A 6-year-old boy is evaluated for short stature, ptosis, low-set ears, a webbed neck, and shield chest. Echocardiography shows valvar pulmonary stenosis. Karyotype is 46,XY. Which of the following best explains this presentation?

• A Mosaicism for a 45,X cell line
• B Mutation in the PTPN11 gene ✓
• C Microdeletion of chromosome 22q11.2
• D Mutation in the fibrillin-1 gene

Explanation

This boy has Noonan syndrome, an autosomal dominant disorder caused by mutations in PTPN11 (encoding SHP-2) in about half of cases, with other RAS-MAPK pathway genes accounting for the rest. The phenotype mimics Turner syndrome, hence the older name male Turner syndrome, but the karyotype is normal. Valvar pulmonary stenosis is the classic cardiac lesion, distinguishing it from the hypertrophic cardiomyopathy also seen. 22q11.2 deletion causes conotruncal defects, not pulmonary stenosis.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.