Genetic Analysis of the Chiari I Malformation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00004738|
Recruitment Status : Completed
First Posted : February 28, 2000
Last Update Posted : July 28, 2020
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.
|Condition or disease|
|Syringomyelia Type I Arnold Chiari Malformation|
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 Type :||Observational|
|Actual Enrollment :||152 participants|
|Official Title:||Genetic Analysis of the Chiari I Malformation|
|Actual Study Start Date :||February 14, 2000|
Chiari 1 Phenotype
The "Chiari I-small Posterior Fossa" phenotype will be defined by an underdeveloped posterior fossa with the Chiari I malformation.
Normal ratio volume of posterior fossa to volume of neural elements
Underdeveloped Posterior Fossa Phenotype
The "Underdeveloped Posterior Fossa" phenotype will be defined by an underdevelopedposterior fossa without the Chiari I malformation.
- Genetic Analysis [ Time Frame: ongoing ]Establish family pedigrees and undertake genetic linkage analysis that will identify geneloci associated with the Chiari I malformation andunderdevelopment of the bone forming the posterior cranial fossa. Genetic analysis of the genomic DNA will be performed with DNApolymorphic markers to identify chromosomal loci linked to the Chiari I and small posterior fossa phenotype.
- lod score [ Time Frame: ongoing ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004738
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Kazan State Medical University|
|Tartar Republic, Russian Federation|
|Principal Investigator:||John D Heiss, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|