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Mutational and biochemical analysis of dopamine in dystonia

Evidence for decreased dopamine D2 receptor inhibition

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Abstract

The dystonias are a group of serious movement disorders characterized by involuntary muscle spasms of different parts of the body. We recently proposed that hypofunction of dopamine D2 receptor-mediated inhibition of the indirect output pathway of the basal ganglia can result in dystonia. In this review, we discuss the results of a variety of genetic and biochemical studies in light of this hypothesis. Several forms of early-onset dystonia show distinct autosomal dominant, recessive, or X-linked genetic transmission patterns. Late onset forms of dystonia, though not showing clear Mendelian transmission patterns, also appear to be highly familial. Recently, several genetic-linkage locations have been identified for early-onset dystonia and for two of these loci, mutations decreasing dopamine synthesis have been demonstrated. Biochemical studies of monkeys and man also demonstrate that several types of dystonia occur in a dopamine-deficiency state. Similarly, mice strains developed to be deficient in several dopamine-pathway components have motor abnormalities consistent with dystonia. Hypofunction of the dopamine D2 receptormediated inhibition of the indirect output pathway of the putamen may be a common feature of many of these heritable and secondary dystonic syndromes.

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  1. Department of Psychiatry and Genetics, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 63110, St. Louis, MO

    Richard D. Todd

  2. Department of Neurology and Neurosurgery Mallinckrodt Institute of Radiology, Washington University School of Medicine, 63110, St. Louis, MO

    Joel S. Perlmutter

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Todd, R.D., Perlmutter, J.S. Mutational and biochemical analysis of dopamine in dystonia. Mol Neurobiol 16, 135–147 (1998). https://doi.org/10.1007/BF02740641

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