WBR0112

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D. and 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 birth. Appropriate work-up is performed; and the patient is diagnosed with tetralogy of Fallot. In the patient's pre-operative chest x-ray, the radiologist notes an absence of the thymic shadow. The patient then undergoes surgery that successfully corrects his cyanosis. Over the next few days, he suffers a seizure that is attributed to low calcium blood levels. Which of the following abnormalities most likely caused this child’s condition?]]
Answer A	AnswerA::Abnormal development of the 1st and 2nd branchial pouches
Answer A Explanation	[[AnswerAExp::DiGeorge syndrome is caused by abnormal development of the 3rd and 4th branchial pouches.]]
Answer B	AnswerB::Abnormal development of the 2nd and 3rd branchial pouches
Answer B Explanation	[[AnswerBExp::DiGeorge syndrome is caused by abnormal development of the 3rd and 4th 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 signs and symptoms of DiGeorge syndrome.]]
Answer D	AnswerD::Abnormal development of only the branchial pouch(es) responsible for the development of the inferior parathyroid glands and the thymus
Answer D Explanation	[[AnswerDExp::The 3rd branchial pouch is responsible for the development of the inferior parathyroid glands (dorsal wings) and the thymus (ventral wings). However, the 3rd branchial pouch is not the only invovled branchial pouch in DiGeorge syndrome. The 4th branchial pouch, responsible for the development of the superior parathyroids (dorsal wings) is also involved.]]
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::DiGeorge syndrome or 22q.11 syndrome is caused by the deletion within chromosome 22q11 resulting in the abnormal embryological development of the third and the fourth branchial pouches that normally give rise to the thymus and the parathyroid glands. Patients suffer from congenital heart disease, especially conotruncal malformations (such as tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus), characteristic facial features, thymic hypoplasia, characterized by loss of thymic shadow on chest x-ray, leading to T-cell immune deficiency and susceptibility to overwhelming infections, palatal abnormalities (velopharyngeal incompetence, cleft palate, bifid uvula), underactive parathyroid gland causing hypocalcemia and hypocalcemia-associated seizures in the neonatal period. Salient features can be summarized using the mnemonic CATCH-22 to describe DiGeorge syndrome: Cardiac Abnormality (especially tetralogy of Fallot) Abnormal facies Thymic aplasia Cleft palate Hypocalcemia/Hypoparathyroidism 22: Chromosome 22 microdeletion Educational Objective: DiGeorge syndrome is caused by a microdeletion on chromosome 22q11. It results in the abnormal development of the 3rd and 4th branchial pouches. Signs, symptoms, and features of DiGeorge syndrome are: Cardiac Abnormality (especially tetralogy of Fallot) Abnormal facies Thymic aplasia Cleft palate Hypocalcemia/Hypoparathyroidism 22: Chromosome 22 microdeletion 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::