Branchio-otic syndrome 3 (BOS3)
OMIM number: 608389
Comments closing date: 12/06/2026
BOS3 is caused by variants in the SIX1 gene. This condition disrupts development of tissues in the neck and causes malformation of the ears. Abnormal development of the second branchial
arch can result in the formation of masses in the neck called branchial cleft cysts. Some affected
individuals have holes, or pits called fistulae in the side of the neck just above the collarbone. Fistulae can form tunnels into the neck, exiting in the mouth near the tonsil. Branchial cleft cysts and fistulae can cause problems if they become infected, so they are often removed surgically.
Most people with BOS have hearing loss and other ear abnormalities. Typical ear malformations
may include malformed auricles (cupped ears), preauricular pits or tags and middle/inner ear
dysplasias. The hearing loss can be sensorineural, mixed (involving both inner and middle ear
abnormalities’) or conductive hearing loss. Hearing impairment ranges from mild to profound.
Additional structural anomalies, including cleft palate, have also been reported at lower frequency. BOS3 has a close clinical overlap with branchio-oto-renal syndrome (BOR) [for which existing HFEA approval is in place], though kidney anomalies are rarely reported in BOS3.
