Identification of Genetic Mutations Involved in Chiari Type I Malformations (ChiariGene)

Assistance Publique - Hôpitaux de Paris

Status: Unknown

Conditions: Chiari Malformation, Type 1

Treatments: Genetic: Blood Sample

Study type: Interventional

Funder types: Other

Identifiers

NCT05165030

APHP210472

Details and patient eligibility

About

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.

Enrollment: 40 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Blood Sample

Experimental group

Description:

Blood Sample

Treatment:

Genetic: Blood Sample