Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Two Families With Alport's Syndrome L. M. ödkvist, P. Kylén & M. Lundberg To cite this article: L. M. ödkvist, P. Kylén & M. Lundberg (1976) Two Families With Alport's Syndrome, Acta Oto-Laryngologica, 82:1-6, 234-237, DOI: 10.3109/00016487609120892 To link to this article: http://dx.doi.org/10.3109/00016487609120892
Published online: 08 Jul 2009.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [ECU Libraries]
Date: 30 March 2016, At: 15:56
Acta Otolaryngol82: 234-237, 1976
TWO FAMILIES WITH ALPORT’S SYNDROME
L. M. Odkvist, P. Kylen and M. Lundberg
Downloaded by [ECU Libraries] at 15:56 30 March 2016
From the ENT Department, Regional and University Hospital, Linkoping, Sweden
intermittent haematuria and albuminuria without any sign of renal failure. Her hearing ability is normal. She and her healthy husband have 3 children, in Fig. 1 named AII, A111 and AIV, who since child-hood have had haematuria and proteinuria. The son A I11 at the age of 20 developed a renal failure and succumbed after a renal transplant at the age of 26. His hearing was normal. The son, AII, at the age of 34 has a moderate renal function weakness. Since the age of 10 he has had a progressive hearing loss. His hearing has been checked several times since A. C . Alport 1927 described a family with a the age of 26. His hearing loss by then was a hereditary kidney disease and hearing loss, a 70 dB flat loss on the right side and on the left syndrome that after a suggestion by William- side 40 dB. His hearing loss has been progresson (1961) carries the name Alport’s syn- sive. Speech audiometry, BCkesy audiometry drome. This syndrome has often been studied and SISI give a cochlear picture. His electroin journals for internal medicine but heretofore nystagmogram is normal with symmetrical the otological side of it with a few exceptions caloric reactions. has been neglected. Hence we feel it important . A11 has two daughters with normal hearing to describe two families with Alport’s syn- but intermittent haematuria (A V and A VI). drome to otologists. A daughter of the patient A I (AIV) has a slight kidney disease without renal failure and a normal hearing, and her daughter (AVII) CASE REPORT has the same symptoms. At the Renal clinic and the Audiological clinic, According to verbal legend it is known that within the family B several relatives in former University Hospital in Linkoping two families with Alport’s syndrome have been examined. generations have died from renal failure, and In family A (Fig. 1) the primary case is a hearing losses have been common. woman, now 60 years of age. As far as it is B I died 1941 from a renal disease and had a known this is the first patient with signs of hearing loss. No hearing tests were performed. renal disease in the family. Her symptoms are B I had 6 children, two with her first husband Abstract. Alport’s syndrome is a hereditary disease striking cochlea, eye and kidney. The diseased women usually have a nonlethal degree of the kidney disease, but the prognosis for the men is worse. They often die from renal failure before the age of 35. Most cases of hearing loss occurs in men. The hearing loss is progressive after the age of 10. Audiological tests are characteristic for a cochlear lesion. The debut of the disease usually appears in the post natal period giving microscopic haematuria. It can, however, occur later with haematuria and proteinuria. The hearing loss may be the first symptom, which is an observandum to otologists. Two families with Alport’s syndrome are described. The patients have been examined concerning kidney disease, audiological and vestibular pathology. The hereditary pattern is described.
Acta Otolaryngol82
Two families with Alport’s syndrome
235
Downloaded by [ECU Libraries] at 15:56 30 March 2016
disease is inherited. (Perkoff, 1967; Stephens et al., 1951; Graham, 1959; Shaw et al., 1961; Arnott et al., 1966; Sarre et al., 1966; Karlberg, 1968.) The disease is most commonly transmitted through mothers having the syndrome, but heritance through fathers may occur, and sometimes the transmittance goes through symptom-free parents. No certain proof has been given for a connection between chromosome changes and Alport’s syndrome, although it is likely that there are chromosome changes. The gene seems to be sex-influenced and not totally penetrant. I
IV 9
0
WOMAN
0
MAN
0
HEALTHY
61
RENAL DISEASE HEARING LOSS AND RENAL DISEASE
Fig. I. Pedigree for two families with Alport’s syndrome.
and four with her second one. Both men were healthy. The son BII at the age of 39 has a renal affection with slightly increased serum creatinine. He has had a hearing loss since the age of 10. The hearing loss has not been progressive beyond the 60 dB level (see Fig. 2). It is of a sensorineural type, audiologically giving the pattern of a cochlear lesion. His nystagmogram is normal. It is interesting to note that a healthy brother, BII, has a son aged 6 with renal disease. His hearing is normal (B IV). B 111, half-sister to B I1 with different fathers, has a microscopic haematuria as has her daughter and grand-daughter (B IV, B VI), all of them showing normal audiograms.
