A neonate with tetralogy of Fallot develops seizures on day 3. Serum calcium is markedly low and T-cell counts are reduced. Fluorescence in situ hybridization demonstrates a microdeletion at 22q11.2. Embryologically, the malformations in this syndrome result from abnormal development of:

• A First pharyngeal arch derivatives
• B Third and fourth pharyngeal pouch derivatives ✓
• C Neural crest migration into the second arch
• D Lateral plate mesoderm forming the outflow tract alone

Explanation

The 22q11.2 deletion syndrome (DiGeorge sequence) arises from failed development of the third and fourth pharyngeal pouches, which give rise to the thymus and parathyroids. Loss of thymus causes T-cell immunodeficiency, and absent parathyroids cause hypocalcemic tetany. Conotruncal cardiac defects occur because the same region contributes cells to cardiac outflow tract development. TBX1 within the deleted segment is the key gene implicated. First arch derivatives relate to Treacher Collins and Pierre Robin anomalies.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.