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Usher's syndrome, temporal bone pathology
InternationalJournal of Pediatric Otorhino~a~~go~o~,16 (1988) 23-30 Elsevier
23
PQROO527
. Cremers ’ Department of Otorhinolarjmgology,Universityof Nijmegen, Nijmegen (lucreNether/an&) and 2 Department of Ophthalmogenetics,OphthalmicResearch Institute, Amsterdam (The Net~e~la~~) (Weceived 31 December 1985) (Revised version received17 May 19881
Key wor&: Congenital deafness; Histopathology; Inner ear; Autosomal recessive i
trophia retina pigmentosa
The histological find blind man are prese=lted.
ffered from the autosomal recessive
s were donat
A 65year-01
deaf and b
started work as a c of vision forced In 1979 he was
recessive an with Usher’s syndrome (autoso e School for the at the age of 18, and ars a progressive loss
Correspondence: C. Cremers,Department of Otorhinolaryngology, St. Radboud Nijmegen, The Netherlands.
0165-5876/88/$03.50 6 1988 ElscvierScience Publishers
iomedkd Division)
24
El0 100 120
right
frequency (Hz 1
left
frequency (tlz~
air conduction : right o,left x boneconduction: right Lleft 3
Fig. 1. Audiogramof 65year-old deaf and blind man with Usher’ssyndrome.
frequently been performed and several reports could be traced. Dystrophia retinae pigmentosa was diagnosed in 1953 after the first operation for cataracts. The visual abilities were VOD a.c. S + 15 = C + 2 axis 165O 2/60 VOS a.c. S + 12 = C + 3 axis 150° 2/60. In 1970 these were VOD a.c. S + 16 = C + 2 axis 170° l/00, VOS a.c. S+12=C+3axis160°1/300. An otological examination in 1980 was normal. At audiometry, a bilateral symmetrical sensorineural hearing loss (Fig. 1) was seen with no understanding of speech at a level of 120 dB.
Family history The parents were closely related (Fig. 2). Ths youngest daughter was also deaf and blind and died in 1962. The subject’s youngcsl brother is also deaf and blind as
t1970 F
t1962
Fig. 2. Pedigreewith Usher’s syndrome.
a result of also be traced. S+1,5=C-I axis 1go= l/3 extracapsular lens extraction an performed. Us parents (Fig. 2). Histopathological procedures and findings Formalin was injected into the middle ears t oral bones were re
and Ear Infirm severely atrophic throughout the 60
Fig. 3. A severelyatrophic organ of Corti ad severeloss of cochlear neurons of the ri
26
Fig. 4. A severelyatrophicorganof Cortiof the rightear(57.9x ). basal 15 mm and consisted elsewhere of a mound of undifferentiated
cells (Fig. 2). There was a severe loss of cochlear neurons with an estimated 5% remaining in turns 1 (Tl) and 2 (T2) and 10% in turn 3 (T3). Many of these neurons appeared to be devoid of fiber processes. There were nerve fibers however in the apical region. It appeared that the efferent nerve fibers in Tl had also degenerated. The afferent or efferent origin of the fibers in T2 and T3 could not be differentiated. The tectorial membrane was missing in one half of Tl and was thin and atrophic in T2 and T3. The stria vascular-is was almost totally atrophic in T2 and T3 and showed patchy atrophy in small areas of Tl. These was Scala communis between T2 and T3, which was not considered to be of clinical significance (Figs. 3 and 4). The Limbus showed decreased cellularity in the basal 6 mm of the cochlea, but appeared normal elsewhere. The tectorial membrane had collapsed throughout the middle turn. There was mild apical hydrops, probably physiological. The utricular and saccular maculi were normal as were all 3 cristae. The vestibular nerves and Scarpa’s ganglia appeared to be normal as well as the facial nerve (Fig. 5). The left ear showed a great deal of artifact involving principally the bony structure. The membranous structures were all present and although there was preparation artifact, the postmortem autolysis was mild and preservation was moderately good. The inner ear structures appeared almost identical to those of the opposite ear. A neuropathological study of the brain was performed. Brain weight was f1300 gram. There was some cortical atrophy and a slight internal hydrocephalus. The pons and brainstem were examined at 5 levels. The
27
Fig. 5. Micrograph of the vestibulum showing normal saccular and utricular struct’ ‘-5 of the right ear (31.6x).
only abnormal finding, exce s of aging, was a s around the exit of one of the roots of the byp nerves were normal.
