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Genetics of the voice
Journal of Voice
Vol. 9, No. 1, pp. 16-19 © 1995 Raven Press, Ltd., New York
Genetics of the Voice Robert Thayer Sataloff Department of Otolaryngology, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
Summary: Substantial advances have led to the evolution of voice as the newest subspecialty of otolaryngology. Nevertheless, little is known about the genetics of voice. Genetic research is needed to further elucidate the relationship between vocal tract structure (including ultrastructure) and function, mechanisms of voice dysfunction, and transmission of normal and abnormal voice characteristics. Key Words: Voice--Genetics--Heredity.
During the last decade, research discoveries, technological advances, and new clinical insights have resulted in the evolution of a new subspecialty of otolaryngology: voice (1,2). These advances have substantially changed the standard of care for patients with voice disorders, led to sophisticated noninvasive voice therapy, and markedly altered surgical techniques used for voice problems (3). Despite many exciting breakthroughs, much remains to be learned about how the voice functions, what causes phonatory dysfunction, and how voice characteristics (normal and abnormal) are transmitted within families and larger groups. Genetic research has barely begun to address these problems.
discussed hereditary voice disorders (5,6,8). The rest of the conditions discussed in this article were identified through the author's clinical experience and through his review of the content and references contained in numerous speech pathology textbooks and reference texts on human genetics. There appears to be no other published review on the subject of the genetics of voice, although there is a valuable text available on genetic aspects of speech and language (9). Normal voice
It is clear that genetic factors influence vocal quality. This has been recognized anecdotally in families and even nationalities (Italians, Welsh, Russians, and others). If one assumes that function is related to structure, the association of voice quality and genetic factors is intuitively comfortable. It is generally accepted that physical characteristics are genetically determined. If these include the size of the laryngeal cartilages, vocal fold length and structure, size and shape of the supraglottic vocal tract, and phenotypic similarities elsewhere in the vocal mechanism, then one might expect similarities in voice quality. If we postulate additional similarities in brain development, musical perception, and neuromotor control, the notion becomes even more attractive. However, to be credible, these issues require further study and careful separation of genetic factors from environmental influences upon development. Some of the most interesting studies to date have
GENETICS OF THE VOICE Genetics of the voice is a fascinating area for speculation and research. Unfortunately, there have been very few studies, and none has been definitive or extensive. In reviewing this subject, a computer search of 8,009,307 references in four databases (MedLine, Health, AidsLine, and CancerLit) was carried out using the following key words: heredity, genetics, voice, voice disorders, and familial. The MedLine database indexes articles from 1966 to present. The computer search produced only five references (4-8), of which only three really Accepted N o v e m b e r 17, 1993. Address correspondence and reprint requests to Dr. R . T . Sataloff at 1721 Pine St., Philadelphia, PA 19103, U.S.A.
16
GENETICS OF VOICE
looked at voice function in twins. In general, monozygotic twins have very similar voices. Dizygotic twins appear to show the same differences that would be expected among any children of the same age (10). Coon and Carey (11) studied genetic and environmental determinants of musical ability in twins. Recognizing that there is more to vocal quality and ability than vocal fold structure alone, such studies are of relevance when studying the genetics of voice. Coon and Carey examined monozygotic and dizygotic twins and found evidence of hereditary variation, although environment appeared to be a more important factor than heredity. Kalmus and Fry (12) studied dysmelodia (inability to sing on tune) and found it to be inheritable as an autosomal dominant trait with imperfect penetrance. They speculated that their findings seemed to indicate the existence of some deep structure of tonality perception comparable with Chomsky's deep language structure. Although Bernstein and Schlaper (13) began looking at the genetic influences on the voice as early as 1922, and subsequent work was carried out by Schilling (14,15), Seeman (16), Gedda et al. (17), and others, the complexities of genetic research in humans have left most of the relevant questions unanswered.
