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Retinitis Pigmentosa and Congenital Deafness*
AMERICAN JOURNAL Published
Monthly
OF OPHTHALMOLOGY
by the Ophthalmic
Publishing
Company
EDITORIAL STAFF DERRICK VAIL, Editor-in-Chief
BERTHA A. KLIEN
FRANCIS HEED ADLER, Consulting Editor
JAMES E. LEBENSOHN
700 North Michigan Avenue, Chicago 11
950 East 59th Street, Chicago 37
313 South 17th Street, Philadelphia 3
4010 West Madison Street, Chicago 24
ALAN C. WOODS, Consulting Editor
DONALD J. LYLE
Johns Hopkins Hospital, Baltimore 5
411 Oak Street, Cincinnati 19
BERNARD BECKER
WILLIAM A. MANN
640 South Kingshighway, Saint Louis 10
251 East Chicago Avenue, Chicago 11
WILLIAM L. BENEDICT
A. EDWARD MAUMENEE
IS Second Street, S.W., Rochester, Minnesota
Johns Hopkins Hospital, Baltimore 5
FREDERICK C. CORDES
P. ROBB MCDONALD
384 Post Street, San Francisco 8
Lankenau Medical Building, Philadelphia 31
SIR STEWART DUKE-ELDER
FRANK W. NEWELL
63 Harley Street, London, W.l
950 East 59th Street, Chicago 37
EDWIN B. DUNPHY
JOHN V. V. NICHOLLS
243 Charles Street, Boston 14
1414 Drummond Street, Montreal
F. HERBERT HAESSLER
ALGERNON B. REESE
12 Apple Tree Lane, Alamo, California
73 East 71st Street, New York 21
PARKER HEATH
PHILLIPS THYGESON
Sullivan Harbor, Maine
University of California Medical Center, San Francisco 22 9730 Wilshire Boulevard, KATHERINE FERGUSON CHALKLEY, Manuscript Editor Beverly Hills, California Lake Geneva, Wisconsin
S. RODMAN IRVINE
Directors: WILLIAM L. BENEDICT, President; FREDERICK C. CORDES, Vice-President; WILLIAM A. MANN, Secretary and Treasurer; ALGERNON B. REESE, DERRICK VAIL, ALAN C. WOODS.
Address original papers, other scientific communications including correspondence, also books for review to Dr. Derrick Vail, 700 North Michigan Avenue, Chicago 11, Illinois; Society Proceedings to Mrs. Katherine F. Chalkley, Lake Geneva, Wisconsin. Manuscripts should be original copies, typed in double space, with wide margins. Exchange copies of the medical journals should be sent to Dr. F. Herbert Haessler, 561 North 15th Street, Milwaukee 3, Wisconsin. Subscriptions, application for single copies, notices of changes of address, and communications with reference to advertising should be addressed to the Manager of Subscriptions and Advertising, 664 North Michigan Avenue, Chicago 11, Illinois. Copy of advertisements must be sent to the manager by the 10th of the month preceding its appearance. Change of address notice should be received not later than the 10th of the month prior to the issue for which the change is to go into effect. Both old and new addresses should be given. Author's proofs should be corrected and returned within forty-eight hours to the Manuscript Editor, Mrs. Katherine F. Chalkley, Lake Geneva, Wisconsin. Fifty reprints of each article will be supplied to the author without charge. Additional reprints may be obtained from the printer, George Banta Company, Inc., Curtis Reed Plaza, Menasha, Wisconsin, if ordered at the time proofs are returned. But reprints to contain colored plates must be ordered when the article is accepted. the pattern given by an autosomal recessive, others that given by a dominant, and still others that given by a sex-linked recessive Retinitis pigmentosa is the classical ex gene. 1 I n addition, there are distinct mutant ample of a condition, at first sight unitary, genes which cause retinitis pigmentosa in which may be caused by several different association with other abnormalities. Just mutant genes. Some affected families show over a hundred years ago, von Graefe 2 re ported the association of retinitis pigmentosa * Reprinted from The Lancet, March 26, 1960, and congenital deafness in three of a family pages 688 and 689, RETINITIS PIGMENTOSA AND CONGENITAL DEAFNESS*
575
576
EDITORIAL
of five. Julia Bell,3 in 1933 collected 93 re corded instances of this association. In 1945 Lindenov4 confirmed that the syndrome was almost certainly due to an autosomal reces sive, and showed that it was responsible for about six percent of cases of congenital deaf ness in Copenhagen and the adjoining coun ties ; hence it may be inferred that the preva lence of the condition there was of the order of three per 100,000. Hallgren 5 has made a new study of the syndrome in Sweden, at tempting to ascertain all the cases in the country. The admirable Swedish system of medical and social support for the deaf of all ages enabled him to identify 151 living patients—which probably represents the ma jority in the country over the