On the genetics of rett syndrome: Analysis of family and pedigree data

Abstract

Pedigree studies of 220 Rett syndrome cases (218 isolated cases, one family with affected half sisters and one family with affected sisters) tested 5 monogenic hypotheses, taking account of apparently absolute gynecotropy and healthy parents. Without increased consanguinity we found a normal sex ratio among sibs; the rate of spontaneous abortions was not increased. There is also no increase in parental conceptional age. As the patients do not propagate, transmission of a supposed gene could not be observed. The results are compatible with either an autosomal dominant mutation with complete sex limitation or (more likely) an X-chromosomal dominant mutation with lethality to the males. As the probability for 2 affected sisters in one sibship differs considerably from the real incidence, alternative models should be taken into consideration and may be tested by linkage analysis.