Identification of Genetic Mutations Involved in Chiari Type I Malformations

NCT05165030 — Not applicable, Completed, 40 participants, Assistance Publique - Hôpitaux de Paris

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Registry	NCT05165030, acronym ChiariGene
Status	Completed
Phase	Not applicable
Study type	Interventional; na, single group, masking: none, other
Enrollment	40 (Actual)
Sponsor	Assistance Publique - Hôpitaux de Paris (Other)
Conditions	Chiari Malformation, Type 1
Interventions	Blood Sample (Genetic)
Dates	start 2022-06-15, primary completion 2022-06-15, completion 2025-07-25, first posted 2021-12-21, last updated 2026-03-17
Locations	1 site in France

-Summary

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.

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+Arms and interventions

Arm	Type	Interventions	Description
Blood Sample	Experimental	Genetic: Blood Sample	Blood Sample

Blood Sample (Genetic): clinical-radiological evaluation, genetic analysis by whole exome sequencing and constitution of a bio-collection

+Outcome measures

Primary outcomes

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

Secondary outcomes

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

+Eligibility

Sex: All, 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

+Locations (1)

Facility	City	Country	Status
Service de Neurochirurgie	Le Kremlin-Bicêtre, Kremlin-Bicêtre	France

+Investigators

Steven Knafo, Principal investigator, APHP