Case of the Week

Background:

• Branchio-oto-renal syndrome (BOR) is a rare, autosomal dominant disorder that may present with hearing loss, branchial fistulas, malformations of the ear, and/or renal anomalies.
• BOR occurs in about 2% of profoundly deaf children, with a prevalence in the general population of 1 in 40,000.
• Hearing impairment is a symptom of approximately 80% of patients with BOR.
• Approximately 50% of affected individuals have detectable genetic mutations, including mutations in EYA1 (~40%) or SIX1 (<4%).
• This patient’s genetic mutation is not confirmed.

Clinical Presentation:

• Current diagnostic criteria are clinically based. The patient must meet 3 major criteria, or 2 major and at least 2 minor criteria, or 1 major criterion with an affected first-degree relative. The major criteria for diagnosis include branchial abnormalities, deafness, preauricular pits, and renal anomalies. The minor criteria include external, middle, and/or inner ear anomalies, preauricular tags, and facial/palate abnormalities.
• Patients commonly initially present with hearing loss.
• Renal abnormalities are often not symptomatic at presentation but are a significant source of morbidity later in life.
• Some patients may never have renal involvement throughout their life, which is defined as branchio-oto-renal spectrum disorder.
• This patient has bilateral mixed hearing loss, profound on the right and severe on the left. The patient’s physical exam includes bilateral preauricular pits and a caved-in appearance of the skull behind the right ear related to temporal bone dysplasia. He also has renal involvement and is status post multiple renal transplants.

Key Diagnostic Features:

• Cochlear anomalies are the hallmark imaging temporal bone finding of BOR. Patients with EYA1 mutations classically have an unwound appearance of the cochlea, with the hypoplastic apical and middle turns abnormally offset from the basal turn. Patients with SIX1 mutations do not typically have offset of the apical and middle turns; instead, they have a shortened, spiky appearance of the apical turn.
• Additional variably present temporal bone abnormalities in BOR include: patulous Eustachian tubes, abnormal course of the facial nerve (particularly medialized), dysmorphic appearance of the internal auditory canals, ossicles, and/or vestibular apparatus, and vestibular aqueduct enlargement with enlarged endolymphatic sac.

Differential Diagnoses:

• Cochlear hypoplasia: This continuum of developmental cochlear anomalies includes at its less severe end hypoplasia of the middle and apical turns (type IV), similar to this case. However, the unwound appearance of the cochlea seen here is not typically seen with cochlear hypoplasia.
• Cochlear incomplete partition type 2 (IP-2): This developmental anomaly results in an apically deficient modiolus with incomplete segmentation of the apical and middle turns of the cochlea. Like BOR, there commonly is associated vestibular aqueduct enlargement and dysmorphic appearance of the vestibule. However, the findings of an unwound cochlear morphology, ossicular anomalies, and enlarged Eustachian tube are not typical for IP-2.

Treatment:

• There is no cure for BOR; therefore, treatment is targeted toward mitigating symptoms. Patients may be candidates for cochlear implantation if more conservative measures fail to improve hearing.