In 1858, only few years after the discovery of the ophthalmosc von Graefe from erIin 1231briefly mentioned the association bet e credited this discovery to his cousin, t retinitis pigmentosa. Alfred Graefe. In 1861, Liebreicb [12], also from erhn, published a description of this syndrome after a systematic examination of the deaf population. high frequency of retinitis pigmentosa that be found among His data are also remarkable for the large number of consa the parents of affected persons. ed this disorder and In 1914, Usher [21] e Liebreich’s daim [ as an eponym to this s
28
It has been estimated that between 10 and 20% of subjects showing recessive retinitis pigmentosa are deaf [lo]. The prevalence of retinitis pigmentosa among profoundly deaf children has been estimated at l-4% [?I. This fits with the 2.4-3,5/1~,~ population prevaknce est~at~ from the surveys from Denmark [13], Sweden [9] and Finland [17], when a prevalence of l/IO00 for profound chihlhood deafness (141is assumed. The pr~en~tion of Usher’s s~drome can be quite variable and a sep~ation into 4 subtypes has been proposed [8]. Type I: profound congenital deafness with onset of retin& pigmentosa by POyears of age, comprising about 90% of the cases. Type II: moderate to severe congenitaI deafness with onset of retinitis pi~entosa in the late teens or early twenties, representing approximately 10% of the cases. Type III: hearing loss that is progressive with retinitis pigmentosa becoming manifest at about puberty, Type IV: is com~atibIe with X-linked i~e~t~~e and exhibits a phe~ot~e similar to type II 2341. Although it is very rare that carriers of an autosomal recessive gene for profound
childhood deafness can be identified as such by clinical features, heterozygotes for Usher’s syndrome may be recog~ed by a slight hearing loss [15] and by elevated dark adaptation thresholds [4]. Initial eye symptoms may appear as early as the preschool age in the form of night bagel, ~h~~olo~~~ ex~nation shows a typical slowly progressive retinitis pigmentosa with the classic pigment clumping giving the appearance of bone-spicules in the mid-periphery of the fundus and a narrowed and p disc. 0ther ocular findings include cataract, loss of color vision and occ gfaucoma.Anterior or posterior cortical cataracts are noted in about 10% of patients at the age of 20 and in about 50% of those over 40 [ll]. Psychosis was diagnosed in about 25% of patients in Hal&en’s group [9]. Vernon’s review f22] of the Iiiterature indicated a simiIar prevaIence of psychosis. The chnical history of our patient is typical of Usher’s syndrome Type II. The cataracts and hospitalization for paranoia also fit with this syndromal diagnosis. The ~n~g~~us marriage of the h~thy parents and the fact that two sibhngs, one of whom is female, are affected, provide sufficient additionsil evidence to establish the diagnosis of Usher’s syndrome in this case., Only a few reports on temporal bone p~t~~~ogyin Usher’s syndrome can be traced in the literature [1,20]. Siebennnann and Bing [20] gave the first detailed description in 1907 followed by Nager [16] in 1927 who presented his histological findings in two patients. Both reports are in the German language. Nager aIso quoted.0 patient described by Alexander in 1919, but there is inadequate evidence that the ophthalmological complaints were indeed the result of Usher’s syndrome. The case reported by Buch and Jorgensen [2] in 1963 was not affected by retinitis pimentos but these authors succeeded in developing additions stains on Nager’s slides [Ml. The most recent description was from elal [1] in 1975. He was unaware of the older European reports [16,20]. ~stoIo~~~ Reid@ SLOWS an extinsive, ahnost total degeneration of the organ of corti amI the cochleae neurons. The stria vascukris was also severely atrophic in T2 and T3. The case of Siebenmann [ZO]and the second case of Nager
29
Nidei from Ziiric
Nager described that the organ of Corti ologically normal by the first qwrter o more recently by Pap robably from the patient
the epithelium of the in the upper turns. severe Atrophy of the spiral
and the primary acoustic centers (g
The authors are indebted to
of the brain an gen, The Netherlands, for his help in this study.
