7Genetic testing in the CI work-up

FTA test that moved to the front

For a child or adult presenting with severe-to-profound deafness, the traditional work-up has leaned on imaging and a scatter of aetiological tests, with genetics — when done — coming late. The proposal is to invert that: order comprehensive genetic testing early, as a cornerstone of the evaluation rather than a footnote. The justification is that the genetic result feeds directly into decisions the rest of the work-up is trying to make.[2014]

CThe testing paradigm

The pathway forks on the first distinction of the chapter — syndromic versus non-syndromic (Module 2). After history, examination, audiometry and ABR, an apparently non-syndromic candidate goes to a comprehensive multigene panel, which both names the gene and catches the Usher/Pendred mimics; a clearly syndromic candidate goes to phenotype-directed single-gene testing with genetic counselling and the relevant specialist referrals. Trace the two routes below.[2014]

CWhat a result changes

A positive genetic result earns its place by changing things concretely. It can reduce other tests (a definitive genetic diagnosis may obviate parts of the metabolic/infective screen); it can change surgical management (an X-linked POU3F4 result warns the surgeon to expect a perilymph gusher); it sharpens selection and prognosis (membranous-labyrinth vs spiral-ganglion gene); and it grounds counselling (recurrence risk, and syndromic surveillance such as a cardiology referral for long-QT). One test informs several decisions.

CLimits and the negative result

Testing is not a panacea. A negative panel does not exclude a genetic cause — the gene may simply not yet be on the panel or known — so a normal result re-opens the door to imaging and the wider aetiological work-up rather than closing the case. Variants of uncertain significance need cautious interpretation, and access and cost remain real barriers, especially in low-resource settings. Genetic testing complements the work-up; it does not replace clinical judgement or imaging.

With the testing in hand, the chapter reaches its central clinical payoff: the principle that lets a genotype predict an implant result — the spiral-ganglion hypothesis (Module 8).