Identification of Genetic Mutations Involved in Chiari Type I Malformations

Study Overview
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Brief Summary
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Although most cases of Chiari malformation type I (CM1) are sporadic, familial cases of CM1, with or without syringomyelia, suggest a genetic cause in the pathogenesis of these malformations. The hypothesis is that there is one or more genes, in particular among those involved in the development of the axial skeleton and the cranium, which could lead to an abnormal morphology of the posterior fossa resulting in tonsillar herniation defining CM1. The abnormal circulation of cerebrospinal fluid due to tonsillar herniation is believed to be responsible, in some patients whose predisposing factors remain to be determined, for the progressive onset of associated syringomyelia. Since the determinants underlying the development of the posterior fossa of the skull are multigenic, the analysis of familial cases would make it possible to reduce genetic and phenotypic heterogeneity allowing to identify common pathogenic variants. For this study the investigators will be taking a blood sample to perform whole exome sequencing, build a biological collection and record imaging and clinical data.

Official Title
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Identification of Genetic Mutations Involved in Chiari Type I Malformations

Conditions
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Chiari Malformation, Type 1

Intervention / Treatment
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* Genetic: Blood Sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having a social security Participant or legal representative having given his consent For patients: Diagnosis of a Chiari malformation type 1, defined morphologically as cerebellar tonsillar herniation beyond the foramen magnum greater than 5 mm, with or without associated syringomyelia, and which has at least one relating to the 1st or 2nd degree (parents, siblings; grandparents, uncles, aunts, cousins) carrying the malformation. For relatives: at least two 1st degree relatives diagnosed with a Chiari type 1 malformation Exclusion Criteria: Syndromic form of Chiari malformation Patient with a legal protection measure Pregnant or breastfeeding woman Contraindication to MRI For patients: diagnosis of Chiari malformation type 1 that could not be confirmed by MRI For relatives: age under 18 years
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Blood sample for all participant during a consultation specific for the study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood Sample<br>Blood Sample | Genetic: Blood Sample<br>* clinical-radiological evaluation, genetic analysis by whole exome sequencing and constitution of a bio-collection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of the gene (s) whose mutations are responsible for the occurrence of a Chiari type I malformation, whether associated with syringomyelia or not. | Description of gene mutations in patients with Chiari type I malformation by whole exome sequencing | At inclusion (as soon as the patient agree) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of the gene (s) whose mutations are associated with the occurrence of syringomyelia in patients with Chiari type I malformation | Description of gene mutations in patients with syringomyelia associated with Chiari type I malformation | At inclusion (as soon as the patient agree) | 
| Establishment of a DNA bank for familial Chiari type I malformations | Bio-collection | At inclusion (as soon as the patient agree) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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syringomyelia, genetic mutation