Syndrome of autosomal recessive polycystic kidneys with skeletal and facial anomalies is not linked to the ARPKD gene locus on chromosome 6p.

We report on two sibs, both males, one born at 37 the other at 24 weeks of gestation, both with a syndrome similar to that seen in three sets of sibs by Gillessen-Kaesbach et al. [1993: Am J Med Genet 45:511-518]. Both propositi had polycystic kidneys and hepatic fibrosis indistinguishable from that seen in autosomal recessive polycystic kidney disease (ARPKD), and skeletal and facial anomalies. Skeletal abnormalities included "butterfly" vertebrae, square shape of pelvis, and brachymelia. The facial anomalies included hypertelorism, epicanthic folds, and anteverted nares. Additional external findings were apparently low-set ears and a short neck. Histopathological examination of the kidneys showed radial orientation and cystic dilatation of the cortical and medullar tubules. The liver showed "congenital hepatic fibrosis." The hepatic findings in the second infant were less severe. Renal abnormalities were limited to focal tubular cystic changes. Linkage analysis with polymorphic markers of the region 6p21.1-p12, flanking the gene locus of ARPKD, showed different haplotypes in the sibs, thus excluding the ARPKD gene locus in this family and indicating genetic heterogeneity.