Pathological voice and syndromes In addition to the voice quality characteristics that appear to be transmitted in healthy groups, numerous pathological conditions are associated with specific voice dysfunctions (18). For example, raspy voice quality has been recognized in hyalinosis cutis et mucosae (19-21), Opitz BBB/G compound syndrome (22-25), pachyonychia congenita syndrome (26-28), Werner syndrome (29,30), Williams syndrome (31-34), and other conditions. High-pitched voice occurs in Bloom syndrome (3538), chondrodystrophic myotonia (39-42), deletion (5p) syndrome (43), Dubowitz syndrome (4A, A.6), Seckel syndrome, Silver-Russell syndrome, and Werner syndrome (29,30). Low-pitched voice has been observed in cutis laxa syndrome (47-49), de Lange syndrome (50-52), deletion (18q) syndrome (53-56), mucopolysaccharidoses (types IH, II, III, VI), and Weaver syndrome (57,58). Other voice abnormalities have been observed in myotonic dystrophy syndrome (18,59) and hereditary dystonias that may be associated with spasmodic dysphonia. A dominant form of spinal muscular atrophy associated with distal muscle atrophy, vocal fold paraly-
17
sis, and sensorineural hearing loss has been reported. Familial vocal fold dysfunction associated with digital anomalies also exists. Verma et al. (5) described familial male pseudohermaphroditism with female external genitalia, male habitus, and male voice. Urbanova (6) reported familial dysphonia and Friol-Vercelletto et al. (8) reported familial oculopharyngeal muscular dystrophia with associated abnormal voice. Hence, evidence for the existence of a genetic component to vocal quality is compelling.
Molecular genetic considerations Developments in genetic research in recent years are exciting and have largely moved from clinical to molecular studies. Unfortunately, close scrutiny still reveals discouraging complexities. Much of today's genetic research is involved with gene mapping. This methodology is elegant, but still of limited clinical value for broad questions like vocal quality. In general, at present, genetic markers are useful for conditions associated with one major gene. They require an extremely specific phenotype description. Indeed, linkage studies are extraordinarily difficult and time consuming without specification not only of phenotype, but also of a candidate gene. Because the basement membrane matrix proteins are found on the long arm of chromosome 1 and other materials may be localized to specific chromosomes, proposal of candidate genes for voice phenomena may actually be practical in selected cases. For example, Mace et al. (60) described a family with hereditary, congenital, bilateral adductor vocal fold paralysis inherited as an autosomal dominant, with linkage with HLA and GLO, a syndrome localized to chromosome 6, position 21.3-23. However, for many questions regarding voice traits and problems, gene mapping is still a cumbersome approach. Undoubtedly, the process will become easier as more of the > I00,000 genes in each human genome are mapped and associated with phenotypic expressions. In the meanwhile, it appears as if the most likely avenue of success will be the study of pathological conditions known to be hereditary and associated with voice abnormalities. This research should include genetic, structural, physiological, and epidemiological studies. Such investigations, together with advances in genetic research, should eventually lead us to the kind of information we seek about normal and exceptional voices. Later research efforts are likely to be facilitated by buildJournal of Voice, Vol. 9, No. 1, 1995
18
R. T. S A T A L O F F
ing a database of pedigree information now. A national registry to coordinate this information may even be appropriate, as suggested by Dr. S. Gray (personal communication). Clinicians should be encouraged to acquire much more meticulous family histories focusing on voice quality, skills, peculiarities, and other nonvoice distinguishing features and diseases. Such clinical research is also likely to provide information that will help clarify the genetic nature of voice traits, not just pathology. In addition, it may give us insight into disease susceptibility. This has been recommended in the past for cancer. However, questions about benign disease still remain to be answered. For example, in families with vocal nodules, we have always assumed environmental factors were causal. Perhaps there are also genetic deficiencies in healing patterns that can be identified. If so, preventive measures may be possible and may guide medical and surgical therapy. CONCLUSION
5.
6. 7. 8.
9. 10. 11. 12. 13. 14. 15.
