WBR0609

{{WBRQuestion |QuestionAuthor=Ayokunle Olubaniyi, M.B,B.S [1] {{Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [2] |ExamType=USMLE Step 1 |MainCategory=Genetics |SubCategory=Cardiology, Endocrine, Neurology |MainCategory=Genetics |SubCategory=Cardiology, Endocrine, Neurology |MainCategory=Genetics |SubCategory=Cardiology, Endocrine, Neurology |MainCategory=Genetics |MainCategory=Genetics |MainCategory=Genetics |SubCategory=Cardiology, Endocrine, Neurology |MainCategory=Genetics |SubCategory=Cardiology, Endocrine, Neurology |MainCategory=Genetics |SubCategory=Cardiology, Endocrine, Neurology |MainCategory=Genetics |SubCategory=Cardiology, Endocrine, Neurology |MainCategory=Genetics |MainCategory=Genetics |SubCategory=Cardiology, Endocrine, Neurology |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. 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. Fluorescent in situ hybridization (FISH) testing confirms a deletion at chromosomal locus 7q11.23. Which of the following supplements should be avoided in this patient?

|Explanation=Williams syndrome (Williams–Beuren syndrome) is a multisystem disorder caused by a deletion of the Williams-Beuren syndrome critical region (WBSCR) gene, 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) or endocrine disorders (hypercalcemia and/or hypothyroidism). The patient in this vignette has a typical presentation of Williams syndrome, given his age, symptoms, and findings on physical examination. His chronic constipation is most likely explained by the hypercalcemia associated with Williams syndrome, which is usually caused by an abnormally increased sensitivity to vitamin D. Since all pediatric multivitamin supplements contain vitamin D, the patient's hypercalcemia will worsen with the administration of multivitamins.

The major features of Williams syndrome include:

Features include:

• Craniofacial dimorphism characterized by a distinctive, elfin facial appearance, along with a low nasal bridge, an unusually cheerful demeanor and ease with strangers.
• Oral abnormalities
• Mild to moderate mental retardation, cognitive disorder.
• Failure to thrive, short stature
• Cardiovascular features include supravalvular aortic stenosis or peripheral pulmonary stenosis, heart murmurs, renal artery stenosis leading to hypertension
• Renal insufficiencies
• Hypercalcemia, hypercalciuria, and subclinical hypothyroidism

The patient has a combination of elfin facies, a systolic murmur suggesting aortic stenosis, and constipation, which is a symptom of high serum calcium.

There is no cure for Williams syndrome. Management suggestions include avoidance of excess calcium and vitamin D, as well as treatment for high levels of blood calcium. |AnswerA=Hypocalcemia |AnswerAExp=Hypocalcemia is a feature seen commonly in DiGeorge syndrome. |AnswerB=Hypokalemia |AnswerBExp=Hypokalemia is a feature seen commonly in Williams syndrome especially when it is complicated by renal artery stenosis, but this is not frequently observed. |AnswerC=Hypermagnesemia |AnswerCExp=Hypermagnesemia is not a feature associated with Williams syndrome. |AnswerD=Hypercalcemia |AnswerDExp=Hypercalcemia is a common feature of Williams syndrome. |AnswerE=Hyperkalemia |AnswerEExp=Hyperkalemia is not a feature associated with Williams syndrome. |EducationalObjectives=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=http://www.wikidoc.org/index.php/Williams_syndrome |RightAnswer=D |WBRKeyword=Williams syndrome, Hypercalcemia, |Approved=No }}