Polycystic kidney disease is expressed as both a recessive and a dominant trait. A recessive genetic trait will not cause disease in a child unless it it inheritied from both parents. A dominant genetic trait can
be inherited from just one parent. Those people affected with autosomal dominant PKD (ADPKD) have the much more common adult onset form. Those with autosomal recessive PKD (ARPKD) have the infantile form.
There are mutations on at least three genes that cause adult onset PKD. Approximately 85% of these cases are known to arise from mutations in the PKD1 gene that has been mapped to a region on the short arm of chromosome 16 (16p13.3-p13.12). Another 10–15% percent of cases of adult onset PKD are thought to be caused by mutations in the PKD2 gene that has been mapped to a region on the long arm of chromosome 4 (4q21-q23). As of early 2001, it is thought that the remainder of the cases of PKD are caused by mutations in the PKD3 gene, which has not yet been mapped. This unidentified "PKD3 gene" may, in fact, be more than one gene.
Adult onset PKD is transmitted from parents to their offspring as a non-sex linked (autosomal) dominant trait. This means that if either parent carries this genetic mutation, there is a 50% chance that their child will inherit this disease. In the case of two affected parents, there is a 75% probability that their children will be affected with adult onset PKD.
Infantile PKD is caused by a non-sex linked (autosomal) recessive genetic mutation that has been mapped to a region on the short arm of chromosome 6 (6p21). Both parents must be carriers of this mutation for their children to be affected with infantile PKD. In the case of two carrier parents, the probability is 25% that their child will be affected by infantile PKD.
A baby born with infantile PKD has floppy, low-set ears, a pointed nose, a small chin, and folds of skin surrounding the eyes (epicanthal folds). Large, rigid masses can be felt on the back of both thighs (flanks), and the baby usually has trouble breathing.
As PKD becomes more advanced, the kidneys' inability to function properly becomes more pronounced. The cysts on the kidney may begin to rupture and the kidneys tend to be much larger than normal. Individuals affected with PKD have a much higher rate of kidney stones than the rest of the population at this, and later stages, of the disease. Approximately 60% of those individuals affected with PKD develop cysts in the liver, while 10% develop cysts in the pancreas.
Because the kidneys are primarily responsible for cleaning the blood, individuals affected with PKD often have problems involving the circulatory system. These include: an underproduction of red blood cells which results in an insufficient supply of oxygen to the tissues and organs (anemia); an enlarged heart (cardiac hypertrophy) probably caused by long term hypertension; and, a leakage of the valve between the left chambers (auricle and ventricle) of the heart (mitral valve prolapse). Less common (affecting approximately 5% of PKD patients) are brain aneurysms. An aneurysm is an abnormal and localized bulging of the wall of a blood vessel. If an aneurysm within the brain leaks or bursts, it may cause a stroke or even death.
Other health problems associated with adult onset PKD include: chronic leg or back pain; frequent infections; and herniations of the groin and abdomen, including herniation of the colon (diverticular disease). A herniation, or hernia, is caused when a tissue, designed to hold the shape of an underlying tissue, becomes weakened at a particular spot. The underlying tissue pushes against this weakened area until the area is no longer able to hold back the underlying tissue and the area forms an abnormal bulge through which the underlying tissue projects. Diverticular disease is caused by a weakening of the muscles that hold the shape of the organs of the digestive tract. These muscles weaken allowing these organs, particularly one section of the colon, to form sac-like projections that can trap feces and become infected, or rupture.
In the final stages of PKD, the major symptom is kidney (renal) failure. Renal failure is indicated by an increase of nitrogen (in the form of urea) in the blood (uremia, or uremic poisoning). Uremia is a rapidly fatal condition without treatment.
Paul A. Johnson, The Gale Group Inc., Gale, Detroit,