Polycystic Kidney Disease (PKD) is an inherited genetic disorder characterized by numerous fluid-filled cysts within the kidneys. These cysts can grow, leading to kidney enlargement and a decline in function. This can ultimately progress to kidney failure, necessitating dialysis or a kidney transplant.
Understanding Polycystic Kidney Disease Inheritance
PKD manifests in two primary forms, each with a distinct inheritance pattern: Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Autosomal Recessive Polycystic Kidney Disease (ARPKD). The way these conditions are passed from parent to child determines their typical onset and progression.
ADPKD is the more common form, affecting approximately 1 in 500 to 1,000 people. An individual needs to inherit only one copy of an altered gene from either parent. If one parent has ADPKD, each child has a 50% chance of inheriting the condition. While cysts can be present from birth, symptoms often begin in adulthood, between ages 30 and 40, and the disease progresses slowly over decades.
ARPKD is a rarer and generally more severe form, affecting an estimated 1 in 20,000 to 40,000 live births. This form requires inheriting two altered gene copies, one from each parent. Parents of a child with ARPKD are typically carriers, usually not exhibiting symptoms themselves. ARPKD symptoms commonly appear shortly after birth or in early infancy, with about half of affected individuals requiring dialysis or a kidney transplant within the first two decades of life.
The Genes Behind Polycystic Kidney Disease
Specific gene mutations are responsible for the development of both ADPKD and ARPKD, disrupting normal kidney cell function and leading to cyst formation. Understanding these genes provides insight into the disease’s mechanisms.
For ADPKD, mutations in the PKD1 and PKD2 genes are the primary causes. PKD1 mutations account for approximately 85% of ADPKD cases, while PKD2 mutations are responsible for about 15%. The PKD1 gene typically leads to a more severe disease course and an earlier onset of kidney failure, often around 55 years of age, compared to PKD2 mutations, which may see kidney failure around 75 years of age. These genes provide instructions for producing polycystin-1 and polycystin-2 proteins, which regulate kidney cell growth, organization, and fluid secretion.
ARPKD is predominantly caused by mutations in the PKHD1 gene, located on chromosome 6p12. This gene provides instructions for making fibrocystin (also known as polyductin), a protein found in the kidney’s distal tubules and the liver’s biliary ducts. Fibrocystin plays a role in cellular adhesion, ciliary function, and cell proliferation in both the kidneys and liver. Mutations in PKHD1 disrupt these functions, leading to cyst development.
Genetic Testing and Family Planning
Genetic testing aids in diagnosing PKD and provides information for family planning. It helps confirm a diagnosis, particularly when symptoms are unclear or appear atypically. This testing can identify the specific gene mutation responsible for the condition.
Genetic testing is considered for individuals with a known family history of PKD, those presenting with early-onset symptoms, or when the diagnosis based on imaging alone is uncertain. For families at high risk, prenatal diagnosis can be performed during pregnancy to check if an unborn baby has inherited ARPKD.
Understanding the genetic basis of PKD through testing informs family planning decisions. Options like preimplantation genetic diagnosis (PGD) are available, where embryos created through in vitro fertilization (IVF) are genetically tested before implantation to select those without the specific PKD mutation. Genetic counseling offers guidance to individuals and families about their risks, reproductive options, and the potential impact of PKD on future generations.