Torsion dystonia

Torsion dystonia is a motor disorder, which is characterized by the obstinate or irregular muscular contractures that condition pathological and usually repetitive movements and/or pathological poses. Dystonic movements are usually of the same type, rotatory and can be accompanied by the tremor. Dystonia usually manifests or increases in voluntary movements and is accompanied by the excessive activation of the muscles. Such patients demonstrate rotatory hyperkinesis, changes in the muscle tonus and various pathological positions of the body.

The forms with proven genetic etiology are considered inherited:

• Autosomal dominant type. Several types belong here, such as DYT1 (OMIM #128100), DYT5 (#128230), DYT6 (#602629), DYT11 (#159900), rapidly developing dystonia-parkinsonism (DYT12, #128235), neuroferritinopathy (NBIA3, #606159), dentatorubral and pallidoluysianatrophy (#125370) and Huntington’s disease (#143100).
• Autosomal recessive type. The list of the autosomal recessive types of the innate dystonia keeps being expanded. It includes Wilson disease (OMIM #277900), PKAN (NBIA1, #234200), PLAN (NBIA2, #256600) and type 2 juvenile parkinsonism (PARK2, #600116), along with the range of metabolic disorders.
• X-linked recessive inheritance. Such innate dystonia includes Lubag syndrome (DYT3, OMIM #314250), Lesch-Nyhan syndrome (#300322) and Mohr-Tranebjaerg syndrome (#304700).
• Mitochondrial inheritance. Mitochondrial forms such as Leigh syndrome (OMIM #256000) or Leber's acute optic neuropathy and dystonia (#500001) are also inherited types of dystonia.

Genetic tests as the only method of diagnostics are not sufficient for the diagnosis of dystonia without clinical signs [Bressman SB et al., 2000; Klein C et al., 1999]. Genetic tests must be done only after clinical diagnosis (B class of recommendations). Diagnostic DYT-1 testing and genetic consulting are recommended for the patients in the cases of disease manifestation with extremities dystonia and primary dystonia before age of 30, as well as the disease onset after 30 if there are members of the family with early dystonia manifestation (B class of recommendations) [Bressman SB et al., 2000; Klein C et al., 1999]. In familial dystonia with no symptoms DYT-1 testing is not recommended. Diagnostic DYT-6 testing is recommended to the patients with early onset of dystonia or in the family dystonia with craniocervical type [Djarmati A. et al., 2009; Bressman SB et al., 2009], or when DYT-1 is excluded.

The patients with early onset of myoclonus with involved extremities and neck, especially if autosomal dominant inheritance is possible, must be tested for DYT-11 gene [Valente EM et al., 2005]. Diagnostics for DYT-8 gene is recommended for the patients with paroxysmal non- kinesiogenic form.

Genetic tests for the mutation in GLUT1 are recommended to the patients with exercise-induced paroxysmal dyskinesia, especially if epileptic fits or hemolytic anemia prompt GLUT1 involvement. The recommendations of the European Federation of Neurological Societies, EFNS, 2011 published the results of the consensus of the EFNS and Movement Disorders Society (MDS) on dystonia (Albanese A. et al., 2011). According to them, the botulinum A toxin is recommended as the first line drug for focal types of dystonia (cervical dystonia, blepharospasm): 23 1. The injections of the botulinum A toxin are the first line therapy for the primary cranial (excluding oromandibular) or cervical dystonia (A class of recommendations). 2. The botulinum A toxin is beneficial for penman's palsy (A class of recommendations) and can be effective for other types of dystonia but more accurate selection of the doses is necessary due to frequent muscle weakness. There is no therapy for genetic forms of the diseases and the treatment is symptomatic