Dystonia is a disabling neurodegenerative disease that causes sustained involuntary muscle contractions, producing twisting, repetitive and patterned movements or abnormal postures. While it is the third most common movement disorder, little is known about ethnic or racial variation in the occurrence of dystonia or about risk factors. To address this problem, we will establish a dystonia incident cohort identified from among approximately 3 million individuals in a large, multiethnic (~40% non-white) health maintenance organization. We expect to identify at least 1000 incident cases of primary torsion dystonia (PTD). This will constitute by far the largest population of PTD patients ever enrolled in an epidemiologic study and will provide the foundation for addressing, for the first time, a number of questions regarding the epidemiology of dystonia.
The first aim of this application is to estimate the incidence and prevalence of PTD overall and for clinically-defined subtypes (including generalized, cranial, cervical, limb and laryngeal dystonias). Incidence and prevalence within groups will be estimated by age, gender and race/ethnicity. This will be the first epidemiologic study of PTD of all types in a racially and ethnically diverse population.
The second aim will be to investigate familial aggregation of dystonia in cases and controls, as measured by validated family history interviews, and to determine if this varies by subtype of dystonia and ethnicity.
The third aim i s to determine the frequency of the DYT1 mutation, associated with PTD, within groups defined by ethnicity and clinical features.
Aim 4 is to investigate the role of environmental exposures that may influence the expression of dystonia and the penetrance of the known gene (DYT1), including specific antecedent health events (trauma, infection) or lifestyle factors (occupation, hobbies, cigarette smoking, physical activity) by comparing the frequency of these events before dystonia onset in cases and approximately 1000 matched controls. This will be the first investigation of the incidence, prevalence, and associated risk factors of PTD in-a large unselected multiethnic population. It will be the largest population of PTD ever studied epidemiologically. Advantages of the study setting include: (1) it is demographically similar to the underlying population of northern California, (2) access to care is unrestricted, reducing biased ascertainment, (3) a large control population is available and (4) certain health-related risk factors can be identified through computerized records, minimizing recall bias. These investigations have the potential to provide significant insights into the determinants of dystonia. In addition, this cohort will provide a rich resource for future investigations including family studies, genetic analyses and further investigations of environmental risk factors.
| Brashear, Allison; Cook, Jared F; Hill, Deborah F et al. (2012) Psychiatric disorders in rapid-onset dystonia-parkinsonism. Neurology 79:1168-73 |
| Barbano, Richard L; Hill, Deborah F; Snively, Beverly M et al. (2012) New triggers and non-motor findings in a family with rapid-onset dystonia-parkinsonism. Parkinsonism Relat Disord 18:737-41 |
| Sharma, Nutan; Armata, Ioanna A; Multhaupt-Buell, Trisha J et al. (2011) Mutation in 5' upstream region of GCHI gene causes familial dopa-responsive dystonia. Mov Disord 26:2140-1 |
| Saunders-Pullman, Rachel; Cabassa, Jose; San Luciano, Marta et al. (2011) LRRK2 G2019S mutations may be increased in Puerto Ricans. Mov Disord 26:1772-3 |
| Brüggemann, Norbert; Hagenah, Johann; Stanley, Kaili et al. (2011) Substantia nigra hyperechogenicity with LRRK2 G2019S mutations. Mov Disord 26:885-8 |
| Shanker, Vicki; Groves, Mark; Heiman, Gary et al. (2011) Mood and cognition in leucine-rich repeat kinase 2 G2019S Parkinson's disease. Mov Disord 26:1875-80 |
| Saunders-Pullman, Rachel; Barrett, Matthew J; Stanley, Kaili M et al. (2010) LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease. Mov Disord 25:2536-41 |
| Marras, C; Van den Eeden, S K; Fross, R D et al. (2007) Minimum incidence of primary cervical dystonia in a multiethnic health care population. Neurology 69:676-80 |
