Is there evidence for anticipation in autosomal-dominant polycystic kidney disease?

Abstract

The heritability of autosomal-dominant polycystic kidney disease (ADPKD) is marked by an apparent high mutation rate, neonatal onset of disease in some patients and intrafamily variability. These findings raise the possibility of genetic anticipation in ADPKD as has been observed in fragile-X syndrome, myotonic dystrophy and Huntington's disease. We reviewed 242 pedigrees obtained during our prospective studies on the natural history of ADPKD. Anticipation was defined as a 10 year earlier onset of ESRD in offspring as compared to their affected parent or a child diagnosed in the first year of life. Due to the slowly progressive nature of ADPKD, 148 pedigrees were uninformative. Anticipation of ESRD was found in 49% of informative families in at least one parent-offspring pair, and when early onset children were included, 53% of informative families had at least one parent-offspring pair with anticipation. Moreover, the transmitting parent in the pairs with anticipation was more often the mother than the father, similar to myotonic dystrophy, where the most dramatic form of anticipation, congenital disease, occurs almost exclusively with maternal transmission. These observations suggest that ADPKD may be another genetic disorder characterized by heritable unstable DNA.