Clinical Guidance

The phenotype associated with heterozygous KCNQ4 pathogenic missense variants is similar in all families: predominantly high-frequency sensorineural hearing loss (SNHL) that is detectable in childhood and 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 congenital onset of DFNA2 nonsyndromic hearing loss has been reported in one of the Dutch families with the variant , it has not been reported in other families with this variant. The high-frequency hearing loss in this family was progressive without substantial loss of speech recognition during the first decades of life .

Source: GeneReviews — "DFNA2 Nonsyndromic Hearing Loss"

Penetrance

The penetrance is complete. All individuals with a heterozygous KCNQ4 pathogenic variant exhibit the hearing loss phenotype; onset age and severity are variable.

Source: GeneReviews — "DFNA2 Nonsyndromic Hearing Loss"

Diagnostic Criteria

Suggestive Findings

DFNA2 nonsyndromic hearing loss should be considered in an individual with the following clinical, imaging, and family history findings:

Clinical findings

• 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.

• Normal physical examination

Source: GeneReviews — "DFNA2 Nonsyndromic Hearing Loss"

Differential Diagnosis

See Hereditary Hearing Loss and Deafness for complete differential diagnosis. Note: Table 4 has a complete listing of the genes and clinical manifestations of autosomal dominant nonsyndromic hearing impairment.

Source: GeneReviews — "DFNA2 Nonsyndromic Hearing Loss"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of hearing loss and needs in an individual diagnosed with DFNA2 nonsyndromic hearing loss, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Audiometry, including bone conduction testing

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

See Hereditary Hearing Loss and Deafness Overview for complete discussion of treatment. When hearing loss is mild to moderate, fitting of hearing aids to provide improved amplification is warranted. When the hearing loss becomes severe to profound, cochlear implants (CIs) can be considered. In individuals with preserved or relatively good low-frequency hearing and severe-to-profound high-frequency loss, a hybrid (short) cochlear implant may be considered. Hybrid implants combine two proven technologies – acoustic amplification and implant technology – to provide electroacoustic hearing. The acoustic component, which is coupled to the cochlear implant sound processor, amplifies residual low-frequency hearing; the electrical component uses cochlear implant technology to provide electrostimulation for high-frequency hearing. For school-age children or adolescents, special assistance for the hearing impaired may be warranted and, where available, should be offered.

Surveillance

Audiograms should be obtained on an annual basis to follow progression of hearing loss.

Source: GeneReviews — "DFNA2 Nonsyndromic Hearing Loss"

Clinical Guidance

The rate of progression of high-frequency hearing loss can be reduced by encouraging individuals with DFNA2 nonsyndromic hearing loss to avoid exposure to loud noise in the workplace and during recreation.

Source: GeneReviews — "DFNA2 Nonsyndromic Hearing Loss"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "DFNA2 Nonsyndromic Hearing Loss"

Surveillance Guidelines

Audiograms should be obtained on an annual basis to follow progression of hearing loss.

Source: GeneReviews — "DFNA2 Nonsyndromic Hearing Loss"