Considerable additional study should be encouraged to elucidate the genetics of voice. This research should investigate not only vocal tract structure and function, but also genetic aspects of cortical function, perception, and neurological control, which are inextricably involved in voice production. Although questions involving heredity are associated with somewhat discouraging difficulties in research design and implementation, they must be addressed along with the more limited anatomical and physiologic questions studied to date. Clinical and molecular genetic research should provide important new insights into healthy and pathological phonation and the relationship between vocal tract structure (such as basement membrane ultrastructure) and function and valuable contributions to the physician's armamentarium for treating voice disorders. REFERENCES 1. Sataloff RT. Professional voice: the science and art o f clinical care. New York: Raven Press, 1991. 2. Sataloff RT. The human voice. Sci A m 1992;267(6): 108-15. 3. Gould WJ, SataloffRT, Spiegel JR. Voice surgery. Chicago: Mosby-Year Book, 1993. 4. Rudiger RA, Schmidt W, Loose DA, Passarge E. Severe developmental failure with coarse facial features, distal limb hypoplasia, thickened palmar creases, bifid uvula, and ureJournal of Voice, Vol. 9, No. 1, 1995
16. 17.
18. 19. 20. 21. 22. 23. 24.
25. 26. 27. 28. 29.
teral stenosis: a previously unidentified familial disorder with lethal outcome. J Pediatr 1971 ;79:977-8 I. Verma IC, Sansi PK, Kumar V, Ahuja MM. Familial male pseudohermaphroditism with female external genitalia, presence of labial testes, male habitus and voice, and complete absence of Muellerian structures and lack of breast development. Birth Defects 1975; 11:145-52. Urbanova O. [Familial occurrence ofdysphonia.] Cesk Otolaryngol 1973;22:180-3. Shriberg LD. Four new speech and prosody-voice measures for genetics research and other studies in developmental phonological disorders. J Speech Hear Res 1993;36:105--40. FrioI-Vercelletto M, Mussini JM, Dumas-Guillemot A, Denis G, Lavenant-Oger F, Feve JR. [Familial cases of oculopharyngeal muscular dystrophy. A case.] Rev Otoneuroophthabnol 1983;55:329-36. Ludlow CL, Cooper JA. Genetic aspects o f speech and language disorders. New York: Academic Press, 1983. Luchsinger R, Arnold GE, eds. Genetics of the voice. In: Voice-speech-language. Belmont: Wadsworth, 1965:122-30. Coon H, Carey G. Genetic and environmental determinants of musical ability in twins. Behav Genet 1989;19:183-93. Kalmus H, Fry DB. On tone deafness (dysmelodia): frequency, development, genetics and musical background. Anti Hum Genet 1980;43:369--82. Bernstein F, Schlaper B. Uber die Tonlage der menschlichen singstimme. Sitzungsberichte der Preuss. Berlin: Akad. Wiss, Math-physikal. Klasse. 1922. Schilling R. Uber die Stimme erbgleicher Zwillinge. Klin Scher 1936;15:756. Schilling R. Uber die Stimme erbgleicher Zwillinge. Folia Phoniatr 1950;2:98-119. Seeman M. Die Bedeutung der Zwillingspathologie fur die Erforschung von Sprachleiden. Arch Sprach-Stimmheilk 1937;I :88. Gedda L, Bianchi A, Bianchi-Neroni L. La voce dei gemelli I. Prova di identificazione intrageminale della voce in 104 coppie (58 Mz e 46 Dz). Acta Genet Med Gernell (Roma) 1955;4:121-30. Gorlin R, Cohen MM, Levin LS. Syndromes o f the head and neck. 3rd edit. New York: Oxford University Press, 1990. Finkelstein MW, Hammond HL, Jones RB. Hyalinosis cutis et mucosae. Oral Surg Oral Med Oral Pathol 1982;54:49-58. Hofer P-A, Ohman J. Laryngeal lesions in Orbach-Wiethe disease. Acta Pathol Microbiol Scand 1974;82A:547-58. Ward WQ, Bianchine J, Hambrick GW. Lipoid proteinosis. Birth Defects 1971;7:288-91. Cordero JF, Holmes LB. Phenotypic overlap of the BBB and G syndromes. Am J Med Genet 1978;2:!45-52. Funderbunk SJ, Stewart R. The G and BBB syndromes: case presentations, genetics, and nosology. Am J Med Genet 1978;2:131-44. Opitz JM. Editorial comment: G syndrome (hypertelorism with esophageal abnormality and hypospadias or hypospadias-dysphagia, or " O p i t z - F r i a s " or " O p t i z - G " syndrome)mperspective in 1987 and bibliography. A m J Med Genet 1987;28:275-85. Opitz JM, Summit RL, Smith DW. The BBB syndrome. Familial telecanthus with associated congenital anomalies. Birth Defects 1969;5:86-94. Cohn AM, McFarland JR. Pachyonychia congenita with involvement of the larynx. Arch Otolaryngol 1976;102:233-5. Jackson ADM, Lawler SK. Pachyonychia congenita: a report of six cases in one family. Ann Eugen 1951;16:142--6. Laing CR, Hayes JR, Scharf G. Pachyonychia congenita. A m J Dis Child 1966;111:649-52. Epstein C J, Martin GM, Schultz AL, Motlusky AG. Werner's syndrome. Medicine 1966;45:177-221.
