WBR0102

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::Cardiology, SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::A 10-year-old girl is taken into the custody of child protective services after her teacher notices that she has had the consistent appearance of new bruises for the second month in a row. She is brought to a pediatrician for medical examination. The pediatrician collects a thorough history during which the girl insists that her parents have not harmed her, she just “plays rough”. Further questioning reveals that the girl would like to perform in a circus, because she is unusually flexible and can contort her limbs in ways her peers cannot. Physical exam is remarkable for hyperextensible skin. The physician reassures the girl and advises child protective services that the child may return to her parents. Which of the following is most true of the child’s condition?]]
Answer A	AnswerA::Caused by defects in fibrillin
Answer A Explanation	[[AnswerAExp::Marfan syndrome is caused by defects in fibrillin.]]
Answer B	AnswerB::Caused by defects in hydroxylation of proline residues
Answer B Explanation	[[AnswerBExp::Vitamin C deficiency causes deficient hydroxylation of proline residues. This manifests clinically as scurvy.]]
Answer C	AnswerC::Caused by defects in type I collagen
Answer C Explanation	[[AnswerCExp::While the arthrochalasia subtype of Ehlers Danlos syndrome can be caused by defects in type I collagen, only 30 cases have been reported. Defects in type I collagen much more commonly cause osteogenesis imperfecta.]]
Answer D	AnswerD::Associated with nephritis
Answer D Explanation	[[AnswerDExp::Alport syndrome is a hereditary cause of nephritis. Alport syndrome is a connective tissue disorder caused by mutations in type IV collagen genes. However, this patient lacks many of the features of Alport syndrome such as hearing loss, or lens abnormalities. Therefore, the diagnosis of Ehlers-Danlos syndrome is far more likely.]]
Answer E	AnswerE::Associated with formation of berry aneurysms
Answer E Explanation	[[AnswerEExp::Berry aneurysms appear as a round outpouching and are the most common form of cerebral aneurysm. The most common cause of berry aneurysms is hypertension. However, berry aneurysms are also associated with connective tissue diseases such as autosomal dominant polycystic kidney disease, Marfan syndrome and the disease in this patient, Ehlers-Danlos syndrome.]]
Right Answer	RightAnswer::E
Explanation	[[Explanation::The child in this vignette is suffering from Ehlers-Danlos syndrome (EDS), a hereditary connective tissue disorder caused by defects in collagen synthesis. There are more than 6 types of EDS. Patients commonly have hyperextensible skin, easy bruising, and hypermobile joints. Due to the genotypic heterogeneity of the disease, the inheritance pattern depends on the family and genetic defect in question. Because collagen is an essential component of vascular structures, its defective synthesis can result in the loss of vascular structural integrity. This manifests clinically as a predisposition to the formation (and rupture) of aneurysms such as cranial berry aneurysms and aortic aneurysms. Educational Objective: Ehlers-Danlos syndrome is associated with berry aneurysms. References: First Aid 2014 page 81]]
Approved	Approved::Yes
Keyword	WBRKeyword::Connective tissue, WBRKeyword::Connective tissue disorder, WBRKeyword::Ehlers-Danlos Syndrome
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::