultrasound may show nuchal edema or a cystic hygroma similar to that of Turner syndrome. With subsequent scanning, some of the above individual clinical features may be present sonographically.
History and etymology
It is named after Jacqueline A Noonan (1928-fl 2019), an American pediatric cardiologist 11.
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- 4. Schinkel AF, Vos J. Biventricular hypertropic obstructive cardiomyopathy in Noonan syndrome. Int. J. Cardiol. 2007;115 (1): e22-3. doi:10.1016/j.ijcard.2006.07.076 - Pubmed citation
- 5. Ho WL, Wang JK, Li YW. Radiological features of late-onset lymphoedema in Noonan's syndrome. Pediatr Radiol. 2003;33 (3): 200-2. doi:10.1007/s00247-002-0768-6 - Pubmed citation
- 6. George CD, Patton MA, El sawi M et-al. Abdominal ultrasound in Noonan syndrome: a study of 44 patients. Pediatr Radiol. 1993;23 (4): 316-8. - Pubmed citation
- 7. Rush WJ, Donnelly LF, Brody AS et-al. "Missing" sternal ossification center: potential mimicker of disease in young children. Radiology. 2002;224 (1): 120-3. doi:10.1148/radiol.2241011202 - Pubmed citation
- 8. Entezami M, Albig M, Knoll U et-al. Ultrasound Diagnosis of Fetal Anomalies. Thieme. (2003) ISBN:1588902129. Read it at Google Books - Find it at Amazon
- 9. Allanson JE, Roberts AE. Noonan Syndrome. 2001 Nov 15 [Updated 2016 Feb 25]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1124/
- 10. Rauen KA. The RASopathies. Annual review of genomics and human genetics. 14: 355-69. doi:10.1146/annurev-genom-091212-153523 - Pubmed
- 11. Noonan JA, Kappelgaard AM. The efficacy and safety of growth hormone therapy in children with noonan syndrome: a review of the evidence. (2015) Hormone research in paediatrics. 83 (3): 157-66. doi:10.1159/000369012 - Pubmed