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Study of Selected X-Linked Disorders: Aicardi Syndrome

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ClinicalTrials.gov Identifier: NCT00697411
Recruitment Status : Recruiting
First Posted : June 13, 2008
Last Update Posted : April 22, 2022
Aicardi Syndrome Foundation
Information provided by (Responsible Party):
Ignatia Van den Veyver, Baylor College of Medicine

Brief Summary:
Based on our current understanding of Aicardi syndrome, the condition is hypothesized to occur due to a genetic change on the X-chromosome. The research team is investigating Aicardi syndrome to identify the specific gene location associated with the disorder. Th investigators are collecting blood and skin biopsy samples from patients and their parents. A permanent cell line is prepared and DNA from the blood and skin samples and cell lines is isolated and then used for genetic testing. The current research includes microarray analysis which which is used to look for duplications or deletions of genetic material, mutation analysis of candidate genes by sequencing, review of medical records to identify trends suggesting possible candidate genes of interest, and X chromosome inactivation studies.

Condition or disease
Aicardi Syndrome Brain Disorders

Detailed Description:

Aicardi syndrome is a sporadic X-linked dominant, presumably male-lethal, neurodevelopmental disorder. It was initially characterized by agenesis of the corpus callosum, neuronal migration defects, eye abnormalities (chorioretinal lacunae, colobomas of the optic nerve and microphthalmia) and severe early-onset seizures and neurodevelopmental delay. It is now well recognized that other brain abnormalities, such as polymicrogyria, agyria, cysts and heterotopias are common features of Aicardi syndrome. The investigators previously hypothesized that the gene causing Aicardi syndrome and possibly additional phenotypically similar disorders with X-linked inheritance, such as Goltz syndrome or Focal Dermal Hypoplasia, are in or near the region on chromosome Xp22 that is deleted in another condition named microphthalmia with linear skin defects syndrome (MLS), because all three have some clinical similarities. However, interim studies have shown that this is likely not the case because no mutations were found in Aicardi syndrome in human holocytochrome c-type synthetase (HCCS) , the gene that is deleted or mutated in MLS. In addition, a mouse model for MLS has no features of Aicardi syndrome. Furthermore, the ivnestigators identified mutations in PORCN (Xp11.3) in Goltz syndrome patients, but not in Aicardi syndrome patients. Therefore, it is likely that the mutated gene is elsewhere on the X-chromosome.

For this study the investigators are collecting information on patients with clinical findings suggesting a diagnosis of Aicardi syndrome, MLS syndrome or a condition that phenotypically overlaps with these disorders. A detailed family history will be obtained, when indicated, and additional family members will be evaluated after appropriately obtained written voluntary consent. A detailed report of the history or physical findings will be obtained from referring physicians for patients identified at outside facilities, or the participants may be evaluated by the study collaborators. Blood and skin biopsy will be obtained from affected individuals, unaffected parents and from other affected or unaffected family members where indicated. It is anticipated that some severely affected patients will expire; in that case, (post mortem) pathological specimens may be obtained. Occasionally, affected individuals may undergo surgical procedures with removal of tissues; in this case we may obtain tissues that would be otherwise discarded or that are not essential for further diagnostic studies or clinical care of the patient. It is anticipated that these specimens will be extremely valuable for understanding the pathogenesis of the investigated conditions. DNA, RNA or protein will be prepared from leukocytes and from tissues and used for mutation analysis and other molecular studies of the identified genes. Permanent lymphoblastoid cell lines will be prepared and stored in the laboratory as a permanent source of DNA for the molecular studies.

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Pathogenesis of Selected X-Linked Dominant Disorders and New Strategies to Identify the Gene Mutated in Aicardi Syndrome
Actual Study Start Date : October 2002
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : January 2025

Individuals with Aicardi syndrome and their first-degree relatives

Primary Outcome Measures :
  1. Identifying the change in the genetic information that causes Aicardi syndrome [ Time Frame: Through study completion, an average of 15 years ]
    The investigators will isolate genetic material from samples of individuals with Aicardi syndrome and their parents (if available). DNA sequencing and other molecular methods along with bioinformatic analysis will be used to find genetic variants (changes) in the genetic code unique to individuals with Aicardi syndrome, not seen in healthy population. When a gene that shows variants that are deleterious to its function is identified in at least 3 unrelated Aicardi syndrome individuals but not in healthy people (whose DNA sequence is in public databases), the outcome (finding the genetic cause of Aicardi syndrome) will be achieved. Aicardi syndrome is very rare, thus recruitment and enrollment of new individuals will continue when they are referred to the study. In this research a key finding in one individual can provide the clue for the entire cohort. It cannot be predicted when this will happen, thus enrollment and data collection will continue as long as the study is ongoing.

Biospecimen Retention:   Samples With DNA
lymphoblast DNA; tissue

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Girls with Aicardi syndrome and their unaffected parents. Sometimes additional family members are also enrolled.

Inclusion Criteria:

  • Features suggestive of Aicardi syndrome (not all features must be present)

    • Agenesis of the corpus callosum
    • Chorioretinal lacunae
    • Seizures (infantile spasms)

Exclusion Criteria:

  • none

Information from the National Library of Medicine

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): NCT00697411

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Contact: Ignatia Van den Veyver, PMD 832-824-8125 iveyver@bcm.edu
Contact: Renee Elawar 832-824-8156 relawar@bcm.edu

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United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Ignatia B Van den Veyver, MD    832-824-8125    iveyver@bcm.edu   
Principal Investigator: Ignatia B Van den Veyver, MD         
Sponsors and Collaborators
Baylor College of Medicine
Aicardi Syndrome Foundation
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Principal Investigator: Ignatia B Van den Veyver, MD Baylor College of Medicine
Publications of Results:

Other Publications:
Aicardi, J, Levebre, J, and Lerique-Koechlin, A (1965) A new syndrome: Spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol 19, 609-610.

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Responsible Party: Ignatia Van den Veyver, Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00697411    
Other Study ID Numbers: BCM Aicardi H12791
First Posted: June 13, 2008    Key Record Dates
Last Update Posted: April 22, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient data with all identification removed will be published following peer review in journals and/or presented at scientific meetings.
Time Frame: At the end of the study.
Access Criteria:

Patient data with all identification removed will be published following peer review in journals and/or presented at scientific meetings.

Reasonable requests from other researchers working on the same disease will be reviewed by the PI and sharing will be done after full deidentification and with institutionally approved of data and material transfer agreements.

Keywords provided by Ignatia Van den Veyver, Baylor College of Medicine:
Aicardi syndrome
Microphthalmia with linear skin defects (MLS) syndrome
X-linked disorders
Additional relevant MeSH terms:
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Brain Diseases
Aicardi Syndrome
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Agenesis of Corpus Callosum
Nervous System Malformations
Eye Diseases, Hereditary
Eye Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Genetic Diseases, X-Linked