WBR0311

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Hematology, SubCategory::General Principles
Prompt	[[Prompt::A 5 month old female is evaluated in a well child visit. The child was born without complications via vaginal delivery to a gravida 2 para 2, 39-year-old woman.The child has skin folds covering the inner angle of the eye, a flat nasal bridge, and small chin; her feet are pictured below. Which of the following is the child at increased risk of? ]]
Answer A	AnswerA::Acute Lymphoblastic Leukemia
Answer A Explanation	AnswerAExp::Patients with Down syndrome are at an increased risk of ALL and AML.
Answer B	AnswerB::Atherosclerosis
Answer B Explanation	AnswerBExp::Down syndrome patients tend to have a decreased risk of atherosclerosis. Other cardiovascular abnormalities are associated with Down syndrome including endocardial cushion defects and atrial septal defects.
Answer C	AnswerC::Crohn’s disease
Answer C Explanation	AnswerCExp::Down syndrome is not associated with an increased risk of Crohn’s disease. Other gastrointestinal abnormalities are associated with Down syndrome including: duodenal atresia, annular pancreas and imperforate anus.
Answer D	AnswerD::Lung cancer
Answer D Explanation	AnswerDExp::Down syndrome patients have a markedly decreased risk of most solid tumors except for testicular cancer.
Answer E	AnswerE::Hyperthyroidism
Answer E Explanation	AnswerEExp::Down syndrome patients have no increased risk of hyperthyroidism. These patients are at an increased risk of hypothyroidism (one third of patients).
Right Answer	RightAnswer::A
Explanation	[[Explanation::The patient in this vignette has Down syndrome. Down syndrome is a chromosomal abnormality caused by an extra copy of chromosome 21. It is typically associated with physical growth delays, a particular set of facial characteristics and a severe degree of intellectual disability. Some of the physical characteristics associated with Down syndrome include: Abnormally small chin Flat nasal bridge Epicanthic fold Single palmar fold (simian crease) A protruding tongue Excessive space between the large toe and second toe (pictured above) Down syndrome is most often caused by meiotic nondisjunction, which occurs during meiosis I. Approximately 2-3% of cases are caused by Robertsonian translocation. On quad screen, Down syndrome is associated with decreased AFP, increased beta-HCG, decreased estriol and increased inhibin A. Note that non-invasive tests using fetal DNA detected in maternal blood are beginning to replace the quad screen for aneuploidy testing. Knowledge of this testing option may be fair game on the USMLE. Mnemomic: AFP goes DOWN in Down syndrome. Down syndrome is associated with the development of several diseases, including Alzheimer's disease and Acute Lymphocytic Leukemia (ALL). The precise reasons why Down syndrome increases the probability of developing ALL is unknown. Cases of ALL arising in Down syndrome children share a similar set of genomic alterations as cases arising in children with euploid genomes. Educational Objective: Down syndrome is associated with an increased risk of ALL. References: Mullighan, Charles G., et al. Rearrangement of CRLF2 in B-progenitor–and Down syndrome–associated acute lymphoblastic leukemia. Nature genetics 41.11 (2009): 1243-1246. Nikolaev, Sergey I., et al. "Frequent cases of RAS-mutated Down syndrome acute lymphoblastic leukaemia lack JAK2 mutations." Nature communications 5 (2014). First Aid 2014 page 90 ]]
Approved	Approved::Yes
Keyword	WBRKeyword::Down syndrome, WBRKeyword::Cancer, WBRKeyword::Leukemia, WBRKeyword::Acute Lymphocytic Leukemia, WBRKeyword::Chromosome, WBRKeyword::Genetics
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::