Genetics, Disability, and Deafness

The Epidemiology of Hereditary Deafness: The Impact of Connexion on the Size and Structure of the Deaf Community

THE EPIDEMIOLOGY OF HEREDITARY DEAFNESS The Impact of Connexin 26 on the Size and Structure of the Deaf Community Walter E. Nance This paper will discuss briefly what we now know about the causes of deafness and how they can change with time. It will not dwell upon the many different forms of genetic deafness that have been identified as part of the Human Genome Project, but it will review what is known about the commonest form of genetic deafness, connexin 26, and share some ideas about why that form of deafness is so frequent. In the process, we will see what an important role genetic studies at Gallaudet University have played in understanding the genetic epidemiology of deafness. Finally, the paper may contribute a new perspective on the ambiguous role that Alexander Graham Bell played in the history of deaf culture. 94 ETIOLOGIC HETEROGENEITY Deafness has many recognized causes, and an important goal of genetic analysis has been to attempt to distinguish causes that are largely genetic from those that are environmental in origin. Long before we learned to map and clone human genes effectively, it was possible to at least estimate the overall contribution of genetic factors to deafness with a high degree of accuracy through the systematic collection and analysis of data on the frequency and distribution of deafness within families. Without question, the largest and most valuable data set of this type that has ever been assembled are the 5,000 pedigrees collected by Edward Allen Fay, a professor at Gallaudet College, and published in a book titled Marriages of the Deaf in America in 1898.1 These data were collected with the active support of Alexander Graham Bell and were analyzed for the first time before the rediscovery of Gregor Mendel’s work in 1900. As a consequence, Fay’s insightful interpretations did not benefit from knowledge of the then-new theory of Mendelian Inheritance. However, the questionnaires that he used were so well designed that the data have been reanalyzed repeatedly during the past 100 years using progressively more sophisticated methods. In the contemporary approach to the analysis of family data of the type Fay collected, we assume that the deafness is genetic in all families 95 THE EPIDEMIOLOGY OF HEREDITARY DEAFNESS Edward Allen Fay with two or more deaf siblings. Then, using knowledge about how genetic traits are transmitted in families, we estimate what proportion of the families with only one deaf child are also genetic cases in which by chance only one child is deaf. This method is analogous to using knowledge about the density of ice and water to estimate the total size of an iceberg by measuring the size of the part that is above the water. When analyses of this type are performed, we can estimate that about half of all cases of profound deafness in this country during the nineteenth century were genetic in origin.2 Of course we know that some of the environmental causes of deafness, such as cytomegalovirus (CMV) infections and the congenital rubella syndrome, can be epidemic in nature, so that the proportions of genetic and environmental deafness can vary tremendously from time to time. Thus, as you might expect, the proportion of genetic cases was much lower during the last rubella epidemic. Genetic deafness may be dominant, recessive, X-linked, or carried through mitochondrial inheritance, and it may be either syndromic or nonsyndromic.3 Further analyses of Fay’s data alone permit at least crude estimates of the proportions of the former groups, if not the latter, types of genetic deafness. More recently, in the mid-1960s, a demographer named Augustine Gentile at Gallaudet initiated the systematic annual collection of demographic data on the 40,000–50,000 children in educational programs for the deaf throughout the nation. During the past forty years, the subsequent directors of the Annual Survey of Deaf and Hard of Hearing Children and Youth have been very receptive to the collection of information on deafness in the families of these children. On two occasions, data on more than 12,000 families have been collected, resulting in the largest samples of family data on a single genetic trait that have ever been subjected to genetic analysis.4 Currently, with support from an NIH grant and in collaboration with scientists at Gallaudet, we are also using families identified through the survey to establish a nationwide repository of DNA...