Genetics of congenital hearing impairment: a clinical approach.
Hearing impairment (HI) is the most frequent sensory disorder, with a genetic etiology in >50% of all cases, due to mutations in >44 identified genes. Autosomal recessive inheritance explains the majority, with GJB2 (connexin 26) mutations accounting for 15-50% of paediatric HI. Delayed presentation of HI to 11-60 months in cases of biallelic GJB2 mutations is a concern, necessitating a good audiological follow-up in addition to neonatal hearing screening. Providing a genetic diagnosis in congenital HI has implications for the prognosis, the possible risk of associated medical manifestations, and precise genetic counseling of the family, and should be integrated into the medical examinations done in order to diagnose syndromic features. Large-scale mutation detection methods, such as micro arrays, are promising for wider genetic testing, but few studies on their clinical utility have been published, so far. Limitations of interpretation of genetic test results, combined with significant ethical issues, currently do not justify to institute genetic screening for GJB2 mutations in neonates before a diagnosis of HI is established.
Tranebaerg
Lisbeth
L
Department of Audiology, Bispebjerg Hospital, Copenhagen, Denmark. tranebjaerg@imbg.ku.dk
D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D042241:Early Diagnosis; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006311:Hearing Disorders / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D009218:Myosins / Q000235:genetics; D015997:Neonatal Screening; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D009218:Myosins