Genetic Analysis of the Chiari I Malformation

Tracking Information

Start Date  ICMJEFebruary 2000
Primary Completion Date 
Current Primary Outcome Measures  ICMJE 
Original Primary Outcome Measures  ICMJE 
Change HistoryComplete list of historical versions of study NCT00004738 on Archive Site

Descriptive Information

Brief Title  ICMJEGenetic Analysis of the Chiari I Malformation
Official Title  ICMJEGenetic Analysis of the Chiari I Malformation
Brief Summary

The purpose of this study is to better understand the genetic factors related to the Chiari I malformation. In people with this abnormality, the lower part of the skull is smaller than normal. As a result, the lowest part of the brain, called the cerebellar tonsils, protrudes out of the hole at the bottom of the skull into the spinal canal. This study will try to discover the location of the genes responsible for the malformation.

Candidates for this study are: 1) Patients with Chiari I malformation who also have a family member with the abnormality or a family member with syringomyelia (a cyst in the spinal cord that is often associated with the Chiari I malformation). 2) Family members of patients with the Chiari I malformation.

Participants will have a medical history and physical and neurologic examinations. They will undergo magnetic resonance imaging (MRI) of the brain and cervical (neck) spinal cord to measure the size of the head and determine the presence of the Chiari I malformation and syringomyelia. A small blood sample (about 2 tablespoons) will be drawn for DNA studies relating to the Chiari I malformation.

Detailed Description

Objectives: The goal of this study is to establish family pedigrees and undertake genetic linkage analysis that will identify gene loci associated with the Chiari I malformation and underdevelopment of the bone forming the posterior cranial fossa.

Study Population: Patients and family members of patients with the Chiari I malformation. Because the research institutions are located in the United States and Russia, subjects will be recruited predominantly from these countries.

Design: Human subjects will undergo 1) neurologic examinations, 2) head and cervical MRI scans to evaluate for the Chiari I malformation, syringomyelia, and maldevelopment of the posterior fossa, and 3) isolation and analysis of genomic DNA from whole blood for linkage analysis.

Outcome Measures: Pedigrees will be established based on the MRI findings. The Chiari I phenotype will be defined as the caudal portion of the cerebellar tonsils lying greater than or equal to 2 mm below the foramen magnum and underdevelopment of the bone of the posterior fossa will be defined as 1) obliteration of the CSF pathways in the inferior portion of the posterior fossa, 2) posterior fossa volume to supratentorial volume ratio of less than or equal to 15%, or 3) abnormal shortening of the bones of the skull base. Genetic analysis of the genomic DNA will be performed with DNA polymorphic markers to identify chromosomal loci linked to the small posterior fossa phenotype. A lod score of 3.0 (equivalent to 1000:1 odds in favor of linkage) will be taken as proof that the Chiari I gene maps to the same genetic region of the human genome as a given DNA marker.

Study Phase 
Study Type  ICMJEObservational
Study Design  ICMJE 
Condition  ICMJE
  • Syringomyelia
  • Type I Arnold Chiari Malformation
Intervention  ICMJE 
Study Arms / Comparison Groups 
Publications *

Recruitment Information

Estimated Enrollment  ICMJE200
Completion Date 
Primary Completion Date 
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA: To be eligible for entry into the study, a candidate must meet the following criteria:

Patient with the Chiari I malformation who has a family member with syringomyelia or Chiari I malformation, or

Family member of a patient with the Chiari I malformation, AND

There are at least two family members diagnosed with Chiari I malformation.

If an adult, able to give informed consent; if a minor, has an adult who is legally responsible for the subject and who is able to give consent.

EXCLUSION CRITERIA: A candidate will be excluded if he:

Has a contraindication to MRI scanning.

Is unable to comprehend the risks of the testing.

Is less than one year of age.

Cannot undergo MRI scanning without sedation.

Ages1 Year and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Patient Recruitment and Public Liaison Office(800)
Contact: TTY1-866-411-1010
Location Countries  ICMJEUnited States,   Russian Federation

Administrative Information

Responsible Party 
Study ID Numbers  ICMJE000089, 00-N-0089
Study Sponsor  ICMJENational Institute of Neurological Disorders and Stroke (NINDS)
Collaborators  ICMJE 
Investigators  ICMJE 
Information Provided ByNational Institutes of Health Clinical Center (CC)