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 report, 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::Presence of a Barr body
Answer C Explanation	[[AnswerCExp::Presence of Barr body, an inactive X chromosome in a female somatic cell, is a normal finding only in women. X chromosomes are inactivated by a process called lyonization. Presence of a Barr body in men is observed among patients with Klinefelter syndrome (karyotype 47, XXY). DiGeorge syndrome in a male patient is not associated with identification of a Barr body.]]
Answer D	AnswerD::Abnormal development of the branchial pouch responsible for the development of the thymus only
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 involved branchial pouch in DiGeorge syndrome. The 4th branchial pouch, which is responsible for the development of the superior parathyroids (dorsal wings), is also involved.]]
Answer E	AnswerE::A microdeletion
Answer E Explanation	[[AnswerEExp::DiGeorge syndrome is caused by a microdeletion within chromosome 22.]]
Right Answer	RightAnswer::E
Explanation	[[Explanation::DiGeorge syndrome or 22q.11 syndrome is caused by a microdeletion within chromosome 22q11 that results in the abnormal embryological development of the third and the fourth branchial pouches. These pouches normally give rise to the thymus and the parathyroid glands. Patients with DiGeorge syndrome suffer from congenital heart disease, especially conotruncal malformations (such as tetralogy of Fallot, interrupted aortic arch, ventricular septal defect (VSD), and truncus arteriosus), characteristic facial features, and thymic hypoplasia, which is characterized by loss of thymic shadow on chest x-ray and results in T-cell immune deficiency and susceptibility to overwhelming infections. Also patients with DiGeorge syndrome often have palatal abnormalities (such as velopharyngeal incompetence, cleft palate, or bifid uvula) and underactive parathyroid gland, which causes hypocalcemia and hypocalcemia-induced 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: Wilson DI, Burn J, Scambler P, et al. DiGeorge syndrome: part of CATCH 22. J Med Genet. 1993;30(10):852-6. 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
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