Branchiootorenal syndrome

Mutations in the 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. There are likely other genes that have not yet been identified that when mutated can cause this syndrome as well.

Branchiootorenal syndrome may be inherited or occur sporadically. The inheritance pattern of branchiootorenal syndrome is autosomal dominant. Autosomal dominant inheritance is when one mutated copy of the gene that causes a disorder in each cell is needed for a person to be affected. Autosomal dominant conditions may occur for the first time in a person in a family due to a spontaneous gene mutation, or these conditions may be inherited from an affected parent. When a person with an autosomal dominant disorder has a child, there is a 50% chance that their child will inherit the condition.

Branchiootorenal syndrome is characterized by birth defects or anomalies of tissues in the neck, malformations of the external ear, hearing loss, and kidney malformations. Symptom and symptom severity can vary greatly from person to person. It can be caused by mutations in the EYA1, SIX1, or SIX5genes. It is passed through families in an autosomal dominant fashion. Treatment may include surgery to remove the anomalies of the neck (i.e., branchial fistulae or cysts), careful assessment and management of hearing loss, and follow-up by a kidney specialist (nephrologist). In some cases dialysis or kidney transplant may be required.

It has been reported that branchiootorenal (BOR) syndrome might be the cause of adult-onset renal failure. One study reported a case of adult-onset renal failure in a 44-year-old man previously believed to have Alport's syndrome. In another study involving nine family groups with BOR syndrome, previously unrecognized renal impairments were diagnosed in more than one family. The findings included vesicoureteral reflux, and only slight elevation of plasma creatinine levels, first degree of chronic renal failure. This study also noted that a high incidence of urological anomalies have been shown by intravenous urography (also known as intravenous pyelography) studies performed on individuals with BOR previously considered to be normal.

Some genetic mutations that cause branchiootorenal (BOR) syndrome disrupt interactions that are necessary for the activation of certain genes during embryonic development, and therefore many of the renal anomalies seen in BOR syndrome are due to abnormal development and formation, and may be evident before or shortly after birth. However, there can be a lot of variability in the presence, severity, and type of renal abnormality from right side to left side in an affected individual and also among individuals in the same family. Although renal anomalies are common in BOR syndrome, the prevalence is difficult to determine because not all affected individuals undergo thorough renal testing including tests such as intravenous pyelography or renal ultrasonography.

Hereditary hearing loss conditions, in general, tend to be managed by a team that includes an otolaryngologist, an audiologist, a clinical geneticist, a pediatrician, sometimes an educator of the Deaf, a neurologist, and in case of branchiootorenal syndrome, a nephrologist (kidney doctor). Treatment of hearing loss may include determining which aids would be most helpful, for example hearing aids or vibrotactile devices; cochlear implantation may be considered in children over age 12 months with severe-to-profound hearing loss. Early hearing intervention through amplification, surgery, or cochlear implantation may be recommended for children who are at risk to lose their hearing before they learn to speak.

People with hereditary hearing loss often require regular follow-up with a hearing specialist such as an audiologist to monitor stability or progression of the hearing loss.

Treatment of branchial fistulae or cysts may require surgery. For people with branchiootorenal syndrome and severe kidney malformations or complications, dialysis or kidney transplant may be required.