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

Several reports exist of the co-occurrence of autosomal dominant polycystic kidney disease (ADPKD) and Marfan syndrome, including a report of ADPKD and "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 complications as well as features of Marfan syndrome. Detailed clinical assessment and linkage analysis were performed with polymorphic microsatellite markers closely linked to the PKD1 and FBN1 loci. Survival data were compared with 10 geographically matched PKD1 families. Although several subjects had features of both ADPKD and Marfan syndrome, detailed clinical examination of the extended family indicated that the two conditions had converged within the kindred. For those with ADPKD, linkage was established to the PKD1 locus (lod score, 6.04). Among those with features of Marfan syndrome, linkage was confirmed to the FBN1 locus (lod score, 1.87). Five of six subjects with both ADPKD and the high-risk FBN1 haplotype had associated vascular complications. In contrast, among the remaining nine individuals with PKD1 alone, seven had aortic assessments, and none were found to have aortic complications. Our experience suggests that when prominent features of connective tissue disease or vascular complications are found in ADPKD patients, alternative additional diagnoses should be considered, including the possibility of a coinherited FBN1 mutation responsible for Marfan syndrome or, alternatively, an associated milder FBN1 phenotype in the absence of sufficient other clinical features to allow Marfan syndrome to be diagnosed.