WBR0609

Author	[[PageAuthor::Ayokunle Olubaniyi, M.B,B.S [1] (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [2])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Cardiology, SubCategory::Endocrine, SubCategory::Neurology
Prompt	[[Prompt::A 4-year-old boy with mild mental retardation is brought to the pediatrician's office for chronic constipation. The patient does not report any symptoms, and his mother states that he has a regular and balanced diet. On physical examination, the child has abnormal facies and exhibits cheerful and friendly demeanor. He has a bulge forehead, a low nasal bridge, and an abnormally wide mouth. His blood pressure is 152/88 mmHg, heart rate is 82/min, and temperature is 36.8 °C (98.2 °F). Cardiac auscultation is remarkable for a grade II/VI, mid-systolic ejection murmur at the right upper sternal border. Echocardiography with Doppler flow studies demonstrates supravalvular aortic stenosis. Lab work-up is remarkable for serum calcium concentration of 11.2 mg/dL. Which of the following supplements is contraindicated in this patient?]]
Answer A	AnswerA::Multivitamin preparation
Answer A Explanation	[[AnswerAExp::Williams syndrome is characterized by hypercalcemia, which is thought to be caused by high sensitivity to vitamin D. Since all pediatric multivitamin preparations contain vitamin D, the patient's hypercalcemia will worsen with the administration of multivitamin supplements.]]
Answer B	AnswerB::Iron supplement
Answer B Explanation	AnswerBExp::Iron supplementation does not affect patients with Williams syndrome.
Answer C	AnswerC::Magnesium supplement
Answer C Explanation	AnswerCExp::Magnesium supplementation does not affect patients with Williams syndrome.
Answer D	AnswerD::Fluoride supplement
Answer D Explanation	AnswerDExp::Fluoride supplementation does not affect patients with Williams syndrome.
Answer E	AnswerE::Zinc supplement
Answer E Explanation	AnswerEExp::Patients with diarrhea may be supplied zinc. Although not needed in this patient, zinc supplementation is not generally contraindicated in patients with Williams syndrome.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Williams syndrome (Williams' syndrome or Williams–Beuren syndrome) is a multisystem disorder caused by a microdeletion of the Williams-Beuren syndrome critical region (WBSCR) group of genes (26 to 28 genes), which surrounds the elastin (ELN) gene in chromosome 7. Williams syndrome is characterized by mild mental retardation, distinctive elfin facies, and overfriendly personality. Patients are typically diagnosed during childhood with symptoms of cardiovascular disease (classically supravalvular aortic stenosis or elastin arteriopathy, which causes arterial narrowing or hour-glass appearance of large arteries), endocrine disorders (hypercalcemia and/or subclinical hypothyroidism), or growth failure. The patient in this vignette has a typical presentation of Williams syndrome, given his age, symptoms (mental retardation, constipation), findings on physical examination (high blood pressure, abnormal elfin facies, friendly demeanor, bulge forehead, low nasal bridge, wide mouth, cardiac murmur), and findings on work-up (hypercalcemia and supravalvular aortic stenosis) . His chronic constipation is most likely explained by the hypercalcemia associated with Williams syndrome, which is usually mild (serum calcium concentration up to 11.5 mg/dL) and is most probably caused by an abnormally increased sensitivity to vitamin D. Since all pediatric multivitamin preparations contain vitamin D, the patient's hypercalcemia will worsen with the administration of multivitamin supplements. Other hypotheses as to why hypercalcemia is common among patients with Williams's syndrome include abnormally high levels of 1,25-dihydroxyvitamin D or abnormal synthesis or release of calcitonin. The diagnosis of Williams syndrome is based on genetic testing to confirm microdeletion in chromosome 7. Management include dietary modification, monitoring for endocrine disorders, and surgical correction of aortic stenoses. Educational Objective: Williams syndrome is a rare neurodevelopmental disorder caused by a deletion at chromosomal locus 7q11.23. The main features include elfin facial appearance, mental retardation, supravalvular aortic stenosis, and hypercalcemia. References: Pober BR. Williams-Beuren syndrome. N Engl J Med. 2010;362:239-52. Morris CA. Williams Syndrome. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1999. First Aid 2014 page 91]]
Approved	Approved::Yes
Keyword	WBRKeyword::Williams syndrome, WBRKeyword::Hypercalcemia, WBRKeyword::Constipation, WBRKeyword::Supravalvular aortic stenosis, WBRKeyword::Multivitamins, WBRKeyword::Vitamin D, WBRKeyword::Supplementation, WBRKeyword::Contraindication, WBRKeyword::Multisystem disorder
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