1 Belal, A., Usher’s syndrome (retinitis pigmentosa and deafness). A temporal bone report, 9. 89 (1975) 175-182.
30
2 Bu&, NH. and Jorgensen, M.B., Pathological studies of deaf-mutes, Arch. OtolaryngoI., 77 (1963) 246-253. 3 Davapo& S.L.M. and Omenn, G.S., The heterogeneity of Usher Syndrome, Abstract 215. Fifth IntcrnationaI Conference on Birth Defects, Montreal, Aug. 21-27. Excerpta Medica, Amsterdam (1977). 4 De Haas, E., Van Lith, G., Rijnders, J., Riimke, A. and Vohner, C., Usher’s syndrome with special reference to heterozygous manifestations, Dot. Ophthalmol., 28 (1970) 166-190. 5 De Wilde, P.A., Onderzoek naar de erfelijkheid en bloedverwantschap bij de doofstommen in Nederland, Ned. Tijdschr. Geneeskd., 1 (1913) 1287-1305. 6 De Wilde, P.A., Venvantschap en erfehjkheid bij doofstomheid en retinitis pigmentosa. Thesis, Van Rossum, Amsterdam, 1919. 7 Fraser, G.R., Profound childhood deafness, J. Med. Genet., 1 (1964) 118-151. 8 GorIm, R.J., Tilsner, T.J., Feinstein, S. and DuvaU, A.J., Usher’s syndrome type III, Arch. Otolaryngal., 105 (1979) 353-354. 9 HaUgren, V., Retinitis pigmentosa combined with congenital deafness; with vestibule-cerebellar ataxia and mental abnormality in a proportion of cases. A clinical and geneticostatistical study, Acta Psychiatr. Stand., 138, Suppl. (1959) l-101. 10 Wein, D., Genetic approach to the nosology of retinal disorders; Birth Defects, OAS VII, 3 (1971) 52-82. 11 Koningsmark, B.W. and Gorhn, R.J., Genetic and metabolic deafness. Saunders, Philadelphia, 1976. 12 Liebreich, R., Abkunft und Ehen unter Blutsverwandten aIs Gnmd von Retinitis pigmentosa, Dtsch. KIin., 13 (1861) 53-55. 13 Lindenov, H., The etiology of deaf-mutism with special reference to heredity. Munksgaard, Copenhagen, 1945. 14 Martin, J.A.M., Bentzen, 0.. CoIIey, J.R.T., Hennebert, D., Holm, C., Iurato, S., De Jonge, G.A., McCuIIen, O., Meyer, M.L., Moore, W.J. and Morgon, A., Childhood deafness in the European community, Stand. Audiol., 10 (1981) 165-174. 15 McLeod, A.C., MC&Me& F., Sweeney, A., Cooper, M. and Nance, W., CIiicaI variation in Usher’s syndrome, Arch. Otolaryngol., 94 (1971) 321-334. 16 Nager, F.R., Zur Histologie der Taubstummheit bei Retinitis pigmentosa, Beitr. Pathol. Anat., 77 (1927) 288-303. 17 NuutiIa, A., Dystrophia retinae pigmentosa-dysacusis syndrome (DRD). A study of the Usher - or HaIlgren - syndrome, J. G&t&. Hum., 18 (1970) 57-88. 18 Paparella, M.M. and Schumrick, D.A., Otolaryngology, Vol. 2: Ear. Saunders, Philadelphia, 1973. 19 Schuknecht, H.F., Temporal bone removal at autopsy, Arch. Otolaryngol., 87 (1968) 129-137. 20 Siebenmarm, F. and Bing, R., Uber den Labyrinth - und Himbefund bei einem an Retinitis pigmentosa erblindeten angeboren Taubstummen, Z. Ohrenheilkd., 54 (1907) 265-280. 21 Usher, C.H., On the inheritance on retinitis pigmentosa, with notes of cases, R. Lond, Ophthahuol. Hosp. Rep., 19 (1914) 130-236. 22 Vernon, M., Usher’s syndrome - deafness and progressive blindness. Clinical cases, prevention, theory and literature survey, J. Chron. Dis., 22 (1959) 133-151. 23 Van Graefe, A., Vereinzelte Beobachttmgen und Bemerkungen exceptionelles verhalten des Gesichtsveldes bei Pigmentenartung der Netzhaut, AIbrecht von Graefe’s Arch. IUin. OphthaImol., 4 (1858) 250-253.
