Dystonia Genotype-Phenotype Correlation

1. Identify a cohort of individuals with known dystonia-related gene mutations, and
individuals with idiopathic but presumed-genetic dystonia. Some of these individuals may
receive botulinum toxin injections to treat their dystonia per standard of care; in
these patients, investigators will image before and after injections to assess for
imaging correlates of treatment response.

2. Analyze DNA samples from both the dystonia and healthy individual cohorts to detect the
presence of mutations and/or polymorphisms in genes associated with dystonia

3. Collect systematic clinical information, including Tsui Torticollis, Burke-Fahn-Marsden,
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), Voice Disability Index,
Unified Myoclonus Rating Scale, Beck Depression Inventory, Beck Anxiety Inventory and
Spielberg Trait Anxiety scales. Scales will be tailored to the type of dystonia, as
determined by the clinician referring into the study (i.e., torticollis scales will only
be performed on patients with cervical dystonia).

4. Use functional MRI (fMRI), diffusion tensor imaging (DTI), and structural MRI to a)
analyze brain activity and structure pre- and post-botulinum toxin injections, b)
determine how different stages of movement (execution, preparation, sequencing)
influence dystonia and the underlying neural mechanisms, c) identify structural
abnormalities shared between clinical sub-types of dystonia. As new MR imaging methods
are introduced that may improve the investigators ability to identify or distinguish
these abnormalities, the investigator will incorporate these novel sequences into the
imaging protocol.

5. Correlate brain activity and structural data with ratings of dystonia severity, location
of dystonia, genetic status, and response to treatment (medications and/or botulinum
toxin injections).

6. Correlate polymorphism data with dystonia severity, response to botulinum toxin,
depression/anxiety severity, and brain activity/structure.

General Exclusion (both Dystonia and Control groups):

- Metal in any part of the body (including metal injury to the eye) OR carrying a
medical device incompatible with MRI (e.g., metal implants such as surgical clips or
pacemakers) OR positive screening per UTSW MRI screening form

- Claustrophobia

- Non-fluent English

- Weight incompatible with MRI safety

- History of head trauma with neurological sequelae, including multiple concussions
and/or history of stroke

- Pregnancy

- Serious medical illness or history of serious medical illness, including cancer that
was treated with radiation or chemotherapy, heart attack, or a known history of HIV-1
+ status

- Subjects with Hepatitis C (by Hepatitis C+ titer)

- Subjects with insulin dependent diabetes mellitus (IDDM)

- Severe respiratory compromise

- In the opinion of the investigator, not able to safely participate in this study

Inclusion Criteria:

- Dystonia group

Previous diagnosis of dystonia which include but is not limited to:

- cervical dystonia (50 subjects)

- blepharospasm (25 subjects)

- limb dystonia (50 subjects)

- spasmodic dysphonia (25 subjects)

- segmental dystonia

- multi-focal dystonia

- Any childhood-onset dystonia (25 subjects) Age > 11 years

- Control group:

No prior dystonia diagnosis (175 subjects) Age > 11 years

Exclusion Criteria:

- Dystonia group Prior history of or concurrent neurological or psychiatric diagnosis -
depression and/or anxiety accepted Current use of non-dystonia neuroactive medications
- SSRI/medication for depression and/or anxiety accepted Current use of cervical brace
designed for dystonia treatment Prior structural brain injury

Control group:

History of or current neurological or psychiatric diagnosis - depression and/or anxiety
accepted, but must not be in active phase Current use of any neuroactive medication,
SSRI/medication for depression and/or anxiety accepted