SNP Shot: Genomic Insights

Congenital anomalies of the kidney and urinary tract (CAKUT) encompass a range of birth defects affecting the kidneys and/or other components of the urinary system. These affected areas can include the bladder, the ureters (tubes connecting the kidneys to the bladder), and the urethra (the tube that carries urine out of the body). CAKUT arises from atypical development of the urinary system during gestation (congenital), although the abnormality may not be immediately obvious and might only be detected later in life.

Individuals diagnosed with CAKUT present with one or more irregularities of the kidneys or urinary tract. In the case of paired organs, such as the kidneys and ureters, either one or both may be affected. A diverse array of developmental abnormalities falls under the CAKUT umbrella, including underdeveloped or absent kidney(s) (renal hypodysplasia or agenesis), kidneys with fluid-filled cysts (multicystic dysplastic kidney), urine accumulation in the kidneys (hydronephrosis), an extra ureter (duplex kidney or duplicated collecting system), a blockage at the junction where the ureter meets the kidney (ureteropelvic junction obstruction), an abnormally enlarged ureter (megaureter), the reflux of urine from the bladder back into the ureter (vesicoureteral reflux), and an obstructing membrane within the urethra (posterior urethral valve).

The severity of CAKUT varies considerably. These abnormalities can lead to recurring urinary tract infections or urine build-up within the urinary tract, potentially causing damage to the kidneys or other structures. In severe cases, CAKUT can result in life-threatening kidney failure and end-stage renal disease.

CAKUT is frequently observed as part of a broader condition affecting multiple body systems (syndromic CAKUT). Examples include renal coloboma syndrome, 17q12 deletion syndrome, renal cysts and diabetes (RCAD) syndrome, Fraser syndrome, Townes-Brocks syndrome, and branchio-oto-renal syndrome, which can all cause kidney or urinary tract abnormalities alongside other health problems. However, urinary system abnormalities can also occur in isolation, without any other associated signs or symptoms; this is known as nonsyndromic or isolated CAKUT.

Inheritance:

The inheritance patterns of CAKUT are intricate and not fully understood. It is estimated that 10 to 20 percent of cases have a familial link. Inherited CAKUT most often follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene in each cell is sufficient to cause the abnormality. However, some individuals carrying the altered gene may never develop CAKUT, a phenomenon referred to as reduced penetrance. Less commonly, CAKUT follows an autosomal recessive inheritance pattern, requiring both copies of the gene in each cell to be mutated. In these cases, both parents carry one copy of the mutated gene but typically do not exhibit any signs or symptoms of the condition. In many instances, the inheritance pattern is unclear, or the condition is not inherited. In some non-inherited cases, a new (de novo) mutation in the gene may occur during the formation of reproductive cells (eggs or sperm) in the affected individual's parent or during early embryonic development. These cases arise in individuals with no prior family history of the disorder.