Early onset primary dystonia.

Dystonia is a syndrome characterized by sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. It is classified by age at onset, by distribution, and by aetiology. The aetiological classification distinguishes the following categories: primary, dystonia plus, secondary, heredo-degenerative and psychogenic dystonia. Primary dystonia is defined as clinical condition characterized by dystonia as the only neurological abnormality apart from tremor. Different genetic alterations and gene loci have been mapped in familial and sporadic patients. Early onset-primary dystonia (EO-PD) is the most severe form of primary dystonia, with clinical and genetic heterogeneity. It usually starts in one body part, subsequently spreads to involve other body regions with frequent generalization. DYT1 dystonia is transmitted as an autosomal dominant trait with reduced penetrance. The unique underlying mutation is a GAG deletion in the coding region of the TOR1A gene, located at chromosome 9q34. DYT16 dystonia is a novel recessive form of EO-PD, recently described in few patients, caused by mutations in the PRKRA gene located at chromosome 2q31. At least other two loci have been mapped, but there remains a large number of patients with EO-PD in whom no genetic alteration is discovered.

[1]  S. Bressman,et al.  The diagnosis of dystonia , 2006, The Lancet Neurology.

[2]  C. Marsden,et al.  Classification of dystonia. , 1998, Advances in neurology.

[3]  E. Altenmüller,et al.  A heterozygous frameshift mutation in PRKRA (DYT16) associated with generalised dystonia in a German patient , 2008, The Lancet Neurology.

[4]  J. Jankovic,et al.  Parkinson's Disease and Movement Disorders , 1988 .

[5]  Christine Klein,et al.  Novel mutation in the TOR1A (DYT1) gene in atypical, early onset dystonia and polymorphisms in dystonia and early onset parkinsonism , 2001, Neurogenetics.

[6]  P. Starr,et al.  Treatment of dystonia with deep brain stimulation , 2008, Neurotherapeutics.

[7]  M. Zeviani,et al.  Frequency of DYT1 mutation in early onset primary dystonia in Italian patients , 2002, Movement disorders : official journal of the Movement Disorder Society.

[8]  J. Dostrovsky,et al.  Globus pallidus internus pallidotomy for generalized dystonia , 1997, Movement disorders : official journal of the Movement Disorder Society.

[9]  J. Villanueva,et al.  Hereditary torsion dystonia in gypsies. , 1988, Advances in neurology.

[10]  C. Marsden,et al.  Natural history of idiopathic torsion dystonia. , 1976, Advances in neurology.

[11]  R. Lencer,et al.  Mutations in DYT1 , 2004, Neurology.

[12]  S Fahn,et al.  Tolcapone , 1998, Neurology.

[13]  S. Hemm,et al.  Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results. , 2004, Journal of neurosurgery.

[14]  C. Kamm.  Early onset torsion dystonia (Oppenheim's dystonia) , 2006, Orphanet journal of rare diseases.

[15]  M. Claustres,et al.  First determination of the incidence of the unique TOR1A gene mutation, c.907delGAG, in a Mediterranean population , 2007, Movement disorders : official journal of the Movement Disorder Society.

[16]  F. Asmus,et al.  Inherited myoclonus-dystonia. , 2004, Advances in neurology.

[17]  N. Nardocci,et al.  Myoclonus–dystonia syndrome: Clinical presentation, disease course, and genetic features in 11 families , 2008, Movement disorders : official journal of the Movement Disorder Society.

[18]  K. Dujardin,et al.  Bilateral, pallidal, deep-brain stimulation in primary generalised dystonia: a prospective 3 year follow-up study , 2007, The Lancet Neurology.

[19]  S. Hemm,et al.  Treatment of DYT1-generalised dystonia by stimulation of the internal globus pallidus , 2000, The Lancet.

[20]  Laurie Ozelius,et al.  Intrafamilial phenotypic variability of the DYT1 dystonia: From asymptomatic TOR1A gene carrier status to dystonic storm , 2002, Movement disorders : official journal of the Movement Disorder Society.

[21]  S. Bressman.  Dystonia genotypes, phenotypes, and classification. , 2004, Advances in neurology.

[22]  T. H. Burnstine,et al.  Movement Disorders 2 , 1988, Neurology.

[23]  C. Sabatti,et al.  The DYT1 phenotype and guidelines for diagnostic testing , 2000, Neurology.

[24]  C. Marras,et al.  Stimulation of the globus pallidus internus for childhood‐onset dystonia , 2005, Movement disorders : official journal of the Movement Disorder Society.

[25]  T. Meitinger,et al.  Mutations in the gene encoding ɛ-sarcoglycan cause myoclonus–dystonia syndrome , 2001, Nature Genetics.

[26]  C. Marsden,et al.  Evidence for locus heterogeneity in autosomal dominant torsion dystonia. , 1993, Genomics.

[27]  Sonja W. Scholz,et al.  DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA , 2008, The Lancet Neurology.

[28]  W. Dauer,et al.  Loss of the Dystonia-Associated Protein TorsinA Selectively Disrupts the Neuronal Nuclear Envelope , 2005, Neuron.

[29]  K. Swoboda,et al.  Diagnosis and treatment of neurotransmitter-related disorders. , 2002, Neurologic clinics.

[30]  H. Topka,et al.  Frequency and phenotypic variability of the GAG deletion of the DYT1 gene in an unselected group of patients with dystonia. , 2003, Archives of neurology.

[31]  N. Risch,et al.  Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population , 1995, Nature Genetics.

[32]  G. Deuschl,et al.  Pallidal deep-brain stimulation in primary generalized or segmental dystonia. , 2006, The New England journal of medicine.

[33]  M. Brin,et al.  Idiopathic torsion dystonia linked to chromosome 8 in two mennonite families , 1997, Annals of neurology.

[34]  S Fahn,et al.  Dystonia in Ashkenazi Jews: Clinical characterization of a founder mutation , 1994, Annals of neurology.

[35]  S. Bressman,et al.  Erratum: Dystonia in Ashkenazi Jews: Clinical characterization of a founder mutation (Annals of Neurology (1994) 36 (771-777)) , 1995 .

[36]  N W Wood,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 , 2001, Annals of neurology.

[37]  Stanley Fahn,et al.  Human gene for torsion dystonia located on chromosome 9q32-q34 , 1989, Neuron.

[38]  N. Risch,et al.  The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein , 1997, Nature Genetics.

[39]  D. Corey,et al.  Effects of genetic variations in the dystonia protein torsinA: identification of polymorphism at residue 216 as protein modifier. , 2006, Human molecular genetics.

[40]  C. Marsden,et al.  The role of DYT1 in primary torsion dystonia in Europe. , 1998, Brain : a journal of neurology.

[41]  N. Risch,et al.  De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia. , 1998, Human molecular genetics.

[42]  J. Jankovic.  Dystonia: medical therapy and botulinum toxin. , 2004, Advances in neurology.

[43]  F. Micheli,et al.  Unusual phenotypic expression of the DYT1 mutation. , 2003, Parkinsonism & related disorders.

[44]  M. Hallett,et al.  The pathophysiological basis of dystonias , 2008, Nature Reviews Neuroscience.