The future role of genetic screening to detect newborns at risk of childhood-onset hearing loss

Abstract

Objective:To explore the future potential of genetic screening to detect newborns at risk of childhood-onset hearing loss.Design:An expert led discussion of current and future developments in genetic technology and the knowledge base of genetic hearing loss to determine the viability of genetic screening and the implications for screening policy.Results and Discussion:Despite increasing pressure to adopt genetic technologies, a major barrier for genetic screening in hearing loss is the uncertain clinical significance of the identified mutations and their interactions. Only when a reliable estimate of the future risk of hearing loss can be made at a reasonable cost, will genetic screening become viable. Given the speed of technological advancement this may be within the next 10 years. Decision-makers should start to consider how genetic screening could augment current screening programmes as well as the associated data processing and storage requirements.Conclusion:In the interim, we suggest that decision makers consider the benefits of (1) genetically testing all newborns and children with hearing loss, to determine aetiology and to increase knowledge of the genetic causes of hearing loss, and (2) consider screening pregnant women for the m.1555A> G mutation to reduce the risk of aminoglycoside antibiotic-associated hearing loss.

Monitoring neonates for ototoxicity

“…The American College of Medical Genetics (ACMG) recommends testing for MTRNR1 mutations in patients exposed to aminoglycosides who already have hearing loss (ACMG, 2002). Although this panel notes that avoiding aminoglycosides in polymorphism-positive individuals reduces the risk of developing hearing loss, clinical testing for this maternally-inherited trait in pregnant women is not yet performed in an anticipatory manner (Linden Phillips et al, 2013).…”

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

“…The most commonly affected gene causing nonsyndromic hearing loss (both in autosomal recessive DFNB1A [MIM 220290] and in autosomal dominant DFNA3A [MIM 601544]) is gap junction beta 2 ( GJB2 , [MIM 121011]), the gene encoding the connexin 26 protein (CX26) (Kelsell et al, 1997; Denoyelle et al, 1997). Depending on the studied population, 20–50% of all recessive nonsyndromic SNHL cases can be attributed to a mutation in GJB2 (Hilgert et al, 2009a; Linden Phillips et al, 2013). For a comprehensive overview of other affected genes, we refer to recent reviews (Hilgert et al, 2009b; Angeli et al, 2012; Shearer and Smith, 2012; Smith et al, 2014 2014; Stelma and Bhutta, 2014).…”

Gene expression dataset for whole cochlea of Macaca fascicularis

“…More than 10% of the cochlear signature genes (35 out of 344) was estimated to associate with hereditary syndromic or nonsyndromic hearing loss. Since several hundreds, but not thousands of genes have been roughly predicted to associate with hereditary hearing loss 20 – 22 in all the human genes (approximately 19,000–20,000) 23 , 24 , cochlear signature genes are presumably rich in deafness genes. Regarding the fact that novel genes associated with hearing loss have been reported every year, it raises the possibility that unreported deafness genes are included in the cochlear signature genes.…”