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NR 10-12/2008
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Usher’s syndrome –
case report
Zespół Ushera – opis
przypadku
Sława Kwiecień, Robert Sulak, Jerzy
Szaflik
Department of Ophthalmology Medical University of Warsaw, Poland
Head: Professor Jerzy Szaflik, MD, PhD |
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| Summary: |
The aim of this study is
to present a case of coincidence of sensorineural
hearing loss with chronic recurrent bilateral cystoid
macular oedema in a 32-year-old woman, who was admitted
to the clinic for deterioration of visual acuity of four
months’ duration. The patient gave a history of hearing
loss for 29 years.
Visual field examination disclosed peripheral ring
scotoma. Electrophysiological examination was performed:
pattern visual evoked response was within normal limits
and electroretinogram displayed diminished both photopic
and scotopic response. As ophthalmoscopy demonstrated no
pigment in the fundus of the eye, the findings were
consisted with diagnosis of retinitis pigmentosis sine
pigmento. The presence of loss of hearing indicated the
necessity of performing the genetic examination for
Usher’s syndrome.
In order to establish a final diagnosis of Usher’s
syndrome genetic examination must be performed, but
family history is relevant. Early investigation for
Usher’s syndrome in children with sensorineural hearing
impairment is of a great significance. The patient may
develop symptoms of retinitis pigmentosa in second or
even third decade of his life. The necessity of thorough
investigation for detecting other systemic abnormalities
should be emphasized.
There is no effective treatment of this syndrome. A
child with Usher’s syndrome requires a comprehensive
care of different medical specialties. Psychological,
educational and sociological attitude is also of a great
importance in the child development. |
| Słowa kluczowe: |
Usher’s syndrome,
bilateral cystoid macular oedema, sensorineural hearing
loss, genetic disorder. |
| Key words: |
Zespół Ushera, obuoczny
torbielowaty obrzęk plamek, niedosłuch typu odbiorczego,
choroby genetyczne. |
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Purpose
The aim of this study is to present a case of coincidence of
sensorineural hearing loss with chronic recurrent bilateral
cystoid macular oedema in a 32-year-old woman.
Clinical description
In February 2006, a 32-year-old woman was admitted to the clinic
for deterioration of visual acuity of four months’ duration.
Bilateral central retinitis was diagnosed in outpatient
department. The patient gave a history of hearing loss for 29
years. It was probably caused by administration of gentamycin in
neonatal period. Audiological examination disclosed
sensorineural hearing loss. Physical examination showed
decreased visual acuity to 0.4 in right eye and up to 0.6 in
left eye. Anterior segment was normal. Indirect ophthalmoscopy
showed pink, of a distinct boarders optic disc, c/d ratio 0.4,
constricted vessels, attached, pink retina, cystoid macular
oedema and lattice degenerations in peripheral part of retina.
Fluorescein and indocyanine green angiography was
non-contributory. OCT examination proved the presence of
cystoids macular eodema. The central retinal thickness is 350 µm
in right eye and 362 µm in left eye. Systemic, connective tissue
and animal borne diseases diagnostic investigations were non-
contributory. The patient was administered Encorton in daily
doses of 35 mg, Diuramid in two equal doses of 250 mg and
Kalipoz 3 tablets daily. The treatment was initiated orally. The
patient’s uneventful recovery and regression of macular eodema
were fallowed by gradual reduction of the medicaments dosage. In
a result recurrence of the symptoms were observed after a month.
After readministration of the Diuramid and Kalipoz the symptoms
and signs subsided rapidly. Attempt of discontinuing of the
treatment resulted in recurrence of the macular oedema. For next
18 months visual acuity was between 0.3 and 1.0, the central
macular thickness was between 201 µm and 446 µm depending on
oral trealtment. In December 2007 Lucentis in a dose of 0,5 mg
was administered intravitreously in the right eye which caused
complete reduction of macular oedema with increase in visual
acuity up to 1.0 of two and half months’ duration. In January
2008 Avastin in a dose of 1.25 mg was injected intravitreously
in the left eye. Reinjection of Lucentis in the right eye was
performed in March 2008. Both the injections caused regression
of oedema of macula. As the rise in intraocular pressure up to
60 mm Hg was noted during a treatment of both medications, the
glaucoma investigations were ordered. Phasing did not revealed
anything specific: right eye: 12-16 mm Hg, left eye: 12-18 mmHg.