GENETICS
30. Zucker-Franklin D, Rifkin H, Jacobson HG. Werner's syndrome. An analysis of ten cases. Geriatrics 1968;23:123-35. 31. Beuren AJ, Apitz J, Harmjanz D. Supravalvular aortic stenosis in association with mental retardation and a certain facial appearance. Circulation 1962;26:1235-40. 32. Beuren AJ, Schultz C, Eheril P, Harmjanz D, Apitz J. The syndrome of supravalvular aortic stenosis, peripheral pulmonary stenosis, mental retardation and similar facial appearance. Am J Cardiol 1964;13:471-83. 33. Jones KL, Smith PW. The Williams elfin facies syndrome: a new perspective. J Pediatr 1975;86:718-23. 34. Kivaol E, Autio L, Palo A, Amnell G. Mental retardation, typical facies and aortic stenosis syndrome. Ann Med Intern Fenn 1965;54:81-7. 35. Bloom F. The syndrome of congenital telangiectatic erythema and stunted growth. J Pediatr 1966;68:103-13. 36. German J. Bloom's syndrome. VIII. Review of clinical and genetic aspects. In: Goodman RM, Motulsky AG, eds. Genetic diseases among Ashkenazi Jews. New York: Raven Press, 1978:121-39. 37. Katzenellenbogen I, Laron Z. A contribution to Bloom's syndrome. Arch Dermatol 1960;82:609-16. 38, Keutel J, Marghesco S, Teller W. Bloom-Syndrom. Z Kinderheilkd 1967;101:165-80. 39. Aberfeld DC, Hinterbuchner LP, Schneider M. Myotonia, dwarfism, diffuse bone disease and unusual ocular and facial abnormalities (a new syndrome). Brain 1965;88:313-22. 40. Aberfeld DC, Namba T, Vye MV, Grob D. Chondrodystrophic myotonia: report of two cases. Myotonia, dwarfism, diffuse bone disease and unusual ocular and facial abnormalities. Arch Neurol 1972;22:455--62. 41. Mereu TR, Porter IH, Hug G. Myotonia, shortness of stature, and hip dysplasia. Schwartz-Jampel syndrome. Am J Dis Child 1969;! 17:470--8. 42. Pavone L, LaRosa M, LiVolti S, Mallica F. Immunologic abnormalities in Schwartz-Jampel syndrome. J Pediatr 1981; 98:512. 43. Manning KP. The larynx in the cri-du-chat syndrome. J Laryngol Otol 1977;91:887-92. 44. M/iller W, Frisch H, Gassner 1, Kofler J. SeckeI-Syndrom. Mschr Kinderheilkd 1978;126:454--6. 45. Wilheim OL, M6hes K. Dubowitz syndrome. Acta Paediatr Hang 1986;27:67-75. 46. Wilroy RS Jr, Tipton RE, Summit RL. The Dubowitz syndrome. A m J Med Genet 1978;2:275-84.
