RETT-SYNDROME - POTENTIAL GENE SOURCES PHENOTYPICAL VARIABILITY

A previous genealogic study on classical Swedish Rett syndrome (RS) fe males documented an increased rate of common ancestry, with a high per centage originating generations ago in the same homestead. The present study, an a pliori test of the first study, examines an additional 20 RS females, who were consecutively traced. Of these, no fewer than 10 /19 (53%) originated from earlier defined ''Rett areas'': 11/19 (58%) could even be traced to the same homestead. In two clusters, each cons isting of three RS females, all six subjects were descendants of the s ame two couples several generations ago. Consanguineous marriages amon g grandparents on both sides were found to have occurred in 11% (4/37) , i.e. significantly more frequently than in the average Swedish popul ation (1%). The results of this second study confirm all points of the first. A clinical analysis of cases with common ancestral origin unde rlines the phenotypical variability which is often seen in interrelate d RS females. We conclude that RS can appear in either its classical f orm or as a variant. Our genealogical data may indicate transmission s tarting with a premutation that over generations can result in a full mutation, probably when the parents have the premutation in a homozygo us form.