Heterogeneity of clinical severity and molecular lesions in Aircardi syndrome

Julie A. Neidich, Robert L. Nussbaum, Roger J. Packer, Beverly S. Emanuel, Jennifer M. Puck

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


All patients with Aicardi syndrome are female or have a 47,XXY karyotype. This finding, along with a report of an Aicardi syndrome patient with an Xp22/autosome translocation, led to the hypothesis that Aicardi syndrome might be caused by an X-linked dominant, male-lethal mutation on the short arm of the X chromosome. To study this hypothesis, we investigated X chromosome inactivation patterns in peripheral lymphocytes from seven patients. We used two methods: methylation-sensitive restriction enzyme analysis and segregation of the active X chromosome in somatic cell hybrids. We found that three of seven cytogenetically normal girls with Aicardi syndrome had profoundly skewed X-inactivation in their lymphocytes, supporting the concept that Aicardi syndrome is X linked. Three of the five girls with the greatest degree of psychomotor retardation and the poorest seizure control had skewed X-inactivation. In contrast, the two highest-functioning children had random X-inactivation. We screened DNA using eight polymorphic probes from the Xp22 region but were unable to identify a deletion in any of the seven patients. Nonrandom X-inactivation in lymphocytes and possibly other tissues in some, but not all, patients with Aicardi syndrome may reflect heterogeneity of their molecular lesions.

Original languageEnglish
Pages (from-to)911-917
Number of pages7
JournalThe Journal of Pediatrics
Issue number6
StatePublished - Jun 1990


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