WBR0107
| 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::Neurology |
| Prompt | [[Prompt::A 22-year-old man presents to the primary care physician's office for a complaint of progressive hearing loss. He works as an elementary school teacher and reports he often cannot hear when students ask him questions during class. Upon further questioning, the patient reports he had an unusual event one week ago that he describes as a moving sensation "as if the whole world was spinning". Several similar episodes ensued since then. Two days before presentation, the patient also noticed he started to have a ringing sound in his ears that he cannot attribute to any particular cause. The patient denies pain, recent ear infections, or discharge. Following appropriate work-up, the physician orders a head MRI (shown below). What is the mode of inheritance of this patient's most likely diagnosis?
|
| Answer A | AnswerA::Autosomal recessive |
| Answer A Explanation | [[AnswerAExp::Neurofibromatosis type 2 (NF2) is an autosomal dominant disease. An example of an autosomal recessive disease is sickle cell disease.]] |
| Answer B | AnswerB::Autosomal dominant |
| Answer B Explanation | AnswerBExp::NF2 is an autosomal dominant disease. |
| Answer C | AnswerC::X-linked recessive |
| Answer C Explanation | [[AnswerCExp::NF2 is an autosomal dominant disease. An example of an X-linked recessive disease is Duchenne muscular dystrophy.]] |
| Answer D | AnswerD::X-linked dominant |
| Answer D Explanation | [[AnswerDExp::Neurofibromatosis type 2 is an autosomal dominant disease. An example of an X-linked recessive disease is Rett syndrome.]] |
| Answer E | AnswerE::Mitochondrial |
| Answer E Explanation | [[AnswerEExp::NF2 is an autosomal dominant disease. An example of mitochondrial inheritance is Myoclonic Epilepsy with Ragged Red Fibers.]] |
| Right Answer | RightAnswer::B |
| Explanation | [[Explanation::Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disorder characterized by the development of bilateral schwannomas, meningiomas, and ependymomas. Unlike NF1, neurofibromas are only rarely present among patients with NF2. Clinical features of NF2 include hearing loss, which is usually unilateral at presentation but eventually progresses to become bilateral if left untreated. Other symptoms include tinnitus, dizziness, and vertigo, as described by the patient presented in this vignette. The hallmark of the disease is bilateral vestibular schwannoma that involve the superior vestibular branch of CNVIII. Less commonly, patients present with symptoms of meningioma, such as headache or seizures. Other presenting features might be related to mononeuropathy due to tumor extension to involve CNVII, resulting in a Bell's-like palsy. Generalizedpolyneuropathy is less common, showing an "onion bulb" appearance on nerve biopsy.
NF2 is caused by loss of heterozygosity of chromosome 22. The NF2 gene normally encodes a cell membrane-related protein called merlin or schwannomin. While both germline and somatic mutations are possible, the former is likely to be a result of nonsense mutations, while the former is likely to be a frameshift mutation.
More than 90% of NF II patients suffer eye lesions. The most common alteration in NF II is the juvenile subcapsular cataract (opacity of the lens) in young people. NF II is caused by mutations of the NF2 gene coding for the "Merlin" protein. "Merlin" localizes to adherens junctions, but its tumor suppressive properties remain poorly understood. The principal treatments consist of neurosurgical removal of the tumors and surgical treatment of the eye lesions.
|
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Cancer, WBRKeyword::Genetics, WBRKeyword::Tumor suppressor gene, WBRKeyword::Tumor suppressor, WBRKeyword::Inheritance, WBRKeyword::Autosomal dominant, WBRKeyword::Oncology |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |
