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

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

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:

1. restriction of the quality of life by unclear disease
2. Cost of not purposeful preliminary diagnostics ( beyond the minimal diagnostic data set )
3. Impact of the diagnosis to therapy and follow-up examinations
4. Time to diagnosis

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:

1. Restriction of the quality of life by unclear disease
2. Cost of not purposeful preliminary diagnostics (beyond the minimal diagnostic data of the diagnosis to therapy and follow-up examinations
3. Time to diagnosis

Inclusion Criteria:

For patients> 18 years

1. 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

2. 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

1. Lack of consent
2. symptom onset > 40 years of age
3. Sudden, abrupt beginning
4. As early as previous history of genetic diagnosis using next-generation sequencing (NGS), also in the form of a panel

For patients <18 years

1. injury brain disorders

   • On the basis of imaging
   • On the basis of medical history (premature baby, hypoxic-ischemic encephalopathy)

2. Inflammatory brain disorders

   • On the basis of imaging
   • On the basis of laboratory parameters (Oligoclonal fractions, cerebrospinal fluid (CSF) cell count increased)

3. 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)

4. Sudden , abrupt beginning

5. Next-generation sequencing (NGS) also in the form of a panel