Autosomal dominant polycystic kidney disease: New information for genetic counselling

• Published in: American Journal of Medical Genetics
• Main Authors: Bear, John C., Parfrey, Patrick S., Morgan, Janet M., Martin, Christopher J., Cramer, Benvon C.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 1992
• Subjects: Newfoundland
• Online Access: http://dx.doi.org/10.1002/ajmg.1320430309; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fajmg.1320430309; https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.1320430309

Abstract We evaluated the accuracy of ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and factors influencing its prognosis in members of 17 Newfoundland families originally described in 1984. In 10 families showing genetic linkage between ADPKD and markers for the PKD1 locus, rates of false negative ultrasonographic diagnosis are estimated as 36% below the age of 10 years and 8% or less thereafter, comparable with findings of genetic linkage studies of a subset of family members. At ages above 30 years, false negative ultrasonographic diagnosis of PKD1 disease is unlikely. In 2 families in which PKD1 disease is unlikely. In 2 families in which ADPKD is not coinherited with PKD1 markers, only 11% of members aged less than 30 years had kidney cysts. The mean (SE) age of onset of ESRD is 56.3 (1.8) years for persons with the PKD1 form of ADPKD, and 68.7 (1.7) years for affected members of families in which ADPKD is not co‐inherited with PKD1 markers (P = 0.01). In the PKD1 families, age of onset of end stage renal disease (ESRD) was unrelated to the sex of the affected individual but was earlier in persons inheriting the disease from their mothers than from their fathers (50.5 vs. 64.8 years, P = 0.004), consistent with an influence of genetic imprinting on disease progresion. In females with a PKD1 mutation, onset of ESRD was not influenced by parity. In PKD1 families, resemblance in age of onset of ESRD was apparent; variation was less within than between families (F = 13.0, P < 0.0001), and risk of false negative ultrasonographic diagnosis appears largely restricted to families in which ESRD occurs relatively late. © 1992 Wiley‐Liss, Inc.