CHILDHOOD-ONSET AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE IN SIBS - CLINICAL PICTURE AND RECURRENCE RISK

In a systematic study on the clinical picture and genetics of cystic k idneys in children, in association with the German working group on pa ediatric nephrology (Arbeitsgemeinschaft fur Padiatrische Nephrologie) , we have investigated 79 children with early manifestation of autosom al dominant polycystic kidney disease (ADPKD). They belonged to 64 fam ilies (64 index patients and 15 affected sibs). Early manifestation wa s defined in this study as clinical symptoms (hypertension, proteinuri a, impaired renal function, palpably enlarged kidneys) occurring befor e the age of 15 years. In order to estimate the recurrence risk to sib s of a previously diagnosed patient with early manifesting ADPKD, we f ound that 15 out of a total of 65 sibs of the 64 index patients (45% o f the theoretically expected 32.5 gene carriers) showed comparable ear ly manifestation. Another 10 symptom free children were diagnosed sono graphically as having ADPKD before the age of 18 years, so that the to tal number of affected sibs was 25/65 in the study group, representing 76% of the gene carriers. Although the gene in childhood manifesting ADPKD can be transmitted through both sexes, a statistically significa nt (p < 0.05) maternal predominance was observed (M:F = 23:41). In aff ected sibs ages of onset, initial presentation, and the development of complications appeared to be similar in the majority of families. Our data indicate a high recurrence risk to sibs for early manifestation of ADPKD which has important implications for genetic counselling and clinical care of affected families and gives clues to the underlying g enetic mechanism of childhood onset ADPKD.