23
PQROO527
. Cremers ’ Department of Otorhinolarjmgology,Universityof Nijmegen, Nijmegen (lucreNether/an&) and 2 Department of Ophthalmogenetics,OphthalmicResearch Institute, Amsterdam (The Net~e~la~~) (Weceived 31 December 1985) (Revised version received17 May 19881
Key wor&: Congenital deafness; Histopathology; Inner ear; Autosomal recessive i
trophia retina pigmentosa
The histological find blind man are prese=lted.
ffered from the autosomal recessive
s were donat
A 65year-01
deaf and b
started work as a c of vision forced In 1979 he was
recessive an with Usher’s syndrome (autoso e School for the at the age of 18, and ars a progressive loss
Correspondence: C. Cremers,Department of Otorhinolaryngology, St. Radboud Nijmegen, The Netherlands.
0165-5876/88/$03.50 6 1988 ElscvierScience Publishers
iomedkd Division)
24
El0 100 120
right
frequency (Hz 1
left
frequency (tlz~
air conduction : right o,left x boneconduction: right Lleft 3
Fig. 1. Audiogramof 65year-old deaf and blind man with Usher’ssyndrome.
frequently been performed and several reports could be traced. Dystrophia retinae pigmentosa was diagnosed in 1953 after the first operation for cataracts. The visual abilities were VOD a.c. S + 15 = C + 2 axis 165O 2/60 VOS a.c. S + 12 = C + 3 axis 150° 2/60. In 1970 these were VOD a.c. S + 16 = C + 2 axis 170° l/00, VOS a.c. S+12=C+3axis160°1/300. An otological examination in 1980 was normal. At audiometry, a bilateral symmetrical sensorineural hearing loss (Fig. 1) was seen with no understanding of speech at a level of 120 dB.
Family history The parents were closely related (Fig. 2). Ths youngest daughter was also deaf and blind and died in 1962. The subject’s youngcsl brother is also deaf and blind as
t1970 F
t1962
Fig. 2. Pedigreewith Usher’s syndrome.
a result of also be traced. S+1,5=C-I axis 1go= l/3 extracapsular lens extraction an performed. Us parents (Fig. 2). Histopathological procedures and findings Formalin was injected into the middle ears t oral bones were re
and Ear Infirm severely atrophic throughout the 60
Fig. 3. A severelyatrophic organ of Corti ad severeloss of cochlear neurons of the ri
26
Fig. 4. A severelyatrophicorganof Cortiof the rightear(57.9x ). basal 15 mm and consisted elsewhere of a mound of undifferentiated
cells (Fig. 2). There was a severe loss of cochlear neurons with an estimated 5% remaining in turns 1 (Tl) and 2 (T2) and 10% in turn 3 (T3). Many of these neurons appeared to be devoid of fiber processes. There were nerve fibers however in the apical region. It appeared that the efferent nerve fibers in Tl had also degenerated. The afferent or efferent origin of the fibers in T2 and T3 could not be differentiated. The tectorial membrane was missing in one half of Tl and was thin and atrophic in T2 and T3. The stria vascular-is was almost totally atrophic in T2 and T3 and showed patchy atrophy in small areas of Tl. These was Scala communis between T2 and T3, which was not considered to be of clinical significance (Figs. 3 and 4). The Limbus showed decreased cellularity in the basal 6 mm of the cochlea, but appeared normal elsewhere. The tectorial membrane had collapsed throughout the middle turn. There was mild apical hydrops, probably physiological. The utricular and saccular maculi were normal as were all 3 cristae. The vestibular nerves and Scarpa’s ganglia appeared to be normal as well as the facial nerve (Fig. 5). The left ear showed a great deal of artifact involving principally the bony structure. The membranous structures were all present and although there was preparation artifact, the postmortem autolysis was mild and preservation was moderately good. The inner ear structures appeared almost identical to those of the opposite ear. A neuropathological study of the brain was performed. Brain weight was f1300 gram. There was some cortical atrophy and a slight internal hydrocephalus. The pons and brainstem were examined at 5 levels. The
27
Fig. 5. Micrograph of the vestibulum showing normal saccular and utricular struct’ ‘-5 of the right ear (31.6x).
only abnormal finding, exce s of aging, was a s around the exit of one of the roots of the byp nerves were normal.
