Paeds Vivas · genetics-dysmorphology-and-metabolism
Noonan syndrome and RASopathies — branching viva
Branching viva on Noonan syndrome and the RASopathies: recognising the shared RAS/MAPK pathway phenotype, distinguishing Noonan from Costello and CFC by gene and cardiac profile, confirming with a multigene panel, and applying the genotype-aware surveillance schedule.
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Target exams
RACP DCEMRCPCH ClinicalRCPSC Pediatrics
Prompt
Postnatal ward: a newborn with a Turner-like phenotype (triangular face, hypertelorism, ptosis, webbed neck, widely spaced nipples), a 46,XY karyotype, and an echocardiogram showing pulmonary valve stenosis with dysplastic leaflets. The examiner asks: what is the unifying diagnosis, how do you confirm it, and what is the surveillance plan — then branches to the same child presenting with a bleeding episode before dental extraction, and finally to a different infant with coarse features, deep creases, and hypertrophic cardiomyopathy.
Opening question
A newborn on the postnatal ward has a Turner-like phenotype with a 46,XY karyotype and pulmonary valve stenosis. What is the unifying diagnosis, and why does the molecular confirmation strategy matter beyond the clinical label? [1] [2]
References5ShowHide
- [1]Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet, 2013.PMID 23312968
- [2]Tartaglia M, Mehler EL, Goldberg R, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet, 2001.PMID 11704759
- [3]Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics, 2010.PMID 20876176
- [4]Niihori T, Aoki Y, Okamoto N, et al. HRAS mutants identified in Costello syndrome patients can induce cellular senescence. J Hum Genet, 2011.PMID 21850009
- [5]Gelb BD, Cavé H, Dillon MW, et al. ClinGen's RASopathy Expert Panel consensus methods for variant interpretation. Genet Med, 2018.PMID 29493581