Visual field examination disclosed peripheral ring scotoma.
Electrophysiological examination was decided to perform: pattern
visual evoked response was within normal limits and
electroretinogram displayed diminished both photopic and
scotopic response. The results of this examination are probably
suggestive of retinitis pigmentosa. As ophthalmoscopy
demonstrated no pigment in the fundus of the eye, the findings
were consisted with diagnosis of retinitis pigmentosis sine
pigmento. The presence of loss of hearing indicated the
necessity of performing the genetic examination for Usher’s
syndrome (Fig. 1-4).
Usher’s syndrome is a disorder inherited in an recessive pattern.
It is characterised by the presence of sensorineural hearing
loss and retinitis pigmentosa. Apart from that other disorders
may be developed (1).
The three types of the Usher’s syndrome are distinguished:
• Type 1 – profound inborn bilateral deafness, difficulties in
maintaining the balance due to disturbance of vestibular system
function, retardation in developing motor skills, speech
impediment, retinitis pigmentosa;
• Type 2 – moderate to severe hearing loss with no balance
disturbances, retinitis pigmentosa;
• Type 3 – normal hearing at birth with progressive hearing loss,
vestibular dysfunction may occur (2,3).
The presence of retinitis pigmentosa in Usher’s syndrome cause
the following symptoms: deterioration of scotopic vision,
restricted visual field by peripheral scotomas (tunnel vision),
diminished contrast sensitivity, decreased visual acuity due to
the presence of posterior subcapsular cataract in advanced
stages of the disease. Direct ophthalmoscopy showes vessel
constriction, pallor of the optic disc, clumps of pigment in
peripheral retina. Histophatological examination discloses
excessive lipid accumulation in retina as well as in Corti’s
organ (4,5).
Epidemiology
Carrier state rate of genes causing Usher’s syndrome amounts 1:
70 in human population. As results of autosomal recessive
disorders the chance for inheritance a disease is 25%.
The Usher’s syndrome results from chromosomal mutations of the
following genes:
• Type 1: CDH 23, CLRN1, GPR 98, MYO7A, PCDH15, USH1C, USH1G and
USH2A;
• Type 2: USH2A and GPR78 (also called VLGR1) and DFNB31;
• Type 3: CLRN1 (1,6,7,8).
Usher’s syndrome is responsible for 3-6% children’s deafness. It
occurs in 4 to 100 000 cases. II type of Usher’s syndrome is
most frequent. The third type appears in only small number of
cases. The incidence of this syndrome like other recessive
diseases correlates with a high degree of relation (9).
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Diagnosis
In order to establish a final diagnosis of Usher’s syndrome
genetic examination must be performed. Hearing loss accompanied
by retinitis pigmentosa is not sufficient for Usher’s syndrome
diagnosis, to be established. The following examinations should
be performed: ophthalmoscopy, visual field test to detect
peripheral vision defect, an electroretinogram (ERG) (10,11,12).
In case of suspicion of the genetically related hearing loss
with the presence of retinitis pigmentosa an accurate physical
systemic examination should be performed especially taking into
account the evidence of dysmorphy. Family history is relevant.
Early investigation for Usher’s syndrome in children with
sensorineural hearing impairment is of a great significance. The
patient may develop symptoms of retinitis pigmentosa in second
or even third decade of his life. The necessity of thorough
investigation for detecting other systemic abnormalities should
be emphasized (13,14,15).
Conclusions
There is no effective causal treatment of this syndrome.
A child with Usher’s syndrome requires a comprehensive care of
different medical specialties. Psychological, educational and
sociological attitude is also of a great importance in the child
development (14,16,17,18).
References:
1. Becirovic E, Ebermann I, Nagy D, Zrenner E, Seeliger MW, Bolz
HJ: Usher syndrome type 1 due to missense mutations on both
CDH23 alleles: investigation of mRNA splicing. Hum Mutat. 2008
Mar, 29(3), 452 tigation of mRNA splicing.
2. Ouyang XM, Yan D, Du LL, Hejtmancik JF, Jacobson SG, Nance
WE, Li AR, Angeli S, Kaiser M, Newton V, Brown SD, Balkany T,
Liu XZ: Characterization of Usher syndrome type I gene mutations
in an Usher syndrome patient population. Hum Genet. 2005 Mar,
116(4), 292-299. Epub 2005 Jan 20.
3. Maubaret C, Hamel C: Genetics of retinitis pigmentosa:
metabolic classification and phenotype/genotype correlations. J
Fr Ophtalmol. 2005 Jan, 28(1), 71-92.
4. Tsilou ET, Rubin BI, Caruso RC, Reed GF, Pikus A, Hejtmancik
JF, Iwata F, Redman JB, Kaiser-Kupfer MI: Usher syndrome
clinical types I and II: could ocular symptoms and signs
differentiate between the two types? Acta Ophthalmol Scand. 2002
Apr, 80(2), 196-201.
5. Edwards A, Fishman GA, Anderson RJ, Grover S, Derlacki DJ:
Visual acuity and visual field impairment in Usher syndrome.
Arch Ophthalmol. 1998 Feb, 116(2), 165-168.
6. Roux AF: Molecular updates on Usher syndrome. J Fr Ophtalmol.
2005 Jan, 28(1), 93-97.
7. Reiners J, Nagel-Wolfrum K, Jürgens K, Märker T, Wolfrum U:
Molecular basis of human Usher syndrome: deciphering the meshes
of the Usher protein network provides insights into the
pathomechanisms of the Usher disease. Exp Eye Res. 2006 Jul,
83(1), 97-
-119. Epub 2006 Mar 20.
8. Ahmed ZM, Riazuddin S, Riazuddin S, Wilcox ER: The molecular
genetics of Usher syndrome. Clin Genet. 2003 Jun, 63(6),
431-444.
9. Nájera C, Beneyto M, Millán JM: Usher syndrome: an example of
genetic heterogeneity. Med Clin (Barc). 2005 Oct 1, 125(11),
423-427.
10. Keats BJ, Corey DP: The usher syndromes. Am J Med Genet.
1999 Sep 24; 89(3), 158-166.
11. Mendieta L, Berezovsky A, Salomăo SR, Sacai PY, Pereira JM,
Fantini SC: Visual acuity and full-field electroretinography in
patients with Usher’s syndrome. Arq Bras Oftalmol. 2005 Mar-Apr,
68(2), 171-176. Epub 2005 May 18.
12. Fishman GA, Bozbeyoglu S, Massof RW, Kimberling W: Natural
course of visual field loss in patients with Type 2 Usher
syndrome. Retina. 2007 Jun, 27(5), 601-608.
13. Iannaccone A, Kritchevsky SB, Ciccarelli ML, Tedesco SA,
Macaluso C, Kimberling WJ, Somes GW: Kinetics of visual field
loss in Usher syndrome Type II. Invest Ophthalmol Vis Sci. 2004
Mar, 45(3), 784-792.
14. Mets MB, Young NM, Pass A, Lasky JB: Early diagnosis of
Usher syndrome in children. Trans Am Ophthalmol Soc. 2000, 98,
237-
-242; discussion 243-245.
15. Petit C: Usher syndrome: from genetics to pathogenesis. Annu
Rev Genomics Hum Genet. 2001, 2, 271-297.
16. Seeliger M, Pfister M, Gendo K, Paasch S, Apfelstedt-Sylla
E, Plinkert P, Zenner HP, Zrenner E: Comparative study of visual,
auditory, and olfactory function in Usher syndrome. Graefes Arch
Clin Exp Ophthalmol. 1999 Apr, 237(4), 301-307.
17. Blanchet C, Roux AF, Hamel C, Ben Salah S, Artières F,
Faugère V, Uziel A, Mondain M: Usher type I syndrome in children:
genotype/phenotype correlation and cochlear implant benefits.
Rev Laryngol Otol Rhinol (Bord). 2007, 128(3), 137-143.
18. Sadeghi AM, Eriksson K, Kimberling WJ, Sjöström A, Möller C:
Longterm visual prognosis in Usher syndrome types 1 and 2. Acta
Ophthalmol Scand. 2006 Aug, 84(4), 537-544.
Praca wpłynęła do redakcji 28.08.2008 r. (1064)
Zakwalifikowano do druku 20.10.2008 r.
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Fig.1. CT scan of the left orbital tumor
Fig.2. Two parts of palpebral and orbital
after tumor removal.
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Fig.1. CT scan of the left orbital tumor
Fig.2. Two parts of palpebral and orbital
after tumor removal.
Fig.2. Two parts of palpebral and orbital
after tumor removal.
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