Co-occurrence of autosomal dominant polycystic kidney disease and Marfan syndrome in a kindred

Several reports exist of the cc-occurrence of autosomal dominant polycystic kidney disease (ADPKD) and Marfan syndrome, including a report of ADPKD an d "overlap" connective tissue disorder in a family with linkage to the PKD1 locus. We report the results of clinical and linkage investigations of an ADPKD family in whom several affected subjects also had aortic vascular com plications as well as features of Marfan syndrome. Detailed clinical assess ment and linkage analysis were performed with polymorphic microsatellite ma rkers closely linked to the PKD1 and FBN1 loci. Survival data were compared with 10 geographically matched PKD1 families. Although several subjects ha d features of both ADPKD and Marfan syndrome, detailed clinical examination of the extended family indicated that the two conditions had converged wit hin the kindred. For those with ADPKD, linkage was established to the PKD1 locus(lod score, 6.04). Among those with features of Marfan syndrome, linka ge was confirmed to the FBN1 locus(lod score, 1.87). Five of six subjects w ith both ADPKD and the high-risk FBN1 haplotype had associated vascular com plications. In contrast, among the remaining nine individuals with PKD1 alo ne, seven had aortic assessments, and none were found to have aortic compli cations. Our experience suggests that when prominent features of connective tissue disease or vascular complications are found in ADPKD patients, alte rnative additional diagnoses should be considered, including the possibilit y of a coinherited FBN1 mutation responsible for Marfan syndrome or, altern atively, an associated milder FBN1 phenotype in the absence of sufficient o ther clinical features to allow Marfan syndrome to be diagnosed. (C) 2000 b y the National Kidney Foundation, Inc.