Heterogeneity of clinical severity and molecular lesions in Aicardi syndrome

J Pediatr. 1990 Jun;116(6):911-7. doi: 10.1016/s0022-3476(05)80649-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agenesis of Corpus Callosum*
  • Blotting, Southern
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosome Mapping
  • DNA / analysis
  • DNA Probes
  • Female
  • Heterozygote
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Polymorphism, Restriction Fragment Length
  • Spasm / genetics*
  • Syndrome
  • X Chromosome* / analysis


  • DNA Probes
  • DNA