Disorder
Dystonia 6

Clinical Characteristics

General description (for patients):

This an involuntary movement disorder in which the onset is frequently in muscles of the head and neck (face, larynx, and tongue) which later spreads to the arms and legs but the order may be reversed.  Twisting movements and abnormal posturing are characteristic. The average age of onset is about 19 years although the range is wide (5 to 35 years). The disorder sometimes involves only one or two limbs but often progresses to become more generalized.  Many types are known.

Medical description (for healthcare providers):

This is one of two dystonia disorders reported among Mennonites.  The onset of DYT6 is usually 5 years later, about age 18 years on average, than the DYT1 form.  It also more frequently begins in the head and neck, such as the larynx, tongue and facial muscles.  Those in whom the limbs are first involved frequently develop more generalized disease with cranial and cervical muscle involvement.  PET scans have shown hypometabolism in the putamen and hypermetabolism in the temporal cortex.

Genetics:

The DYT6 gene has been localized to chromosome 8 (8p21-q22) and segregates as an autosomal dominant.  A total of 23 members of three Midwestern Mennonite families, descended from several  Amish ancestors, were recently (2009) found to have an insertion/deletion frameshift mutation in exon 2 of the THAP1 gene that likely results in a defect in its DNA-binding function.  See also Dystonia 1


Management:

A variety of treatments including deep brain stimulation, botulinum toxin, and dopamine are available but must be customised for the individual.

Support, mobility training.

Prognosis:

Gradual worsening of the dystonia.

Specialists and specialty centers:

Neurologist.

References:

Fuchs, T, Gavarini, S., Saunders-Pullman, R., Raymond, D., Ehrlich, M.E., Bressman, S.B., and Ozelius, L.J.:  Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia.  Nat. Genet. 41: 286-288, 2009.  PubMed ID: 19182804

Almasy, L, Bressman, S.B., Raymond, D., Kramer, P.L., Greene, P.E., Heiman, G.A., Ford, B., Yount, J., de Leon, D., Chouinard, S., Saunders-Pullman, R., Brin, M.F., Kapoor, R.P., Jones, A.C., Shen, H., Fahn, S., Risch, N.J., and Nygaard, T.G.:  Idiopathic torsion dystonia linked to chromosome 8 in two Mennonite families.  Ann. Neurol. 42: 670-673, 1997. PubMed ID: 9382482

Carbon, M., Su, S., Dhawan, V., Raymond, D., Bressman, S., and Eidelberg, D.: Regional metabolism in primary torsion dystonia: effects of penetrance and genotype.  Neurology 62: 1384-1390, 2004.  PubMed ID: 15111678

Muller, U., Steinberger, D., and Nemeth, A.H.:  Clinical and molecular genetics of primary dystonias.  Neurogenetics 1: 165-177, 1998.  PubMed ID: 10737119

Xiao, J., Zhao, Y., Bastian, R.W., Perlmutter, J.S., Racette, B.A., Tabbal, S.D., Karimi, M., Paniello, R.C., Wazolek, Z.K., Uitti, R.J., Van Gerpen, J.A., Simon D.K., Tarsy, D., Hedera, P., Truong, D.D., Frei, K.P., Dev Batish, S., Blitzer, A., Pfeiffer, R.F., Gong, S., and LeDoux, M.S.:  Novel THAP1 sequence variants in primary dystonia.  Neurology. 74: 229-238, 2010

Resources:

Dystonia Medical Research Foundation
NIH-NINDS