Clinical Guidance

Class of GJB2 Pathogenic Variants

Truncating vs nontruncating variants. The strong genotype-phenotype correlations with GJB2-AR NSHL can be recognized by classifying GJB2 variants as truncating (T) or nontruncating (NT) and then defining three genotype classes: biallelic truncating (T/T), biallelic nontruncating (NT/NT), and compound heterozygous (T/NT) . Hearing loss across these classes is nonrandomly distributed, with loss in the T/T class being more severe than in the T/NT class, which is more severe than in the NT/NT class. See Figure 3 (full text), which provides audiograms for various genotypes, showing the average hearing thresholds (50th centile) and the expected range (10th centile and 90th centile) for common genotypes.

Source: GeneReviews — "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss"

Diagnostic Criteria

Suggestive Findings

The diagnosis of GJB2-related autosomal recessive nonsyndromic hearing loss (GJB2-AR NSHL) should be considered in two scenarios: an and a .

Scenario 1: Abnormal Newborn Hearing Screening (NBHS) Result

Universal NBHS using physiologic screening (either otoacoustic emissions [OAE], which measure the response of cochlear outer hair cells to auditory stimuli, or automated auditory brain stem response [ABR], which measures the physiologic response of cochlear inner hair cells, auditory nerve, brain stem, and brain to auditory stimuli) is required by law or rule in all 50 states in the United States and is performed on 98% of children in the US typically within days after birth (see 2020 Summary of National CDC EHDI Data).

Source: GeneReviews — "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss"

Differential Diagnosis

As of this writing, more than 70 genes have been associated with autosomal recessive nonsyndromic hearing loss. For a list of selected genes associated with distinctive clinical features, see Genetic Hearing Loss Overview, Table 3. For a current, comprehensive list of all identified autosomal recessive nonsyndromic hearing loss genes, see Hereditary Hearing Loss Homepage.

Source: GeneReviews — "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss"

Management Guidelines

No clinical practice guidelines specific to GJB2-related autosomal recessive nonsyndromic hearing loss (GJB2-AR NSHL) have been published. Management ideally occurs in the context of a multidisciplinary clinic with specialists in otolaryngology, audiology, and genetic counseling. See Genetic Hearing Loss Overview, Management.

Evaluations Following Initial Diagnosis

To establish the extent of involvement and needs in an individual diagnosed with GJB2-AR NSHL, the following evaluations by an otolaryngologist are recommended:

Source: GeneReviews — "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss"

Clinical Guidance

Individuals with hearing loss should avoid environmental exposures known to cause hearing loss. Most important for persons with GJB2-related mild-to-moderate hearing loss is avoidance of repeated overexposure to loud noises, particularly secondary to earbud use. The headphone safety feature built into most smartphones can be set a maximum limit of 75 dB. Headphone/earbud safety features can be found in the phone settings menu:

• In iPhones, under Settings Sounds Haptics Headphone Safety

• In Android phones, under Settings Sounds Vibrations Volume Media volume limit

Also see these general resources on noise reduction:

• 6 Simple Ways To Check If Your Headphones Are Too Loud

• How Do I Prevent Hearing Loss from Loud Noise?

Source: GeneReviews — "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss"

Therapies Under Investigation

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

Source: GeneReviews — "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss"

Surveillance Guidelines

To monitor the individual's response to habituation and to identify any changes in severity of hearing loss, the following evaluations are recommended. Most children with severe-to-profound GJB2-AR NSHL with a cochlear implant will initially have frequent evaluations recommended by their cochlear implant team (otolaryngologist, audiologist, and speech and language pathologist). At follow-up appointments, the following may be performed: speech recognition testing, equipment checks (including device adjustment and troubleshooting), and provision of replacement or upgraded equipment . As the cochlear implant recipient becomes comfortable with the cochlear implant, many of the above tasks can be performed by the family at home, obviating the need for routinely scheduled appointments unless the need for a clinic visit arises.

Children with mild-to-moderate GJB2-AR NSHL

Source: GeneReviews — "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss"