Genetic Analysis of the Chiari I Malformation
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.
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 Design
N/A
Conditions
Syringomyelia
Location
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892
Status
Recruiting
Source
National Institutes of Health Clinical Center (CC)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00004738
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Syringomyelia
Longitudinal cavities in the spinal cord, most often in the cervical region, which may extend for multiple spinal levels. The cavities are lined by dense, gliogenous tissue and may be associated with SPINAL CORD NEOPLASMS; spinal cord traumatic injuries; and vascular malformations. Syringomyelia is marked clinically by pain and PARESTHESIA, muscular atrophy of the hands, and analgesia with thermoanesthesia of the hands and arms, but with the tactile sense preserved (sensory dissociation). Lower extremity spasticity and incontinence may also develop. (From Adams et al., Principles of Neurology, 6th ed, p1269)
Spina Bifida Cystica
A form of spinal dysraphism associated with a protruding cyst made up of either meninges (i.e., a MENINGOCELE) or meninges in combination with spinal cord tissue (i.e., a MENINGOMYELOCELE). These lesions are frequently associated with spinal cord dysfunction, HYDROCEPHALUS, and SYRINGOMYELIA. (From Davis et al., Textbook of Neuropathology, 2nd ed, pp224-5)
Spinal Cord Neoplasms
Benign and malignant neoplasms which occur within the substance of the spinal cord (intramedullary neoplasms) or in the space between the dura and spinal cord (intradural extramedullary neoplasms). The majority of intramedullary spinal tumors are primary CNS neoplasms including ASTROCYTOMA; EPENDYMOMA; and LIPOMA. Intramedullary neoplasms are often associated with SYRINGOMYELIA. The most frequent histologic types of intradural-extramedullary tumors are MENINGIOMA and NEUROFIBROMA.
Clinical Trials
Establishing the Physiology of Syringomyelia
The brain and spinal cord are surrounded by fluid called cerebrospinal fluid (CSF). The CSF flows through channels in the brain and around the spinal cord. Occasionally, people are born...
Study and Surgical Treatment of Syringomyelia
The goal of this study is to establish the mechanism(s) of progression of primarily spinal syringomyelia (PSS). Our preliminary study of syringomyelia emphasized syringomyelia associated...
A Prospective Natural History Study of Patients With Syringomyelia
Background: - Syringomyelia is a disorder in which a cyst (syrinx) forms within the spinal cord and causes spinal cord injury, with symptoms worsening over many years, including...
The Genetics of Chiari Type I Malformation
The Duke Center for Human Genetics, is investigating the hereditary basis of Chiari type I malformations with or without syringomyelia (CM1/S). Our research is aimed at learning if CM1/S i...
PubMed Articles
Noncommunicating syringomyelia may complicate repeated untethering procedures in patients with spinal lipomas. Surgical intervention is indicated when syringomyelia is symptomatic. However, the prefer...
Abstract Although it is easier to accurately diagnose syringomyelia with the advent of magnetic resonance (MR) imaging, syringomyelia still poses challenges to clinicians because of its complex sympto...
Charcot shoulder caused by Chiari type I malformation with syringomyelia with six-year follow-up.
We are presenting a case report of neuropathic arthropathy of the shoulder secondary to a syringomyelia and Chiari type I malformation, with detailed clinical and radiological findings. Neuropathic jo...
ABSTRACT: BACKGROUND: With increasing use of magnetic resonance imaging (MRI), underlying syringomyelia is increasingly found in patients with presumed idiopathic scoliosis. To determine the indicatio...
HISTORY: A 20-year-old male presented with neck pain and motor impairment of the upper extremities because of recurrent syringomyelia caused by ventriculoperitoneal shunt malfunction. EXAMINATION AND...
