Alport Syndrome: Dealing with Hearing Loss and Advances in Technology Abby Meyer M.D. Assistant Professor, Pediatric Otolaryngology Director, Lions Children’s Hearing Center University of Minnesota Department of Otolaryngology

Sensorineural hearing loss

Hearing Loss Syndromic 1/3 Nonsyndromic 2/3 Childhood Hearing Loss Genetic 50% Idiopathic 25% Disease, Treatment Side Effects, Environment 25% Syndromic 1/3 Nonsyndromic 2/3 CMV, Herpes, Rubella, Syphilis, Toxoplasmosis, Varicella, Aminoglycosides, Exchange transfusion, Ventilation, ECMO, Fetal Alcohol Syndrome, Lead poisoning, Head trauma. Recessive 75-85% Dominant 15-24% X-linked 1-2%

Hearing Loss Syndromic 1/3 Nonsyndromic 2/3 Childhood Hearing Loss Genetic 50% Idiopathic 25% Disease, Treatment Side Effects, Environment 25% Syndromic 1/3 Nonsyndromic 2/3 CMV, Herpes, Rubella, Syphilis, Toxoplasmosis, Varicella, Aminoglycosides, Exchange transfusion, Ventilation, ECMO, Fetal Alcohol Syndrome, Lead poisoning, Head trauma. Recessive 75-85% ALPORT SYNDROME Dominant 15-24% X-linked 1-2%

Why is there hearing loss associated with Alport Syndrome? Alport Syndrome is caused by abnormalities of the COL4A3, COL4A4 or COL4A5 genes, resulting in abnormal type IV collagen Type IV collagen is important in the structure and function of the basilar membrane HL is a frequent extrarenal finding and one of the first symptoms of AS.

Characteristics of the hearing loss seen in Alport Syndrome Hearing loss tends to be: SENSORINEURAL BILATERAL SYMMETRIC PROGRESSIVE DURING LATER CHILDHOOD MIDDLE AND/OR HIGH FREQUENCY VARIABLE IN DEGREE Most patients retain some hearing capacity. Can be one of the first and most useful signs in patients with hematuria.

Hearing loss in males vs hearing loss in females with Alport Syndrome Significant hearing loss is more common in males than in females 55% vs 45% but in X-linked Alport Syndrome (mutation in COL4A5), significant hearing loss develops in 80-90% of affected males by the age of 40. In general, hearing loss in affected females tends to occur later in life than in males. In general, hearing loss in females may be relatively mild or even subclinical.

But….. There are no gender differences in the incidence or course of hearing loss in autosomal recessive Alport Syndrome. Hearing loss in autosomal dominant Alport Syndrome tends to be slowly progressive and may not develop until relatively later in life (well into adulthood). Characteristics of the genetic abnormality itself can result in different risks for hearing loss (different ages of onset of hearing loss). Ex: Nonsense vs missense mutations A lot depends on inheritance/mutation. In individuals with large rearrangements of COL4A5, nonsense mutations, frameshift mutations and splice site mutations, risk for deafness is 50% at age 10 years. In individuals with missense mutations, the risk for deafness does not reach 50% until age 20 years.

Management of hearing loss Monitoring of hearing in patients with Alport Syndrome is vital Hearing loss with Alport Syndrome is never congenital, so it will not be picked up on routine universal newborn hearing screening. Audiograms every 1-2 years beginning at age 6 would be a conservative place to start. Hearing loss typically becomes detectable by audiogram in late childhood (6-10 years) in boys with X-lined Alport Syndrome and in boys and girls with autosomal recessive Alport Syndrome.

Options Sign language Total communication Cued speech Amplification Hearing aids Cochlear implant Combinations of technology and various communication can be used

Hearing aids Cochlear implant Options Sign language Total communication Cued speech Amplification Hearing aids Cochlear implant Combinations of technology and various communication can be used

Hearing Aids Other options such as BAHA don’t typically pertain to Alport patients given their hearing loss is symmetric typically.

Cochlear Implantation Eligibility criteria Bilateral moderate to severe sensorineural hearing loss Age > 12 months (FDA) Many centers implant as young as 6 months No upper limit on age Trial of hearing aids > 6 months Many centers will decrease time for young children Present cochlear nerve Cochlear anomalies are NOT a contraindication

Cochlear implantation—Postlingual deafness Postlingually deafened children and adults tend to do well with cochlear implantation Duration of deafness correlates with post-implant performance Better performance with shorter duration

Cochlear implantation— The process Internal device implanted (surgery) Wait 3-4 weeks for swelling to subside Lots of programming and therapy

Cochlear implant devices Parents (patient if adult) work with the audiologist to choose the device 3 cochlear implant manufacturers Cochlear Advanced Bionics Med El

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