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Alport Syndrome

Alport syndrome is a rare genetic disorder that causes progressive kidney disease and abnormalities of the inner ears and eyes1. Alport syndrome is caused by mutations in genes that create type IV collagen. Type IV collagen is a substance that is important in maintaining the structure and function of parts of the kidney as well as the inner ear and the eyes, and thus mutations in the type IV collagen genes lead to disease in those areas of the body. There are three genetic types of Alport syndrome. X-linked Alport syndrome (XLAS) is the most common (80% of cases) and will be the focus of this description2.

XLAS is caused by genetic variants in the COL4A5 gene on the X chromosome, and males typically have more severe disease than affected females (see section below). The other types are autosomal recessive Alport syndrome (ARAS) and autosomal dominant Alport syndrome (ADAS) which are caused by genes that are not on the X chromosome, so males and females are affected similarly to one another.

Males with XLAS will usually have blood in their urine early in life, with progressive worsening in the function of their kidneys that eventually leads to kidney failure. Kidney failure develops in about 50% of untreated males by age 35, 90% by age 40, and nearly 100% by age 601. These patients will require intensive treatment including dialysis and/or kidney transplants. About 60-80% of male patients also develop progressive hearing loss from damage to the inner ear (sensorineural hearing loss) and ~80% develop abnormalities of the eyes (specifically anterior lenticonus and central or perimacular fleck retinopathy) that usually do not result in vision loss2.

 

Females with XLAS

Overall, females with XLAS are affected by the disease less frequently, and usually less severely, than males with XLAS. However, signs and symptoms of disease are still quite common among females3 (“females with XLAS” referring to heterozygotes, i.e. females who have a COL4A5 mutation on one of their two X chromosomes).

Kidney failure develops in 15-40% of females with XLAS and it typically develops later in life compared to males with XLAS3,4. Around 20% of females with XLAS are reported to have kidney failure by age 60, with the risk increasing after 60 years of age2,4. The median age of kidney failure in women who develop it is somewhere between 50 and 65 years, meaning that half of women who end up with kidney failure from XLAS develop it before the age of 50-65, and half develop it after the age of 50-652,5. The chance of developing kidney failure before the age of 40 was found to be 12% in one study on females with XLAS (compared to a 90% chance by that age in males)3.

While kidney disease only progresses to full kidney failure in the minority of females with XLAS, over 90% will have blood in their urine (hematuria) indicating that they have milder kidney damage2,3.  This blood in the urine is often not visible, just microscopic and found while doing lab tests. Similarly, protein in the urine (proteinuria), another sign of kidney damage, was seen in 75% of females with XLAS in one study3.

Hearing loss is less common among women with XLAS (reported in 28% of female carriers in one study) and develops later in life than in males when present3. The risk of developing deafness before the age of 40 was found to be 10% in females in that study (compared with 80% risk in males)3. Eye changes are reported in only 15-20% of females (<5% develop anterior lenticonus while ~20% develop fleck retinopathy)2,3.

There is significant variability in the severity of XLAS experienced by individual females, including between members of the same family who have the same genetic defect in the COL4A5 gene. This variability is likely to be explained in part by skewed X-inactivation. However, one study found that X-inactivation patterns did not correlate well with disease severity, indicating that there are likely other genetic or environmental factors that affect the disease development in females which remain poorly understood6. Regardless, the severity and features of disease that a female with XLAS will develop can not be predicted well. So, it is important for all females with XLAS, like males, to be monitored closely throughout life to assess for progression of kidney disease, hearing loss and eye abnormalities.

Of note, though not the focus of this page, females with the autosomal recessive form of Alport syndrome, ARAS, usually develop kidney failure in their teenage years or early adulthood, and females with the dominant form, ADAS, tend to have milder kidney disease with kidney failure not occurring until later adulthood. Females with ARAS commonly also develop progressive hearing loss and eye changes early in life like those seen in males with XLAS, while ear and eye changes are rarely seen in ADAS. In both ARAS and ADAS, the way that females are affected is equal to males with the same condition1.

This page was last updated in July, 2026. Please note that research into females with this condition is limited. As a result, percentages and prevalence rates may not be accurate or widely applicable. Decisions regarding your own health should be made in consultation with your medical provider.

  1. Alport Syndrome – Symptoms, Causes, Treatment | NORD. Accessed July 24, 2026. https://rarediseases.org/rare-diseases/alport-syndrome/
  2. Nozu K, Yamamura T, Horinouchi T. Alport Syndrome. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews®. University of Washington, Seattle; 1993. Accessed July 24, 2026. http://www.ncbi.nlm.nih.gov/books/NBK1207/
  3. X-Linked Alport Syndrome : Journal of the American Society of Nephrology. Ovid. Accessed July 24, 2026. https://www.ovid.com/jnls/jasn/fulltext/10.1097/01.asn.0000090034.71205.74~x-linked-alport-syndrome-natural-history-and
  4. Vivante A. Genetics of Chronic Kidney Disease. N Engl J Med. 2024;391(7):627-639. doi:10.1056/NEJMra2308577
  5. Kim JH, Lim SH, Song JY, et al. Genotype–phenotype correlation of X-linked Alport syndrome observed in both genders: a multicenter study in South Korea. Sci Rep. 2023;13:6827. doi:10.1038/s41598-023-34053-7
  6. Günthner R, Knipping L, Jeruschke S, et al. Renal X-inactivation in female individuals with X-linked Alport syndrome primarily determined by age. Front Med. 2022;9:953643. doi:10.3389/fmed.2022.953643