Inherited Kidney Diseases

Overview

When a genetic disorder is diagnosed in a family, family members often want to know the likelihood that they or their children will develop the condition. Although the chances of inheriting a genetic condition appear straightforward, factors such as a person's family history and the results of genetic testing can sometimes modify those chances.

In addition, some people with a disease-causing variant never develop any health problems or may experience only mild symptoms of the disorder. If a disease that runs in a family does not have a clear-cut inheritance pattern, predicting the likelihood that a person will develop the condition can be particularly difficult.

It is important to note that the chance of passing on a genetic condition applies equally to each pregnancy. For example, if a couple has a child with an autosomal recessive disorder, the chance of having another child with the disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not “protect” future children from inheriting the condition. Conversely, having a child without the condition does not mean that future children will definitely be affected.

How do you know if a disease is inherited?

It is not always easy to determine whether a condition in a family is inherited. A genetics professional can use a person’s family health history (a record of health information about a person’s immediate and extended family) to help determine whether a disorder has a genetic component. He or she will ask about the health of people from several generations of the family, usually first-, second-, and third-degree relatives.

Ways inherited diseases are passed down through families

Inherited disease can be difficult to predict in some cases because many factors influence a person's chances of developing a genetic condition. One important factor is how the condition is inherited. For example:

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  Autosomal dominant inheritance: A person affected by an autosomal dominant disorder has a 50 percent chance of passing the altered gene to each child. The chance that a child will not inherit the altered gene is also 50 percent. However, in some cases an autosomal dominant disorder results from a new (de novo) variant that occurs during the formation of egg or sperm cells or early in embryonic development. In these cases, the child's parents are unaffected, but the child may pass on the condition to his or her own children.
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  Autosomal recessive inheritance: Two unaffected people who each carry one copy of the altered gene for an autosomal recessive disorder (carriers) have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent. If only one parent is a carrier of the altered gene and the other parent does not carry the variant, none of their children will develop the condition, and the chance with each pregnancy of having an unaffected child who is a carrier is 50 percent.
• 
  X-linked dominant inheritance: The chance of passing on an X-linked dominant condition differs between men and women because men have one X chromosome and one Y chromosome, while women have two X chromosomes. A man passes on his Y chromosome to all of his sons and his X chromosome to all of his daughters. Therefore, the sons of a man with an X-linked dominant disorder will not be affected, but all of his daughters will inherit the condition. A woman passes on one or the other of her X chromosomes to each child. Therefore, a woman with an X-linked dominant disorder has a 50 percent chance of having an affected daughter or son with each pregnancy.
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  X-linked recessive inheritance: Because of the difference in sex chromosomes, the probability of passing on an X-linked recessive disorder also differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the altered gene. With each pregnancy, a woman who carries an altered gene for X-linked recessive has a 50 percent chance of having sons who are affected and a 50 percent chance of having daughters who carry one copy of the altered gene. Females with one gene variant associated with an X-linked recessive disorder typically have no or very mild signs or symptoms of the condition.

There are over 60 known inherited kidney diseases, which range from common conditions to very rare diseases. Some inherited kidney conditions include:

Autosomal dominant polycystic kidney disease (ADPKD)

An autosomal dominant inherited kidney disease characterized by the growth of numerous cysts in the kidneys. Symptoms can vary in severity. Most people start developing symptoms between the ages of 30 and 40. ADPKD is a progressive disease, which means the symptoms tend to get worse over time.

ADPKD is the most common type of inherited kidney disease. In the United States, about 1 in every 800 people have ADPKD and it is the fourth leading cause of kidney failure. It is found equally in men and women and causes about 5% of all kidney failure. 

The most common symptoms of ADPKD are:

• kidney cysts
• pain in the back and the sides
• headaches. 

Other symptoms include:

• liver and pancreatic cysts
• urinary tract infections
• abnormal heart valves
• high blood pressure
• kidney stones
• brain aneurysms

Treatment for ADPKD involves managing the symptoms and slowing disease progression. The most serious complication of ADPKD is kidney disease and kidney failure.[1][2]

Alport syndrome

An inherited genetic disease that damages kidneys. Alport syndrome is caused by changes (mutations) in collagen protein genes. Collagen is an important protein that is needed to maintain normal function in the kidneys.

