WBR0122

Author	[[PageAuthor::William J Gibson (reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Endocrine, SubCategory::General Principles
Prompt	[[Prompt::A 14-year-old boy is brought for evaluation by a genetics counselor. The mother explains that the boy now suffers difficulties in school and has an IQ of 70. In addition to his intellectual deficits, he displays frequent tempter tantrums and compulsive behaviors. He also reports being constantly hungry. His past medical history is significant for delayed development of language and motor milestones. Physical examination is remarkable for short stature, morbid obesity, and small testes. The child’s symptoms are most likely caused by which of the following genetic disorders?]]
Answer A	AnswerA::Deletion of a maternal-derived allele; methylation of a paternal-derived allele on chromosome 14
Answer A Explanation	[[AnswerAExp::Prader-Willi syndrome is most commonly caused by a deletion of the paternal-derived allele and imprinting of the maternal-derived allele on chromosome 15.]]
Answer B	AnswerB::Deletion of a paternal-derived allele; methylation of a maternal-derived allele on chromosome 14
Answer B Explanation	[[AnswerBExp::Prader-Willi syndrome is most commonly caused by a deletion of the paternal-derived allele and imprinting of the maternal-derived allele on chromosome 15.]]
Answer C	AnswerC::Deletion of a maternal-derived allele; methylation of a paternal-derived allele on chromosome 15
Answer C Explanation	[[AnswerCExp::Prader-Willi syndrome is most commonly caused by a deletion of the paternal-derived allele and imprinting of the maternal-derived allele on chromosome 15.]]
Answer D	AnswerD::Deletion of a paternal-derived allele; methylation of a maternal-derived allele on chromosome 15
Answer D Explanation	[[AnswerDExp::Prader-Willi syndrome is most commonly caused by deletion of the normally imprinted paternal-derived allele on chromosome 15.]]
Answer E	AnswerE::Methylation of two paternal-derived alleles on chromosome 15
Answer E Explanation	[[AnswerEExp::Prader-Willi syndrome is caused by deletion of the paternal-derived allele and imprinting of the maternal-derived allele of the gene in the PWS/AS region of chromosome 15.]]
Right Answer	RightAnswer::D
Explanation	[[Explanation::Prader-Willi syndrome (PWS) is a rare genetic disorder caused by no expression of imprinted genes within the paternal-derived PWS/Angelman syndrome (AS) region in chromosome 15. The cause for absence of gene expression includes imprinting (methylation) defect, paternal deletion, and maternal uniparental disomy. On chromosome 15, a defect of the maternal-derived allele leads to AS, whereas a defect of the paternal-derived allele leads to PWS. Although PWS and AS are both disorders of chromosome 15, the diseases are clinically distinct. AS is characterized by more severe neurologic defects than PWS, whereas behavioral disorders and hypothalamic insufficiency are more frequently observed among patients with PWS. PWS is characterized by hypotonia and delay in language development and motor milestones in early childhood. Patients usually have low IQ and exhibit unique behavior that includes temper tantrums, manipulative behavior, and obsessive-compulsive features. Physical examination is usually remarkable for morbid obesity, unique facial features, strabismus, and small testes due to hypogonadism. Diagnosis is made by genetic testing using DNA-methylation testing, fluorescence in situ hybridization (FISH) analysis, imprinting defect analysis, or uniparental disomy analysis. Educational Objective: Prader-Willi syndrome is most commonly caused by the deletion of the normally imprinted paternal-derived allele on chromosome 15. References: Elena G, Bruna C, Benedetta M, et al. Prader-willi syndrome: clinical aspects. J Obes. 2012;2012:473941. Cassidy SB, Schwartz S, Miller JL, et al. Prader-Willi syndrome. Genet Med. 2012;14(1):10-26. First Aid 2014 page 85]]
Approved	Approved::Yes
Keyword	WBRKeyword::Prader Willi Syndrome, WBRKeyword::Genetics, WBRKeyword::Epigenetics, WBRKeyword::Imprinting, WBRKeyword::Chromosome 15, WBRKeyword::Prader-willi syndrome, WBRKeyword::Prader-Willi syndrome, WBRKeyword::Prader willi syndrome
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