Program Overview

Resonate® is a no-charge genetic testing and counseling program for sensorineural hearing loss, sponsored by Akouos, Inc. Resonate uses a comprehensive panel of nearly 300 genes to potentially determine whether there is an underlying genetic cause of hearing loss. U.S. healthcare providers can order directly through PreventionGenetics; alternatively, providers (including audiologists) can refer patients to genetic counselors at InformedDNA who can provide pre- and post-test counseling and ordering of sponsored sensorineural hearing loss genetic testing. Providers will receive a genetic testing report and a report from the genetic counselor (if applicable).

Criteria For Test

  • Individuals under 40 years of age in the U.S. with at least one of the following:
    • Bilateral sensorineural hearing loss (by auditory brainstem response or behavioral testing) of moderate, moderately severe, severe, or profound degree
    • Auditory neuropathy
  • Individuals under 18 years of age in Brazil or Mexico with at least one of the following:
    • Bilateral sensorineural hearing loss (by auditory brainstem response or behavioral testing) of severe or profound degree
    • Auditory neuropathy

Clinical Features

Hearing loss or deafness is the most common sensory deficit in humans, affecting an estimated 5% of the world's population. Hearing loss may be caused by environmental or genetic factors (Azaiez et al. 2018. PubMed ID: 30245029). Hearing loss can be classified by type (conductive, sensorineural, or mixed), age at onset (congenital, prelingual, post-lingual, or age-related), audiologic characteristics (severity and affected frequencies), associated clinical features (syndromic or nonsyndromic), and mode of inheritance (autosomal dominant, autosomal recessive, X-linked, or mitochondrial).

Genetic testing is available for many types of hearing loss and may play a prominent role in diagnosis and counseling (Li et al. 2022. PubMed ID: 35802133).


Early diagnosis and intervention is crucial in children with hearing loss. More than 60% of congenital hearing loss is due to an underlying genetic cause. Hearing loss genetic testing is recommended by the International Pediatric Otolaryngology Group (IPOG) (Liming et al. 2016. PubMed ID:27729144) and American College of Medical Genetics and Genomics (ACMG) (Li et al. 2022. PubMed ID:35802133) as best medical practice for individuals with bilateral sensorineural hearing loss and auditory neuropathy. A genetic diagnosis may provide useful information about likelihood of a syndromic condition, whether genetic hearing loss is expected to be stable or progressive, the inheritance risk, and the prospect of benefit of clinical interventions.

This comprehensive hearing loss panel consists of genes that have been associated with all types of hearing loss. Importantly, both syndromic and nonsyndromic hearing loss genes are included in this panel.

In developed countries, hearing loss is primarily genetic and nonsyndromic (Sloan-Heggen et al. 2016. PubMed ID: 26969326). Congenital or pre-lingual hearing loss is estimated to be as high as 80% genetic as compared to 20% acquired or environmental. Of pre-lingual genetic hearing loss, up to 80% is nonsyndromic and 20% is syndromic. Of pre-lingual genetic nonsyndromic hearing loss, up to 80% is recessive, 19% is dominant, and the remainder is X-linked or mitochondrial (Shearer et al. 2017. PubMed ID: 20301607). Although de novo variants causing hearing loss have been documented, they are not thought to be a common cause of disease for the genes in this panel.

The gene most commonly associated with nonsyndromic hearing loss is GJB2 (also known as connexin 26), which accounts for up to 50% of cases of autosomal recessive nonsyndromic hearing loss in many world populations (Snoeckx et al. 2002. PubMed ID: 16380907). The most prevalent pathogenic GJB2 variant is c.35delG, having a global population frequency of 0.62%, and a frequency of 0.96% in European populations (gnomAD population database).

The most common types of syndromic hearing loss are Usher, Waardenburg, and Pendred syndromes (Koffler et al. 2015. PubMed ID: 26443487). Other less common syndromic causes of hearing loss are also included in this panel (Perrault, Treacher Collins, Stickler, Jervell and Lange-Nielsen, branchio-oto-renal (BOR), Wolfram, Heimler, and Alport syndromes).

In a study of 1,119 individuals with any type of hearing loss, 82% of positive diagnoses were due to 15 genes (GJB2, STRC, SLC26A4, TECTA, MYO15A, MYO7A, USH2A, CDH23, ADGRV1, TMC1, PCDH15, OTOF, TMPRSS3, LOXHD1, and OTOA) (Sloan-Heggen et al. 2016. PubMed ID: 26969326).

