WBR0103
| Author | PageAuthor::William J Gibson |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Endocrine, SubCategory::Musculoskeletal/Rheumatology |
| Prompt | [[Prompt::A 32 year old man with dwarfism has recently married a woman of normal stature. Neither of his parents had dwarfism, nor did any of his two siblings. He and his wife are interested in having children and seek genetic counseling? Which of the following statements is most likely true?]] |
| Answer A | AnswerA::The patient’s condition is caused by inactivating mutations in the FGFR3 gene and his children have a near 0% chance of developing dwarfism. |
| Answer A Explanation | AnswerAExp::While achondroplasia is caused by mutations of the FGFR3 gene, they are mutations that cause hyperactive signaling of this receptor. |
| Answer B | AnswerB::The patient’s condition is caused by activating mutations in the FGFR3 gene and his children have a 50% chance of developing dwarfism. |
| Answer B Explanation | AnswerBExp::The patient in this vignette most likely has achondroplasia, the most common cause of dwarfism. |
| Answer C | AnswerC::The patient’s condition is caused by defects in Type I Collagen and his children have a 50% chance of developing dwarfism. |
| Answer C Explanation | [[AnswerCExp::While Type I collagen is responsible for constituting bone, defects in Type I collagen are responsible for Osteogenesis Imperfecta, not achondroplasia.]] |
| Answer D | AnswerD::The patient’s condition is caused by defects in Growth Hormone synthesis and his children have a 0% chance of developing dwarfism. |
| Answer D Explanation | AnswerDExp::While growth hormone deficiency can cause dwarfism, achondroplasia is more common. |
| Answer E | AnswerE::The patient’s condition is caused by defects in Growth Hormone receptor signaling and his children have a 50% chance of developing dwarfism. |
| Answer E Explanation | AnswerEExp::While defects in the growth hormone receptor can cause dwarfism, they are extremely rare. |
| Right Answer | RightAnswer::B |
| Explanation | [[Explanation::Achondroplasia is caused by gain of function mutations in the FGFR3 gene. The activated receptor continually signals for bone to cease growing. Longitudinal bone growth is primarily affected as a result of defective endochondral ossification. Because membranous ossification is not affected, these patients often have large heads relative to the size of their limbs.
80% of achondroplasia cases are caused by sporadic mutations (associated with advanced paternal age) or may be inherited as an autosomal dominant genetic disorder. In this case, we know that the patient will transmit his altered FGFR3 gene with 50% probability, meaning that his children have a 50% chance of developing dwarfism. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Achondroplasia, WBRKeyword::Dwarfism, WBRKeyword::Genetics, WBRKeyword::Autosomal dominant |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |