3Patterns of inheritance

FFour ways to inherit deafness

Hereditary hearing loss follows one of four transmission patterns: autosomal recessive, autosomal dominant, X-linked, and mitochondrial. Each produces a characteristic pedigree, a defined recurrence risk, and a different short-list of candidate genes. Select a pattern below to see its family tree, its recurrence figure, and the genes that follow it.

FTAutosomal recessive — the dominant pattern

Around 80% of non-syndromic genetic deafness is autosomal recessive. Two unaffected carrier parents each pass a faulty allele to a quarter of their children; the recurrence risk is a fixed 1 in 4 per pregnancy. Because the parents hear normally, there is often no family history — the deafness seems to come from nowhere — and because relatives share alleles, consanguinity sharply raises its frequency (Chapter 5). Most of the major deafness genes, GJB2 foremost, act this way.[2005]

CAutosomal dominant

About 20% of non-syndromic genetic deafness is autosomal dominant: a single affected parent transmits it to half their children, so it runs visibly down the generations. Dominant forms are more often postlingual and progressive — hearing that is normal at first and declines through life — which is one reason the candidate may be an adult rather than a child.

CX-linked

A small fraction (~1–2%) is X-linked, passed from carrier mothers chiefly to sons. The most important example, POU3F4 (DFNX2), carries a specific surgical warning: it is associated with an abnormal cochlea and a risk of a perilymph “gusher” — a torrential flow of fluid on opening the cochlea at implantation. Knowing the genotype lets the surgeon anticipate it.

CMitochondrial

Mitochondrial deafness is inherited only down the maternal line — an affected mother passes it to all her children, fathers to none. It is often postlingual, progressive, and sometimes syndromic. Its single most clinically vital member is m.1555A>G, which makes a carrier exquisitely vulnerable to aminoglycoside ototoxicity — a single ordinary dose can deafen (Chapter 5). A maternal-line history of deafness after antibiotics is the warning sign.[1993]

CWhy inheritance matters clinically

The pattern does real work. It sets the recurrence risk for counselling future pregnancies; it shapes expectations (a dominant, progressive loss in an adult versus a recessive, congenital one in a child); and it occasionally flags a hazard — the X-linked gusher, the mitochondrial drug sensitivity.

Inheritance is the scaffold; the next modules hang specific genes, and their implant consequences, upon it — beginning with the gene that accounts for half of recessive deafness, GJB2 (Module 4).