WBR0217

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 12 year old male presents to the clinic for recurrent seizures. The child was born via normal vaginal delivery to consanguineous parents and no defects were observed at birth. The patient began experiencing seizures at the age of 4. The parents’ description of the seizures is consistent with a diagnosis of partial seizures. The patient is mildly autistic, and suffers mental retardation. On physical exam, the patient has a long face with everted ears. On cardiac auscultation, a mid-systolic click followed by a systolic murmur is appreciated at the apex. Which of the following is true of the patient’s likely disease?]]
Answer A	AnswerA::Caused by sporadic mutation
Answer A Explanation	AnswerAExp::'''Incorrect''' - Fragile X syndrome is caused by a trinucleotide repeat on the X chromosome. An example of a disease caused by spontaneous mutation is Rett syndrome.
Answer B	AnswerB::Caused by trinucleotide repeat
Answer B Explanation	AnswerBExp::'''Correct''' - See explanation
Answer C	AnswerC::Caused by chromosomal deletion
Answer C Explanation	AnswerCExp::'''Incorrect''' - Fragile X syndrome is caused by a trinucleotide repeat on the X chromosome. An example of a disease caused by a chromosomal deletion is William’s syndrome, which is caused by a deletion of a part of chromosome 7.
Answer D	AnswerD::Autosomal recessive inheritance
Answer D Explanation	AnswerDExp::'''Incorrect''' - Fragile X syndrome is an X-linked disorder. An example of an autosomal recessive disease is Tay-Sachs disease.
Answer E	AnswerE::Autosomal dominant inheritance
Answer E Explanation	AnswerEExp::'''Incorrect''' - Fragile X syndrome is an X-linked disorder. An example of an autosomal dominant disease is Marfan syndrome.
Right Answer	RightAnswer::B
Explanation	[[Explanation::The patient in this vignette is suffering from Fragile X syndrome. Fragile X syndrome is caused by a trinucleotide expansion of CGG repeats in the FMR1 gene on the X chromosome. Expansion of CGG repeats beyond a certain threshold causes silencing of the FMR1 gene which leads to pathology. Fragile X syndrome is the second most common cause of mental retardation, behind Down syndrome. Aside from intellectual disability, prominent characteristics of the syndrome include an elongated face, large or protruding ears, flat feet, larger testes (macroorchidism), and low muscle tone. Fragile X syndrome has traditionally been considered an X-linked dominant condition with variable expressivity and possibly reduced penetrance. However, due to genetic anticipation and X-inactivation in females, the inheritance of Fragile X syndrome does not follow the usual pattern of X-linked dominant inheritance. Example of facial characteristics of patient with Fragile X. Educational Objective: Fragile X syndrome is caused by expansion of CGG repeats in the FMR1 gene on the X Chromosome. References: First Aid 2012 page 92 Educational Objective: References: ]]
Approved	Approved::Yes
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