Biomarker Research in Inherited Movement Disorders
Inherited movement disorders are rare conditions, whose cumulative prevalence are in the order of 5-10/100,000 inhabitants, in most cases progressive and can lead to a significant loss of autonomy after one or more decades of evolution. They include spinocerebellar ataxias and hyperkinetic disorders (dystonias, choreas, tremor, parkinsonism and myoclonus with variable combination of those, or more complex alteration of movements). The existence of the National Reference Centre (CMR) for Rare Diseases (CMR Neurogenetics, devoted to ataxias and spastic paraparesis, dystonia and rare movement disorders and CMR Huntington, devoted to Huntington Disease) has allowed a more integrated vision of these diseases. This is illustrated, in the same family, by the occurrence of different clinical expressions of spinocerebellar ataxias and hyperkinetic disorders that share the same genetic background. Conversely, different causal mutations within the same gene may have very different ages at onset and a wide range of clinical expression, and the spectrum of new phenotypes linked to a single gene is still expanding . Many ataxia and dystonia genes are involved in similar pathways. There are numerous arguments supporting a share pathogenesis including synaptic transmission and neurodevelopment . BIOMOV project aims to : 1. establish the clinical spectrum and natural history of these diseases, 2. understand the role of genetic and familial factors on the phenotype, 3. elucidate the molecular basis of these disorders and evaluate diagnostic strategies involving molecular tools for clinical and genetic management, 4. develop multimodal biomarkers both for physiopathological studies and for accurate measures of disease progression, 5. develop trial ready cohorts of well characterized genetic patients, 6. test new therapies either symptomatic or based on pathophysiological mechanisms.
⁃ Common inclusion criteria for all participants:
⁃ \- - Affiliated with a social security system or beneficiary of such a regime
⁃ Group of patients:
⁃ Any patient with inherited hyperkinetic movement disorders can be included in the study according to the following criteria:
⁃ Woman or man;
• Clinical diagnosis of inherited hyperkinetic movement disorders with or without a genetic diagnosis
• With or without familial history of the disease
• Age ≥ 7 years;
• Signed Informed consent by the patient or both of holders of the parental authority for minors, or by the le;gal guardian for adults under guardianship
⁃ Group of at-risk individuals:
• Woman or man;
• Age ≥ 18 years old;
• A first-degree relative of a patient with inherited hyperkinetic movement disorders
• OR a carrier of an identified pathogenic variant or expansion in one of the pathological gene variant involved in one of these diseases;
• Normal neurological examination; according to disease specific scales
• Signed Informed consent by the subject or by the legal guardian for adults under guardianship
⁃ Group of healthy controls:
• Woman or man;
• Aged ≥ 18 years old;
• Free of known neurological pathology;
• No significant neurological symptoms;
• Signed Informed consent by the subject
⁃ Common inclusion criteria for elective participant for skin biopsy (optional): - Age ≥10 ans
• Ability to undergo a skin biopsy
⁃ Common inclusion criteria for elective participant for MRI examination (optional): - Ability to undergo a MRI.