Association of optic atrophy and type 1 diabetes: clinical ... · José Luiz Pedroso et al. Optic...
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466 DOI: 10.1590/0004-282X20150021 IMAGES IN NEUROLOGY Association of optic atrophy and type 1 diabetes: clinical hallmarks for the diagnosis of Wolfram syndrome Associação de atrofia óptica e diabetes tipo 1: marcadores clínicos para o diagnóstico da síndrome de Wolfram José Luiz Pedroso 1 , Leandro Tavares Lucato 2,3 , Fernando Kok 4 , Juliana Sallum 5 , Orlando G. P. Barsottini 1 , Acary Souza Bulle Oliveira 1 A 25-year-old woman presented with a 3-year history of progressive visual loss. She had type 1 diabetes mellitus (DM1) since 18-year-old. Fundoscopy showed atrophic op- tic discs (Figure 1). MRI disclosed bilateral optic nerve atro- phy (Figure 2). Optic coherence temography demonstrated disease progression (Figure 3). Exome sequencing disclosed two deleterious mutations in WFS gene [the novel variant c.1228_1231delCTCT (p.Leu410Leufs*31) and the already reported mutation 1 c.472 G>A (p.Glu158Lys)], confirming Wolfram syndrome (WFS). Full consent was obtained from the patient for the case publication WFS is a rare autosomal recessive disease characterized by DM1, optic atrophy, deafness, and diabetes insipidus 2,3 . e coexistence of DM1 and optic atrophy suggest WFS but molecular confirmation is mandatory 4 . Besides optic atrophy, MRI findings in WFS may include hyperintense signal in pons and in optic tracts, brainstem atrophy and absence of neuro- hypophyseal “bright signal” 5 . 1 Universidade Federal de São Paulo, Departamento de Neurologia, Sao Paulo SP, Brazil; 2 Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neuroradiologia, Sao Paulo SP, Brazil; 3 Centro de Diagnósticos Brasil, Sao Paulo SP, Brazil; 4 Mendelics Análises Genômicas, Sao Paulo SP, Brazil; 5 Universidade Federal de São Paulo, Departamento de Oftalmologia, Sao Paulo SP, Brazil. Correspondence: José Luiz Pedro; Avenida Onze de Junho, 582 / ap. 131; 04041-002 São Paulo SP, Brasil; E-mail: [email protected] Conflict of interests: There is no conflict of interest to declare. Received 20 November 2014; Received in final form 02 January 2015; Accepted 22 January 2015. Figure 1. Fundus image discloses marked bilateral atrophic optic discs with temporal pallor. RE LE
Transcript of Association of optic atrophy and type 1 diabetes: clinical ... · José Luiz Pedroso et al. Optic...
466
DOI: 10.1590/0004-282X20150021
IMAGES IN NEUROLOGY
Association of optic atrophy and type 1 diabetes: clinical hallmarks for the diagnosis of Wolfram syndromeAssociação de atrofia óptica e diabetes tipo 1: marcadores clínicos para o diagnóstico da síndrome de WolframJosé Luiz Pedroso1, Leandro Tavares Lucato2,3, Fernando Kok4, Juliana Sallum5, Orlando G. P. Barsottini1, Acary Souza Bulle Oliveira1
A 25-year-old woman presented with a 3-year history of progressive visual loss. She had type 1 diabetes mellitus (DM1) since 18-year-old. Fundoscopy showed atrophic op-tic discs (Figure 1). MRI disclosed bilateral optic nerve atro-phy (Figure 2). Optic coherence temography demonstrated disease progression (Figure 3). Exome sequencing disclosed two deleterious mutations in WFS gene [the novel variant c.1228_1231delCTCT (p.Leu410Leufs*31) and the already reported mutation1 c.472 G>A (p.Glu158Lys)], confirming
Wolfram syndrome (WFS). Full consent was obtained from the patient for the case publication
WFS is a rare autosomal recessive disease characterized by DM1, optic atrophy, deafness, and diabetes insipidus2,3. The coexistence of DM1 and optic atrophy suggest WFS but molecular confirmation is mandatory4. Besides optic atrophy, MRI findings in WFS may include hyperintense signal in pons and in optic tracts, brainstem atrophy and absence of neuro-hypophyseal “bright signal”5.
1Universidade Federal de São Paulo, Departamento de Neurologia, Sao Paulo SP, Brazil;2Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neuroradiologia, Sao Paulo SP, Brazil;3Centro de Diagnósticos Brasil, Sao Paulo SP, Brazil;4Mendelics Análises Genômicas, Sao Paulo SP, Brazil;5Universidade Federal de São Paulo, Departamento de Oftalmologia, Sao Paulo SP, Brazil.
