WBR0764

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::A 17 year old male achondroplastic dwarf is brought by his mother to the physician's office to inquire about his condition. The physician informs the patient that his condition is caused by an abnormal functioning of a growth factor receptor that affects his bone development. Which of the following abnormalities of osteogenesis most likely have occurred in this patient?]]
Answer A	AnswerA::Failure of intramembranous ossification with normal endochondral ossification
Answer A Explanation	AnswerAExp::Achondroplasia is characterized by failure of endochondral ossification with normal intramembranous ossification.
Answer B	AnswerB::Continuous activation of chondrocytes
Answer B Explanation	AnswerBExp::FGF3 activation leads to inhibition of chondrocyte activation
Answer C	AnswerC::Failure of both endochondral and intramembranous ossifications.
Answer C Explanation	AnswerCExp::Achondroplasia is characterized by failure of endochondral ossification with normal intramembranous ossification.
Answer D	AnswerD::Constitutive inhibition of FGF3 receptors
Answer D Explanation	AnswerDExp::FGF3 receptors are constitutively activated in achondroplasia
Answer E	AnswerE::Tyrosine kinase overactivity
Answer E Explanation	AnswerEExp::FGF3 is a growth factor that has an intrinsic tyrosine kinase signaling pathway. Constitutive activation of the pathway inhibits the proliferation of chondrocytes and leads to failure of endochondral ossification in achondroplasia.
Right Answer	RightAnswer::E
Explanation	[[Explanation::Achondroplasia is a form of chondrodysplasia and is the most common cause of dwarfism. It is an autosomal dominant disorder that causesfailure of endochondral ossification with normal intramembranous ossification due to constitutive activation of fibroblast growth factor (FGF3) receptor. As such, patients tend to have normal heads (intramembranous ossification of the skull) with short limbs (failure of endochondral ossification of long bones of the extremities). I FGF3 receptor is activated by intrinsic tyrosine kinase activity, similar to all other growth factor receptors and insulin receptors. Educational Objective: FGF3 receptor has an intrinsic tyrosine kinase signaling pathway. Constitutive activation of FGF3 receptor causes achondroplasia, an autosomal dominant disorder. Reference: Laederich MB, Horton WA. Achondroplasia: pathogenesis and implications for future treatment. Curr Opin in Pediatr. 2010;22(4):516-523. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::tyrosine, WBRKeyword::kinase, WBRKeyword::signaling, WBRKeyword::pathway, WBRKeyword::achondroplasia, WBRKeyword::failure, WBRKeyword::longitudinal, WBRKeyword::bone, WBRKeyword::growth, WBRKeyword::ossification, WBRKeyword::osteogenesis, WBRKeyword::limb, WBRKeyword::skull, WBRKeyword::limbs, WBRKeyword::FGF3, WBRKeyword::fibroblast, WBRKeyword::growth, WBRKeyword::factor, WBRKeyword::dwarf, WBRKeyword::dwarfism, WBRKeyword::endochondral, WBRKeyword::intramembranous, WBRKeyword::membranous, WBRKeyword::chondrocyte, WBRKeyword::inhibition, WBRKeyword::constitutive, WBRKeyword::acitvation, WBRKeyword::receptor, WBRKeyword::receptors, WBRKeyword::autosomal, WBRKeyword::dominant
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