Dentatorubral- pallodoluysian Atrophy (DRPLA) DRPLA Trinucleotide Repeat Disorder Trinucleotide Repeat Disorder CAG repeat on Chromosome 12 CAG repeat on Chromosome 12 6 to 35 normal, 48 to 93 mutation 6 to 35 normal, 48 to 93 mutation DRPLA disease named after DRPLA gene DRPLA disease named after DRPLA gene Family inherited and anticipation illness Family inherited and anticipation illness The age of onset is from one to 62 years with a mean age of onset of 30 years. (Shoji Tsuji, MD, PhD ) The age of onset is from one to 62 years with a mean age of onset of 30 years. (Shoji Tsuji, MD, PhD ) Dentatorubral and pallidoluysian parts of the central nervous system. Dentatorubral and pallidoluysian parts of the central nervous system. cerebral white matter, putamen, Goll's nucleus of the medulla oblongata, and lateral corticospinal and Goll's tract of the spinal cord cerebral white matter, putamen, Goll's nucleus of the medulla oblongata, and lateral corticospinal and Goll's tract of the spinal cord Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene polyglutamine region in atrophin-1 is expanded with the expansion of the CAG repeat, becomes, altering its interactions with other proteins neurotransmitters in the brain are blocked ataxia (loss of balance) ataxia (loss of balance) choreoathetosis (involuntary rapid, irregular, jerky movements or slow, writhing movements that flow into one another) choreoathetosis (involuntary rapid, irregular, jerky movements or slow, writhing movements that flow into one another) dementia (inability to clearly think; confusion, poor judgment; failure to recognize people, places, and things; personality changes) dementia (inability to clearly think; confusion, poor judgment; failure to recognize people, places, and things; personality changes) myoclonus (involuntary spasms of a muscle or muscle group) myoclonus (involuntary spasms of a muscle or muscle group) epilepsy (seizures) epilepsy (seizures) loss of intellectual function (mental retardation) (encyclopedia of genetic disorders) loss of intellectual function (mental retardation) (encyclopedia of genetic disorders) Masks Huntingtons Disease, Alzheimer's, M.S., and Parkinson's Disease Masks Huntingtons Disease, Alzheimer's, M.S., and Parkinson's Disease DNA testing for CAG repeat, prenatal testing is available if 50% chance or more DNA testing for CAG repeat, prenatal testing is available if 50% chance or more Neuroimaging. MRI within white regions of the brain Neuroimaging. MRI within white regions of the brain Treatment and management Treatment and management There is currently no cure for DRPLA; treatment is supportive. Epilepsy is treated with anti-seizure medication. There is currently no cure for DRPLA; treatment is supportive. Epilepsy is treated with anti-seizure medication. Prognosis Prognosis Patients with DRPLA have progressive disease, which means symptoms become worse over time. Patients with DRPLA have progressive disease, which means symptoms become worse over time. 18 years old 22 years old 26 yrs. old 27 yrs. old 28 yrs. old 32YRSOLD32YRSOLD Last BirthdayWeeks before he passed