age of 10 years, and a high proportion of those younger than this. The prevalence over the whole country was 2.4 per 100,000, which is close to Lindenov's figures for Denmark. The disorder is commoner in the more sparsely populated northern counties of Sweden than in the south. In the three most northern counties, the prevalence was found to be over one in 10,000; whereas in Stock holm there were only three cases in a pop ulation of over half a million. Besides the two main features of the syn drome, vestibular ataxia, cataract, mental defect, and psychosis may be found. Cata ract, which develops in the majority of pa tients over the age of 40 years, may be re garded as another manifestation of the gene. The majority of patients show ataxia in the form of a swinging gait; the degree of this ataxia is related to the degree of hearing loss, and Hallgren showed that it is probably due to loss of labyrinthine function. The question whether true mental deficiency is associated with the syndrome is not easily answered, because of the handicap of con genital deafness. Hallgren tried to overcome this difficulty by comparing the abilities of his patients with those of patients with con genital deafness of other types. He con sidered that over 20 percent were, to some degree, mentally retarded, but that only two
to three percent were imbeciles or idiots. This does, however, suggest a real genetic association with mental deficiency. The in cidence of psychosis—mainly schizophrenic like illnesses—in the patients was also over 20 percent. This may reasonably be attribut ed to the stress of congenital deafness and the inexorably progressive loss of vision in early adult life. Hallgren has also made a genetic analysis, which is especially valuable since it is based on much the largest consecutive series of pa tients. He confirms that a recessive mutant gene is the cause. The proportion affected among the sibs of propositi is close to one in four: about a third of the propositi are the products of consanguineous marriages, and a sixth the product of first-cousin mar riages. The frequency of the heterozygous carriers of the gene is estimated to be be tween one in 200 and one in 100. Genealogi cal investigation showed that there were an cestral connections between 30 of the 102 families. One large pedigree contained no less than 12 affected sibships. The control of recessively determined dis orders of this kind depends essentially on detection of the heterozygous carrier. Hall gren found no clinical manifestations of the gene in heterozygotes; and detection of these carriers may have to wait until the exact nature of the underlying gene-determined chemical abnormality is discovered. REFERENCES
1. Sorsby, A.: Genetics in Ophthalmology. Lon don, 1951. 2. von Graefe, A.: Arch. f. Ophth., 4:250, 1858. 3. Bell, J.: The Treasury of Human Inheritance. London, 1933, v. 2, p. 1. 4. Lindenov, H.: Op. Dom. Biol. hered. hum., Kbh., 8: 1945. 5. Hallgren, B.: Acta Psychiat, Kbh., 34: suppl. 138, 1959.
Monthly
OF OPHTHALMOLOGY
by the Ophthalmic
Publishing
Company
EDITORIAL STAFF DERRICK VAIL, Editor-in-Chief
BERTHA A. KLIEN
FRANCIS HEED ADLER, Consulting Editor
JAMES E. LEBENSOHN
700 North Michigan Avenue, Chicago 11
950 East 59th Street, Chicago 37
313 South 17th Street, Philadelphia 3
4010 West Madison Street, Chicago 24
ALAN C. WOODS, Consulting Editor
DONALD J. LYLE
Johns Hopkins Hospital, Baltimore 5
411 Oak Street, Cincinnati 19
BERNARD BECKER
WILLIAM A. MANN
640 South Kingshighway, Saint Louis 10
251 East Chicago Avenue, Chicago 11
WILLIAM L. BENEDICT
A. EDWARD MAUMENEE
IS Second Street, S.W., Rochester, Minnesota
Johns Hopkins Hospital, Baltimore 5
FREDERICK C. CORDES
P. ROBB MCDONALD
384 Post Street, San Francisco 8
Lankenau Medical Building, Philadelphia 31
SIR STEWART DUKE-ELDER
FRANK W. NEWELL
63 Harley Street, London, W.l
950 East 59th Street, Chicago 37
EDWIN B. DUNPHY
JOHN V. V. NICHOLLS
243 Charles Street, Boston 14
1414 Drummond Street, Montreal
F. HERBERT HAESSLER
ALGERNON B. REESE
12 Apple Tree Lane, Alamo, California
73 East 71st Street, New York 21
PARKER HEATH
PHILLIPS THYGESON
Sullivan Harbor, Maine
University of California Medical Center, San Francisco 22 9730 Wilshire Boulevard, KATHERINE FERGUSON CHALKLEY, Manuscript Editor Beverly Hills, California Lake Geneva, Wisconsin
S. RODMAN IRVINE
Directors: WILLIAM L. BENEDICT, President; FREDERICK C. CORDES, Vice-President; WILLIAM A. MANN, Secretary and Treasurer; ALGERNON B. REESE, DERRICK VAIL, ALAN C. WOODS.