Pathogenesis Several theories concerning the pathogenesis have been suggested by different authors. Goldbloom et al. (1957) suspect an inherited enzyme defect with progressive accumulation of a toxic substance. Johnson & Hagan (1965) support this theory. Perkoff et al. (1958) are suggesting a defect lipid metabolism with secondary changes in cochlea and kidney. Iversen (1974) has a theory concerning a specific collagen defect in the patients and that this defect collagen is specific for the basilar membrane in the glomerulus, cochlea and lens. Hinglais et al. (1972) support this
-10
0 10
20
30
40 50 60 70
ao 90
DISCUSSION Heredity Several authors after having studied different families with Alport’s syndrome have proposed different theories concerning how the
I00 110 I20
I30
Fig. 2 . Audiometry findings in the patient named B 11. Acia Oiolaryngol82
236
L . M . Odkvist et al.
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theory concerning degenerations in collagen tissue. Morphology Kidney: The histopathological picture in the kidney usually has features in common with glomerulonephritis, interstitial nephritis and secondary pyelonephritis. The glomerulonephritelike alterations consist of thickening and hyalinisation of capillary basement membrane in glomeruli. Some glomeruli remain intact. The characteristic sign seems to be the presence of foam cells. At immuno-fluorescence microscopy no positive reactions for immunoglobuline have been found. Renal biopsies in our material so far has not succeeded to show any pathology. Cochlea: Lachheim et al. (1968) have found collagen changes in the organ of Corti in some cases. Crawfurd et al. (1968) in one case describe atrophy of the organ of Corti and foam cells in the saccus endolymphaticus, changes also described by Gregg & Becker (1963). Eye: Pathology in the eye is unusual and is described only in few cases. The changes appear in the lens and consist of cataracts, lenticular opacities and occasionally keratoconus. Some cases with retinopathy have been described (Ohlson, 1963). Symptoms The disease usually starts with a microscopical haematuria. In the majority of the cases this haematuria exists already in the post natal period. In women the disease usually includes only an intermittent microscopic haematuria and a slight proteinuria without renal failure. This type of cases is common in our families A and B. Men more commonly run into a renal failure causing death before the age of 35. This is shown by case A 111. The hearing loss is most common in men and starts after the age of 10 as in our cases A 11 and B 11. It is important to know that the disease may start with a hearing loss without symptoms of renal disease. This is pointed out by Cassady et al. (1965). In our families A and B no such case is Acfa Ofolaryngol82
present. According to the literature a debut with hearing loss is mere common in some families with the disease. These cases starting with the hearing loss to the otologist is an observandum not to forget questions about heredity for hearing loss and renal disease in his case history. Urine tests may give the diagnosis when a case of inexplicable sensorineural hearing loss is investigated. The audiological picture is cochlear in our cases as well as in the literature. The hearing loss in men usually progresses to a level that give social problems. Surditas is uncommon. In our families we found no lenticular pathology. The first symptom noticeable when the eye gets affected usually is myopia. Therapy At present no treatment can cure the kidney disease or prevent its progress. Ordinary diet, salt and water restrictions are used in cases of renal failure. In several cases hemodialysis has been used. Several successful renal transplants have been described in the literature, and it is also shown that patients with hereditary nephropathy has a somewhat better 2 year survival than other patients with kidney transplants. (The 9th report of the Renal Transplant Registry, 1972.) Conclusion Alport’s syndrome is a hereditary disease concerning the kidney, cochlea and sometimes the eye. It is important to trace the cases as the prognosis may be pessima. Early diagnosis is of value, as treatment may save the patient for many years and hemodialysis and renal transplant may be necessary. Knowledge concerning this hereditary disease is important in family planning. Early diagnosis also gives the patient with a hearing loss the chance to get a hearing-aid before he has suffered social problems due to his hearing loss.
