Semin Neurol 2007; 27(2): 151-158
DOI: 10.1055/s-2007-971170
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Inherited Dystonias

Pedro Gonzalez-Alegre1
  • 1Department of Neurology, Carver College of Medicine at The University of Iowa, Iowa City
Further Information

Publication History

Publication Date:
27 March 2007 (online)

ABSTRACT

During the last decade, we have witnessed significant advances in the study of inherited dystonias. This article will review some of those discoveries and summarize their significance for the practicing neurologist. A clinical classification of dystonia based on features that can be determined by the clinician is proposed, aiming to facilitate the evaluation of patients with suspected inherited dystonia. Subsequently, DYT1 dystonia is used as an example of how genetics can aid in the evaluation of patients presenting with this group of heritable diseases. Finally, a brief summary of the most significant recent advances in this field will focus on those aspects most helpful to the clinician.

REFERENCES

  • 1 Fahn S, Bressman S B, Marsden C D. Classification of dystonia.  Adv Neurol. 1998;  78 1-10
  • 2 Nemeth A H. The genetics of primary dystonias and related disorders.  Brain. 2002;  125 695-721
  • 3 de Carvalho Aguiar P M, Ozelius L J. Classification and genetics of dystonia.  Lancet Neurol. 2002;  1 316-325
  • 4 Bressman S B. Dystonia genotypes, phenotypes, and classification.  Adv Neurol. 2004;  94 101-107
  • 5 Bandmann O, Wood N W. Dopa-responsive dystonia: the story so far.  Neuropediatrics. 2002;  33 1-5
  • 6 Furukawa Y. Update on dopa-responsive dystonia: locus heterogeneity and biochemical features.  Adv Neurol. 2004;  94 127-138
  • 7 Bressman S B, Fahn S, Ozelius L J, Kramer P L, Risch N J. The DYT1 mutation and nonfamilial primary torsion dystonia.  Arch Neurol. 2001;  58 681-682
  • 8 Valente E M, Warner T T, Jarman P R et al.. The role of DYT1 in primary torsion dystonia in Europe.  Brain. 1998;  121 2335-2339
  • 9 Paulson H L. Diagnostic testing in neurogenetics: principles, limitations, and ethical considerations.  Neurol Clin. 2002;  20 627-643
  • 10 Bird T D. Risks and benefits of DNA testing for neurogenetic disorders.  Semin Neurol. 1999;  19 253-259
  • 11 Klein C, Friedman J, Bressman S et al.. Genetic testing for early-onset torsion dystonia (DYT1): introduction of a simple screening method, experiences from testing of a large patient cohort, and ethical aspects.  Genet Test. 1999;  3 323-328
  • 12 O'Riordan S, Raymond D, Lynch T et al.. Age at onset as a factor in determining the phenotype of primary torsion dystonia.  Neurology. 2004;  63 1423-1426
  • 13 Greene P, Kang U J, Fahn S. Spread of symptoms in idiopathic torsion dystonia.  Mov Disord. 1995;  10 143-152
  • 14 Ozelius L J, Hewett J W, Page C E et al.. The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein.  Nat Genet. 1997;  17 40-48
  • 15 Breakefield X O, Kamm C, Hanson P I. TorsinA: movement at many levels.  Neuron. 2001;  31 9-12
  • 16 Walker R H, Shashidharan P. Developments in the molecular biology of DYT1 dystonia.  Mov Disord. 2003;  18 1102-1107
  • 17 Kabakci K, Hedrich K, Leung J C et al.. Mutations in DYT1: extension of the phenotypic and mutational spectrum.  Neurology. 2004;  62 395-400
  • 18 Bressman S B, Raymond D, Wendt K et al.. Diagnostic criteria for dystonia in DYT1 families.  Neurology. 2002;  59 1780-1782
  • 19 Fasano A, Nardocci N, Elia A E, Zorzi G, Bentivoglio A R, Albanese A. Non-DYT1 early-onset primary torsion dystonia: comparison with DYT1 phenotype and review of the literature.  Mov Disord. 2006;  21 1411-1418
  • 20 Chinnery P F, Reading P J, McCarthy E L, Curtis A, Burn D J. Late-onset axial jerky dystonia due to the DYT1 deletion.  Mov Disord. 2002;  17 196-198
  • 21 Gatto E M, Pardal M M, Micheli F E. Unusual phenotypic expression of the DYT1 mutation.  Parkinsonism Relat Disord. 2003;  9 277-279
  • 22 Grundmann K, Laubis-Herrmann U, Bauer I et al.. Frequency and phenotypic variability of the GAG deletion of the DYT1 gene in an unselected group of patients with dystonia.  Arch Neurol. 2003;  60 1266-1270
