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Genetic Analysis of the Chiari I Malformation

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: February 26, 2000
Last updated: March 14, 2014
Last verified: November 2013

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.

Type I Arnold Chiari Malformation

Study Type: Observational
Official Title: Genetic Analysis of the Chiari I Malformation

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 200
Study Start Date: February 2000
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.


Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00004738

Contact: Rene K Smith, R.N. Not Listed

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Russian Federation
Kazan State Medical University Recruiting
Tartar Republic, Russian Federation
Sponsors and Collaborators
Principal Investigator: John D Heiss, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications: Identifier: NCT00004738     History of Changes
Other Study ID Numbers: 000089, 00-N-0089
Study First Received: February 26, 2000
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Arnold Chiari Malformation
Skeletal Dysplasia
Chiari I Malformation

Additional relevant MeSH terms:
Congenital Abnormalities
Arnold-Chiari Malformation
Neural Tube Defects
Nervous System Malformations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases processed this record on October 19, 2014