ZUSAMMENFASSUNG Alports Syndrom ist eine erbliche Krankheit, die an der Gehorschnecke, am Auge und an der Niere auftritt. Die
Downloaded by [ECU Libraries] at 15:56 30 March 2016
Two families with Alport’s syndrome erkrankten Frauen haben im allgemeinen einen nichttotlichen Grad der Nierenkrankheit, wahrend die Prognose fur Manner schlechter ist. Diese sterben oft an Nierenversagen, bevor sie 35 Jahre alt werden. Die meicten Falle von Gehorverlust treten bei Mannern auf. Der Gehorverlust ist fortschreitend nach einem Alter von 10 Jahren. Audiologische Tests zeigen eine charakteristische Schneckengang-Beschadigung. Erstmalig tritt die Krankheit gewohnlich in der Zeit nach der Geburt als mikroskopische Hamaturia auf. Sie kann spater auch als Hamaturia mit Proteinuria vorkommen. Der Gehorverlust kann das erste Symptom sein, welches ein Observandum for Otologen ist. Es werden zwei Familien mit Alports Syndrom beschrieben. Die Patienten sind wegen Nierenerkrankung, audiologischer und vestibularer Pathologie untersucht worden. Es wird berichtet, daS die Krankheit erblich ist.
REFERENCES Alport, A. C. 1927. Hereditary familial congenital haemorrhagic nephritis. Br M J I , 504. Amott, E. J., Crawfurd, M. D. A. & Toghill, P. J. 1966. Anterior lenticonus and Alport’s syndrome. Br J Ophthalmol SO, 390. Cassady, G., Brown, K., Cohen. M. & DeMaria, W. 1965. Hereditary renal dysfunction and deafness. Pediatrics 35, 967. Crawfurd, M. D. A. & Toghill, P. J. 1968. Alport’s syndrome of hereditary nephritis and deafness. Q J Med 37, 563. Goldbloom, R. B., Fraser, F. C., Waugh, D., .kenovitch, M . & Wiglesworth, F. W. 1957. Hereditary renal disease associated with nerve deafness and ocular lesions. Pediatrics 20, 241. Graham, J. B. 1959. Hereditary chronic kidney disease: An alternative to partial sex-linkage in the Utah Kindred. A m J Hum Genet 11, 333. Gregg, J. B. & Becker. S . F. 1963. Concomitant pro-
16-762959
237
gressive deafness, chronic nephritis, and ocular lens disease. Arch Ophrhulmol69, 293. Hinglais, N . , Griinfeld, J.-P. & Bois, E. 1972. Characteristic ultrastructural lesion of the glomerular basement membrane in progressive hereditary nephritis (Alport’s syndrome). Lab Invest 27, 413. Iversen, U . M. 1974. Hereditary nephropathy with hearing loss “Alport’s syndrome”. Acta Paediat Scand, Suppl. 245. Johnson, W. J. & Hagan, P. J . 1965. Hereditary nephropathy and loss of hearing. Ann Otolaryngol Chir Cervicofac 82, 166. Karlberg, B. 1969. Alport’s Syndrome. Nordisk Medicin 82, 1254. Lachhein, L., Kemnitz, P., Buttner, H., Thal, W. & Witkowski, R. 1968. Erbliche Nephritis mit Innenohrschwerhorigkeit (Alport-Syndrom). Drsch Med Wochenschr 93, 1891. Ohlsson, L. 1963. Congenital renal disease deafness and myopia in one family. Acta Med Scand 174, 77. Perkoff, G. T. 1967. The hereditary renal diseases. New Engl J Med 277, 19. Perkoff, G. T., Nugent, C. A., Dolowitz, D. A , , Stephens, F. E., Carnes, W. H. & Tyler, F. H. 1958. A followup study of hereditary chronic nephrit. Arch Intern Med 102, 733. Sarre, H., Rother, K., Schmitt, Ch., Unger, H.-H., Beickert, P. & Baitsch, H . 1966. Neue Befunde zur hereditaren chronischen Nephritis (Alport-Syndrom). Arch Klin M e d 2 1 2 , 1. Shaw, R. F. & Glover, R. A. 1961. Abnormal segregation in hereditary renal disease with deafness. A m J Hum Genet 13. 89. Stephens, F. E., Perkoff, G. T., Dolowitz, D. A. & Tyler, F. H. 1951. Partially sex-linked dominant inheritance of interstitial pyelonephritis. A m J Hum Genet 3, 303. Williamson, D. A. J. 1961. Alport’s syndrome of hereditary nephritis with deafness. Lancet II, 1321. The Ninth Report of the Human Renal Transplant Registry. 1972. JAMA 220, 253.