Correspondence: José Luiz Pedro; Avenida Onze de Junho, 582 / ap. 131; 04041-002 São Paulo SP, Brasil; E-mail: [email protected]
Conflict of interests: There is no conflict of interest to declare.
Received 20 November 2014; Received in final form 02 January 2015; Accepted 22 January 2015.
Figure 1. Fundus image discloses marked bilateral atrophic optic discs with temporal pallor.
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467José Luiz Pedroso et al. Optic atrophy and DM1: Wolfram syndrome
Figure 2. MRI of Wolfram patient (A, C, E) compared with an age-matched healthy subject (B, D, F). Coronal T2-weighted image using fat saturation (A) demonstrates striking hypoplasia of both optic nerves in the orbits (arrows); note the normal appearance in the healthy subject (B). The same sequence in the axial plane shows the same finding in the patient (C - arrows), compared to the normal aspect (D). Optic chiasm is also hypoplastic in Wolfram patient, demonstrated in a coronal post-contrast T1-weighted image (E - arrow), while a normal optic chiasm is appreciated in the healthy subject (F - arrow).
A C
E
B
D F
Figure 3. Optic coherence tomography measure around the disc showing thin retina, mainly thin nerve fiber layer performed at two dates (Nov 05th 2012 and May 21st 2014). Comparing both exams one can see progressive decrease on the retina thickness (Continua).
0TMP NAS
Position(*)
Baseline 05/nov/2012
Classification
INP TMPSUP
300240180120
600
45 90 135 180 225 270 315 360
0TMP NAS
Position(*)INP TMPSUP
300240180120
600
45 90 135 180 225 270 315 360Outside Normal Limits
TO64
T34
N20
Q42
NS56
TI70
NI41
200 µm200µm
0TMP NAS
Position(*)
Follow-up #1 21/mai/2014
Classification
INP TMPSUP
300240180120
600
45 90 135 180 225 270 315 360
0TMP NAS
Position(*)INP TMPSUP
300240180120
600
45 90 135 180 225 270 315 360Outside Normal Limits
TS60
T33
N20
Q40
NS56
TI64
NI36
200 µm200 µm
RE
468 Arq Neuropsiquiatr 2015;73(5):466-468
Figure 3. (Continuação) Optic coherence tomography measure around the disc showing thin retina, mainly thin nerve fiber layer performed at two dates (Nov 05th 2012 and May 21st 2014). Comparing both exams one can see progressive decrease on the retina thickness.
0TMP NAS
Position(*)
Baseline 05/nov/2012
Classification
INP TMPSUP
300240180120
600
45 90 135 180 225 270 315 360
0TMP NAS
Position(*)INP TMPSUP
300240180120
600
45 90 135 180 225 270 315 360 Outside Normal Limits
NS54
N9
T29
Q36
TS60
NI47
TI50
200 µm200µm
0TMP NAS
Position(*)
Follow-up #1 21/mai/2014
Classification
INP TMPSUP
300240180120
600
45 90 135 180 225 270 315 360
0TMP NAS
Position(*)INP TMPSUP
300240180120
600
45 90 135 180 225 270 315 360 Outside Normal Limits
NS47
N5
T29
Q33
TS60
NI40
TI48
200 µm200 µm
LE
References
1. Gasparin MR, Crispim F, Paula SL, Freire MBS, Dalbosco IS, Manna TD et al. Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome. Eur J Endocrinol. 2009;160(2):309-16. http://dx.doi.org/ 10.1530/EJE-08-0698
2. Marshall BA, Permutt MA, Paciorkowski AR, Hoekel J, Karzon R, Wasson J et al. Phenotypic characteristics of early Wolfram syndrome. Orphanet J Rare Dis. 2013;8:64. http://dx.doi.org/10.1186/1750-1172-8-64
3. Zmysłowska A, Borowiec M, Fendler W, Jarosz-Chobot P, Myśliwiec M, Szadkowska A et al. The prevalence of Wolfram syndrome
in a paediatric population with diabetes. Endokrynol Pol. 2014;65(4):295-7. http://dx.doi.org/10.5603/EP.2014.0040
4. Zmyslowska A, Borowiec M, Fichna P, et al. Delayed recognition of Wolfram syndrome frequently misdiagnosed as type 1 diabetes with early chronic complications. Exp Clin Endocrinol Diabetes. 2014;122(1):35-8. http://dx.doi.org/10.1055/s-0033-1357160
5. Gocmen R, Guler E. Teaching NeuroImages: MRI of brain findings of Wolfram (DIDMOAD) syndrome. Neurology. 2014;83(24):e213-4. http://dx.doi.org/10.1212/WNL.0000000000001082