Address original papers, other scientific communications including correspondence, also books for review to Dr. Derrick Vail, 700 North Michigan Avenue, Chicago 11, Illinois; Society Proceedings to Mrs. Katherine F. Chalkley, Lake Geneva, Wisconsin. Manuscripts should be original copies, typed in double space, with wide margins. Exchange copies of the medical journals should be sent to Dr. F. Herbert Haessler, 561 North 15th Street, Milwaukee 3, Wisconsin. Subscriptions, application for single copies, notices of changes of address, and communications with reference to advertising should be addressed to the Manager of Subscriptions and Advertising, 664 North Michigan Avenue, Chicago 11, Illinois. Copy of advertisements must be sent to the manager by the 10th of the month preceding its appearance. Change of address notice should be received not later than the 10th of the month prior to the issue for which the change is to go into effect. Both old and new addresses should be given. Author's proofs should be corrected and returned within forty-eight hours to the Manuscript Editor, Mrs. Katherine F. Chalkley, Lake Geneva, Wisconsin. Fifty reprints of each article will be supplied to the author without charge. Additional reprints may be obtained from the printer, George Banta Company, Inc., Curtis Reed Plaza, Menasha, Wisconsin, if ordered at the time proofs are returned. But reprints to contain colored plates must be ordered when the article is accepted. the pattern given by an autosomal recessive, others that given by a dominant, and still others that given by a sex-linked recessive Retinitis pigmentosa is the classical ex gene. 1 I n addition, there are distinct mutant ample of a condition, at first sight unitary, genes which cause retinitis pigmentosa in which may be caused by several different association with other abnormalities. Just mutant genes. Some affected families show over a hundred years ago, von Graefe 2 re ported the association of retinitis pigmentosa * Reprinted from The Lancet, March 26, 1960, and congenital deafness in three of a family pages 688 and 689, RETINITIS PIGMENTOSA AND CONGENITAL DEAFNESS*
575
576
EDITORIAL
of five. Julia Bell,3 in 1933 collected 93 re corded instances of this association. In 1945 Lindenov4 confirmed that the syndrome was almost certainly due to an autosomal reces sive, and showed that it was responsible for about six percent of cases of congenital deaf ness in Copenhagen and the adjoining coun ties ; hence it may be inferred that the preva lence of the condition there was of the order of three per 100,000. Hallgren 5 has made a new study of the syndrome in Sweden, at tempting to ascertain all the cases in the country. The admirable Swedish system of medical and social support for the deaf of all ages enabled him to identify 151 living patients—which probably represents the ma jority in the country over the age of 10 years, and a high proportion of those younger than this. The prevalence over the whole country was 2.4 per 100,000, which is close to Lindenov's figures for Denmark. The disorder is commoner in the more sparsely populated northern counties of Sweden than in the south. In the three most northern counties, the prevalence was found to be over one in 10,000; whereas in Stock holm there were only three cases in a pop ulation of over half a million. Besides the two main features of the syn drome, vestibular ataxia, cataract, mental defect, and psychosis may be found. Cata ract, which develops in the majority of pa tients over the age of 40 years, may be re garded as another manifestation of the gene. The majority of patients show ataxia in the form of a swinging gait; the degree of this ataxia is related to the degree of hearing loss, and Hallgren showed that it is probably due to loss of labyrinthine function. The question whether true mental deficiency is associated with the syndrome is not easily answered, because of the handicap of con genital deafness. Hallgren tried to overcome this difficulty by comparing the abilities of his patients with those of patients with con genital deafness of other types. He con sidered that over 20 percent were, to some degree, mentally retarded, but that only two
to three percent were imbeciles or idiots. This does, however, suggest a real genetic association with mental deficiency. The in cidence of psychosis—mainly schizophrenic like illnesses—in the patients was also over 20 percent. This may reasonably be attribut ed to the stress of congenital deafness and the inexorably progressive loss of vision in early adult life. Hallgren has also made a genetic analysis, which is especially valuable since it is based on much the largest consecutive series of pa tients. He confirms that a recessive mutant gene is the cause. The proportion affected among the sibs of propositi is close to one in four: about a third of the propositi are the products of consanguineous marriages, and a sixth the product of first-cousin mar riages. The frequency of the heterozygous carriers of the gene is estimated to be be tween one in 200 and one in 100. Genealogi cal investigation showed that there were an cestral connections between 30 of the 102 families. One large pedigree contained no less than 12 affected sibships. The control of recessively determined dis orders of this kind depends essentially on detection of the heterozygous carrier. Hall gren found no clinical manifestations of the gene in heterozygotes; and detection of these carriers may have to wait until the exact nature of the underlying gene-determined chemical abnormality is discovered. REFERENCES
1. Sorsby, A.: Genetics in Ophthalmology. Lon don, 1951. 2. von Graefe, A.: Arch. f. Ophth., 4:250, 1858. 3. Bell, J.: The Treasury of Human Inheritance. London, 1933, v. 2, p. 1. 4. Lindenov, H.: Op. Dom. Biol. hered. hum., Kbh., 8: 1945. 5. Hallgren, B.: Acta Psychiat, Kbh., 34: suppl. 138, 1959.