Acra Otolaryngol82
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Two Families With Alport's Syndrome L. M. ödkvist, P. Kylén & M. Lundberg To cite this article: L. M. ödkvist, P. Kylén & M. Lundberg (1976) Two Families With Alport's Syndrome, Acta Oto-Laryngologica, 82:1-6, 234-237, DOI: 10.3109/00016487609120892 To link to this article: http://dx.doi.org/10.3109/00016487609120892
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 2
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [ECU Libraries]
Date: 30 March 2016, At: 15:56
Acta Otolaryngol82: 234-237, 1976
TWO FAMILIES WITH ALPORT’S SYNDROME
L. M. Odkvist, P. Kylen and M. Lundberg
Downloaded by [ECU Libraries] at 15:56 30 March 2016
From the ENT Department, Regional and University Hospital, Linkoping, Sweden
intermittent haematuria and albuminuria without any sign of renal failure. Her hearing ability is normal. She and her healthy husband have 3 children, in Fig. 1 named AII, A111 and AIV, who since child-hood have had haematuria and proteinuria. The son A I11 at the age of 20 developed a renal failure and succumbed after a renal transplant at the age of 26. His hearing was normal. The son, AII, at the age of 34 has a moderate renal function weakness. Since the age of 10 he has had a progressive hearing loss. His hearing has been checked several times since A. C . Alport 1927 described a family with a the age of 26. His hearing loss by then was a hereditary kidney disease and hearing loss, a 70 dB flat loss on the right side and on the left syndrome that after a suggestion by William- side 40 dB. His hearing loss has been progresson (1961) carries the name Alport’s syn- sive. Speech audiometry, BCkesy audiometry drome. This syndrome has often been studied and SISI give a cochlear picture. His electroin journals for internal medicine but heretofore nystagmogram is normal with symmetrical the otological side of it with a few exceptions caloric reactions. has been neglected. Hence we feel it important . A11 has two daughters with normal hearing to describe two families with Alport’s syn- but intermittent haematuria (A V and A VI). drome to otologists. A daughter of the patient A I (AIV) has a slight kidney disease without renal failure and a normal hearing, and her daughter (AVII) CASE REPORT has the same symptoms. At the Renal clinic and the Audiological clinic, According to verbal legend it is known that within the family B several relatives in former University Hospital in Linkoping two families with Alport’s syndrome have been examined. generations have died from renal failure, and In family A (Fig. 1) the primary case is a hearing losses have been common. woman, now 60 years of age. As far as it is B I died 1941 from a renal disease and had a known this is the first patient with signs of hearing loss. No hearing tests were performed. renal disease in the family. Her symptoms are B I had 6 children, two with her first husband Abstract. Alport’s syndrome is a hereditary disease striking cochlea, eye and kidney. The diseased women usually have a nonlethal degree of the kidney disease, but the prognosis for the men is worse. They often die from renal failure before the age of 35. Most cases of hearing loss occurs in men. The hearing loss is progressive after the age of 10. Audiological tests are characteristic for a cochlear lesion. The debut of the disease usually appears in the post natal period giving microscopic haematuria. It can, however, occur later with haematuria and proteinuria. The hearing loss may be the first symptom, which is an observandum to otologists. Two families with Alport’s syndrome are described. The patients have been examined concerning kidney disease, audiological and vestibular pathology. The hereditary pattern is described.
Acta Otolaryngol82
Two families with Alport’s syndrome
235
Downloaded by [ECU Libraries] at 15:56 30 March 2016
disease is inherited. (Perkoff, 1967; Stephens et al., 1951; Graham, 1959; Shaw et al., 1961; Arnott et al., 1966; Sarre et al., 1966; Karlberg, 1968.) The disease is most commonly transmitted through mothers having the syndrome, but heritance through fathers may occur, and sometimes the transmittance goes through symptom-free parents. No certain proof has been given for a connection between chromosome changes and Alport’s syndrome, although it is likely that there are chromosome changes. The gene seems to be sex-influenced and not totally penetrant. I
IV 9
0
WOMAN
0
MAN
0
HEALTHY
61
RENAL DISEASE HEARING LOSS AND RENAL DISEASE
Fig. I. Pedigree for two families with Alport’s syndrome.
and four with her second one. Both men were healthy. The son BII at the age of 39 has a renal affection with slightly increased serum creatinine. He has had a hearing loss since the age of 10. The hearing loss has not been progressive beyond the 60 dB level (see Fig. 2). It is of a sensorineural type, audiologically giving the pattern of a cochlear lesion. His nystagmogram is normal. It is interesting to note that a healthy brother, BII, has a son aged 6 with renal disease. His hearing is normal (B IV). B 111, half-sister to B I1 with different fathers, has a microscopic haematuria as has her daughter and grand-daughter (B IV, B VI), all of them showing normal audiograms.