  • 23 Bentivoglio A R, Loi M, Valente E M, Ialongo T, Tonali P, Albanese A. Phenotypic variability of DYT1-PTD: does the clinical spectrum include psychogenic dystonia?.  Mov Disord. 2002;  17 1058-1063
  • 24 Edwards M, Wood N, Bhatia K. Unusual phenotypes in DYT1 dystonia: a report of five cases and a review of the literature.  Mov Disord. 2003;  18 706-711
  • 25 Opal P, Tintner R, Jankovic J et al.. Intrafamilial phenotypic variability of the DYT1 dystonia: from asymptomatic TOR1A gene carrier status to dystonic storm.  Mov Disord. 2002;  17 339-345
  • 26 Bressman S B, Sabatti C, Raymond D et al.. The DYT1 phenotype and guidelines for diagnostic testing.  Neurology. 2000;  54 1746-1752
  • 27 Krause M, Fogel W, Kloss M, Rasche D, Volkmann J, Tronnier V. Pallidal stimulation for dystonia.  Neurosurgery. 2004;  55 1361-1368 discussion 1368-1370
  • 28 Vidailhet M, Vercueil L, Houeto J L et al.. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia.  N Engl J Med. 2005;  352 459-467
  • 29 Eidelberg D, Moeller J R, Antonini A et al.. Functional brain networks in DYT1 dystonia.  Ann Neurol. 1998;  44 303-312
  • 30 Rothwell J C, Edwards M, Huang Y Z, Bhatia K P. Physiological studies in carriers of the DYT1 gene mutation.  Rev Neurol (Paris). 2003;  159 880-884
  • 31 Heiman G A, Ottman R, Saunders-Pullman R J, Ozelius L J, Risch N J, Bressman S B. Increased risk for recurrent major depression in DYT1 dystonia mutation carriers.  Neurology. 2004;  63 631-637
  • 32 Gonzalez-Alegre P, Paulson H L. Aberrant cellular behavior of mutant torsinA implicates nuclear envelope dysfunction in DYT1 dystonia.  J Neurosci. 2004;  24 2593-2601
  • 33 Goodchild R E, Dauer W T. Mislocalization to the nuclear envelope: an effect of the dystonia causing torsinA mutation.  Proc Natl Acad Sci USA. 2004;  101 847-852
  • 34 Naismith T V, Heuser J E, Breakefield X O, Hanson P I. TorsinA in the nuclear envelope.  Proc Natl Acad Sci USA. 2004;  101 7612-7617
  • 35 Gonzalez-Alegre P, Miller V M, Davidson B L, Paulson H L. Toward therapy for DYT1 dystonia: allele-specific silencing of mutant TorsinA.  Ann Neurol. 2003;  53 781-787
  • 36 Gonzalez-Alegre P, Bode N, Davidson B L, Paulson H L. Silencing primary dystonia: lentiviral-mediated RNA interference therapy for DYT1 dystonia.  J Neurosci. 2005;  25 10502-10509
  • 37 Almasy L, Bressman S B, Raymond D et al.. Idiopathic torsion dystonia linked to chromosome 8 in two Mennonite families.  Ann Neurol. 1997;  42 670-673
  • 38 Valente E M, Bentivoglio A R, Cassetta E et al.. Identification of a novel primary torsion dystonia locus (DYT13) on chromosome 1p36 in an Italian family with cranial-cervical or upper limb onset.  Neurol Sci. 2001;  22 95-96
  • 39 Valente E M, Bentivoglio A R, Cassetta E et al.. DYT13, a novel primary torsion dystonia locus, maps to chromosome 1p36.13-36.32 in an Italian family with cranial-cervical or upper limb onset.  Ann Neurol. 2001;  49 362-366
  • 40 Parker N. Hereditary whispering dysphonia.  J Neurol Neurosurg Psychiatry. 1985;  48 218-224
  • 41 Ahmad F, Davis M B, Waddy H M, Oley C A, Marsden C D, Harding A E. Evidence for locus heterogeneity in autosomal dominant torsion dystonia.  Genomics. 1993;  15 9-12
  • 42 Leube B, Rudnicki D, Ratzlaff T, Kessler K R, Benecke R, Auburger G. Idiopathic torsion dystonia: assignment of a gene to chromosome 18p in a German family with adult onset, autosomal dominant inheritance and purely focal distribution.  Hum Mol Genet. 1996;  5 1673-1677
  • 43 Gimenez-Roldan S, Delgado G, Marin M, Villanueva J A, Mateo D. Hereditary torsion dystonia in gypsies.  Adv Neurol. 1988;  50 73-81
  • 44 Fletcher N A, Harding A E, Marsden C D. A genetic study of idiopathic torsion dystonia in the United Kingdom.  Brain. 1990;  113 379-395
  • 45 Khan N L, Wood N W, Bhatia K P. Autosomal recessive, DYT2-like primary torsion dystonia: a new family.  Neurology. 2003;  61 1801-1803
  • 46 Moretti P, Hedera P, Wald J, Fink J. Autosomal recessive primary generalized dystonia in two siblings from a consanguineous family.  Mov Disord. 2005;  20 245-247
