Genetic Studies of Questionnaire Data from a Residential School for the Deaf
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Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 1981 Genetic Studies of Questionnaire Data from a Residential School for the Deaf Frederick Robert Bieber Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Genetics Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/4365 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. r� , r��i .. Pt'U:!_ I -, J GENETIC STUDIES OF QUESTIONNAIRE DATA FROM A RESIDENTIAL SCHOOL FOR THE DEAF by Frederick Robert Bieber B.A., State University of New York, 1972 M.S., University of Rochester, 1976 Thesis submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosphy in the Department of Human Genetics at the Medical College of Virginia Virginia Commonwealth University Richmond, Virginia December, 1981 .\ Copyright (D1981 Frederick Robert Bieber ALL RIGHTS RESERVED Table 1 from Hearing· in Children, Second edition, by J.L. Northern and M.P. Downs. Copyright (c) 1978 by The Hilliams and Hil kins Company, Baltimore. Reprinted by permission of The Hi 11 iams and Hilkins Company. Figure 1 repyinted by permission from Luria, Gould and Singer, A View of Life, �1enlo Park, California: The Benjamin/Cummings Publishing Company, Inc., 1981, p. 540, fig. 23-6. Figure 2 from HEARING AND DEAFNESS, Third Edition, edited by Hallowell Davis and S. Richard Silverman. Copyright 1947 (c) 1960, 1970 by Holt, Rinehart and Hinston, Inc. Reprinted by permission of Holt, Rinehart and Winston. Figures 3 and 4 from THE HUMAN NERVOUS SYSTEM, Second edition, by Noback and Demarest. Copyright (c) 1975, The �1cGraw-Hill Book Company. Used with the permission of tkGraw-Hill Book Company. This thesis by Frederick Robert Bieber is accepted in its present form as satisfying the thesis requirement for the degree of Doctor of Philosophy Date: Ap roved: . , isor, Chairman of Graduate Commr .... !0/�.!�t76o/,fr . ..... f(!:.:.(�(. � .....11� /9!... ... !!�C!.(f::... APPROVED . Chairman, �1CV Graduate Council, Dean, School of Basic Sciences.... iv The Author v ACKN0!4LEDGEt1ENTS Completion· of this project would not have been possible without the generous help and guidance of many individuals. My special thanks go to those parents and guardians of the students at the t1aryland School for the Deaf who so kindly volunteered to participate in this study; to David Denton, Superintendent of the Maryland School for the Deaf; to the members of the MSD staff and Board of Visitors, whose cooperation and enthusiasm made this study possible. I am especially grateful to �Ialter E. Nance, my thesis advisor, for his able guidance throughout the course of m.v thesis 11ork, for providing funds for production of the Hearing Loss Questionnaire, and for his untiring encour· agement and patience during my tenure as his student. In addition, I gratefully acknowledge: Linda Corey, Martin Lenhardt, Peter Mamunes, John Povlishock, and McCay Vernon, members of my graduate committee, for their help and guidance throughout the course of my thesis research and writing; Joann Boughman, Michael Conneally, and Ne�1ton f1orton for consultations concerning segregation analysis; Ed Peeples, Phillip Smith, and Vernon Williams for their generous advice with regard to various aspects of the data analysis; the many colleagues, associates, and friends who offered advice and assistance with the questionnaire design and distribution; members of the staff of the Tompkins-McCaw Library at the Medical College of Virginia and of the Francis A. Countway Library of t·1edicine in Boston, Massachusetts for their help in providing access to the vi older literature; Carol Nance, for her careful editorial revisions, and Gayle Hylton, for expert typing of parts of this thesis; the A.D. Williams Foundation, the National Institutes of Health, and the Office of the Dean of the School of Basic Sciences at MCV, for providing tuition and stipendiary support; all of the students, staff, and faculty at the �1edical College of Virginia v1ho helped make my time at MCV both intellectually stimulating and otherwi.se enjoyable; my friends, especially Gordon and Shelley Grumbine, and family, especially Jane McNamara Bieber, for unfailing encouragement, and for all that for which there are no adequate words. FRB April, 1981 Boston, Massachusetts "Because as Galen says in his seventh book of the Method of the Art of Healing, a work in any science or art is propounded for three reasons. First, to satisfy one's friends. Second, that one may obtain a most useful exercise, that is by the mind. Third, so that one may be saved from forgetfulness, which comes 1�ith a')e. Hence it is that, moved by these three causes, I have proposed to put together a certain work in medicine for my scholars." Mondino; Anathomia, 1316 ABSTRACT viii GENETIC STUDIES OF QUESTIONNAIRE DATA FROM