Pathogenesis Several theories concerning the pathogenesis have been suggested by different authors. Goldbloom et al. (1957) suspect an inherited enzyme defect with progressive accumulation of a toxic substance. Johnson & Hagan (1965) support this theory. Perkoff et al. (1958) are suggesting a defect lipid metabolism with secondary changes in cochlea and kidney. Iversen (1974) has a theory concerning a specific collagen defect in the patients and that this defect collagen is specific for the basilar membrane in the glomerulus, cochlea and lens. Hinglais et al. (1972) support this
-10
0 10
20
30
40 50 60 70
ao 90
DISCUSSION Heredity Several authors after having studied different families with Alport’s syndrome have proposed different theories concerning how the
I00 110 I20
I30
Fig. 2 . Audiometry findings in the patient named B 11. Acia Oiolaryngol82
236
L . M . Odkvist et al.
Downloaded by [ECU Libraries] at 15:56 30 March 2016
theory concerning degenerations in collagen tissue. Morphology Kidney: The histopathological picture in the kidney usually has features in common with glomerulonephritis, interstitial nephritis and secondary pyelonephritis. The glomerulonephritelike alterations consist of thickening and hyalinisation of capillary basement membrane in glomeruli. Some glomeruli remain intact. The characteristic sign seems to be the presence of foam cells. At immuno-fluorescence microscopy no positive reactions for immunoglobuline have been found. Renal biopsies in our material so far has not succeeded to show any pathology. Cochlea: Lachheim et al. (1968) have found collagen changes in the organ of Corti in some cases. Crawfurd et al. (1968) in one case describe atrophy of the organ of Corti and foam cells in the saccus endolymphaticus, changes also described by Gregg & Becker (1963). Eye: Pathology in the eye is unusual and is described only in few cases. The changes appear in the lens and consist of cataracts, lenticular opacities and occasionally keratoconus. Some cases with retinopathy have been described (Ohlson, 1963). Symptoms The disease usually starts with a microscopical haematuria. In the majority of the cases this haematuria exists already in the post natal period. In women the disease usually includes only an intermittent microscopic haematuria and a slight proteinuria without renal failure. This type of cases is common in our families A and B. Men more commonly run into a renal failure causing death before the age of 35. This is shown by case A 111. The hearing loss is most common in men and starts after the age of 10 as in our cases A 11 and B 11. It is important to know that the disease may start with a hearing loss without symptoms of renal disease. This is pointed out by Cassady et al. (1965). In our families A and B no such case is Acfa Ofolaryngol82
present. According to the literature a debut with hearing loss is mere common in some families with the disease. These cases starting with the hearing loss to the otologist is an observandum not to forget questions about heredity for hearing loss and renal disease in his case history. Urine tests may give the diagnosis when a case of inexplicable sensorineural hearing loss is investigated. The audiological picture is cochlear in our cases as well as in the literature. The hearing loss in men usually progresses to a level that give social problems. Surditas is uncommon. In our families we found no lenticular pathology. The first symptom noticeable when the eye gets affected usually is myopia. Therapy At present no treatment can cure the kidney disease or prevent its progress. Ordinary diet, salt and water restrictions are used in cases of renal failure. In several cases hemodialysis has been used. Several successful renal transplants have been described in the literature, and it is also shown that patients with hereditary nephropathy has a somewhat better 2 year survival than other patients with kidney transplants. (The 9th report of the Renal Transplant Registry, 1972.) Conclusion Alport’s syndrome is a hereditary disease concerning the kidney, cochlea and sometimes the eye. It is important to trace the cases as the prognosis may be pessima. Early diagnosis is of value, as treatment may save the patient for many years and hemodialysis and renal transplant may be necessary. Knowledge concerning this hereditary disease is important in family planning. Early diagnosis also gives the patient with a hearing loss the chance to get a hearing-aid before he has suffered social problems due to his hearing loss.
