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http://dx.doi.org/10.1016/S0387-7604(01)00344-8, A gene for Methyl-CpG binding protein 2 (MECP2), which locates Xq28, was recently found to be responsible for Rett syndrome. Although mutational analyses of MECP2 in Rett syndrome have been extensively analyzed, the mechanism(s) by which variable clinical phenotype occurred between affected monozygotic twins or sisters have not been clarified. We hypothesized that the difference of X-inactivation pattern might explain this phenomenon. With the method based on methylation-specific PCR, we analyzed polymorphic trinucleotide repeat in the human andorogen receptor gene mapped on Xq11.2-12, using DNA samples derived from previously described monozygotic twins and sisters together with their parents. Their clinical phenotypes were reported to be significantly different between siblings. We found that (1) maternally derived allele is predominantly active than paternally derived one in three out of four patients analyzed, (2) remaining one twin patient, whose ratio of active paternal allele is almost the same level as maternal allele, showed far much severe phenotype when compared with her counterpart. Together with the finding that most of the alleles with de novo mutation are from paternal X chromosome in sporadic cases, the existence of a mechanism that suppresses mutated paternal allele activation, resulting skewed X-inactivation to make clinical phenotype milder, might be speculated. Thus, when this mechanism fails to work sufficiently by an unknown reason, severer clinical phenotype could occur. Author

Familial cases of Rett syndrome (RS) are rare. No significant differences have been reported in the clinical courses of concordant monozygotic twins with RS. We present the variability of clinical expression in two Japanese sisters with classic RS. The younger sister, currently 6 years and 6 months old, never stood or walked alone, showed severe spasticity, growth retardation, and microcephaly and developed sleep-wake rhythm disturbance from age 4 years and seizures from age 5 years. The elder, currently 7 years and 9 months old, walked alone and had mild spasticity, no growth retardation, normal sleep-wakefulness rhythm and no seizures. RS is most likely to be transmitted as an X-linked dominant, male-lethal (XDML) disorder, although this is still contested. If RS is an XDML disorder, lyonization may account for variability of expression in the sisters.

The case is presented of a 6-month-old girl with theophylline-induced focal seizures associated with tachycardia, tremor and irritability. The serum level of theophylline was 20.0 micrograms/ml 30 min after the onset of seizures, and declined to half this level at 19 h. The ratio of the concentration in cerebrospinal fluid (CSF; 8.9 micrograms/ml) to serum (16.4 micrograms/ml) was 0.54 at 4.5 h after the onset. Despite the cessation of seizures, the EEG showed periodic high voltage delta waves over the right hemisphere and left-sided flatness. Since theophylline diffuses easily through the blood-brain barrier in infancy, serum levels should be maintained below 15 micrograms/ml unless severe bronchial asthma occurs.