Branchio-oto-renal syndrome

Branchio-oto-renal syndrome, also known as Melnick-Fraser syndrome, is an inherited disorder that affects the development of the kidneys, ears and structures of the neck together, reflecting its name: branchial (neck), oto (ear) and renal (kidney). It follows an autosomal dominant inheritance pattern, so a single altered gene copy inherited from a parent is enough to cause it, and it most often results from mutations in the EYA1 gene, accounting for roughly two in five cases, with a smaller share caused by mutations in the related SIX1 or SIX5 genes; in about half of diagnosed cases no mutation is found in any of the three known genes. The kidneys may be underdeveloped or malformed, sometimes progressing to chronic kidney disease, while ear involvement is highly variable and can include small pits or skin tags in front of the ear, malformed outer ears, abnormalities of the middle ear, and hearing loss ranging from mild to profound. Some affected people also develop cysts or open channels, called fistulae, in the neck left over from structures that should have closed before birth. Diagnosis is largely clinical, based on recognizing this characteristic combination of features, since genetic testing identifies a causative mutation in only about half of cases. Treatment is directed at each affected organ: hearing aids or other auditory support and monitoring for ear disease, nephrology follow-up and, in severe cases, dialysis or kidney transplantation for renal disease, and surgical removal of problematic neck cysts or fistulae.