OF VOICE
19
47. Beighton P. The dominant and recessive forms of cutis laxa. J Med Genet 1972;9:216-21. 48. Goltz RW, Hult A, Goldfarb M, Gorlin RJ. Cutis laxa, a manifestation of generalized elastolysis. Arch Dermatol 1965;92:373-87. 49. Wilsch L, Schmid G, Haneke E. Sp~itmanifeste Dermatochalasis. Dtsch Med Wochenschr 1977;102:1451--4. 50. Berg JM, McCreary BD, Ridler MAC, Smith GF. The de Lange syndrome. New York: Pergamon, 1970. 51. Breslau EJ, Disteche C, Hall JG, Thuline H, Cooper P. Prometaphase chromosomes in five patients with the Brachmann-de Lange syndrome. Am J Med Genet 1981;10:179--86. 52. Fraser WI, Campbell BM. A study of six cases of de Lange Amsterdam dwarf syndrome, with special attention to voice, speech and language characteristics. Dev Med Child Neurol 1978;20:189-98. 53. Gorlin RJ. 18q-syndrome. In: Yunis JJ, ed. New chromosomal syndromes, vol 3. New York: Academic Press, 1977:72-4. 54. Rethor6 MO. Deletions and ring chromosomes. In: Vinken JP, Bruyn GW, eds. Handbook o f clinical neurology: congenital malformations o f the brain and skull. Amsterdam: North-Holland, 197.7:26--7. 55. Schinzel A, Hayashi K, Schmid W. Structural aberrations of chromosome 18. II. The 18q-syndrome. Report of three cases. Humangenetik 1975;26:123-32. 56. Wilson MG, Towner JW, Forsman I, Siris E. Syndromes associated with deletion of the long arm of chromosome 18[del(18q)]. Am J Med Genet 1979;3:155-74. 57. Bosch-Banyeras JM, Saleedo S, Lucaya J, Laverde R, Boronat M, Marti-Henneberg C. Acceleration du development postnatal, hypertome, elargissement des phalanges m6diaries et des metaphyses distales du femur, facies particuliar: s'agit-il d'un syndrome de Weaver? Arch Fr Pediatr 1978; 35:177-83. 58. Weisswichert PH, Knapp G, Willich F. Accelerated bone maturation syndrome of the Weaver type. Fur J Pediatr 1981 ;137:329-33. 59. Salomonson J, Kawamoto H, Wilson L. Velopharyngeal incompetences as the presenting symptoms of myotonic dystrophy. Cleft Palate J 1988;25:296-300. 60. Mace M, WiUiamson E, Worgan D. Autosomal dominantly inherited adductor laryngeal paralysis--a new syndrome with a suggestion of linkage to HLA. Clin Genet 1978;14: 265-70.
Journal of Voice, VoL 9, No. 1, 1995
Vol. 9, No. 1, pp. 16-19 © 1995 Raven Press, Ltd., New York
Genetics of the Voice Robert Thayer Sataloff Department of Otolaryngology, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
Summary: Substantial advances have led to the evolution of voice as the newest subspecialty of otolaryngology. Nevertheless, little is known about the genetics of voice. Genetic research is needed to further elucidate the relationship between vocal tract structure (including ultrastructure) and function, mechanisms of voice dysfunction, and transmission of normal and abnormal voice characteristics. Key Words: Voice--Genetics--Heredity.
During the last decade, research discoveries, technological advances, and new clinical insights have resulted in the evolution of a new subspecialty of otolaryngology: voice (1,2). These advances have substantially changed the standard of care for patients with voice disorders, led to sophisticated noninvasive voice therapy, and markedly altered surgical techniques used for voice problems (3). Despite many exciting breakthroughs, much remains to be learned about how the voice functions, what causes phonatory dysfunction, and how voice characteristics (normal and abnormal) are transmitted within families and larger groups. Genetic research has barely begun to address these problems.
