Yes, Alport syndrome is inherited, and the pattern of risk in a family depends on which of the three genes carries the pathogenic variant.

X-linked Alport syndrome, caused by changes in COL4A5, follows the same logic as other conditions carried on the X chromosome. A father with X-linked Alport syndrome passes his altered X chromosome to every one of his daughters, who become carriers, and to none of his sons, since sons receive his Y chromosome instead. A mother who carries an altered COL4A5 gene has, with each pregnancy, a 1-in-2 chance of passing it to a child of either sex. Sons who inherit it will develop the condition, usually more severely and consistently than daughters, because they have no second, working copy of the gene to compensate. Daughters who inherit it are often described as carriers, but this term can be misleading: because of a natural process in every female cell called X-inactivation, in which one of the two X chromosomes is randomly switched off, the proportion of cells relying on the working versus the altered copy varies from person to person. As a result, affected daughters can range from having no symptoms at all to developing kidney failure themselves, and the family history alone cannot predict where an individual daughter will fall on that range.

Autosomal recessive Alport syndrome, caused by changes in both copies of COL4A3 or COL4A4, requires that a child inherit one altered copy from each parent, who are usually unaffected carriers themselves. When both parents are carriers, each future pregnancy carries a 1-in-4 chance of an affected child, a 1-in-2 chance of an unaffected carrier child, and a 1-in-4 chance of a child with two working copies. This form affects sons and daughters equally.

Autosomal dominant Alport syndrome, caused by a single altered copy of COL4A3 or COL4A4, means an affected person has, with each pregnancy, a 1-in-2 chance of passing on the condition to a child of either sex, generally with a milder course than the other forms.

Because the risk calculation depends entirely on which gene and which inheritance pattern applies, genetic counseling and testing of the specific variant found in the family are strongly recommended before making decisions about future pregnancies or testing other relatives, including apparently healthy ones.