T H E AUTOSOMAL DOMINANT SYNDROME O F PROGRESSIVE OPTIC ATROPHY AND CONGENITAL DEAFNESS C A R O L R. K O L L A R I T S , M.D., M A R I L Y N L. P I N H E I R O , P H . D . , E D W I N R. S W A N N , D A N I E L F. M A R C U S , M.D., AND W. S T E P H E N C O R R I E , M.D. Toledo,
Konigsmark and associates 1 described six persons in four generations of a family with a dominantly inherited association between congenital deafness and progres sive optic atrophy. We describe herein a second family affected by congenital deafness and progressive optic atrophy (Figure). Hearing evaluation revealed that the family members with this syn drome had a potentially treatable form of deafness. The affected individuals could hear amplified speech, even though they could not recognize and repeat the words because they had learned only manual language. If they had had amplification in early childhood and training in oral as well as in manual language, they could have developed adequate speech. 2 ' 3 CASE REPORTS Case 1—The proposita, a 48-year-old deaf woman (IV-2, Figure), noted bilateral gradual decrease in vision beginning at age 30 years. Bilateral optic disk pallor and severe deafness were the only neurologic abnormalities. Visual acuity was corrected to R.E.: 6/30 (20/100) and L.E.: 6/21 (20/70) with -1.50 sphere. An enlarged blind spot and a central scotoma were plotted by Goldmann perimetry in the visual field of each eye. The patient's pupils reacted normally. Bilateral eyelid signs of Graves' disease were present. Results of the slit-lamp examination and intraocular pressures were normal. Ophthalmoscopic examination showed moderate pallor of the optic disk in each eye. Vessel caliber, posterior pole,
From the Sections of Ophthalmology, Depart ments of Surgery, Medical College of Ohio and St. Vincent's Hospital (Drs. Kollarits, Swann, and Mar cus); the Audiology Laboratory (Dr. Pinheiro); and the Department of Neurosciences (Drs. Pinheiro and Corrie), Medical College of Ohio, Toledo, Ohio. This study was supported in part by the Ohio Lions Eye Research Foundation. Reprint requests to Carol R. Kollarits, M.D., Sec tion of Ophthalmology, Medical College of Ohio, Caller Service Number 10008, Toledo, OH 43699.
M.D.,
Ohio and peripheral retina were normal. Results of electroretinography and electro-oculography were normal for the patient's age. Thyroid studies confirmed the diagnosis of Graves' disease, which required radioiodine thera py. Follow-up visits six months and one year later revealed resolution of eyelid signs of Graves' dis ease. No deterioration of vision occurred during this follow-up period. Case 2—The 25-year-old son (V-l, Figure) of the proposita had been deaf since birth. He had com plained of slight decrease in vision in both eyes for the past three to four years. On examination, his best corrected visual acuity was R.E.: 6/9 (20/30) and L.E.: 6/12 (20/40) with -1.00 sphere. Results of external and slit-lamp examinations were normal. Results of the ophthalmoscopic examination were normal except for a generalized slight pallor of both optic disks. The right disk had a 0.4 cup-disk ratio, and the left disk had a 0.5 cup-disk ratio. Visual field examination showed no central scotoma or enlarge ment of the blind spot. The electroretinogram was normal. Cases 3 and 4—The 23 and 24-year-old sons of the proposita had normal visual acuity and normal optic disks. The 24-year-old son (V-2) had normal hearing, whereas the 23-year-old son (V-3) was congenitally deaf. Cases 5 and 6—The proposita's first cousin (III-2) and her maternal aunt (IV-1) had bilateral optic atrophy and congenital deafness. The mother was 70 years old at the time and the daughter was 47 years old. The daughter had visual acuity of 6/30 (20/100) in each eye with a refractive error of -3.0 sphere. The proposita's deceased maternal uncle and aunt (III-3 and IH-4) and her maternal grandmother (II-6) had congenital deafness and moderately poor vision occurring in the third or fourth decade of life. However, visual loss did not progress to complete blindness. Four deaf members of this family, the proposita, her husband, and her two sons (IV-2, IV-3, V-l, and V-3), were given hearing evaluations. Pure tone audiometry and speech reception thresholds were conducted in a double wall sound-treated room with a one-way window. Earphones with cushions were used for all tests administered through an audiome ter. The thresholds of hearing sensitivity were bilat erally symmetrical in the proposita and her two sons, sloping from a severe impairment in the lowest test frequencies to profound deafness at 1,000 Hz. Speech reception thresholds were defined as the level at which spondaic words could be heard. Because these three patients used manual language and had little oral speech, it was impossible for them
AMERICAN JOURNAL O F OPHTHALMOLOGY 87:789-792, 1979
789
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Figure (Kollarits and associates). Pedigree showing seven affected persons in the last four generations of this family. to repeat words. The father in this family was also deaf. He was unable to hear either pure tones or speech at the maximum output of the audiometer. The pure tone thresholds of the two deaf sons resembled the audiogram of their mother. DISCUSSION
The five known hereditary syndromes 4 in which hearing loss is associated with optic atrophy include: progressive optic atrophy and congenital sensorineural deafness 1 ; optic atrophy with diabetes and sensorineural hearing loss 5 ; optic at rophy, ataxia, and progressive sensorineu ral hearing loss (Sylvester syndrome) 6 ; opticochleodentate degeneration 7 ; and op tic atrophy, polyneuropathy and sensori neural deafness. 8 The mode of inheri tance and associated characteristics of patients with these syndromes are listed in the Table. This family had the syndrome previ ously described as dominantly inherited
progressive optic atrophy and congenital sensorineural deafness. 1 With the excep tion of the Sylvester syndrome, the mode of inheritance in the other syndromes with hereditary deafness and optic atro phy is autosomal recessive or X-chromosome linked recessive. 5 ' 7,8 The Sylves ter syndrome (optic atrophy, ataxia, and progressive sensorineural hearing loss) has a dominant mode of inheritance, but none of the members of our family had early onset of visual loss or ataxia, as seen in Sylvester syndrome. 6 The age at which visual loss occurs in patients with pro gressive optic atrophy and congenital sensorineural deafness was reported pre viously as being about age 30 years. 1 Our patients noticed a decrease in vision be tween age 24 and 30 years. Age of onset and severity of hearing loss also distinguish progressive optic at rophy and congenital sensorineural deaf-
Optic atrophy, polyneuropathy, and sensorineural deafness (Rosenberg-Chutorran syndrome) 3 , 8
Optic atrophy, ataxia, and progressive hearing loss (Sylvester syndrome) 3,6 Opticocochleodentate degeneration 3,7
Progressive optic atrophy and congenital sensorineural deafness 1,3 Optic atrophy with diabetes mellitus and sensorineural hearing loss 3,5
Syndrome
TABLE
X-chromosome linked or autosomal recessive
Autosomal recessive
Visual loss with optic atrophy beginning at age 20 years
Progressive sensori neural hearing loss with deafness by age 6 years
Progressive hearing loss resulting in severe deafness
Moderate to severe progressive sensori neural deafness
Ataxia particularly in volving the legs, weakness and muscle wasting particu larly involving the shoulder girdle and hands Onset in infancy of progressive spastic quadriplegia, progressive mental deterioration, and death in childhood Progressive peripheral polyneuropathy beginning in early childhood
Diabetes mellitus with onset in the first or second decade
Onset in child hood. Progressive hearing loss
Progressive visual loss Bilateral optic atrophy before age 16 years Progressive visual loss secondary to optic atrophy onset 2 V2 to 9 years of age Optic atrophy with onset of visual loss in infancy
Autosomal recessive
Autosomal dominant
None
Associated Findings
Congenital severe sensorineural deafness
Hearing
Progressive optic atrophy with visual loss in middle to
late life
Vision
Autosomal dominant
Inheritance
