Alport Syndrome - Inheritance Patterns

Inheritance Patterns

Alport syndrome can have different inheritance patterns that are dependent on the genetic mutation.

• In most people with Alport syndrome, the condition is inherited in an X-linked pattern, due to mutations in the COL4A5 gene. A condition is considered X-linked if the gene involved in the disorder is located on the X chromosome. In males, who have only one X chromosome, one altered copy of the COL4A5 gene is sufficient to cause severe Alport syndrome, explaining why most affected males eventually develop kidney failure. In females, who have two X chromosomes, a mutation in one copy of the COL4A5 gene usually results in blood in the urine, but most affected females do not develop kidney failure.
• Alport syndrome can be inherited in an autosomal recessive pattern if both copies of the COL4A3 or COL4A4 gene, located on chromosome 2, have been mutated. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.
• Past descriptions of an autosomal dominant form are now usually categorized as other conditions, though some uses of the term in reference to the COL4A3 and COL4A4 loci have been published. Autosomal dominant transmission is rare and only accounts for 5% of affected patients.The clinical features of autosomal dominant Alport syndrome are similar to those of X-linked disease. However, deterioration of renal function tends to occur more slowly.