Rett syndrome: the Swedish Genealogic Research Project. New data and present position

Using the genealogical method on both classical and atypical cases of Rett syndrome (RS) the assumption that atypical RS are true variants of the classical or nuclear group of RS was investigated. Also common ancestry, common geographical origins, and consanguinity were investigated. The pedigrees of 96 classical and 32 atypical ("forme fruste") RS individuals were examined. None of the RS females was born to first-cousin couples, but 7.3 +/- 1.9% of the classical and 6.6 +/- 3.2% of the atypical RS females had grandparents who were consanguineous. Eleven or 34% of the atypical RS females and 49 or 51% of the classical RS females could be traced to the same small, separate "Rett area". Furthermore, no less than 6 (19%) of the atypical and 28 (29%) of the classical RS females had originated in the same homestead as another RS female examined by us. Nineteen of the explored pedigrees of RS females belonged to 8 pedigrees. The pedigrees contained a mixture of typical and atypical forms of RS indicating that many or most of the variants of RS and the classical types have a common genetic background. The data gathered suggest that transmission starts with a premutation that can result over generations in a full mutation giving rise to RS. Both the X-chromosomes and an autosome pair of chromosomes may be involved.