URINARY TRACT MALFORMATION extended panel

Scientific Background

Congenital anomalies of the kidney and urinary tract (CAKUT) are observed in approximately 3-6:1,000 newborns and are the main cause of chronic kidney failure in children. CAKUT comprises a wide spectrum of structural and functional malformations leading to defective morphogenesis of the kidneys and/or efferent urinary tract; the phenotypic spectrum ranges from vesicoureteral reflux to renal agenesia. CAKUT is observed both in isolation and in connection with complex malformation syndromes.

In about 6% of cases, numerical changes of whole chromosomes are the cause, so that CAKUT occurs, for example, in trisomies 13, 18, 21 or the Ullrich-Turner syndrome. Copy number variations (microdeletions or duplications) occur in about 10-15% of CAKUT patients; the chromosomal bands 1q21.1, 16p11.2, 17q12 and 22q11.2 are most frequently affected. In another 10-20% of CAKUT patients, pathogenic changes in individual genes can be detected. Causal variants in about 50 genes associated with CAKUT have been identified, with the HNF1B and PAX2 genes being most frequently affected (about 5% of cases).

According to the clinical symptoms, in some cases it is useful to request an appropriate subpanel, e.g:

• Abnormalities of the urinary tract
• LUTO (Lower Urinary TractObstruction) / Megacystis
• Renal agenesia/hypoplasia

References

Kosfeld et al. 2018, medgen 30:448 / Bockenhauer et Jaureguiberry 2016, Pediatr Nephrol 31:707 / Verhave et al. 2016, Am Soc Nephrol 27:345 / Bergmann et al. 2011, J Am Soc Nephrol 22:2047 / Saisawat et al. 2011, Kidney Int 81:196