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"Obstructive uropathy" is a generic term which combines different diseases in infants and childhood. Both the upper and lower urinary tract may be affected. Diseases of the urinary tract can cause an intrinsic obstruction. Sometimes tumours may cause a compression and as secondary effect an obstruction (extrinsic). Ultrasound is the key diagnostic tool and shows dilatation of the obstructed urinary tract. But for the functional exploration of babies and toddlers, renal scanning and X-ray examinations are necessary. These examinations lead to an exposure to radiation which necessitates careful indication. Some of the congenital diseases (for example ureteropelvic junction obstruction, megaureter) show a maturation without any intervention. So one has to decide whether to wait and see or to operate. A percutaneous nephrostomy or a DJ-catheter is not often used in the treatment of obstruction in general. These forms of drainage are more often used in the treatment of stones or of extrinsic obstruction. A pyelocutaneostomy or ureterocutaneostomy is a special surgical procedure in pediatric urology for transient drainage of the upper urinary tract (megaureter). The operation of a seriously ill new-born should be done in a centre for pediatric urology and pediatric nephrology. When the upper urinary tract is dilated, patients may need an antibiotic prophylaxis, because the dilatation of the upper urinary tract increases the risk of urinary tract infections (UTI). The indication for antibiotic prophylaxis should by guided by the criteria of the APN-Consensus Paper. Long-term follow-up is necessary and should comprise ultrasound, physical examination, controlling the blood pressure, urine analysis and blood tests. The aims of diagnostics, treatment and long-term follow-up are the preservation of renal function and to protect the children from UTI. This goal must be reached under conditions that are appropriate for children and their parents.

Genetic studies have implicated the short arm of chromosome 6 in congenital hydronephrosis. In previous studies, we described a fetus carrying a t(6;19)(p21;q13.1) as the sole cytogenetic anomaly and suffering from bilateral multicystic renal dysplasia caused by a bilateral complete pelviureteric junction obstruction, resulting in a massive hydronephrosis. Characterization of the chromosome 19 breakpoint region revealed that the transcription factor-encoding USF2 gene is affected. In this report, we show that the CDC5L gene on chromosome 6p is rearranged in the cells of the fetus. CDC5L encodes a protein that is related to the product of the Schizosaccharomyces pombe Cdc5 gene, which exerts its effects at the G2/M transition during cell cycle progression. We have established the genomic organization of the CDC5L gene and found that it consists of at least 16 exons spanning approximately 50 kb of chromosome segment 6p21. Northern blot analysis indicated that the gene is ubiquitously expressed as a single mRNA of about 3.4 kb in both fetal and adult tissues. The translation product of the CDC5L gene has an electrophoretic mobility of about 100 kDa and is predicted to be a nuclear protein, since it contains a Myb-related DNA binding domain and potential nuclear localization signals in its aminoterminal region. Immunocytochemical analysis confirmed the nuclear localization of the CDC5L protein. CDC5L was also predicted to contain a hydrophilic, proline-rich region in its central part, which might function as a transcriptional activating domain. The chromosome 6 breakpoint was found in the intron between exons 9 and 10, indicating that, as a direct result of the 6;19 translocation, the Myb-related DNA binding domains and the nuclear localization signals are separated from the putative transactivating domain. Northern blot and RT-PCR experiments revealed that the other CDC5L allele is unaffected, and in Western blot experiments, expression of the 100-kDa protein was detected in fibroblasts of the fetus. Expression of a truncated or hybrid CDC5L transcript resulting from the CDC5L rearrangement could not be demonstrated.

Hydronephrosis caused by pelvi-ureteric junction obstruction (PUJO) is a frequent urological malformation assumed to result from a deficient development of the ureteric bud. The exact etiology of pelvi-ureteric junction stenosis is unknown, but there is convincing evidence for a genetic cause, with linkage analysis predicting a hereditary hydronephrosis locus on chromosome 6p. We encountered a patient with a de novo autosomal t(6;19)(p21;q13.1) and attendant bilateral multicystic renal dysplasia (MRD), bilateral PUJO resulting in massive hydronephrosis, and an associated von Mayer-Rokitansky-Kuster disorder. On the basis of the presumption that in this patient the putative hydronephrosis gene might be disrupted by the translocation, we sought to isolate DNA from the breakpoint regions as the initial step in a strategy to identify genes affected by the t(6; 19). Using sequential rounds of fluorescence in situ hybridization (FISH) with cosmids selected from a detailed integrated map of the long arm of chromosome 19, we have identified a cosmid clone that spans the breakpoint. The position of the breakpoint was further localized by Southern blot analysis. Using a vectorette PCR approach, rearranged DNA fragments were isolated and, by comparative nucleotide sequence analysis, these were shown to contain ectopic sequences. A cosmid clone containing these ectopic sequences was isolated and shown by CASH (chromosome assignment using somatic cell hybrids) and FISH (fluorescence in situ hybridization) analysis to map to the short arm of chromosome 6 and to span the breakpoint found in the MRD patient. The isolated cosmid clones are useful reagents for analysis of other MRD patients and for the search for genes at or flanking the breakpoints.