Copy number variant (CNV) detection is an important component of clinical genetic testing for genetic hearing loss, with CNVs contributing 18.7% of all positive genetic diagnoses in a large cohort of nonsyndromic hearing loss patients (Shearer et al. 2014. PubMed ID: 24963352). The majority of CNVs detected in this study were in two genes: STRC (73%) and OTOA (13%). The carrier frequency of STRC CNVs was estimated at 1.1-1.6% in individuals without hearing loss, indicating that STRC CNVs may be an equal or potentially larger contributor to autosomal recessive nonsyndromic hearing loss than GJB2 in some populations (Shearer et al. 2014. PubMed ID: 24963352). STRC CNVs often include the nearby CATSPER2 gene. Although CATSPER2 is not known to directly cause hearing loss, it is included in this panel because together with STRC, these two genes are associated with deafness-infertility syndrome. This test is able to detect CNVs in STRC, CATSPER2, and OTOA.

This hearing loss genetic test includes probes for CNV detection that cover all known GJB2 cis-regulatory element deletions associated with hearing loss, previously associated with digenic GJB2/GJB6 hearing loss and spanning from GJB6 to CRYL1. This includes the 309 kb GJB6-D13S1830 and 232 kb GJB6-D13S1854 deletions reported to be most common (del Castillo et al. 2003. PubMed ID: 14571368; del Castillo. 2005. PubMed ID: 15994881). The 95 kb region included in all published GJB2 regulatory element deletions has been especially targeted with CNV probes in this test (Tayoun et al. 2016. PubMed ID: 26444186).

This hearing loss panel also includes syndromic causes of hearing loss affecting the external structure of the ear such as microtia (HOXA2) and aural atresia (TSHZ1). Genes that cause hearing loss as an early occurring feature (FITM2) and genes with new or rarely reported associations with hearing loss are also included (AP1B1, ASIC5, ATOH1, CLDN9, DE1C, DMXL2, GRAP, IFNLR1, MAFB, MAP1B, MPZL2, REST, TBX1, TMEM126A, TMEM43, TRRAP, SLC44A4, NOG, PLS1, REEP6).

Testing Strategy

This hearing loss genetic test is performed using Next-Gen sequencing (NGS) with additional Sanger sequencing as necessary. This panel provides 99.6% coverage of all coding exons of the genes, plus 10 bases of flanking non-coding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.


  1. Ordering healthcare provider will determine if the individual meets eligibility criteria and discuss the test with the patient and/or caregiver.
  2. Either order the test using or refer for genetic counseling, plus test ordering using InformedDNA.
  3. If ordering test directly through PreventionGenetics, collect a specimen in the collection tube. For information on ordering specimen kits, see Specimen Collection and Shipping section.
  4. The genetic test will be processed at PreventionGenetics and the results will be sent to the ordering healthcare provider about 3 to 4 weeks after the lab receives the specimens and all appropriately completed paperwork. The ordering healthcare provider and/or genetic counselor will discuss the results with the patient and/or caregiver.

Genetic Counseling

There are two options for genetic counseling through the Resonate program:

  • Option 1: No-charge pre- and post-test counseling, plus ordering of hearing loss genetic testing by InformedDNA (a third-party service provider).
  • Option 2: When the healthcare provider orders genetic testing directly through PreventionGenetics, optional no-charge, post-test genetic counseling with InformedDNA (a third-party service provider) is available to patients.

Specimen Collection and Shipping


OCD-100 Buccal Swab (Preferred)

OCD-100 Buccal Swab used according to manufacturer instructions.

Specimens may be shipped at room temperature.

Specimen collection kits: Buccal specimen collection kits, which contain the TRF and the shipping label, may be ordered through the online order form or

Whole Blood

Collect 3 ml to 5 ml of whole blood in EDTA (purple top tube) or ACD (yellow top tube), minimum 1 ml for small infants.


Oragene™ or GeneFiX™ Saliva Collection kit used according to manufacturer instructions. DNA from saliva specimens is invariably contaminated with microbial and food DNA, which can impact specimen quality and may result in delayed testing and/or the need for a second specimen.


Label the specimen container with the patient's name, date of birth, and/or ID number. At least two identifiers should be listed on the specimen container. Specimen deliveries are accepted Monday-Saturday for all specimen types. Holiday schedules will be posted on our website at least one week prior to major holidays.