Familial ureteral abnormalities syndrome: genomic mapping, clinical findings

Abstract

Abnormal development of the ureter during embryogenesis, when occurring in multiple family members, appears to be a genetically determined defect with autosomal dominant inheritance and high penetrance, which can lead to significant kidney damage, renal failure, and death. We have studied 48 individuals within a large kindred in which ureteral-related abnormalities (including vesicoureteral reflux, ureteropelvic junction obstruction, duplicated ureters, and medullary sponge kidney) were segregated. Family members who had not had previous diagnostic studies were evaluated for presence or absence of ureteral abnormalities and we attempted to map the locus for this familial ureteral abnormalities syndrome (FUAS). These studies identified 11 asymptomatic individuals, previously assumed to be unaffected, with minor abnormalities. When linkage analysis between the inheritance of ureteral abnormalities and six marker loci glyoxalase I (GLO- ), major histocompatibility antigens (HLA-A, B, and DR/DQ), D6S288, and factor XIII antigen (F13A1) on the short arm of chromosome 6 was performed, the lod scores significantly rejected linkage over a 77.1-cM distance. These findings are in contrast to previous data suggesting linkage between the presence of ureteral abnormalities and HLA, and indicate the possibility of genetic heterogeneity of FUAS.

Familial Vesicoureteral Reflux: Testing Replication of Linkage in Seven New Multigenerational Kindreds

“…Because VCUG is an invasive test, our study could not recommend this procedure to determine whether these two patients had concurrent VUR. Nevertheless, these two individuals were considered as affected because UPJ obstruction is a clear abnormality, and previous studies have suggested that VUR and UPJ obstruction have a common genetic cause (4,21). Affected individuals had no evidence of secondary causes of VUR or syndromic abnormalities.…”

Familial inheritance of crossed fused renal ectopia

“…Several renal and urologic malformations including refluxing or obstructive uropathies as well as dysplastic kidneys are commonly found in a familial pattern [3,4]. Nevertheless, only two descriptions of familial crossed renal ectopia have previously been published.…”

Genetic Aspects of Congenital Urologic Anomalies

“…Hydronephrosis is not uncommonly part of several congenital syndromes and has been described in families, mainly in siblings and with few affected members for up to three generations [4]. Familial cases may be more common than is clinically evident: Ultrasound examinations in smaller studies have shown that approximately 50% of siblings are affected [5].…”