*REGISTRY - an observational study of the European Huntington's Disease Network (EHDN)*

Huntington*s disease (HD) is an autosomal dominant neurodegenerative disorder
that results from an unstable expansion of the trinucleotide repeat CAG in the
HD gene IT-15. HD has a prevalence of 5-10 per 100,000 in the general
population. The clinical features of HD usually emerge in adulthood (mean age
of 40 years) with a movement disorder, cognitive dysfunction and psychiatric
symptoms. The course of HD is relentless, leading to functional disability and
death over a period of 10-30 years. With genetic testing (following genetic
counseling) it is possible to predict that a person will develop HD a long time
before clinical symptoms and signs develop. To date, there is no treatment that
has been shown to alter the progression of the disease. Benefical effects have
been reported when applied in model systems of HD but the predictive value of
these results for patients are unknown. As HD is a rare disease, extensive
cooperation is essential to be able to include the number of participants
required for conclusion well powered studies.

Registry is the core study of the European Huntington*s disease Network
(EHDN). The aim of the Registry study is to collect prospective data on the
phenotypical characteristics of Huntington's disease (HD) mutation carriers
regardless of whether they display clinical symptoms and signs of HD and of
individuals who are part of an HD family (irrespective of their mutation
carrier status), in order
•to obtain natural history data on a wide spectrum of HD patients, HD mutation
carriers and individuals who are part of an HD family
•to relate phenotypical characteristics with genetic factors and biomarkers
•to expedite identification and recruitment of participants for clinical trials
•to plan for future research studies (observational and interventional trials
aimed at better symptom control or aimed at slowing or postponing the onset and
progression of HD).

The registration will take place once a year within regular visits at the
out-patient clinic of the department of Neurology or nursing home. Participant
evaluation is carried out clinically using the Unified Huntington Disease
Rating Scale (UHDRS 1999) and supplementary optional questionnaires.
Furthermore participants are asked to donate biosamples (blood and urine) for
studies to identify genetic modifiers of HD and to establish and validate
biological markers tracking the progressive course of HD; in this context a
family history is requested as well in order to understand the relationships of
clinical data sets and biosamples from related donors. In addition,
non-mutation carrying family members of participants are asked to consider
donating biosamples to serve as controls. The biosamples are stored in a
central repository, BioRep, Milan.
Participant data are entered electronically via internet-based technology after
creating a unique pseudonym for each individual, based on unchanging
information. The pseudonym is a nine-figure number created by a secure one-way
algorithm. The identifying data are never stored electronically. An
investigator is only allowed to see their own patients* data. The whole
database is saved in the portal. Central Coordination is allowed to view all
data of all centres for plausibility checks, quality control and monitoring.

Since Registry is an observational study, participants do not undergo specific
risks by participating. Their burden is limited to a minimum as the
evaluations occur within the ambulant care of the Neurology department on a
regular basis.
Participants will receive no immediate benefit from participation in this
study. The only potential benefit is a better understanding of HD and the
possibility that the information obtained in this study lead to potential
treatments and to plan future research studies of experimental drugs aimed at
slowing disease progression or postponing the onset of HD.