Identification of Genetic Mutations Involved in Chiari Type I Malformations

NCT05165030 | Completed

• 1 other identifier: APHP210472
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chiari Malformation, Type 1

Keywords

genetic mutation; syringomyelia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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)

• Establishment of a DNA bank for familial Chiari type I malformations

  At inclusion (as soon as the patient agree)

Study Arms (1)

Blood Sample

EXPERIMENTAL

Blood Sample

Genetic: Blood Sample

Interventions

Blood Sample GENETIC

clinical-radiological evaluation, genetic analysis by whole exome sequencing and constitution of a bio-collection

Blood Sample

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service de Neurochirurgie

Le Kremlin-Bicêtre, Kremlin-Bicêtre, 94270, France

Location

MeSH Terms

Conditions

Arnold-Chiari Malformation; Syringomyelia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neural Tube Defects; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Spinal Cord Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Steven Knafo

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Blood sample for all participant during a consultation specific for the study

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: December 21, 2021
• Study Start: June 15, 2022
• Primary Completion: June 15, 2022
• Study Completion: July 25, 2025
• Last Updated: March 17, 2026

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)