Genetic Analysis of the Chiari I Malformation

This study is currently recruiting patients.

Sponsored by

National Institute of Neurological Disorders and Stroke (NINDS)


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

MEDLINEplusrelated topics:SpinalCordDiseases

Study Type:Natural History

Further Study Details:

Objective: The goal of this study is to establish family pedigrees and undertake genetic linkage analysis that will identify gene loci associated with underdevelopment of the bone forming the posterior cranial fossa, which is manifested radiographically as a small volume posterior fossa and the Chiari I malformation.

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. Preference will be given to protocol subjects in families from geneticlly-isolated populations and with multiple known family members affected by the Chiari I malformation, because these families are more informative for linkage analysis than families without these characteristics.

Design: Human subjects will undergo 1) neurologic examinations, 2) head and cervical MRI scans to evaluate for the Chiari I malformation, syringomyelia, and underdevelopment 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 phenotype being studied is underdevelopment of the bone forming the posterior cranial fossa. Underdevelopment of the bone of the posterior fossa will be defined by a neuroradiologist using the standard radiographic criteria of 1) obliteration of the CSF pathways in the inferior portion of the posterior fossa, 2) posterior fossa volume to supratentorial volume ration of less than or equal to 15%, or 3) abnormal shortening of the bones of the skull base. These radiographic criteria will also be used to confirm that subjects with the Chiari I malformation (defined as the caudal portion of the cerebellar tonsils lying greater than or equal to 2 mm below the foramen magnum) have a small posterior fossa. 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 underdeveloped posterior fossa gene maps to the same genetic region of the human genome as a given DNA marker.


Genders Eligible for Study: Both


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. Adults must be able to give informed consent. Minors must have an adult who is legally responsible for the subject and who is able to give consent. Must not have a contraindication to MRI scanning. Must be able to comprehend the risks of the testing. Must not be less than one year of age.

Location and Contact Information

National Institute of Neurological Disorders and Stroke (NINDS),9000 Rockville Pike Bethesda, Maryland, 20892, United States;Recruiting

PRPL 1-800-411-1222

More Information

Detailed Web Page


Barkovich. 1986. Significance of cerebellar tonsillar position on MR, AJNR Am J Neuroradiol, Vol. 7, p. 795

Badie. 1995. Posterior fossa volume and response to suboccipital decompression in patients with Chirari I malformation, Neurosurgery, Vol. 37, p. 214

Milhorat. 1999. Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients, Neurosurgery, Vol. 44, p. 1005

Study ID Numbers 00-N-0089
NLM Identifier NCT00004738

Date study startedFebruary 24, 2000
Record last reviewed January 19, 2001
Last Updated January 19, 2001