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ness from the other four syndromes. In this family, the hearing loss was congeni tal and severe. Konigsmark and associ ates 1 noted the same finding. This is in contrast to the other four syndromes. In all of these, the hearing loss was progres sive with onset either in infancy or child hood. Of the five syndromes with heredi tary optic atrophy and sensorineural hear ing loss, the one that this family had is the only one without associated anomalies or systemic illness. The other syndromes are associated with various disorders includ ing diabetes mellitus, ataxia, progressive spastic quadriplegia and mental deterio ration, or progressive peripheral polyneuropathy. 4 None of the members of this family showed evidence of having any of these disorders. One family member in this pedigree did have Graves' disease that was treated medically. SUMMARY
Four members of a family had the heriditary syndrome of dominantly inherited progressive optic atrophy and congeni
JUNE, 1979
tal sensorineural deafness. Hearing eval uations revealed that two members had a potentially treatable form of deafness. REFERENCES 1. Konigsmark, B. W., Knox, D. L., Hussels, I. E., and Moses, H.: Dominant congenital deafness and progressive optic atrophy. Arch. Ophthalmol. 91:99, 1974. 2. Fry, D. B.: Language development in the deaf child. A psycholinguistic approach. In Bess, F. E. (ed.): Childhood Deafness. Causation, Assessment, and Management. New York, Grune and Stratton, 1977, p p . 295-312. 3. Northern, J. L., and Downs, M. P.: Hearing in Children. Baltimore, Williams and Wilkins, 1974, p p . 245-270. 4. Konigsmark, B. W., and Gorlin, R.: Genetic and metabolic deafness. Philadelphia, W. B. Saunders, 1976, p p . 74-135. 5. Rose, F . C : The association of juvenile diabe tes mellitus and optic atrophy. Clinical and genetic aspects. Q. J. Med. 35:385, 1966. 6. Sylvester, P.: Some unusual findings in a fami ly with Friedreich's ataxia. Arch. Dis. Child. 33:217, 1958. 7. Muller, J., and Zeman, W.: Degenerescence. systematisee optico-cochleo-dentelee. Acta Neuropathol. (Berl.) 5:26, 1965. 8. Rosenberg, R. N., and Chutoran, A.: Familial opticoacoustic nerve degeneration and polyneuropathy. Neurology (Minrieap.) 17:827, 1967.
Konigsmark and associates 1 described six persons in four generations of a family with a dominantly inherited association between congenital deafness and progres sive optic atrophy. We describe herein a second family affected by congenital deafness and progressive optic atrophy (Figure). Hearing evaluation revealed that the family members with this syn drome had a potentially treatable form of deafness. The affected individuals could hear amplified speech, even though they could not recognize and repeat the words because they had learned only manual language. If they had had amplification in early childhood and training in oral as well as in manual language, they could have developed adequate speech. 2 ' 3 CASE REPORTS Case 1—The proposita, a 48-year-old deaf woman (IV-2, Figure), noted bilateral gradual decrease in vision beginning at age 30 years. Bilateral optic disk pallor and severe deafness were the only neurologic abnormalities. Visual acuity was corrected to R.E.: 6/30 (20/100) and L.E.: 6/21 (20/70) with -1.50 sphere. An enlarged blind spot and a central scotoma were plotted by Goldmann perimetry in the visual field of each eye. The patient's pupils reacted normally. Bilateral eyelid signs of Graves' disease were present. Results of the slit-lamp examination and intraocular pressures were normal. Ophthalmoscopic examination showed moderate pallor of the optic disk in each eye. Vessel caliber, posterior pole,
From the Sections of Ophthalmology, Depart ments of Surgery, Medical College of Ohio and St. Vincent's Hospital (Drs. Kollarits, Swann, and Mar cus); the Audiology Laboratory (Dr. Pinheiro); and the Department of Neurosciences (Drs. Pinheiro and Corrie), Medical College of Ohio, Toledo, Ohio. This study was supported in part by the Ohio Lions Eye Research Foundation. Reprint requests to Carol R. Kollarits, M.D., Sec tion of Ophthalmology, Medical College of Ohio, Caller Service Number 10008, Toledo, OH 43699.