In 1858, only few years after the discovery of the ophthalmosc von Graefe from erIin 1231briefly mentioned the association bet e credited this discovery to his cousin, t retinitis pigmentosa. Alfred Graefe. In 1861, Liebreicb [12], also from erhn, published a description of this syndrome after a systematic examination of the deaf population. high frequency of retinitis pigmentosa that be found among His data are also remarkable for the large number of consa the parents of affected persons. ed this disorder and In 1914, Usher [21] e Liebreich’s daim [ as an eponym to this s
28
It has been estimated that between 10 and 20% of subjects showing recessive retinitis pigmentosa are deaf [lo]. The prevalence of retinitis pigmentosa among profoundly deaf children has been estimated at l-4% [?I. This fits with the 2.4-3,5/1~,~ population prevaknce est~at~ from the surveys from Denmark [13], Sweden [9] and Finland [17], when a prevalence of l/IO00 for profound chihlhood deafness (141is assumed. The pr~en~tion of Usher’s s~drome can be quite variable and a sep~ation into 4 subtypes has been proposed [8]. Type I: profound congenital deafness with onset of retin& pigmentosa by POyears of age, comprising about 90% of the cases. Type II: moderate to severe congenitaI deafness with onset of retinitis pi~entosa in the late teens or early twenties, representing approximately 10% of the cases. Type III: hearing loss that is progressive with retinitis pigmentosa becoming manifest at about puberty, Type IV: is com~atibIe with X-linked i~e~t~~e and exhibits a phe~ot~e similar to type II 2341. Although it is very rare that carriers of an autosomal recessive gene for profound
childhood deafness can be identified as such by clinical features, heterozygotes for Usher’s syndrome may be recog~ed by a slight hearing loss [15] and by elevated dark adaptation thresholds [4]. Initial eye symptoms may appear as early as the preschool age in the form of night bagel, ~h~~olo~~~ ex~nation shows a typical slowly progressive retinitis pigmentosa with the classic pigment clumping giving the appearance of bone-spicules in the mid-periphery of the fundus and a narrowed and p disc. 0ther ocular findings include cataract, loss of color vision and occ gfaucoma.Anterior or posterior cortical cataracts are noted in about 10% of patients at the age of 20 and in about 50% of those over 40 [ll]. Psychosis was diagnosed in about 25% of patients in Hal&en’s group [9]. Vernon’s review f22] of the Iiiterature indicated a simiIar prevaIence of psychosis. The chnical history of our patient is typical of Usher’s syndrome Type II. The cataracts and hospitalization for paranoia also fit with this syndromal diagnosis. The ~n~g~~us marriage of the h~thy parents and the fact that two sibhngs, one of whom is female, are affected, provide sufficient additionsil evidence to establish the diagnosis of Usher’s syndrome in this case., Only a few reports on temporal bone p~t~~~ogyin Usher’s syndrome can be traced in the literature [1,20]. Siebennnann and Bing [20] gave the first detailed description in 1907 followed by Nager [16] in 1927 who presented his histological findings in two patients. Both reports are in the German language. Nager aIso quoted.0 patient described by Alexander in 1919, but there is inadequate evidence that the ophthalmological complaints were indeed the result of Usher’s syndrome. The case reported by Buch and Jorgensen [2] in 1963 was not affected by retinitis pimentos but these authors succeeded in developing additions stains on Nager’s slides [Ml. The most recent description was from elal [1] in 1975. He was unaware of the older European reports [16,20]. ~stoIo~~~ Reid@ SLOWS an extinsive, ahnost total degeneration of the organ of corti amI the cochleae neurons. The stria vascukris was also severely atrophic in T2 and T3. The case of Siebenmann [ZO]and the second case of Nager
29
Nidei from Ziiric
Nager described that the organ of Corti ologically normal by the first qwrter o more recently by Pap robably from the patient
the epithelium of the in the upper turns. severe Atrophy of the spiral
and the primary acoustic centers (g
The authors are indebted to
of the brain an gen, The Netherlands, for his help in this study.