discussed hereditary voice disorders (5,6,8). The rest of the conditions discussed in this article were identified through the author's clinical experience and through his review of the content and references contained in numerous speech pathology textbooks and reference texts on human genetics. There appears to be no other published review on the subject of the genetics of voice, although there is a valuable text available on genetic aspects of speech and language (9). Normal voice
It is clear that genetic factors influence vocal quality. This has been recognized anecdotally in families and even nationalities (Italians, Welsh, Russians, and others). If one assumes that function is related to structure, the association of voice quality and genetic factors is intuitively comfortable. It is generally accepted that physical characteristics are genetically determined. If these include the size of the laryngeal cartilages, vocal fold length and structure, size and shape of the supraglottic vocal tract, and phenotypic similarities elsewhere in the vocal mechanism, then one might expect similarities in voice quality. If we postulate additional similarities in brain development, musical perception, and neuromotor control, the notion becomes even more attractive. However, to be credible, these issues require further study and careful separation of genetic factors from environmental influences upon development. Some of the most interesting studies to date have
GENETICS OF THE VOICE Genetics of the voice is a fascinating area for speculation and research. Unfortunately, there have been very few studies, and none has been definitive or extensive. In reviewing this subject, a computer search of 8,009,307 references in four databases (MedLine, Health, AidsLine, and CancerLit) was carried out using the following key words: heredity, genetics, voice, voice disorders, and familial. The MedLine database indexes articles from 1966 to present. The computer search produced only five references (4-8), of which only three really Accepted N o v e m b e r 17, 1993. Address correspondence and reprint requests to Dr. R . T . Sataloff at 1721 Pine St., Philadelphia, PA 19103, U.S.A.
16
GENETICS OF VOICE
looked at voice function in twins. In general, monozygotic twins have very similar voices. Dizygotic twins appear to show the same differences that would be expected among any children of the same age (10). Coon and Carey (11) studied genetic and environmental determinants of musical ability in twins. Recognizing that there is more to vocal quality and ability than vocal fold structure alone, such studies are of relevance when studying the genetics of voice. Coon and Carey examined monozygotic and dizygotic twins and found evidence of hereditary variation, although environment appeared to be a more important factor than heredity. Kalmus and Fry (12) studied dysmelodia (inability to sing on tune) and found it to be inheritable as an autosomal dominant trait with imperfect penetrance. They speculated that their findings seemed to indicate the existence of some deep structure of tonality perception comparable with Chomsky's deep language structure. Although Bernstein and Schlaper (13) began looking at the genetic influences on the voice as early as 1922, and subsequent work was carried out by Schilling (14,15), Seeman (16), Gedda et al. (17), and others, the complexities of genetic research in humans have left most of the relevant questions unanswered.
Pathological voice and syndromes In addition to the voice quality characteristics that appear to be transmitted in healthy groups, numerous pathological conditions are associated with specific voice dysfunctions (18). For example, raspy voice quality has been recognized in hyalinosis cutis et mucosae (19-21), Opitz BBB/G compound syndrome (22-25), pachyonychia congenita syndrome (26-28), Werner syndrome (29,30), Williams syndrome (31-34), and other conditions. High-pitched voice occurs in Bloom syndrome (3538), chondrodystrophic myotonia (39-42), deletion (5p) syndrome (43), Dubowitz syndrome (4A, A.6), Seckel syndrome, Silver-Russell syndrome, and Werner syndrome (29,30). Low-pitched voice has been observed in cutis laxa syndrome (47-49), de Lange syndrome (50-52), deletion (18q) syndrome (53-56), mucopolysaccharidoses (types IH, II, III, VI), and Weaver syndrome (57,58). Other voice abnormalities have been observed in myotonic dystrophy syndrome (18,59) and hereditary dystonias that may be associated with spasmodic dysphonia. A dominant form of spinal muscular atrophy associated with distal muscle atrophy, vocal fold paraly-
17
sis, and sensorineural hearing loss has been reported. Familial vocal fold dysfunction associated with digital anomalies also exists. Verma et al. (5) described familial male pseudohermaphroditism with female external genitalia, male habitus, and male voice. Urbanova (6) reported familial dysphonia and Friol-Vercelletto et al. (8) reported familial oculopharyngeal muscular dystrophia with associated abnormal voice. Hence, evidence for the existence of a genetic component to vocal quality is compelling.
