MEN (General Swiss-German Mennonite)

Inheritance: autosomal dominant
Genes: DYT1

Dystonia musculorum deformans 1
DYT1
Early onset torsion dystonia
EOTD

Dystonia
Torsion dystonia
Deformans
Involuntary movements
Facial grimacing
Blepharospasm
Torticollis
Speech difficulties

Dystonia 1

Clinical Characteristics

General description (for patients):

This is an involuntary movement disorder in which muscle contractions are prolonged with delayed relaxation.  Often patients exhibit twisting and writhing movements in affected body parts.  Tremors and distorted speech also may be a part of this condition.  It may affect only one part of the body such as an arm or a leg or become more generalized to involve multiple limbs as well as the face and tongue.  Onset is usually in childhood, and often early in the second decade.  There is a wide range of severity and muscle involvement.  The tongue, eyelids, throat, neck and facial muscles may be involved but in this type the disease infrequently begins in this world. Regardless of the region of onset, the disorder becomes generalized within several years.  Mental function is rarely affected although speech and fine motor skills are negatively impacted.

Medical description:  

Dystonia 1 is one of multiple types of torsion dystonia that may be difficult to differentiate. DYT1 is more likely to begin in one or more limbs but soon becomes more generalized with head and neck involvement. Blepharospasm, torticollis, speech difficulties and facial grimacing are common.  PET scans show hypometabolism in the inferior cerebellum ad putamen with a decrease in the anterior cingulate in contrast to DYT6 (see %602629).  It has also been reported that plasma dopamine-beta-hydroxylase is elevated.

Genetics:

Like most dystonias, DYT1 is an autosomal dominant disease.  It is found in high frequency in Ashkenazi Jews but is also found around the world.  Only one case of this type has been found in plain people, in a male with Swiss-Mennonite ancestry who was a distant relative of a Mennonite family in which DYS6 (see Dystonia 6 and OMIM %602629) segregated in autosomal dominant fashion.  The mutation has been linked to a chromosome 9 locus gene, DYT1 (9q34).  There are two more related Mennonite families who seem to have yet another mutation causing dystonia (see Dystonia 6 for a full discussion of this heterogeneity).

Treatment:

 A variety of treatments including deep brain stimulation, dopamine, and botulinum toxin have been tried with variable outcomes depending on the characteristics of the specific type of dystonia.  Treatments must be customized to the individual.
PROGNOSIS:  This is a progressive disease that can lead to significant disabilities.

Ancillary treatments and support:

General support, mobility training.

Specialists and specialty centers:

Neurologist.

References:

Klein, C., Brin, M.F., de Leon, D., Limborska, S.A., Ivanova-Smolenskaya, I.A., Bressman, S.B., Friedman, A., Markova, E.D., Risch, N.J., Breakefield, X.O., and Ozelius, L.J.:  De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia.  Hum. Mol. Genet. 7: 1133-1136, 1998.  PubMed ID: 9618171

Bressman, S.B., Raymond, D., Wendt, K., Saunders-Pullman, R., de Leon, D., Fahn, S., Ozelius, L., and Risch, N.:  Diagnostic criteria for dystonia in DYT1 families.  Neurology 59: 1780-1782, 2002.  PubMed ID: 12473770

Nemeth, A.H.:  The genetics of primary dystonias and related disorders. Brain 125: 695-721, 2002.  PubMed ID: 11912106

Resources:

Dystonia Research Foundation
NIH-NINDS