WBR0764

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
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 have most likely 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 results in inhibition of chondrocyte activation.]]
Answer C	AnswerC::Failure of both endochondral and intramembranous ossification processes
Answer C Explanation	[[AnswerCExp::Achondroplasia manifests with failure of endochondral ossification and 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::Similar to other growth factors and insulin, FGF3 is a growth factor that employs the intrinsic tyrosine kinase signaling pathway. Constitutive activation of the pathway inhibits the proliferation of chondrocytes and leads to failure of endochondral ossification among patients with 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 characterized by constitutive activation of fibroblast growth factor (FGF3) receptor, which is a receptor tyrosine kinase (RTK) that employs the intrinsic tyrosine kinase pathway. Achondroplasia manifests with failure of endochondral ossification and normal intramembranous ossification. Patients typically have normal heads (normal intramembranous ossification of the skull) with short limbs (failure of endochondral ossification of long bones of the extremities). Educational Objective: FGF3 receptor is a receptor tyrosine kinase (RTK) that employs the intrinsic tyrosine kinase signaling pathway. Constitutive activation of FGF3 receptor causes achondroplasia. References: Laederich MB, Horton WA. Achondroplasia: pathogenesis and implications for future treatment. Curr Opin in Pediatr. 2010;22(4):516-523. First Aid 2014 page 419]]
Approved	Approved::Yes
Keyword	WBRKeyword::Tyrosin kinase signaling pathway, WBRKeyword::Receptor tyrosine kinase, WBRKeyword::RTK, WBRKeyword::Growth factors, WBRKeyword::FGF3 receptor, WBRKeyword::Achondroplasia, WBRKeyword::Autosomal dominant disorder, WBRKeyword::Dwarfism, WBRKeyword::Endochondral ossification, WBRKeyword::Intramembranous ossification
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