TY - CHAP M1 - Book, Section TI - Noonan Syndrome and Related Disorders A1 - Weismann, Constance A1 - Gelb, Bruce D. A2 - Murray, Michael F. A2 - Babyatsky, Mark W. A2 - Giovanni, Monica A. A2 - Alkuraya, Fowzan S. A2 - Stewart, Douglas R. Y1 - 2014 N1 - T2 - Clinical Genomics: Practical Applications in Adult Patient Care AB - Disease summary:Noonan syndrome is the “prototype” of a spectrum of clinical entities that during the last few years was found to be caused by mutations in various genes along the RAS-MAPK pathway. This pathway is well known for its role in cancer. There is a strong correlation between the clinical phenotype and the genetic defect, which so far is unique to this disease entity.Features: congenital heart disease (especially pulmonary stenosis), hypertrophic cardiomyopathy, facial dysmorphia, webbed neck, lymphedema, short stature, mild developmental delay, delayed onset of puberty, cryptorchidism, male infertility, bleeding disorders, malignancies, malrotation, hepatosplenomegaly, renal anomalies, ophthalmologic and dermatologic problems to a variable degreeIncidence: 1:1000-1:2500Disease genes:PTPN11(41%), SOS1(11%), RAF1(5%), BRAF(1%), KRAS(1%), NRAS(<1%), SHOC2(2%)Hereditary basis:Autosomal dominant, de novo mutation; complete penetrance, variable phenotypeDifferential diagnosis:Noonan syndrome with multiple lentigines: formerly known as LEOPARD syndrome with major features including lentigines, echocardiogram (ECG) conduction anomalies, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness, same cardiac defects as Noonan syndrome, but higher prevalence of hypertrophic cardiomyopathyCardiofaciocutaneous syndrome: more severe variant of Noonan syndrome with more coarse facial features, hyperkeratotic skin, curly hair and sparse eyebrows and eyelashes, severe developmental delay, hypotonia, seizures, structural brain anomaliesCostello syndrome: more severe variant of Noonan syndrome with prenatal overgrowth and postnatal growth delay, more coarse facial features, benign cutaneous papillomata, and 15% childhood incidence of solid tumors (rhabdomyosarcoma, neuroblastoma, bladder carcinoma)Neurofibromatosis-Noonan syndrome: features of both neurofibromatosis type 1 and Noonan syndromeLegius syndrome: axillary freckling, café-au-lait spots, macrocephaly, and facial dysmorphism resembling Noonan syndrome SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessmedicine.mhmedical.com/content.aspx?aid=1102706657 ER -