DiGeorge syndrome
USMLE Step 1Difficulty: easyLast updated:
A 2-day-old boy develops jitteriness and carpopedal spasm. He has low-set ears, hypertelorism, a shortened philtrum, and a small receding mandible. Echocardiography shows truncus arteriosus. Serum calcium is 6.4 mg/dL with an inappropriately low parathyroid hormone level. Chest x-ray shows no thymic shadow.
Which of the following is the most likely underlying genetic abnormality?
Answer and explanation
Correct answer: D. Microdeletion at chromosome 22q11.2
Neonatal hypocalcemic tetany from hypoparathyroidism, a conotruncal heart defect, characteristic facial features, and an absent thymic shadow indicate DiGeorge syndrome (22q11.2 deletion syndrome). The source states that DiGeorge syndrome results from gene deletions in the DiGeorge chromosomal region at 22q11, as well as other genetic changes, which cause abnormal development of structures derived from the pharyngeal pouches. The result is thymic and parathyroid hypoplasia or aplasia, causing T-cell deficiency and hypoparathyroidism. Hypocalcemic tetany appears within 24 to 48 hours of birth. The source also lists congenital heart disorders such as interrupted aortic arch, truncus arteriosus, and tetralogy of Fallot, and facial features such as low-set ears, hypertelorism, a shortened philtrum, and a small receding mandible.
Each option explained
- A. Deletion of chromosome 5pIncorrect. 5p deletion (cri-du-chat) causes a high-pitched cry, microcephaly, and intellectual disability.
- B. 45,X karyotypeIncorrect. Turner syndrome (45,X) is seen in females and is associated with coarctation and bicuspid aortic valve.
- C. Trisomy 21Incorrect. Trisomy 21 is associated with endocardial cushion defects but not with hypoparathyroidism and an absent thymus.
- D. Microdeletion at chromosome 22q11.2Correct. 22q11.2 deletion causes thymic and parathyroid hypoplasia, conotruncal heart defects, and typical facies.
- E. Microdeletion at chromosome 7q11.23Incorrect. 7q11.23 deletion (Williams syndrome) causes supravalvular aortic stenosis and hypercalcemia, not hypocalcemia.
Key point
DiGeorge (22q11.2 deletion): thymic and parathyroid hypoplasia causing T-cell deficiency and neonatal hypocalcemia, with conotruncal heart defects.
From the source
“They also may have thymic and parathyroid hypoplasia or aplasia, causing T-cell deficiency and hypoparathyroidism.”