A RESIDENTIAL SCHOOL FOR THE DEAF Frederick R. Bieber, Ph.D. f�edical College of Virginia - Virginia Commom�ealth University, 1981. Major Professor: Walter E. Nance, M.D., Ph.D. A self-administered thirteen page Hearing Loss Questionnaire (HLQ) was designed in order to systematically collect medical and family his tory data on deaf children and their families. Data were collected from over 400 families with one or more children enrolled in September 1979 at the Maryland School for the Deaf (MSD). Almost 70% of the parents provided pedigree and family history information by completing the detailed HLQ. Computer analyses of the collected data allowed a thorough examination of almost 200 medical and family history variables, providing useful reference data on the MSD probands. Parental responses to a four-step rating scale of proband hearing ability were compared with actual audiometric data, allowing comparison �lith similar data from previous studies of hearing populations. Family history data on the non-respondents were available from school records, providing a unique opportunity to assess the potential response bias in question naire studies of genetic disease. Segregation analysis was performed on the informative sibships ascertained by incomplete truncate se lection. The pooled estimate of the ascertqinment probability, II, was 0.488, with no significant evidence of heterogeneity among the re spondents and non-respondents. The hypothesis of fully penetrant domi nant inheritance (H0:p=0.50) was accepted in the Deaf by Hearing mat- ings. However, the maximum likelihood estimate of the segregation ix ratio (p=0.257) was consistent with reduced penetrance in these fami lies, as it also was in the Deaf by Deaf matings (p=0.31). There were no significant differences in the maximum likelihood estimates of£ or of the proportion of sporadic cases, �· between respondents and non respondents in the Hearing by Hearing matings. Among the non-consanguin eous Hearing by Hearing matings with no family history of hearing loss, the maximum likelihood estimate of x was 0.81. The removal of 46 sib ships with probands born during the 1964-65 rubella epidemic reduced x to 0.71, indicating the potential value of segregation analysis for moni� taring the secular trends in sporadic vs. genetic deafness. Among Hear ing by Hearing matings with a family history of early onset hearing loss, a recessive hypothesis wit.h no sporadic cases (H0:p=0.25, x=O.OO) fit the data well. However, the same hypothesis 1vas rejected among the Hearing by Hearing matings w.ith a family history of "presbycusis", where x=0.59. Thus, although a family history of early onset hearing loss appears to ·be a much more reliable index of a genetic etiology that does a family history of "presbycusis", the results of this study suggest that the latter may also be a positive risk factor. The HLQ data implied that both parents and doctors may underestimate the extent to which genetic factors contribute to childhood hearing loss, even in the presence of a· positive family history. Genetic factors were estimated to account for approximately 35% of the deafness in the MSD population. In the group with genetic deafness, the estimated proportions of recessive, dominant, and X-linked deafness were 57%, 39.%, and 5% respectively. Comparison of the estimates in the respondent vs. the non-respondent·groups revealed remarkable similarity betv;een the two groups, indiccti:ing that the use of the HLQ did not further confound existing biases. This study has demon strated the value and utility of using self-administered questionnaires· in genetic research. Indeed, the HLQ may serve as a usefu 1 prototype for future large scale population based studies of deafnes-s in man. X TABlE OF CONTENTS ABSTRACT viii INTRODUCTION 1 GENERAl BACKGROUND & OVERVIEW OF THE LITERATURE 4 The Nature of the Hearing Process 6 The Nature of Heqring Disability 18 Genetic and-developmental factors 20 Environmental factors 26 Hearing loss in adults 36 Population Studies of Hearing Loss Measurement, prevalence, and demographic considerations 42 Additional handicapping conditions 61 Causes of hearing loss 65 Genetic studies of childhood hearing loss 73 MATERIALS AND METHODS 109 RESULTS 115 The Proband's Hearing Loss 125 The r·1other' s Pregnancy with the Proband 143 Proband Birth and Delivery 147 Health History of the Proband 161 Other Medical Conditions 165 Segregation Analysis 169 Classification of Deafness 180 DISCuSSION 187 BIBLIOGRAPHY 210 APPENDICES 232 I. Hearing loss Questionnaire II. Mailings and Notices to Study Participants 248 III. The Philosopher and Her Father 257 xi LIST OF TABLES Table Title Paoe 1 SUMt�ARY OF EAR DEVELOPt�ENT 7 2 PERCENTAGE OF U.S. CHILDREN, AGED 6-11 YEARS (1963-65), AND YOUTHS, AGED 12-17 YEARS (1966-70), WITH HISTORY 31 OF SELECTED ILLNESS OR OTHER NEDICAL CONDITION 3 PERCENTAGE OF U.S.