Dominant inheritance of Wiedemann-Beckwith syndrome: further evidence for transmission of "unstable premutation" through carrier women.

We report on a 4-generation family in which the Wiedemann Beckwith syndrome (WBS) was transmitted as an autosomal dominant trait. The condition occurred in sibs born to carrier women and in children born to affected mothers. Presumptive carrier women were examined for microsigns of WBS in an attempt to determine whether extreme variability of the disorder, rather than an unaffected carrier state, was present. No minor stigmata of the WBS could be found in the presumptive carriers. Our study supports a previous hypothesis that in some families the WBS can be transmitted in a 2-step process involving first an unstable premutation and then a "telomutation." Because only females appear to be transmitters of the telomutation, an ovum-mediated sex-associated factor may be involved in the process of telomutation.