Molecular genetic considerations Developments in genetic research in recent years are exciting and have largely moved from clinical to molecular studies. Unfortunately, close scrutiny still reveals discouraging complexities. Much of today's genetic research is involved with gene mapping. This methodology is elegant, but still of limited clinical value for broad questions like vocal quality. In general, at present, genetic markers are useful for conditions associated with one major gene. They require an extremely specific phenotype description. Indeed, linkage studies are extraordinarily difficult and time consuming without specification not only of phenotype, but also of a candidate gene. Because the basement membrane matrix proteins are found on the long arm of chromosome 1 and other materials may be localized to specific chromosomes, proposal of candidate genes for voice phenomena may actually be practical in selected cases. For example, Mace et al. (60) described a family with hereditary, congenital, bilateral adductor vocal fold paralysis inherited as an autosomal dominant, with linkage with HLA and GLO, a syndrome localized to chromosome 6, position 21.3-23. However, for many questions regarding voice traits and problems, gene mapping is still a cumbersome approach. Undoubtedly, the process will become easier as more of the > I00,000 genes in each human genome are mapped and associated with phenotypic expressions. In the meanwhile, it appears as if the most likely avenue of success will be the study of pathological conditions known to be hereditary and associated with voice abnormalities. This research should include genetic, structural, physiological, and epidemiological studies. Such investigations, together with advances in genetic research, should eventually lead us to the kind of information we seek about normal and exceptional voices. Later research efforts are likely to be facilitated by buildJournal of Voice, Vol. 9, No. 1, 1995
18
R. T. S A T A L O F F
ing a database of pedigree information now. A national registry to coordinate this information may even be appropriate, as suggested by Dr. S. Gray (personal communication). Clinicians should be encouraged to acquire much more meticulous family histories focusing on voice quality, skills, peculiarities, and other nonvoice distinguishing features and diseases. Such clinical research is also likely to provide information that will help clarify the genetic nature of voice traits, not just pathology. In addition, it may give us insight into disease susceptibility. This has been recommended in the past for cancer. However, questions about benign disease still remain to be answered. For example, in families with vocal nodules, we have always assumed environmental factors were causal. Perhaps there are also genetic deficiencies in healing patterns that can be identified. If so, preventive measures may be possible and may guide medical and surgical therapy. CONCLUSION
5.
6. 7. 8.
9. 10. 11. 12. 13. 14. 15.
Considerable additional study should be encouraged to elucidate the genetics of voice. This research should investigate not only vocal tract structure and function, but also genetic aspects of cortical function, perception, and neurological control, which are inextricably involved in voice production. Although questions involving heredity are associated with somewhat discouraging difficulties in research design and implementation, they must be addressed along with the more limited anatomical and physiologic questions studied to date. Clinical and molecular genetic research should provide important new insights into healthy and pathological phonation and the relationship between vocal tract structure (such as basement membrane ultrastructure) and function and valuable contributions to the physician's armamentarium for treating voice disorders. REFERENCES 1. Sataloff RT. Professional voice: the science and art o f clinical care. New York: Raven Press, 1991. 2. Sataloff RT. The human voice. Sci A m 1992;267(6): 108-15. 3. Gould WJ, SataloffRT, Spiegel JR. Voice surgery. Chicago: Mosby-Year Book, 1993. 4. Rudiger RA, Schmidt W, Loose DA, Passarge E. Severe developmental failure with coarse facial features, distal limb hypoplasia, thickened palmar creases, bifid uvula, and ureJournal of Voice, Vol. 9, No. 1, 1995
16. 17.
18. 19. 20. 21. 22. 23. 24.
