On the genetics of Rett syndrome: analysis of family and pedigree data.
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.
D000022:Abortion, Spontaneous / Q000235:genetics; D000328:Adult; D002648:Child; D003241:Consanguinity; D005190:Family; D005260:Female; D005799:Genes, Dominant; D005804:Genes, Lethal; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008423:Maternal Age; D009069:Movement Disorders / Q000235:genetics*; D009154:Mutation; D010331:Paternal Age; D010375:Pedigree; D011247:Pregnancy; D012744:Sex Ratio; D013577:Syndrome; D014960:X Chromosome