M.D.,
Ohio and peripheral retina were normal. Results of electroretinography and electro-oculography were normal for the patient's age. Thyroid studies confirmed the diagnosis of Graves' disease, which required radioiodine thera py. Follow-up visits six months and one year later revealed resolution of eyelid signs of Graves' dis ease. No deterioration of vision occurred during this follow-up period. Case 2—The 25-year-old son (V-l, Figure) of the proposita had been deaf since birth. He had com plained of slight decrease in vision in both eyes for the past three to four years. On examination, his best corrected visual acuity was R.E.: 6/9 (20/30) and L.E.: 6/12 (20/40) with -1.00 sphere. Results of external and slit-lamp examinations were normal. Results of the ophthalmoscopic examination were normal except for a generalized slight pallor of both optic disks. The right disk had a 0.4 cup-disk ratio, and the left disk had a 0.5 cup-disk ratio. Visual field examination showed no central scotoma or enlarge ment of the blind spot. The electroretinogram was normal. Cases 3 and 4—The 23 and 24-year-old sons of the proposita had normal visual acuity and normal optic disks. The 24-year-old son (V-2) had normal hearing, whereas the 23-year-old son (V-3) was congenitally deaf. Cases 5 and 6—The proposita's first cousin (III-2) and her maternal aunt (IV-1) had bilateral optic atrophy and congenital deafness. The mother was 70 years old at the time and the daughter was 47 years old. The daughter had visual acuity of 6/30 (20/100) in each eye with a refractive error of -3.0 sphere. The proposita's deceased maternal uncle and aunt (III-3 and IH-4) and her maternal grandmother (II-6) had congenital deafness and moderately poor vision occurring in the third or fourth decade of life. However, visual loss did not progress to complete blindness. Four deaf members of this family, the proposita, her husband, and her two sons (IV-2, IV-3, V-l, and V-3), were given hearing evaluations. Pure tone audiometry and speech reception thresholds were conducted in a double wall sound-treated room with a one-way window. Earphones with cushions were used for all tests administered through an audiome ter. The thresholds of hearing sensitivity were bilat erally symmetrical in the proposita and her two sons, sloping from a severe impairment in the lowest test frequencies to profound deafness at 1,000 Hz. Speech reception thresholds were defined as the level at which spondaic words could be heard. Because these three patients used manual language and had little oral speech, it was impossible for them
AMERICAN JOURNAL O F OPHTHALMOLOGY 87:789-792, 1979
789
790
AMERICAN JOURNAL OF OPHTHALMOLOGY
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Figure (Kollarits and associates). Pedigree showing seven affected persons in the last four generations of this family. to repeat words. The father in this family was also deaf. He was unable to hear either pure tones or speech at the maximum output of the audiometer. The pure tone thresholds of the two deaf sons resembled the audiogram of their mother. DISCUSSION
The five known hereditary syndromes 4 in which hearing loss is associated with optic atrophy include: progressive optic atrophy and congenital sensorineural deafness 1 ; optic atrophy with diabetes and sensorineural hearing loss 5 ; optic at rophy, ataxia, and progressive sensorineu ral hearing loss (Sylvester syndrome) 6 ; opticochleodentate degeneration 7 ; and op tic atrophy, polyneuropathy and sensori neural deafness. 8 The mode of inheri tance and associated characteristics of patients with these syndromes are listed in the Table. This family had the syndrome previ ously described as dominantly inherited
progressive optic atrophy and congenital sensorineural deafness. 1 With the excep tion of the Sylvester syndrome, the mode of inheritance in the other syndromes with hereditary deafness and optic atro phy is autosomal recessive or X-chromosome linked recessive. 5 ' 7,8 The Sylves ter syndrome (optic atrophy, ataxia, and progressive sensorineural hearing loss) has a dominant mode of inheritance, but none of the members of our family had early onset of visual loss or ataxia, as seen in Sylvester syndrome. 6 The age at which visual loss occurs in patients with pro gressive optic atrophy and congenital sensorineural deafness was reported pre viously as being about age 30 years. 1 Our patients noticed a decrease in vision be tween age 24 and 30 years. Age of onset and severity of hearing loss also distinguish progressive optic at rophy and congenital sensorineural deaf-
