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Your genes are like a cookbook for your body: They give instructions on how to make proteins that help everything work properly. Some people inherit genes with jumbled instructions from their parents, which puts them at risk for hereditary diseases. Depending on the mutations (changes) to their genes, they may be at risk of developing a rare kidney disease.
This article covers rare hereditary genetic kidney diseases and how they develop. We’ll also discuss the importance of genetic testing when it comes to inherited diseases. To learn more about rare kidney diseases and how they’re passed down, talk to your doctor.
To understand hereditary diseases, it helps to cover the basics of human genetics. Chromosomes contain genes that provide instructions for proteins. Humans typically have 23 pairs of chromosomes (46 total) — one pair from each of their biological parents.
Humans have 22 pairs of autosomal chromosomes and one pair of sex chromosomes. The sex chromosomes are X and Y. While females typically have two X chromosomes (XX) and males typically have one X and one Y chromosome (XY), some individuals have different chromosomal patterns. (For simplicity, this article will refer to females as having two X chromosomes and males as having one X and one Y when discussing hereditary kidney diseases.) The term “autosomal” refers to any chromosome that isn’t a sex chromosome. Having pairs of each chromosome typically means having two copies of each gene.
Health experts classify genetic diseases based on how they’re passed down. Autosomal genetic diseases affect genes found on autosomal chromosomes. There are two main types — dominant and recessive. The term “dominant” means you need only one faulty copy of a gene to have a disease. Even if you have a healthy copy on another chromosome, you’ll still be affected. “Recessive” means you need to have two faulty copies of a gene inherited from both parents.
X-linked diseases affect genes found on the X chromosome. Males have a higher risk of developing X-linked diseases because they have only one X chromosome. Females have two X chromosomes, so a healthy gene copy on one chromosome can make up for a faulty gene on another. X-linked diseases can’t be passed down from male parents to their male children. This is because males give their Y chromosome to their male children, not their X chromosome.
There are over 60 types of rare hereditary kidney diseases. A few examples of these diseases include:
PKD is a genetic disorder that causes the growth of cysts (fluid-filled sacs) in the kidneys. Some simple cysts are harmless and develop with older age. However, cysts in PKD are usually much larger and affect the kidney’s shape and function.
There are two forms of PKD based on how they’re inherited. Autosomal dominant PKD (ADPKD) is more common and affects 1 in every 400 to 1,000 people in the United States. In fact, this is the most common genetic kidney disease. It occurs due to mutations in the PKD1 or PKD2 gene. ADPKD usually affects adults ages 30 to 50.
On the other hand, autosomal recessive PKD (ARPKD) is much rarer. Studies show this disease only affects 1 in 20,000 children in the U.S. It occurs due to changes in the PKHD1 gene. Doctors can diagnose ARPKD in fetuses still in the womb or newborn infants.
PKD symptoms depend on your disease type. Adults with ADPKD may experience:
Early signs of ARPKD in children include:
Alport syndrome is a rare genetic disease that affects the kidneys, eyes, and ears. It affects around 1 in every 50,000 newborn babies. Those with Alport syndrome have changes in genes responsible for making collagen IV (clotting factors are typically described with Roman numerals — in this instance, IV stands for the number four). This protein gives structure to the glomeruli (delicate filters) in the kidneys. Collagen IV is also found in the inner ear and eyes.
There are a few ways families pass down Alport syndrome. Research shows about two-thirds of cases affect the COL4A5 gene on the X chromosome. Since males have only one X chromosome, they’re more likely to develop Alport syndrome. Males are also at risk of severe symptoms, including:
Females with two X chromosomes who inherit a faulty COL4A5 gene typically have milder symptoms. Hematuria is common, but some can also have more severe health problems.
Another 20 percent to 30 percent of Alport syndrome cases are autosomal dominant. People with this type have changes in the COL4A3 or COL4A4 genes. Symptoms of autosomal dominant Alport syndrome range from hematuria only to progressive kidney disease. Researchers aren’t sure why some people have more severe symptoms than others.
Autosomal recessive Alport syndrome occurs in 15 percent of cases. It’s also caused by changes in the COL4A3 and COL4A4 genes. People carrying only one faulty copy of a COL4 gene are carriers. Some carriers have symptoms like hematuria, while others have none.
Nephronophthisis (NPHP) causes inflammation and scar tissue buildup, both of which affect kidney function. It’s a rare disease that affects 1 in every 922,000 children in the U.S. According to the National Kidney Foundation, NPHP is the most common genetic cause of kidney failure in children.
There are several types of NPHP based on its genetic causes. NPHP type 1 one occurs most often and is related to changes in the NPHP1 gene. All types of NPHP are autosomal recessive and need to be passed down from both parents. Some people are carriers for gene mutations, but they usually don’t have any symptoms.
Researchers believe the NPHP1 gene helps make cilia (finger-like projections found on kidney cells). Cilia are also important parts of how the eyes, brain, and liver function. If you have NPHP, you may:
If your doctor thinks you have a rare kidney disease, they’ll run a series of tests to make a diagnosis. Your primary healthcare provider will likely refer you to a nephrologist (kidney specialist) with experience in treating these diseases.
Standard tests measure your kidney function. Urine tests check for blood or protein as a sign of damage. Blood tests help doctors figure out your glomerular filtration rate (GFR), which tells doctors how well your kidneys filter your blood. For some kidney diseases, a kidney biopsy is the best way to confirm a diagnosis. Your nephrologist or a radiologist will take a small tissue sample and send it to a lab for a closer look.
Be sure to tell your doctor about any personal or family history of kidney disease. This is especially important if other closely related family members have hereditary diseases. Your doctor can order genetic testing to look for specific changes or mutations in your DNA. All that’s needed is a blood or saliva sample.
If you have a personal or family history of hereditary kidney disease, talk to your doctor. It’s important to work closely with your care team to slow disease progression and keep your kidneys healthy. Many of these diseases cause other health problems that need treatment as well.
On MyKidneyDiseaseTeam, people with kidney disease and their loved ones come together to ask questions, give advice, and share their stories with others who understand life with kidney disease.
Are you living with a rare hereditary kidney disease? Has it been passed down from other family members? How did genetic testing help you get a diagnosis? Share your story in the comments below, or start a conversation by posting on your Activities page.
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