Hearing loss and Deafness

Nearly 1 out of every 4 adult Canadians reports having some degree of hearing loss, although close to 10% of people actually identify as culturally Deaf, oral deaf, deafened, or hard of hearing.¹ Approximately 4 in 1,000 Canadian babies are born with some degree of hearing loss or will develop early progressive childhood hearing loss.² Hearing loss is the third most prevalent chronic condition in older adults and the most widespread disability. Its prevalence rises with age – 46% of people aged 45 to 87 have hearing loss.³

Hearing loss can be categorized by type (conductive, sensorineural, mixed, or central auditory dysfunction), age of onset (prelingual or postlingual, meaning before or after normal speech development), and severity (degree of impairment). Hearing loss can be due to a genetic predisposition or be acquired through exposure to noise, infections, or certain medications.³

Approximately 80% of prelingual deafness is genetic.⁴ Genetic factors may also cause some people to be more susceptible to acquired hearing loss than others. It is estimated that the causes of age-related hearing loss are 35-55% genetic.⁵

 Genetics and Hearing loss

 Pinpointing the genetic causes for a specific hearing loss is complicated. Many different genes can cause the same type of hearing loss and the same genes can also be involved in different types of hearing loss. Two people with the same gene mutation may still have very different levels of hearing ability. Genetic forms of hearing loss and deafness can be further subdivided as syndromic or non-syndromic. Syndromic hearing impairment is associated with malformations of the external ear or with other medical problems. Over 400 genetic syndromes that include hearing loss have been described. Non-syndromic hearing loss has no associated visible anomalies but can be associated with changes to the middle and/or inner ear. Non-syndromic hearing loss is characterized by extreme genetic heterogeneity. To date, more than 6,000 causative variants have been identified in more than 110 genes.

Reasons for Genetic Testing

 Variable expressivity is common, so the correct diagnosis may depend on molecular genetic testing. Molecular genetic testing for hereditary hearing loss and deafness historically relied on single-gene testing. However, this testing approach has largely been replaced by multi-gene panels, which are more comprehensive. Confirmation of a clinical diagnosis through genetic testing can direct medical management, help predict progression of the disease, and provide essential information related to risk for relatives. Given the various modes of inheritance possible in hereditary deafness, establishing an accurate diagnosis may help provide risks to family members.

 LifeLabs Genetics offers the following Next-Generation Sequencing panel 

• Deafness/Hearing loss panel (autosomal dominant and recessive)

ABHD12, ACTG1, ADCY1, ADGRV1, AIFM1, ALMS1, ANKH, ATP6V1B1, ATP6V1B2, BCS1L, BDP1, BSND, CABP2, CACNA1D, CCDC50, CD164, CDC14A, CDH23, CEACAM16, CEP78, CHD7, CIB2, CLDN14, CLIC5, CLPP, CLRN1, COCH, COL11A1, COL11A2, COL2A1, COL4A3, COL4A4, COL4A5, COL4A6, CRYM, DCDC2, DFNA5, DFNB59, DIABLO, DIAPH1, DIAPH3, DNMT1, DSPP, EDN3, EDNRB, ELMOD3, EPS8, ESPN, ESRRB, EYA1, EYA4, FAM65B, FGF3, FGFR3, FOXI1, GATA3, GIPC3, GJA1, GJB2, GJB3, GJB6, GPSM2, GRHL2, GRXCR1, GRXCR2, HARS, HARS2, HGF, HOMER2, HSD17B4, ILDR1, KARS, KCNE1, KCNJ10, KCNQ1, KCNQ4, LARS2, LHFPL5, LOXHD1, LRTOMT, MARVELD2, MIR96, MITF, MSRB3, MYH14, MYH9, MYO15A, MYO3A, MYO6, MYO7A, NDP, NLRP3, OSBPL2, OTOA, OTOF, OTOG, OTOGL, P2RX2, PAX3, PCDH15, PDZD7, PEX1, PNPT1, POLR1C, POLR1D, POU3F4, POU4F3, PRPS1, RDX, S1PR2, SEMA3E, SERPINB6, SIX1, SIX5, SLC17A8, SLC26A4, SLC26A5, SLC33A1, SLC52A2, SLC52A3, SLITRK6, SMPX, SNAI2, SOX10, STRC, SYNE4, TBC1D24, TCOF1, TECTA, TJP2, TMC1, TMIE, TMPRSS3, TNC, TPRN, TRIOBP, TSPEAR, USH1C, USH1G, USH2A, WFS1

References

1. CHS Awareness Survey 2002. https://www.chs.ca/facts-and-figures
2. Ontario Ministry of Children and Youth Services, 2007
3. Cruickshanks KJ, et al. (1998) Am J Epidemiol.
4. https://www.hear-it.org/Genetic-hearing-loss
5. Shearer AE, et al. (2017) Hereditary Hearing Loss and Deafness Overview. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®