1 Belal, A., Usher’s syndrome (retinitis pigmentosa and deafness). A temporal bone report, 9. 89 (1975) 175-182.
30
2 Bu&, NH. and Jorgensen, M.B., Pathological studies of deaf-mutes, Arch. OtolaryngoI., 77 (1963) 246-253. 3 Davapo& S.L.M. and Omenn, G.S., The heterogeneity of Usher Syndrome, Abstract 215. Fifth IntcrnationaI Conference on Birth Defects, Montreal, Aug. 21-27. Excerpta Medica, Amsterdam (1977). 4 De Haas, E., Van Lith, G., Rijnders, J., Riimke, A. and Vohner, C., Usher’s syndrome with special reference to heterozygous manifestations, Dot. Ophthalmol., 28 (1970) 166-190. 5 De Wilde, P.A., Onderzoek naar de erfelijkheid en bloedverwantschap bij de doofstommen in Nederland, Ned. Tijdschr. Geneeskd., 1 (1913) 1287-1305. 6 De Wilde, P.A., Venvantschap en erfehjkheid bij doofstomheid en retinitis pigmentosa. Thesis, Van Rossum, Amsterdam, 1919. 7 Fraser, G.R., Profound childhood deafness, J. Med. Genet., 1 (1964) 118-151. 8 GorIm, R.J., Tilsner, T.J., Feinstein, S. and DuvaU, A.J., Usher’s syndrome type III, Arch. Otolaryngal., 105 (1979) 353-354. 9 HaUgren, V., Retinitis pigmentosa combined with congenital deafness; with vestibule-cerebellar ataxia and mental abnormality in a proportion of cases. A clinical and geneticostatistical study, Acta Psychiatr. Stand., 138, Suppl. (1959) l-101. 10 Wein, D., Genetic approach to the nosology of retinal disorders; Birth Defects, OAS VII, 3 (1971) 52-82. 11 Koningsmark, B.W. and Gorhn, R.J., Genetic and metabolic deafness. Saunders, Philadelphia, 1976. 12 Liebreich, R., Abkunft und Ehen unter Blutsverwandten aIs Gnmd von Retinitis pigmentosa, Dtsch. KIin., 13 (1861) 53-55. 13 Lindenov, H., The etiology of deaf-mutism with special reference to heredity. Munksgaard, Copenhagen, 1945. 14 Martin, J.A.M., Bentzen, 0.. CoIIey, J.R.T., Hennebert, D., Holm, C., Iurato, S., De Jonge, G.A., McCuIIen, O., Meyer, M.L., Moore, W.J. and Morgon, A., Childhood deafness in the European community, Stand. Audiol., 10 (1981) 165-174. 15 McLeod, A.C., MC&Me& F., Sweeney, A., Cooper, M. and Nance, W., CIiicaI variation in Usher’s syndrome, Arch. Otolaryngol., 94 (1971) 321-334. 16 Nager, F.R., Zur Histologie der Taubstummheit bei Retinitis pigmentosa, Beitr. Pathol. Anat., 77 (1927) 288-303. 17 NuutiIa, A., Dystrophia retinae pigmentosa-dysacusis syndrome (DRD). A study of the Usher - or HaIlgren - syndrome, J. G&t&. Hum., 18 (1970) 57-88. 18 Paparella, M.M. and Schumrick, D.A., Otolaryngology, Vol. 2: Ear. Saunders, Philadelphia, 1973. 19 Schuknecht, H.F., Temporal bone removal at autopsy, Arch. Otolaryngol., 87 (1968) 129-137. 20 Siebenmarm, F. and Bing, R., Uber den Labyrinth - und Himbefund bei einem an Retinitis pigmentosa erblindeten angeboren Taubstummen, Z. Ohrenheilkd., 54 (1907) 265-280. 21 Usher, C.H., On the inheritance on retinitis pigmentosa, with notes of cases, R. Lond, Ophthahuol. Hosp. Rep., 19 (1914) 130-236. 22 Vernon, M., Usher’s syndrome - deafness and progressive blindness. Clinical cases, prevention, theory and literature survey, J. Chron. Dis., 22 (1959) 133-151. 23 Van Graefe, A., Vereinzelte Beobachttmgen und Bemerkungen exceptionelles verhalten des Gesichtsveldes bei Pigmentenartung der Netzhaut, AIbrecht von Graefe’s Arch. IUin. OphthaImol., 4 (1858) 250-253.