WBR0112

Author	[[PageAuthor::William J Gibson (reviewed by Rim Halaby, M.D. [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Embryology, MainCategory::Genetics, MainCategory::Immunology
Sub Category	SubCategory::Cardiology, SubCategory::Infectious Disease
Prompt	[[Prompt::A newborn boy is found to be cyanotic following a natural birth. He is diagnosed with tetralogy of Fallot and undergoes surgery that successfully corrects his cyanosis. Over the next few years, the boy suffers an unusually large number of severe bacterial infections. His pediatrician requests a chest x-ray and the radiologist notes an absence of the thymic shadow. Which of the following is most likely to have caused this child’s condition?]]
Answer A	AnswerA::Abnormal development of the 1st branchial pouch
Answer A Explanation	[[AnswerAExp::DiGeorge syndrome is caused by abnormal development of the third and fourth branchial pouches.]]
Answer B	AnswerB::Abnormal development of the 2nd branchial pouch
Answer B Explanation	[[AnswerBExp::DiGeorge syndrome is caused by abnormal development of the third and fourth branchial pouches.]]
Answer C	AnswerC::Microdeletion on 7q
Answer C Explanation	[[AnswerCExp::Microdeleion of a region on 7q causes William’s syndrome. The patient in this vignette has DiGeorge syndrome.]]
Answer D	AnswerD::Microdeletion on chromosome 15
Answer D Explanation	[[AnswerDExp::Microdeletion of a region on chromosome 15 causes either Prader-Willi or Angelman’s syndromes.]]
Answer E	AnswerE::Microdeletion on chromosome 22
Answer E Explanation	AnswerEExp::DiGeorge syndrome is caused by a microdeletion on chromosome 22.
Right Answer	RightAnswer::E
Explanation	[[Explanation::The patient in this vignette is suffering from DiGeorge syndrome or 22q.11 syndrome. DiGeorge syndrome is caused by the deletion of a small piece of chromosome 22. Patients suffer from cardiac abnormalities (40%), and conditions resulting from abnormal development of the third and fourth branchial pouches. The third and fourth branchial pouches give rise to the thymus and the parathyroid glands. As a result, patients experience hypocalcemia due to deficiency of parathyroid hormone and immunodeficiency of T cells due to lack of a thymus. The unusually large number of infections in this patient is due to said T cell deficiency. Salient features can be summarized using the mnemonic CATCH-22 to describe DiGeorge syndrome, with the 22 to remind one the chromosomal abnormality is found on the 22 chromosome, as below: Cardiac Abnormality (especially tetralogy of Fallot) Abnormal facies Thymic aplasia Cleft palate Hypocalcemia/Hypoparathyroidism. Educational Objective: DiGeorge syndrome is caused by a microdeletion on chromosome 22. References: First Aid 2014 page 91]]
Approved	Approved::Yes
Keyword	WBRKeyword::Immunodeficiency, WBRKeyword::Genetics, WBRKeyword::T cell, WBRKeyword::Thymus, WBRKeyword::Infection. Cardiology, WBRKeyword::Tetralogy of Fallot
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::