People with Alport syndrome have tiny blood vessels in the glomeruli of the kidneys that are damaged, which means they cannot filter the wastes and extra fluid produced by the body. Many people with Alport syndrome also have hearing problems and abnormalities with their eyes due to the changes in their collagen genes. 

Cystinosis

An autosomal recessive inherited disorder, which occurs when a person receives an abnormal copy of the cystinosin gene from each parent. In people with cystinosis, a buildup of cystine can lead to the formation of crystals. Cystinosis can impact many parts of the body, including the eyes, muscles, brain, heart, white blood cells, thyroid, and pancreas as well as causing serious kidneys problems.

Fabry disease

An inherited disorder that happens when the gene that controls the body's ability to make the enzyme, alpha GAL, is abnormal. As a result, the body makes little or no alpha GAL, or the enzyme does not function properly. Fabry disease can affect the heart, nervous system and kidneys. Because of the way the Fabry disease is inherited, men tend to develop more severe symptoms and are at higher risk for kidney disease. Women may have no symptoms or mild symptoms. However, women can still develop symptoms of Fabry disease, such as neuropathic pain and digestive problems. Heart disease is also more common among women with Fabry disease.

Gitelman syndrome

An autosomal recessive inherited disorder which occurs when a person receives an abnormal copy of the SLC12A3 or CLCNKB genes from each parent. Gitelman syndrome is a kidney function disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.[1] It is usually diagnosed during late childhood or adulthood.[2] The most common symptoms of Gitelman syndrome include[3]:

• fatigue
• salt craving
• thirst
• frequent urination
• muscle cramping
• muscle weakness
• dizziness
• tingling or numbness
• low blood pressure
• heart palpitations

Tuberous sclerosis complex (TSC)

An autosomal dominant inherited genetic disorder, which occurs when a person receives an abnormal copy of the TSC gene from one parent. Symptoms of tuberous sclerosis complex begin before birth and might be noted on ultrasound, such as tumors in the brain and heart. Seizures, intellectual disability, and developmental delay usually appear in childhood. Other symptoms that might develop in childhood include skin changes and kidney symptoms caused by tumors. Brain tumors usually grow during childhood and in teen years, which may lead to other concerns, such as hydrocephalus. In adulthood, kidney and pulmonary symptoms become more common.[1][2]

Nephronophthisis (NPHP)

Nephronophthisis (NPHP) is an autosomal recessive inherited disorder characterized by inflammation and scarring that impairs kidney function.

These abnormalities can lead to:

• increased urine production
• excessive thirst 
• general weakness
• extreme tiredness

In addition, people with NPHP develop fluid-filled cysts in the kidneys, usually in an area known as the corticomedullary region. Another feature of NPHP is a shortage of red blood cells, a condition known as anemia.

NPHP often leads to kidney failure, a life-threatening condition that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. NPHP can be classified by the approximate age at which kidney failure begins -- around age 1 (infantile), around age 13 (juvenile), and around age 19 (adolescent).

It is the most frequent genetic cause of kidney failure in children. NPHP may be combined with other health problems other than kidney disease, such as liver fibrosis or cardiac malformations. When NPHP is combined with retinitis pigmentosa, the disorder is known as Senior-Loken syndrome (NPHP1); when it is combined with cerebellar vermis hypoplasia, the disorder is known as Joubert syndrome; and when it is combined with multiple developmental and neurologic abnormalities, the disorder is often known as Meckel-Gruber syndrome. Because most NPHP genetic abnormalities occur in the cilium, NPHP and the related syndromes are known as “ciliopathies.” 

There are at least 20 genetic variants (types) of NPHP that have been identified, with more pending confirmation. These variants are caused by genetic mutations (changes) that occur within different genes.  For example, NPHP1 is caused by mutation in the nephrocystin 1 gene.

Genetic testing

Genetic testing is a type of medical test that identifies changes in genes, chromosomes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. More than 77,000 genetic tests are currently in use, and others are being developed.

Takeaways

Estimating the chance of developing or passing on a genetic disorder can be complex. Genetics professionals can help people understand these chances and help them make informed decisions about their health. 

NPHP1: A resource for families of children affected by NPHP1 gene mutations and their associated ciliopathies