Neurogenetics & neurocutaneous flashcards
19 high-yield MRCP Part 1 cards from the Intellect Medicos Neurology course. Try to answer each question before you open it — then study them properly with spaced repetition, which brings each card back just before you would forget it.
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Huntington's disease is autosomal dominant, caused by a ______ trinucleotide repeat expansion in the huntingtin gene on chromosome 4.
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CAG
Why? Longer repeats mean earlier onset. The repeat tends to expand down the generations (anticipation), especially when passed from the father.
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Huntington's disease is autosomal dominant, caused by a CAG trinucleotide repeat expansion in the huntingtin gene on chromosome ______.
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4
Why? Longer repeats mean earlier onset. The repeat tends to expand down the generations (anticipation), especially when passed from the father.
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Myotonic dystrophy type 1 is autosomal dominant, caused by a ______ repeat expansion in the DMPK gene on chromosome 19.
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CTG
Why? It shows anticipation. Type 2 (milder, proximal weakness) is a CCTG repeat in CNBP on chromosome 3.
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Myotonic dystrophy type 1 is autosomal dominant, caused by a CTG repeat expansion in the ______ gene on chromosome 19.
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DMPK
Why? It shows anticipation. Type 2 (milder, proximal weakness) is a CCTG repeat in CNBP on chromosome 3.
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A 35-year-old man has distal weakness, frontal balding, bilateral ptosis, cataracts and cannot let go after a handshake. Which systemic complication must be screened for regularly, and which drug can treat the myotonia?
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Cardiac conduction defects and arrhythmias (ECG); mexiletine.
Why? This is myotonic dystrophy type 1. Heart block and arrhythmias can cause sudden death. Mexiletine is a sodium-channel blocker that reduces myotonia.
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Friedreich's ataxia is autosomal ______, caused by a GAA trinucleotide repeat in the frataxin gene on chromosome 9.
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recessive
Why? Unlike Huntington's and myotonic dystrophy, Friedreich's does NOT show anticipation. Onset is usually at 10-15 years.
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Friedreich's ataxia is autosomal recessive, caused by a ______ trinucleotide repeat in the frataxin gene on chromosome 9.
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GAA
Why? Unlike Huntington's and myotonic dystrophy, Friedreich's does NOT show anticipation. Onset is usually at 10-15 years.
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What is the most common cause of death in Friedreich's ataxia?
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Hypertrophic cardiomyopathy.
Why? Other features: diabetes, optic atrophy, kyphoscoliosis, pes cavus, and absent ankle jerks with extensor plantars.
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Charcot-Marie-Tooth type 1: which gene, which inheritance pattern, and what do nerve conduction studies show?
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PMP22 (peripheral myelin protein 22); autosomal dominant; markedly reduced conduction velocity (demyelinating).
Why? CMT1 is demyelinating. CMT2 is axonal, with relatively preserved velocity and reduced amplitudes.
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The NF1 gene (neurofibromin) is on chromosome ______; the NF2 gene (merlin) is on chromosome 22. Both are autosomal dominant.
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17
Why? NF1 mainly affects peripheral nerves and skin. NF2 mainly causes CNS tumours.
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The NF1 gene (neurofibromin) is on chromosome 17; the NF2 gene (merlin) is on chromosome ______. Both are autosomal dominant.
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22
Why? NF1 mainly affects peripheral nerves and skin. NF2 mainly causes CNS tumours.
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Name the two genes, and their proteins, mutated in tuberous sclerosis.
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TSC1 (hamartin) and TSC2 (tuberin). Inheritance is autosomal dominant.
Why? Loss of either protein switches on mTOR signalling, causing hamartomas in many organs.
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Duchenne muscular dystrophy: what is the inheritance pattern and gene location?
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X-linked recessive; dystrophin gene at Xp21.
Why? Frameshift mutations mean no dystrophin is made (Duchenne). In-frame mutations give reduced dystrophin and milder Becker dystrophy.
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Von Hippel-Lindau syndrome: which chromosome, and what is the characteristic CNS tumour?
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Chromosome 3p (VHL tumour suppressor gene, autosomal dominant); haemangioblastoma (cerebellum, spinal cord, retina).
Why? VHL also causes clear cell renal carcinoma, phaeochromocytoma and pancreatic cysts.
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What is the most common genetic cause of motor neurone disease?
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C9orf72 repeat expansion.
Why? It also causes frontotemporal dementia, so a family history of either is relevant.
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Ataxia telangiectasia: which gene and inheritance, and which immunoglobulin is typically low?
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ATM gene, autosomal recessive; IgA deficiency.
Why? ATM repairs double-strand DNA breaks, so patients are radiosensitive and prone to cancer and sinopulmonary infections.
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Migraine with aura, recurrent subcortical strokes and early dementia with widespread white-matter change on MRI: which gene?
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NOTCH3 (CADASIL), autosomal dominant.
Why? CADASIL is a hereditary small-vessel arteriopathy. Migraine with aura is often the first symptom.
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Which drug is used for subependymal giant cell astrocytoma or renal angiomyolipoma in tuberous sclerosis, and how does it work?
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Everolimus, an mTOR inhibitor.
Why? Loss of hamartin or tuberin switches on mTOR, so blocking mTOR shrinks the tumours.
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Wilson's disease: which gene, which chromosome, and what inheritance?
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ATP7B on chromosome 13; autosomal recessive.
Why? Defective copper excretion into bile lets copper build up in liver and basal ganglia, causing parkinsonism, tremor or chorea in young people.