Next Generation Sequencing Diagnostics - On the Road to Rapid Diagnostics for Rare Diseases

Study Overview
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Brief Summary
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In the study, NextGen SE are on-hand a cohort comprising each 50 pediatric and 50 adult patients, and in which there are an unclear movement disorder or an unclear cognitive disorder, examines the following questions : Primary: Number of diagnoses made by NGS Secondary: restriction of the quality of life by unclear disease Cost of not purposeful preliminary diagnostics ( beyond the minimal diagnostic data set ) Impact of the diagnosis to therapy and follow-up examinations Time to diagnosis

Detailed Description
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In the study NextGen SE (single-center, prospective, open diagnostic study) are on-hand a cohort comprising each 50 pediatric and 50 adult patients, and in which there are an unclear movement disorder or an unclear cognitive disorder, examines the following questions: Primary: Number of diagnoses made by next-generation sequencing (NGS) Secondary: Restriction of the quality of life by unclear disease Cost of not purposeful preliminary diagnostics (beyond the minimal diagnostic data of the diagnosis to therapy and follow-up examinations Time to diagnosis

Official Title
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Next Generation Sequencing Diagnostics - On the Road to Rapid Diagnostics for Rare Diseases

Conditions
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Movement Disorder, Cognitive Decline

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For patients> 18 years Unclear movement disorder o Progressive ataxia after minimal exclusion diagnostics: magnetic resonance tomography (MRT) (structural lesions such as cerebellar tumor, malformation) Laboratory (Vitamin B12, thyroid peroxidase (TPO) antibodies, glutamate decarboxylase (GAD) II-antibodies (AK) In medullary lesions: Liquor exclusion Friedreich ataxia (FRDA) and spinocerebellar ataxia type (SCA)1-2-3-6 o Progressive para-spasticity by minimal exclusion diagnostics: MRT neuro axis (structural lesions such as cervical myelopathy) Laboratory (Vitamin B12, human T-cell lymphotrophic virus ((HTLV)-AK) In medullary lesions: Liquor Unclear cognitive decline o After minimal exclusion diagnosis MRT (intracranial pressure, focal brain lesions explanatory) laboratory (Thyroid-stimulating hormone (TSH), TPO-AK, antibody profile limbic encephalitis) Liquor (inflammation, meningitis) Electroencephalography (EEG) (Status) Exclusion chromosome 9 open reading frame 72 (C9orf72) For patients <18 years Patients with (penetrating) suspected cerebral neurogenetic diseases Unclear movement disorder (spasticity, ataxia, dyskinesia) Unclear cognitive disorder with probability of monogenic origin Fragile X Syndrome (Fra-X) at mentally retarded boy, Friedreich ataxia (FRDA) with ataxia should be genetically excluded Exclusion Criteria: For patients > 18 years Lack of consent symptom onset > 40 years of age Sudden, abrupt beginning As early as previous history of genetic diagnosis using next-generation sequencing (NGS), also in the form of a panel For patients <18 years injury brain disorders On the basis of imaging On the basis of medical history (premature baby, hypoxic-ischemic encephalopathy) Inflammatory brain disorders On the basis of imaging On the basis of laboratory parameters (Oligoclonal fractions, cerebrospinal fluid (CSF) cell count increased) Light, isolated mental developmental disorder or behavioral disorder (rare monogenetic) - (less than 2 standard deviartion of normal or - < 6 year olds - less than 1 year in development history back) Sudden , abrupt beginning Next-generation sequencing (NGS) also in the form of a panel
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult patients<br>Unclear movement disorder, unclear cognitive decline | |
| Patients < 18 years<br>Patients with (penetrating) suspected cerebral neurogenetic diseases | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of diagnoses made by next gereration sequency (NGS) |  | Within the study period of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Restriction of the quality of life by unclear disease measured rated by Quality of Life Questionnaire (EQ5D), Depression Questionnaire (PHQ) | EQ-5D: Calculation preference value PHQ: Categorical analysis carried out by modified evaluation algorithms of the Diagnostic and Statistical Manual of Mental Disorders (DSM) -IV B | At day 1 | 
| Cost of not purposeful preliminary diagnostics rated by questionnaire on costs (number of outpatient performances, stationary investigations, repetition 's imaging, genetic single diagnostics, high-priced diagnostic |  | At day 1 | 
| Time to diagnosis | For patients whose diagnosis can be made by NGS | At day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NGS, Quality of life, Diagnosis, Rare disease, Next-generation sequencing