Young-onset dystonia or rare movement disorders

Carried by: BRAINTEAM

References:

Clinician(s): Aurélie MENERET

Biologist(s): Fabienne CLOT

Presentation

Dystonia and rare movement disorders are characterised by the onset, in children or adults, of dystonia (focal, segmental or generalised) and/or other movement disorders such as myoclonus, tremor, parkinsonism or chorea. Their molecular bases are numerous and heterogeneous. The standard diagnostic strategy recommends first ruling out acquired causes, then performing biomarker testing and next-generation sequencing simultaneously.

Criteria before considering a discussion in MDM-FMG

Sporadic cases with onset <50 years (<20 years for focal dystonia) or familial cases:

Thorough clinical examination
Brain MRI with T2*/SWI sequences, +/- brain CT scan if iron/calcium deposits are suspected
If dopa-responsive dystonia is suspected, neurotransmitter levels in the CSF will be measured or a trial treatment with L-Dopa will be carried out
If chorea is the primary symptom, genetic disorders caused by triplet expansion (HTT, JPH3, C9ORF72, SCA17, DRPLA genes) must be ruled out before proceeding genome sequencing
In cases of complex symptoms or abnormal MRI scans suggesting a metabolic abnormality, biomarkers should be measured in parallel with the GS request.

Send in pairs at a minimum, trios if possible (except *) :

Sample ≥ 1 other affected person (preferably distant relatives) and/or
Sample ≥ 1 healthy parent:
Sporadic case: both parents if possible
Healthy relative (first cousin, etc.): favour the ‘non-at-risk’ branch ;
Healthy but at-risk relative: favour those older than the age at which the disease began in the index case
Incomplete penetrance and variable expressivity of diseases: be aware of the risk of unwanted presymptomatic diagnosis in at-risk individuals
* ‘Solo’ sampling authorised in exceptional cases : if onset of disease < 20 years of age or clear family context (≥ 2 affected individuals, consanguinity)