Clinical characteristics: DFNA2 nonsyndromic hearing loss is characterized by symmetric, predominantly high-frequency sensorineural hearing loss (SNHL) that is progressive across all frequencies. At younger ages, hearing loss tends to be mild in the low frequencies and moderate in the high frequencies; in older persons, the hearing loss is moderate in the low frequencies and severe to profound in the high frequencies. Although the hearing impairment is often detected during routine hearing assessment of a school-age child, it is likely that hearing is impaired from birth, especially at high frequencies. Most affected persons initially require hearing aids to assist with sound amplification between ages ten and 40 years. By age 70 years, all persons with DFNA2 nonsyndromic hearing loss have severe-to-profound hearing impairment.
Diagnosis/testing: The diagnosis of DFNA2 nonsyndromic hearing loss is established in an individual with a characteristic audioprofile, a family history consistent with autosomal dominant inheritance, and identification of a heterozygous pathogenic variant in KCNQ4.
Management: Treatment of manifestations: Hearing aids for those with mild-to-moderate hearing loss; consideration of cochlear implants when hearing loss is severe to profound; special assistance in school for hearing-impaired children and adolescents.
Surveillance: At least annual audiogram to follow progression of hearing loss.
Agents/circumstances to avoid: Avoiding exposure to loud noise may reduce the rate of progression of high-frequency SNHL.
Evaluation of relatives at risk: Determining in infancy or early childhood whether a family member of the proband has inherited a pathogenic variant in KCNQ4 allows for early support and management of the child and family.
Genetic counseling: DFNA2 nonsyndromic hearing loss is inherited in an autosomal dominant manner. Most individuals with DFNA2 nonsyndromic hearing loss have a parent with hearing loss; the proportion of individuals with a de novo KCNQ4 pathogenic variant is unknown. Each child of an individual with DFNA2 nonsyndromic hearing loss has a 50% chance of inheriting the KCNQ4 pathogenic variant. Once the KCNQ4 pathogenic variant has been identified in a family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for DFNA2 nonsyndromic hearing loss are possible.
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