risca : prospective study of individuals at risk for sca1, sca2, sca3, sca6, sca7

Conditions: Spinocerebellar Ataxias

Summary: the spinocerebellar ataxias (scas) are a clinically and genetically heterogeneous group of autosomal dominantly inherited progressive ataxia disorders. it is estimated that there are 30,000 individuals in the european community that directly descend from individuals affected by a sca disorder and thus carry a 50% risk of having inherited an sca mutation. these at risk individuals provide a unique research opportunity to prospectively study the presymptomatic phase of sca disorders and to identify the earliest and most sensitive clinical signs and biological markers that herald the onset of the illness. this information is of critical importance for the development of future therapeutic interventions aimed at postponing the clinical onset of ataxia. we therefore propose to perform a prospective observational study of individuals at risk for the most common sca disorders, sca1, sca2, sca3 and sca6 (risca). it is our aim to answer the following questions: (1) what is the incidence of disease manifestation in mutation carriers? (2) which clinical signs precede the onset of manifest ataxia in sca1, sca2, sca3 and sca6? (3) what are the prevalence and incidence of preceding signs? (4) are the prevalence and incidence of preceding signs affected by genotype, gender, age, estimated time until disease manifestation and repeat length? (5) does the presence of certain preceding signs predict the manifestation of ataxia ? (6) are there mri alterations that precede the onset of ataxia? it is planned to enroll 480 study participants and to follow them at regular intervals over six years. at each visit, study participants are asked in a structured interview for a number of predefined clinical signs that potentially precede the onset of ataxia. in addition, the following self-assessment scales will be applied: pittsburgh sleep quality index (psqi), diagnostic criteria for restless legs syndrome, patient´s health questionnaire (phq-9). all study participants will undergo a physical examination including the scale for the assessment and rating of ataxia (sara). study participants will further perform the sca functional composite (sca-fc) which is a comprehensive measure of functional capacity based on results in quantitative tests related to gait (8m timed walk), speech (pata rate) and hand function (9 hole pegboard). in a subset of study participants, we will record eye movements and obtain volumetric mris. the study will also be used to collect and store blood and urine samples for proteomic and gene expression studies. risca is conducted by the ataxia study group (asg). it relies on the network structure created by the eurosca project.


Eligibility criteria:
inclusion criteria: * individuals at risk for spinocerebellar ataxia type 1, type 2, type 3, type 6 and type 7 (sca1, sca2, sca3, sca6 and sca7) * age between 18 and 50 years old for sca1, sca2, sca3 or sca7 * age between 35 and 70 years old for sca6 * no clinical sign of ataxia (sara \< 3) exclusion criteria: * no writing consent * no family members affected * presence of clinical sign of ataxia (sara \> 3)

Keywords: individuals at risk for sca1, sca2, sca3, sca6 and sca7