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

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.

Study Overview

• Status: Completed
• Conditions: Chiari Malformation, Type 1
• Intervention / Treatment: Genetic: Blood Sample

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Kremlin-Bicêtre
    • Le Kremlin-Bicêtre, Kremlin-Bicêtre, France, 94270
      • Service de Neurochirurgie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Steven Knafo, APHP

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): July 25, 2025

Study Registration Dates

• First Submitted: October 28, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: genetic mutation; syringomyelia
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Congenital Abnormalities; Spinal Cord Diseases; Nervous System Malformations; Neural Tube Defects; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Syringomyelia; Arnold-Chiari Malformation; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: APHP210472

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No