Optic atrophy, polyneuropathy, and sensorineural deafness (Rosenberg-Chutorran syndrome) 3 , 8
Optic atrophy, ataxia, and progressive hearing loss (Sylvester syndrome) 3,6 Opticocochleodentate degeneration 3,7
Progressive optic atrophy and congenital sensorineural deafness 1,3 Optic atrophy with diabetes mellitus and sensorineural hearing loss 3,5
Syndrome
TABLE
X-chromosome linked or autosomal recessive
Autosomal recessive
Visual loss with optic atrophy beginning at age 20 years
Progressive sensori neural hearing loss with deafness by age 6 years
Progressive hearing loss resulting in severe deafness
Moderate to severe progressive sensori neural deafness
Ataxia particularly in volving the legs, weakness and muscle wasting particu larly involving the shoulder girdle and hands Onset in infancy of progressive spastic quadriplegia, progressive mental deterioration, and death in childhood Progressive peripheral polyneuropathy beginning in early childhood
Diabetes mellitus with onset in the first or second decade
Onset in child hood. Progressive hearing loss
Progressive visual loss Bilateral optic atrophy before age 16 years Progressive visual loss secondary to optic atrophy onset 2 V2 to 9 years of age Optic atrophy with onset of visual loss in infancy
Autosomal recessive
Autosomal dominant
None
Associated Findings
Congenital severe sensorineural deafness
Hearing
Progressive optic atrophy with visual loss in middle to
late life
Vision
Autosomal dominant
Inheritance
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ness from the other four syndromes. In this family, the hearing loss was congeni tal and severe. Konigsmark and associ ates 1 noted the same finding. This is in contrast to the other four syndromes. In all of these, the hearing loss was progres sive with onset either in infancy or child hood. Of the five syndromes with heredi tary optic atrophy and sensorineural hear ing loss, the one that this family had is the only one without associated anomalies or systemic illness. The other syndromes are associated with various disorders includ ing diabetes mellitus, ataxia, progressive spastic quadriplegia and mental deterio ration, or progressive peripheral polyneuropathy. 4 None of the members of this family showed evidence of having any of these disorders. One family member in this pedigree did have Graves' disease that was treated medically. SUMMARY
Four members of a family had the heriditary syndrome of dominantly inherited progressive optic atrophy and congeni
JUNE, 1979
tal sensorineural deafness. Hearing eval uations revealed that two members had a potentially treatable form of deafness. REFERENCES 1. Konigsmark, B. W., Knox, D. L., Hussels, I. E., and Moses, H.: Dominant congenital deafness and progressive optic atrophy. Arch. Ophthalmol. 91:99, 1974. 2. Fry, D. B.: Language development in the deaf child. A psycholinguistic approach. In Bess, F. E. (ed.): Childhood Deafness. Causation, Assessment, and Management. New York, Grune and Stratton, 1977, p p . 295-312. 3. Northern, J. L., and Downs, M. P.: Hearing in Children. Baltimore, Williams and Wilkins, 1974, p p . 245-270. 4. Konigsmark, B. W., and Gorlin, R.: Genetic and metabolic deafness. Philadelphia, W. B. Saunders, 1976, p p . 74-135. 5. Rose, F . C : The association of juvenile diabe tes mellitus and optic atrophy. Clinical and genetic aspects. Q. J. Med. 35:385, 1966. 6. Sylvester, P.: Some unusual findings in a fami ly with Friedreich's ataxia. Arch. Dis. Child. 33:217, 1958. 7. Muller, J., and Zeman, W.: Degenerescence. systematisee optico-cochleo-dentelee. Acta Neuropathol. (Berl.) 5:26, 1965. 8. Rosenberg, R. N., and Chutoran, A.: Familial opticoacoustic nerve degeneration and polyneuropathy. Neurology (Minrieap.) 17:827, 1967.