ZUSAMMENFASSUNG Alports Syndrom ist eine erbliche Krankheit, die an der Gehorschnecke, am Auge und an der Niere auftritt. Die
Downloaded by [ECU Libraries] at 15:56 30 March 2016
Two families with Alport’s syndrome erkrankten Frauen haben im allgemeinen einen nichttotlichen Grad der Nierenkrankheit, wahrend die Prognose fur Manner schlechter ist. Diese sterben oft an Nierenversagen, bevor sie 35 Jahre alt werden. Die meicten Falle von Gehorverlust treten bei Mannern auf. Der Gehorverlust ist fortschreitend nach einem Alter von 10 Jahren. Audiologische Tests zeigen eine charakteristische Schneckengang-Beschadigung. Erstmalig tritt die Krankheit gewohnlich in der Zeit nach der Geburt als mikroskopische Hamaturia auf. Sie kann spater auch als Hamaturia mit Proteinuria vorkommen. Der Gehorverlust kann das erste Symptom sein, welches ein Observandum for Otologen ist. Es werden zwei Familien mit Alports Syndrom beschrieben. Die Patienten sind wegen Nierenerkrankung, audiologischer und vestibularer Pathologie untersucht worden. Es wird berichtet, daS die Krankheit erblich ist.
REFERENCES Alport, A. C. 1927. Hereditary familial congenital haemorrhagic nephritis. Br M J I , 504. Amott, E. J., Crawfurd, M. D. A. & Toghill, P. J. 1966. Anterior lenticonus and Alport’s syndrome. Br J Ophthalmol SO, 390. Cassady, G., Brown, K., Cohen. M. & DeMaria, W. 1965. Hereditary renal dysfunction and deafness. Pediatrics 35, 967. Crawfurd, M. D. A. & Toghill, P. J. 1968. Alport’s syndrome of hereditary nephritis and deafness. Q J Med 37, 563. Goldbloom, R. B., Fraser, F. C., Waugh, D., .kenovitch, M . & Wiglesworth, F. W. 1957. Hereditary renal disease associated with nerve deafness and ocular lesions. Pediatrics 20, 241. Graham, J. B. 1959. Hereditary chronic kidney disease: An alternative to partial sex-linkage in the Utah Kindred. A m J Hum Genet 11, 333. Gregg, J. B. & Becker. S . F. 1963. Concomitant pro-
16-762959
237
gressive deafness, chronic nephritis, and ocular lens disease. Arch Ophrhulmol69, 293. Hinglais, N . , Griinfeld, J.-P. & Bois, E. 1972. Characteristic ultrastructural lesion of the glomerular basement membrane in progressive hereditary nephritis (Alport’s syndrome). Lab Invest 27, 413. Iversen, U . M. 1974. Hereditary nephropathy with hearing loss “Alport’s syndrome”. Acta Paediat Scand, Suppl. 245. Johnson, W. J. & Hagan, P. J . 1965. Hereditary nephropathy and loss of hearing. Ann Otolaryngol Chir Cervicofac 82, 166. Karlberg, B. 1969. Alport’s Syndrome. Nordisk Medicin 82, 1254. Lachhein, L., Kemnitz, P., Buttner, H., Thal, W. & Witkowski, R. 1968. Erbliche Nephritis mit Innenohrschwerhorigkeit (Alport-Syndrom). Drsch Med Wochenschr 93, 1891. Ohlsson, L. 1963. Congenital renal disease deafness and myopia in one family. Acta Med Scand 174, 77. Perkoff, G. T. 1967. The hereditary renal diseases. New Engl J Med 277, 19. Perkoff, G. T., Nugent, C. A., Dolowitz, D. A , , Stephens, F. E., Carnes, W. H. & Tyler, F. H. 1958. A followup study of hereditary chronic nephrit. Arch Intern Med 102, 733. Sarre, H., Rother, K., Schmitt, Ch., Unger, H.-H., Beickert, P. & Baitsch, H . 1966. Neue Befunde zur hereditaren chronischen Nephritis (Alport-Syndrom). Arch Klin M e d 2 1 2 , 1. Shaw, R. F. & Glover, R. A. 1961. Abnormal segregation in hereditary renal disease with deafness. A m J Hum Genet 13. 89. Stephens, F. E., Perkoff, G. T., Dolowitz, D. A. & Tyler, F. H. 1951. Partially sex-linked dominant inheritance of interstitial pyelonephritis. A m J Hum Genet 3, 303. Williamson, D. A. J. 1961. Alport’s syndrome of hereditary nephritis with deafness. Lancet II, 1321. The Ninth Report of the Human Renal Transplant Registry. 1972. JAMA 220, 253.
Acra Otolaryngol82
