Chronic kidney disease is a growing public health problem with a huge economic burden on society. In children, congenital anomalies of the kidneys and urinary tract are the most common cause for chronic kidney dieseases. Normal development of the kidneys and urinary tract progresses through a complex series of events and requires the expression of key transcription factors to occur with precision in the fetus. It is now known that many genetic defects can lead to congenital anomalies of the kidneys and urinary tract. Most of them can be indentified prenatally with antenatal ultrasonography. For infants born with severe renal impairment, transfer to a center specializing in infant dyalisis has been shown to be reasonably good, and survival improves further if kidney transplantation can eventually be achieved.
Congenital anomalies of the kidneys and urinary tract is not a single disease but merely descriptive for a large collection of diverse developmental disorders that arise during the formation of the kidneys, ureters, bladder and urethra in fetal life. They are not unified in the sense of having any single genetic etiology or common pattern of injury but can result from a wide array of genetic and/or environtmental factors that make an impact on the precise orchestration and timing of organogenesis of the kidneys and urinary tract.
Congenital anomalies of the kidneys and urinary tract include structural defects as antenatal hydronephrosis, renal agenesis, renal dysplasia, renal ectopia,ureteropelvic junction obstruction, vesicoureteral reflux, duplicated renal collecting systems, and posterior urethral valves.
Congenital anomalies of the kidneys and urinary tract can be seen with single gen mutations, such as Alagille syndrome, caused from a mutation in the JAG1 gene, and showing defects in the liver, heart, face and kidneys. The kidneys anomalies in the Alagille syndrome can vary in severity but can include renal agenesis, hypoplastic kidneys, , ureteropelvic junction obstructions and vesicoureteral reflux.
Other disorders with a congenital anomalies of the kidneys and urinary tract component will be associated with well recognized syndromes or nonrandom associations, displaying both renal and extrarenal defects, such as the VACTERL syndromes, which has the nonrandom pattern of vertebral abnormalities, anal atresia, cardiovascular defects, tracheoesophageal fistula, renal anomalies and limb defects. At least 3 of the defects need to be present for the present for the condition to be classified as VACTERL. The renal anomalies in VACTERL can vary in type and severity and may include hydronephrosis, ectopic kidneys, renal agenesis and dysplasia. There are some well-described single-gene defects that can include features of VACTERL. Holt-Oram and Smith-Lemli-Opitz syndromes are 2 such conditions, with patients with Holt-Oram syndrome having defects in limbs and heart due to mutation in transcription factor TBX5 and patients with Smith-Lemli-Opitz syndrome exhibiting facial anomalies, limb defects and developmental delay due to mutation in the DHCR7 gene. VACTERL is also sometimes associated with chromosomal anomaly trisomy 18.
Most cases of VACTERL syndrome, however, are not associated with other syndromes outside of the VACTERL spectrum. The etiology of most cases of VACTERL syndrome is not clear, but several gene have been identified to be involved with this phenotype, including mutations in mitochondial DNA, in the PTEN tumor-suppressor gene and in Fanconi anemia genes. This would to suggest that there are multiple potential genetic etiologies leading to a common constellation of defects and that VACTERL is not a single disease.
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