Alport syndrome

Alport syndrome (AS) is an inherited disorder that affects mainly the kidneys, eyes and hearing. Affected individuals typically start having blood in their urine in childhood as a sign of kidney issues. The kidneys progressively deteriorate leading to kidney failure usually by the time the individual turns 30 years of age. Affected individuals will also have abnormal eye lenses or abnormal retina but typically will not experience any vision loss. Progressive hearing loss begins in late childhood but can be helped by the use of hearing aids. There is no cure for Alport syndrome though kidney transplantation can help to extend life expectancy when kidneys begin to fail. Typically the eye issues do not require any intervention. Intellect is not affected by Alport syndrome. One of the causes of Alport syndrome is pathogenic variants in the COL4A3 gene.

Alport syndrome can be inherited in different ways. About 10% of the time it is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for autosomal recessive Alport syndrome, but about 50% of carriers exhibit intermittent or permanent microhematuria. However, the risk to have a child affected with autosomal recessive Alport syndrome is increased. Testing of reproductive partners is recommended for carriers of COL4A3 pathogenic variants.

Alport syndrome is estimated to affect 1 in 50,000 newborns.

The following websites may be informative: Genetic Home Reference: Alport syndrome (http://ghr.nlm.nih.gov/)($) National Kidney Foundation: Alport syndrome (http://www.kidney.org/)

Gene Reviews: Alport syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1116/) OMIM: [203780. ALPORT SYNDROME, AUTOSOMAL RECESSIVE] (http://www.ncbi.nlm.nih.gov/omim)

• Full gene sequencing