The use of ultrasonography and linkage studies for early diagnosis of autosomal dominant polycystic kidney disease (ADPKD)

Abstract

To define possibly affected members of 69 families and to identify the factors influencing the progression of autosomal dominant polycystic kidney disease (ADPKD), 276 subjects at risk of having inherited the mutant gene underwent ultrasonographic scanning (US), using an ultrasound real-time scanner. At a mean age of 26 +/- 12 years (range 4-71), 85/276 individuals (31%) presented ultrasound evidence of the disease (at least two cysts in one kidney and one cyst in the other) (US: positive), while only 19/85 (22%) had one or more manifestations of ADPKD prior to diagnosis. The prevalence of the disease in subjects at risk aged < 30 years was 53/154 (34%), while hepatic cysts were also detected in 7/85 ADPKD probands (8%) (five females) at a mean age of 40 +/- 6 years (range 30-45) and their frequency correlated with the number of pregnancies. History was proved to be important in suspecting the disease since symptoms were more common in US positive as compared to negative subjects (22% vs 6%, p < 0.001). On the other hand, physical examination and routine laboratory data at presentation revealed abnormal signs mainly in US positive individuals aged 30-39 years. Forty ADPKD families met the criterion for genetic study (at least two members affected) but in three of them (7.5%), no linkage to DNA-markers for the short arm of chromosome 16 was detected ("unlinked" or ADPKD2). DNA-analysis in the rest 37 "linked" (ADPKD1) families identified the gene-carrier state in 18/123 (15%) US negative subjects at risk, at a mean age of 13 +/- 7 years (range 3-25). There were significantly more US positive subjects aged > or = 30 years in ADPKD2 as compared to ADPKD1 families (83% vs 35%, p < 0.05) suggesting that the progression of the disease is slower in the former families. During a 5-year follow-up, 6/18 gene-carriers (33%) had already developed distinct renal cysts on US, at a mean age of 20 +/- 9 years (range 8-29). On the contrary, none of the ADPKD1 non-carriers and the US negative ADPKD2 subjects had shown any ultrasound findings of cystic renal disease at that period.