WBR0249

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 2-year-old boy is brought to the physician's office for an abdominal mass. The mother also reports that the child is frequently irritable, cries more than usual, and has a slowed growth. The infant's weight falls lower than the 3rd percentile on the standard growth chart. Physical examination is remarkable for opsoclonus-myoclonus, abdominal distention, and a palpable left abdominal mass. Urine testing demonstrates elevated levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA). Amplification of which gene is associated with worse clinical outcomes in this patient's condition?]]
Answer A	AnswerA::''N-MYC''
Answer A Explanation	[[AnswerAExp::'Presence of 'N-MYC oncogene amplification is associated with worse clinical outcomes in neuroblastoma.]]
Answer B	AnswerB::RET
Answer B Explanation	[[AnswerBExp::RET is associated with multiple endocrine neoplasia (MEN) types 2A and 2B]]
Answer C	AnswerC::
Answer C Explanation	[[AnswerCExp::The Abl oncogene is associated with CML.]]
Answer D	AnswerD::L-MYC
Answer D Explanation	[[AnswerDExp::L-MYC oncogene is associated with lung cancer.]]
Answer E	[[AnswerE::C-MYC]]
Answer E Explanation	[[AnswerEExp::C-MYC oncogene is associated with Burkitt's lymphoma.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::Neuroblastoma is a neural crest cell-derived embryonal tumor of the autonomic nervous system. It commonly affects children of 1 or 2 years of age. Neuroblastoma commonly manifests as an adrenal tumor or a tumor of the paraspinal ganglia in the neck, chest, abdomen, or pelvis. The clinical disease may range from a completely asymptomatic course with an incidental palpation of a unilateral/bilateral abdominal mass to severe illness, including neurological manifestations (Horner syndrome, blindness, opsoclonus, which is multivectorial, conjugate fast eye movements, and myoclonus, which is involuntary muscle twitching). The tumor results in defective synthesis of catecholamines and leads to the accumulation of catecholamine-metabolites, such as homovanillic acid (HVA) and vanillylmandelic acid (VMA). Elevations in these metabolites are observed in more than 90% of neuroblastoma cases and provide an important diagnostic clue. The development of familial neuroblastoma has recently been attributed to either activating mutations in anaplastic lymphoma kinase (ALK) oncogene or loss-of-function mutations in homeobox gene PHOX2B. Familial neuroblastoma has also been associated with other disorders, such as congenital hypoventilation syndrome and Hirschsprung's disease. In contrast, sporadic development of neuroblastoma has been attributed to multiple polymorphic gene interactions with no unique causative mutation. The presence of the N-MYC oncogene, a target of the high-level amplification at chromosome 2, is present in 20% of neuroblastoma cases. Identification of N-MYC amplification in neuroblastoma is clinically important because it is associated with worse clinical outcomes and may affect the management strategy through intensification of chemoradiation. Educational Objective: Neuroblastoma is a neural crest cell-derived embryonal tumor of the autonomic nervous system. Identification of N-MYC amplification in neuroblastoma is clinically important because N-MYC amplification is associated with worse clinical outcomes. References: Maris JM. Recent advances in Neuroblastoma. N Engl J Med. 2010;362:2202-11. First Aid 2014 page 318]]
Approved	Approved::Yes
Keyword	WBRKeyword::Neuroblastoma, WBRKeyword::Opsoclonus, WBRKeyword::Myoclonus, WBRKeyword::N-MYC, WBRKeyword::Oncogene, WBRKeyword::Prognosis, WBRKeyword::Abdominal mass
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::