Neurogenetic Self-Assessment John K. Fink, M.D., Professor, Department of Neurology, University of Michigan Feb. 24, 2009 Movement disorders: Parkinson’s, Huntingtons, Dystonia, Wilson’s Ataxia: SCAs, Friedreich’s, et al. Motor sensory neuropathies Motor neuron disorders: Kennedy syndrome, ALSs, HSPs, PLS, SMA, DHMN Dementias: CJD,GSS, FFI, Tau, PS1, PS2, APP, APOE, Metabolic:Lysosomal storage, Urea cycle, Amino acidurias, Mucopolysacharideoses, Glycogen storage diseases, Mucolipidoses Mitochondrial: MERRF, NARP, Leighs, et al. Phakomatoses: Tuberous sclerosis, Neurofibromatosis I & II, Sturge Weber, Von Hipple Lindau, Fabry Stroke: heritable coagulaopathies Myopathies Periodic paralyses Epilepsy Sleep disorders Behavioral disorders The following questions are intended as a screening, self-assessment of knowledge of neurogenetic topics. Suggestion: Take this exam as a timed, 60-minute exercise to identify those areas in which greater familiarity is needed. Request: Comments and suggestions are welcome !

Leukodystrophy 15 yo male with dementia, progressive spasticity, muscle weakness. Had brother who died at 4yo. Mother has mild spastic gait. MRI of another patient with similar condition is shown. What is the most likely diagnosis? 24 yo female with juvenile cataracts, dementia and progressive spastic gait. Diagnostic test? Treatment?

Leukodystrophy: keywords (“handles”) 15 yo male with dementia, progressive spasticity, and muscle weakness. Had brother who died at 4yo. Mother is c/o mild spastic gait. MRI of another patient with similar condition is shown. What is the most likely diagnosis? –Posteriorly affected white matter abnormalities. –Possibility of X-linked disorder –Adrenoleukodystrophy. 24 yo female with dementia and progressive spastic gait. History of cataract (7yo). Her lower extremities are shown. What would you choose as a single lab test to add clue to her diagnosis? –Xanthomas –Consider cerebrotendinous xanthomatosis (with a history of cataract) –Cholestanol

Which of the following single gene mutations cause Alzheimer’s disease? 1. Presenilin 1 and Presenilin 2 2. ApoE 3. Amyloid precursor protein 4. Tau

Which of the following single gene mutations cause Alzheimer’s disease? 1. Presenilin 1 and Presenilin 2 2. ApoE 3. Amyloid precursor protein 4. Tau

7 Parkinson’s disease: 1. Risk of Parkinson’s disease is significantly increased in first-degree relatives of subjects with Parkinson’s disease. 2.  -synuclein and LRRK2 mutations cause Autos. Dom PD 3. The concordance rate for Parkinson’s disease in monozygotic twins greatly exceeds that for dizygotic twins 4. PINK1, Parkin2, and DJ-1 cause Autos. Recessive PD.

7 Parkinson’s disease: 1. Risk of Parkinson’s disease is significantly increased in first-degree relatives of subjects with Parkinson’s disease. 2.  -synuclein and LRRK2 mutations cause Autos. Dom PD 3. The concordance rate for Parkinson’s disease in monozygotic twins greatly exceeds that for dizygotic twins 4. PINK1, Parkin2, and DJ-1 cause Autos. Recessive PD.