WBR0102

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D. and 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 noticed 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 become a performer in a circus because she is unusually flexible and can contort her limbs in ways her peers cannot. Physical examination is remarkable for hyperextensible skin with multiple widened atrophic scars. The physician reassures the girl, and advises child protective services that the child may return to her parents. Which of the following statements is true of the child’s condition?]]
Answer A	AnswerA::The patient's condition is caused by defects in fibrillin
Answer A Explanation	[[AnswerAExp::Marfan syndrome is caused by defects in fibrillin.]]
Answer B	AnswerB::The patient's condition is 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::The patient's condition is caused by defects in type I collagen
Answer C Explanation	[[AnswerCExp::Although the arthrochalasia subtype of Ehlers Danlos syndrome can be caused by defects in type I collagen, few cases have been reported. Defects in type I collagen much more commonly cause osteogenesis imperfecta.]]
Answer D	AnswerD::The patient's condition is 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 more likely.]]
Answer E	AnswerE::The patient's condition is associated with inguinal hernia
Answer E Explanation	AnswerEExp::Generalized tissue extensibility and fragility among EDS patients may be clinically evident by the presence of umbilical, inguinal, or incisional herniation.
Right Answer	RightAnswer::E
Explanation	[[Explanation::Ehlers Danlos syndrome (EDS) is a hereditary connective tissue disorder caused by defects in collagen synthesis. It is characterized by skin hyperextrensibility, abnormal wound healing (eg. widened atrophic scarring, prolonged bleeding despite normal coagulation profile), and joint hypermotility. There are more than 6 types of EDS. Generally, EDS is associated with several cutaneous, musculoskeletal, cardiovascular, and pregnancy-related manifestations that may be related to its pathogenesis and the overall tissue fragility observed in the disease. Most importantly, EDS is associated with berry aneurysms , arteriovenous fistulae, spontaneous rupture of large arteries,and mitral and tricuspid valve prolapse. Tissue outpouchings are also common, such as colonic and esophageal diverticula, and hernias, including umbilical, inguinal, hiatal, and incisional hernias. Recurrent rectal prolapse is common among patients with EDS in early childhood. Due to the genotypic heterogeneity of the disease, the inheritance pattern depends on the family and genetic defect. The "hypermotility type" is the most common subtype of EDS. However, the patient in this vignette most likely has "classical type" EDS. The hallmark of "classical type" EDS is the presence of joint instability and cutaneous manifestations due to mutation in type V collagen. Less commonly, EDS is caused by type III collagen, resulting in "vascular type" EDS due to the presence of vascular signs. Other collagen defects, such as type I collagen defects, have also been described in EDS. Educational Objective: Ehlers Danlos syndrome is associated with cardiovascular manifestations, such as berry aneurysms, and tissue outpouchings, such as hernias and diverticula. References: Malfait F, Wenstrup RJ, De Paepe A. Clinical and genetic aspects of Ehlers-Danlos syndrome classic type. Genet Med. 2010;12(10):597-605 First Aid 2014 page 81]]
Approved	Approved::Yes
Keyword	WBRKeyword::Connective tissue, WBRKeyword::Connective tissue disorder, WBRKeyword::Ehlers-Danlos Syndrome, WBRKeyword::EDS, WBRKeyword::hyperextensibility, WBRKeyword::widened atrophic scar, WBRKeyword::widened atrophic scarring, WBRKeyword::hernia, WBRKeyword::herniation, WBRKeyword::fragility
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