WBR0122
| Author | [[PageAuthor::William J Gibson (reviewed by Rim Halaby, M.D. [1])]] |
|---|---|
| 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 mutations?]] |
| 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. Understanding the etiology for absence of gene expression in PWS is important in genetic counseling for the evaluation of risk among siblings. While the risk of sibling involvement is less than 1% among patients with uniparental disomy or paternal deletion, the risk increases substantially to reach up to 25-50% among patients with imprinting defects. |
| 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 |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |