Branchiootorenal syndrome

Branchiootorenal (BOR) syndrome is a genetic condition that typically disrupts the development of tissues in the neck and causes malformations of the ears and kidneys. The signs and symptoms of this condition can vary, however.

"Branchio-" refers to the second branchial arch, which is a structure in the developing embryo that gives rise to tissues in the front and side of the neck. In people with branchiootorenal syndrome, abnormal development of the second branchial arch can result in the formation of masses in the neck called branchial cleft cysts. In some people, abnormal connections called fistulae form passages between these cysts and the surface of the neck. Fistulae can also develop between the skin of the neck and the throat, near the tonsils. Branchial cleft cysts and fistulae can cause medical problems if they become infected.

"Oto-" refers to the ear; most people with branchiootorenal syndrome have hearing loss and other ear abnormalities. The hearing loss is known as sensorineural deafness if it is caused by changes in the inner ear, and conductive deafness if it is caused by changes in the middle ear. Branchiootorenal syndrome can also involve hearing loss that results from changes in both the inner ear and the middle ear, which is called mixed hearing loss. Other ear abnormalities associated with branchiootorenal syndrome include malformations of the inner ear or middle ear and abnormally shaped outer ears (pinnae). Some affected people also have tiny holes in the skin (preauricular pits) or small flaps of skin (preauricular tags) just in front of the ear.

"Renal" refers to the kidneys; branchiootorenal syndrome causes abnormalities of kidney structure and function. These abnormalities range from mild to severe and can affect one or both kidneys. In some cases, end-stage renal disease (ESRD) develops later in life. This serious condition occurs when the kidneys become unable to filter fluids and waste products from the body effectively.

Researchers estimate that branchiootorenal syndrome affects about 1 in 40,000 people.

Mutations in three genes, EYA1, SIX1, and SIX5, are known to cause branchiootorenal syndrome. About 40 percent of people with this condition have a mutation in the EYA1 gene. SIX1 and SIX5 mutations are much less common causes of the disorder.

The proteins produced from the EYA1, SIX1, and SIX5 genes play important roles in development before birth. The EYA1 protein interacts with several other proteins, including SIX1 and SIX5, to regulate the activity of genes involved in many aspects of embryonic development. Research suggests that these protein interactions are essential for the normal formation of many organs and tissues, including the second branchial arch, ears, and kidneys. Mutations in the EYA1, SIX1, or SIX5 gene often disrupt the proteins' ability to interact with one another and regulate gene activity. The resulting genetic changes affect the development of organs and tissues before birth, which leads to the characteristic features of branchiootorenal syndrome.

EYA1 and SIX1 mutations have also been found in some people with a condition known as branchiooto (BO) syndrome. This condition includes many of the same features as branchiootorenal syndrome, but affected individuals do not have kidney (renal) abnormalities. The two conditions are otherwise so similar that researchers often consider them together (BOR/BO syndrome). It is unclear why some EYA1 and SIX1 mutations are associated with kidney abnormalities and others are not.

Some people with branchiootorenal syndrome do not have an identified mutation in the EYA1, SIX1, or SIX5 gene. In these cases, the cause of the condition is unknown.

Read more about the EYA1, SIX1, and SIX5 genes.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 90 percent of cases, an affected person inherits the mutation from one affected parent. The remaining cases result from new mutations in the gene, and occur in people with no history of the disorder in their family.