Identification of Genetic Mutations Involved in Chiari Type I Malformations

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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Key information

Conditions

Chiari Malformation, Type 1 Arnold-Chiari Malformation Central Nervous System Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Nervous System Diseases Nervous System Malformations Neural Tube Defects Spinal Cord Diseases Syringomyelia

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Service de Neurochirurgie

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

blood sample

Genetic

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

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.

Time frame: 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

Time frame: 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

Time frame: At inclusion (as soon as the patient agree)

Bio-collection

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: ChiariGene

Important dates

Study start: 2022
Primary completion: 2022
Study completion: 2025
First posted: Dec 21, 2021
Registry last updated: Mar 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed