A 4-year-old boy with a friendly, outgoing personality, elfin facies, and a history of infantile hypercalcaemia has a harsh systolic murmur at the right upper sternal border with a normal second heart sound. Echocardiography shows narrowing above the sinuses of Valsalva with a 60 mmHg peak gradient. Which genetic defect underlies this presentation?

• A Mutation of the NOTCH1 gene on chromosome 9q34
• B Mutation of the fibrillin-1 gene on chromosome 15q21
• C Deletion of the elastin gene on chromosome 7q11.23 ✓
• D Mutation of the PTPN11 gene on chromosome 12q24

Explanation

Williams syndrome results from a microdeletion of chromosome 7q11.23 that includes one copy of the elastin gene, producing elfin facies, hypersocial personality, infantile hypercalcaemia, and supravalvular aortic stenosis. Fibrillin-1 mutation causes Marfan syndrome, NOTCH1 mutation causes bicuspid aortic valve and familial calcific aortic stenosis, and PTPN11 mutation causes Noonan syndrome with dysplastic pulmonary valve stenosis.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.