Genes, Hearing, and Deafness: From Molecular Biology to Clinical Practice PDF

Preface

Frequently, hearing impairment has been considered to require no more than the provision of a hearing aid, with little understanding of the need for thorough aetiological investigation to ensure prevention and remediation where possible and structured rehabilitation programmes, if the distressing personal and social consequences of hearing impairment are to be avoided.

It is worth pointing out that one in every 1,000 new-born babies suffers from congenital severe or profound hearing impairment. Furthermore, epidemiological studies demonstrate that the percentage of the population who have a hearing impairment that exceeds 45 dB HL and 65 dB HL are about 1.3% and 0.3% between the ages of 30 and 50 years, and 7.4% and 2.3% between the ages of 60 and 70 years, respectively (Davis, 1989). Hearing loss has for some time, been considered a permanent effect and consequence of factors such as infections, ototoxicity, trauma and ageing. In recent years, molecular biology and molecular genetics have made a key contribution to the understanding of the normal and defective inner ear, not only in congenital profound hearing impairment but also in late onset/progressive hearing impairment.

The HEAR and GENDEAF projects

In September 1994, when a Preparatory Workshop for the Constitution of a European study group on genetic deafness was held in Milan, only four loci of non-syndromal hearing impairment and only three genes responsible for syndromal hearing impairment had been discovered, whereas at the time of writing, some 45 genes which can cause non-syndromal hearing impairment have been identifies and over 110 loci found.

The importance of establishing common terminology and definitions and co-ordinating the multi-disciplinary approach was the core aim of HEAR project-European Concerted Action HEAR (Hereditary Deafness: Epidemiology and Clinical Research 1996–1999). The idea was to deal with the problem of combining clinical in-depth family and phenotype studies with basic molecular genetics and gene mapping methods in a more standardized way, with the aim of establishing a stable international collaboration. The initiative also wanted to create a bank of updated information on these disorders that would be useful not only to experts but to the entire scientific community in identifying sources of information and specialized centres to which specific cases may be referred. This project stimulated a considerable amount of work in this field leading to developments in molecular genetics and the mapping of human loci associated with hearing disorders. The numerous and scattered loci mapped reflect a heterogeneous set of genes and mechanisms responsible for human hearing and suggest a complicated interaction between these genes (Lalwani and Castelein, 1999).

GENDEAF European Union Thematic Network Project 2001–2005 has helped to further open and widen the analysis of genotype/phenotype correlations, the effects of deafness on the family and the psychosocial aspects (also involving patient associations).

This book is aimed as a follow up of these two projects. It endeavours to provide a broad and up to date overview of genetic hearing impairment for audiologists, otolaryngologists, paediatricians and clinical geneticists to improve the quality of care for the large group of patients with suspected genetic hearing impairment. It does not set out to be a comprehensive description of syndromes such as the excellent and complete text of Toriello, Reardon, and Gorlin (2004), but to provide an easily read sourcebook for those students and clinicians with an interest in this field.

The book is divided into three parts:

The first part reports the important elements of current knowledge of the various situations in which genes have an influence on inner ear dysfunction. Chapters 1 and 2 provide the reader with an appropriate background, presenting an introduction to auditory function, basic genetics and genetic techniques significant to this field. Chapter 3 does not list the various syndromes, but intends to discuss and help clinicians to interpret the signs in order to better understand how molecular genetics can be informative. Chapter 4 tackles the complex genetic aspect of deaf/blindness. Chapter 5 analyses the role of the various genes as a causative of non-syndromal hearing loss. Chapters 6 to 9 analyse the responsibility of genetic factors in certain complex situations such as ageing, noise exposure, ototoxic drugs and otosclerosis.

Part II discusses current approaches to and management of hearing impairment in different ways. Thus Chapters 10 and 11 review the psychosocial impact of genetic hearing impairment and how culturally Deaf people react to genetic interventions. Chapter 12 looks at the related area of genetic factors in speech and language while Chapters 13 to 15 provide guidance on the identification of specific genotypes from phenotypic information, steps which should be taken in this respect in deaf children and how geneticists approach such a challenge. Developments in the pharmacological approach to hearing impairment and tinnitus are covered in Chapters 16 and 20, while Chapters 17 to 19 discuss the medical and surgical management of specific genetic disorders affecting the outer/middle ear, the cochlea and the cochlear nerve respectively.

Finally, the third part delves into our future and is an update of various lines of research covering a range of therapeutic strategies. These include the use of stem cells, tissue transplantation into the inner ear, gene therapy and finishes with an overview of the important process of apoptosis and how it can be prevented.

The contributing experts are all authoritative in their fields and have been asked to present up to date, concise and brief reviews of their particular subject matter; the reader should find this book follows the rapid pace of change in medical science.