In order to understand the pathophysiology of CHI, it is important to appreciate peripheral ear physiology. While problems in the structure of the ear all the way from the pinna to the auditory nerve easily explain the hearing loss due to a breach in the onwards transmission and transduction of the acoustic signal, there are numerous proteins and enzymes vital for normal cochlear and nerve function. Mutations which can either be sporadic and de novo or inherited lead to dysfunction.

13.3 Aetiology of Congenital Hearing Impairment

So far, as many as 427 clinical syndromes and 170 chromosomal anomalies have been identified with CHI. Many syndromes can now be mapped to a specific chromosome. Some syndromes are non-genetic or not hereditary.

13.4 Non-Syndromic Genetic Hearing Impairment

Non-syndromic hearing losses are characterised by involvement of the hearing mechanism only, typically sparing other organs. They can be pre- or post-lingual, predominantly sensorineural losses. Dominant inheritance usually results in the latter while the recessive pattern usually results in the former. X-linked inheritance may result in both or a mixed loss.

In addition, there is a group of genetic hearing losses which are a result of mutations in the mitochondria.

The autosomal dominant pattern dubbed DFNA is characterised by marked heterogeneity and often cannot be mapped to a single locus which generates markedly variable hearing losses which can affect certain frequencies only and are late onset and post-lingual; however, DFNA 3, 6, 8, 12 and 19 are pre-lingual. The intensity is usually mild-to-moderate hearing impairment. About 70 loci have been identified and mapped. A cookie bite audiogram may be observed in 30% cases and conductive and unilateral hearing losses have been reported.

The autosomal recessive pattern, on the other hand, is characterised by less heterogeneity and can be mapped to a single locus. Hearing loss may be predictable and is pre-lingual except in the case of DFNB8 which is post-lingual. These mutations are designated as DFNB. They may present with profound sensorineural hearing loss. The commonest gene mutation is Connexin 26/30 which encodes for gap junction proteins GJB2 and GJB6 in the stria vascularis and supporting cells. It is the commonest genetic cause for hearing loss which affects maintenance of the endocochlear potential and structural integrity of the outer hair cell (OHC).

The X-linked inheritance includes DFNX 1, 2, 3, 4 and 6 which are usually post-lingual except DFNX2 and X3 which lead to the X-linked gusher syndrome characterised by a mixed loss. It is a rare but important cause of pre-lingual deafness in children.

The mitochondrial mutations are usually maternally inherited and are responsible for non–dose-dependent aminoglycoside ototoxicity in A1555 del AG.

13.5 Syndromic Genetic Hearing Impairment