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Genetic and Rare Diseases Information Center (GARD)

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Autosomal recessive Alport syndrome

Other Names for this Disease
  • Alport syndrome autosomal recessive
  • Alport syndrome recessive type
  • Nephropathy and deafness
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Your Question

What causes Alport syndrome? Is it always inherited?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What causes Alport syndrome?

Alport syndrome may be caused by mutations in either the COL4A3, COL4A4, or COL4A5 genes. These genes each provide instructions for making one component of a protein called type IV collagen, which plays an important role in the glomeruli of the kidneys. Glomeruli are clusters of specialized blood vessels that remove water and waste products from the blood and create urine. Mutations in the genes mentioned above result in abnormalities of the type IV collagen in glomeruli, which prevents the kidneys from properly filtering the blood. As a result, blood and protein pass into the urine. Over time, the kidneys become scarred and many people with Alport syndrome develop kidney failure.[1]

Type IV collagen is also an important component of the organ of Corti, an inner ear structure that transforms sound waves into nerve impulses for the brain. Alterations in type IV collagen may result in abnormal inner ear function, which can lead to hearing loss. In addition, type IV collagen plays a role in the eye, where it helps maintain the shape of the lens and the normal color of the retina. Mutations found in Alport syndrome may affect the shape of the lenses and the color of the retina.[1]

Last updated: 8/1/2013

How is Alport syndrome inherited?

Alport syndrome can have different inheritance patterns. About 80 percent of cases are caused by mutations in the COL4A5 gene and are inherited in an X-linked recessive pattern. This gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the COL4A5 gene in each cell is sufficient to cause kidney failure and other severe symptoms of the disorder. In females (who have two X chromosomes), a mutation in only one copy of the COL4A5 gene usually only results in hematuria, but some women experience more severe symptoms. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.[1]

In approximately 15 percent of cases, Alport syndrome results from mutations in both copies of the COL4A3 or COL4A4 gene and is inherited in an autosomal recessive pattern. The parents of an individual with the autosomal recessive form of this condition each have one copy of the mutated gene and are called carriers. Some carriers are unaffected and others develop a less severe condition called thin basement membrane nephropathy, which is characterized by hematuria.[1]

Alport syndrome has an autosomal dominant pattern of inheritance in about 5 percent of cases. People with this form of Alport syndrome have one mutation in either the COL4A3 or COL4A4 gene in each cell. It remains unclear why some individuals with one mutation in the COL4A3 or COL4A4 gene have autosomal dominant Alport syndrome and others have thin basement membrane nephropathy.[1]

Last updated: 8/1/2013

Are all cases of Alport syndrome inherited?

Approximately 10%-15% of affected individuals have X-linked Alport syndrome as the result of a de novo (new) mutation. While these individuals did not inherit the genetic mutation, they can pass the mutated gene onto their children. Affected males transmit the disease-causing mutation to all of their daughters and to none of their sons.[2]

Most individuals diagnosed with an autosomal dominant Alport syndrome have an affected parent. In some cases, the disorder may result from a de novo gene mutation. The proportion of cases of autosomal dominant Alport syndrome that result from de novo gene mutations in unknown. Each child of an individual with autosomal dominant Alport syndrome has a 50% chance of inheriting the mutation.[2]

Additional information about the different ways that Alport syndrome may be inherited (and how other family members might be impacted) can be accessed through GeneReviews. A genetics professional can help to better understand the risks for individuals and family members to develop Alport syndrome.

Last updated: 8/1/2013

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 10/18/2013