  • 47 Grotzsch H, Pizzolato G P, Ghika J et al.. Neuropathology of a case of dopa-responsive dystonia associated with a new genetic locus, DYT14.  Neurology. 2002;  58 1839-1842
  • 48 Schneider S A, Mohire M D, Trender-Gerhard I et al.. Familial dopa-responsive cervical dystonia.  Neurology. 2006;  66 599-601
  • 49 Tassin J, Durr A, Bonnet A M et al.. Levodopa-responsive dystonia: GTP cyclohydrolase I or parkin mutations?.  Brain. 2000;  123 1112-1121
  • 50 Khan N L, Graham E, Critchley P et al.. Parkin disease: a phenotypic study of a large case series.  Brain. 2003;  126 1279-1292
  • 51 Rainier S, Thomas D, Tokarz D et al.. Myofibrillogenesis regulator 1 gene mutations cause paroxysmal dystonic choreoathetosis.  Arch Neurol. 2004;  61 1025-1029
  • 52 Lee H Y, Xu Y, Huang Y et al.. The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway.  Hum Mol Genet. 2004;  13 3161-3170
  • 53 Bruno M K, Hallett M, Gwinn-Hardy K et al.. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria.  Neurology. 2004;  63 2280-2287
  • 54 Valente E M, Misbahuddin A, Brancati F et al.. Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.  Mov Disord. 2003;  18 1047-1051
  • 55 Schule B, Kock N, Svetel M et al.. Genetic heterogeneity in ten families with myoclonus dystonia.  J Neurol Neurosurg Psychiatry. 2004;  75 1181-1185
  • 56 Zimprich A, Grabowski M, Asmus F et al.. Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome.  Nat Genet. 2001;  29 66-69
  • 57 de Carvalho Aguiar P, Sweadner K J, Penniston J T et al.. Mutations in the Na + /K + -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism.  Neuron. 2004;  43 169-175
  • 58 Nolte D, Niemann S, Muller U. Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism.  Proc Natl Acad Sci USA. 2003;  100 10347-10352
  • 59 Grimes D A, Han F, Lang A E, St George-Hyssop P, Racacho L, Bulman D E. A novel locus for inherited myoclonus-dystonia on 18p11.  Neurology. 2002;  59 1183-1186
  • 60 Klein C, Brin M F, Kramer P et al.. Association of a missense change in the D2 dopamine receptor with myoclonus dystonia.  Proc Natl Acad Sci USA. 1999;  96 5173-5176
  • 61 Leung J C, Klein C, Friedman J et al.. Novel mutation in the TOR1A (DYT1) gene in atypical early onset dystonia and polymorphisms in dystonia and early onset parkinsonism.  Neurogenetics. 2001;  3 133-143
  • 62 Klein C, Liu L, Doheny D et al.. Epsilon-sarcoglycan mutations found in combination with other dystonia gene mutations.  Ann Neurol. 2002;  52 675-679
  • 63 De Vries D D, Went L N, Bruyn G W et al.. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia.  Am J Hum Genet. 1996;  58 703-711
  • 64 Desguerre I, Pinton F, Nabbout R et al.. Infantile spasms with basal ganglia MRI hypersignal may reveal mitochondrial disorder due to T8993G MT DNA mutation.  Neuropediatrics. 2003;  34 265-269
  • 65 Jun A S, Brown M D, Wallace D C. A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia.  Proc Natl Acad Sci USA. 1994;  91 6206-6210
  • 66 Shoffner J M, Brown M D, Stugard C et al.. Leber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation.  Ann Neurol. 1995;  38 163-169
  • 67 Simon D K, Friedman J, Breakefield X O et al.. A heteroplasmic mitochondrial complex I gene mutation in adult-onset dystonia.  Neurogenetics. 2003;  4 199-205
  • 68 Solano A, Roig M, Vives-Bauza C et al.. Bilateral striatal necrosis associated with a novel mutation in the mitochondrial ND6 gene.  Ann Neurol. 2003;  54 527-530
  • 69 Sudarsky L, Plotkin G M, Logigian E L, Johns D R. Dystonia as a presenting feature of the 3243 mitochondrial DNA mutation.  Mov Disord. 1999;  14 488-491
  • 70 Binder J, Hofmann S, Kreisel S et al.. Clinical and molecular findings in a patient with a novel mutation in the deafness-dystonia peptide (DDP1) gene.  Brain. 2003;  126 1814-1820

Pedro Gonzalez-AlegreM.D. 

Assistant Professor, Department of Neurology, 2-RCP, Carver College of Medicine at The University of Iowa

200 Hawkins Drive, Iowa City, IA 52242

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