25. 26. 27. 28. 29.
teral stenosis: a previously unidentified familial disorder with lethal outcome. J Pediatr 1971 ;79:977-8 I. Verma IC, Sansi PK, Kumar V, Ahuja MM. Familial male pseudohermaphroditism with female external genitalia, presence of labial testes, male habitus and voice, and complete absence of Muellerian structures and lack of breast development. Birth Defects 1975; 11:145-52. Urbanova O. [Familial occurrence ofdysphonia.] Cesk Otolaryngol 1973;22:180-3. Shriberg LD. Four new speech and prosody-voice measures for genetics research and other studies in developmental phonological disorders. J Speech Hear Res 1993;36:105--40. FrioI-Vercelletto M, Mussini JM, Dumas-Guillemot A, Denis G, Lavenant-Oger F, Feve JR. [Familial cases of oculopharyngeal muscular dystrophy. A case.] Rev Otoneuroophthabnol 1983;55:329-36. Ludlow CL, Cooper JA. Genetic aspects o f speech and language disorders. New York: Academic Press, 1983. Luchsinger R, Arnold GE, eds. Genetics of the voice. In: Voice-speech-language. Belmont: Wadsworth, 1965:122-30. Coon H, Carey G. Genetic and environmental determinants of musical ability in twins. Behav Genet 1989;19:183-93. Kalmus H, Fry DB. On tone deafness (dysmelodia): frequency, development, genetics and musical background. Anti Hum Genet 1980;43:369--82. Bernstein F, Schlaper B. Uber die Tonlage der menschlichen singstimme. Sitzungsberichte der Preuss. Berlin: Akad. Wiss, Math-physikal. Klasse. 1922. Schilling R. Uber die Stimme erbgleicher Zwillinge. Klin Scher 1936;15:756. Schilling R. Uber die Stimme erbgleicher Zwillinge. Folia Phoniatr 1950;2:98-119. Seeman M. Die Bedeutung der Zwillingspathologie fur die Erforschung von Sprachleiden. Arch Sprach-Stimmheilk 1937;I :88. Gedda L, Bianchi A, Bianchi-Neroni L. La voce dei gemelli I. Prova di identificazione intrageminale della voce in 104 coppie (58 Mz e 46 Dz). Acta Genet Med Gernell (Roma) 1955;4:121-30. Gorlin R, Cohen MM, Levin LS. Syndromes o f the head and neck. 3rd edit. New York: Oxford University Press, 1990. Finkelstein MW, Hammond HL, Jones RB. Hyalinosis cutis et mucosae. Oral Surg Oral Med Oral Pathol 1982;54:49-58. Hofer P-A, Ohman J. Laryngeal lesions in Orbach-Wiethe disease. Acta Pathol Microbiol Scand 1974;82A:547-58. Ward WQ, Bianchine J, Hambrick GW. Lipoid proteinosis. Birth Defects 1971;7:288-91. Cordero JF, Holmes LB. Phenotypic overlap of the BBB and G syndromes. Am J Med Genet 1978;2:!45-52. Funderbunk SJ, Stewart R. The G and BBB syndromes: case presentations, genetics, and nosology. Am J Med Genet 1978;2:131-44. Opitz JM. Editorial comment: G syndrome (hypertelorism with esophageal abnormality and hypospadias or hypospadias-dysphagia, or " O p i t z - F r i a s " or " O p t i z - G " syndrome)mperspective in 1987 and bibliography. A m J Med Genet 1987;28:275-85. Opitz JM, Summit RL, Smith DW. The BBB syndrome. Familial telecanthus with associated congenital anomalies. Birth Defects 1969;5:86-94. Cohn AM, McFarland JR. Pachyonychia congenita with involvement of the larynx. Arch Otolaryngol 1976;102:233-5. Jackson ADM, Lawler SK. Pachyonychia congenita: a report of six cases in one family. Ann Eugen 1951;16:142--6. Laing CR, Hayes JR, Scharf G. Pachyonychia congenita. A m J Dis Child 1966;111:649-52. Epstein C J, Martin GM, Schultz AL, Motlusky AG. Werner's syndrome. Medicine 1966;45:177-221.
GENETICS
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Journal of Voice, VoL 9, No. 1, 1995