Enfermedades heredo

degenerativas de la retina
Presentacin Sociedad Argentina de Retina
y Vtreo
Abril 2016
CARGO
Dr PERDOMO
Strasbourg
 Edad de aparicin
Distrofias retinianas/ de la infancia

Distrofias retinianas / adulto joven

Fenotipos tardos
 ?
Caso espordico/ familiar

Consanguinidad, origine tnico, modo de

transmisin

Retinopata aislada/ contexto sindrmico

Patologa estacionaria o evolutivo

Proyecto parental (grado de urgencia)

 Sntomas y signos oftalmolgicos
photophobie
hespranopie
AV
Alt. de la vision des couleurs
photopsies
mtamorphopsies
nystagmus
apraxie oculomotrice/ strabisme
mouvements erratiques des yeux
signe de Franceschetti
troubles du CV
Ptosis
Pleur papillaire
 Sntomas y signos extra-
oftalmolgicos
Polydactylie
Obsit
Retard psychomoteur
Anomalies morphologiques rnales/ IRC
Anomalies morphologiques lIRM crbrale
Dficience auditive
Cardiomyopathie/ altrations du rythme
Ataxie
Difficults dapprentissage
Hypotonie
Anomalies dentaires
Anomalies des organes gnitaux
Etc
 Examen oftalmolgico
AV, fixation centrale ou excentre
Rfraction (hypermtropie forte, myopie, emmtropie)
S.A (Iris, cristallin, etc)
FO dilat (ophtalm. Indirect, verres)
CV Goldmann, Humphrey
OCT, FAF
Micro-primtrie
Examen des apparents (DR lies lX +++, AR, AD)
Electrophysiologie (ERG, PERG, EOG, mfERG, PEV) Dg
fonctionnel +++
 The electroretinogram (ERG) is a mass potential, which
reflects the summed electrical activity of the retina.
http://www.iscev.org/standards

Full-field electroretinography is a well- The multifocal ERG (mfERG) technique provide a

established clinical technique for evaluating
global retinal function
topographic measure of retinal electrophysiological
activity
Many local ERG responses, typically 61 or 103, are
recorded from the cone-driven retina under light
adapted conditions
mfERG test does not replace the full-field ERG test
the retina is stimulated with an array of hexagonal
elements

Fixation targets Stable fixation is essential for

obtaining reliable mfERG recordings.

Espion Profile System

Pattern electroretinogram (PERG) is a retinal biopotential evoked by a temporally modulated

patterned stimulus (e.g. checkerboard or grating) of constant mean luminance.
PERG arises largely in the ganglion cells, driven by the photoreceptors and corresponding retinal
cells. Since the PERG (in contrast to the flash ERG) is a local response from the area covered by
the retinal stimulus image, it can be used as a sensitive indicator of dysfunction within the
macular region and it reflects the integrity of the optics, photoreceptors, bipolar cells and
retinal ganglion cells
 rod-driven response
of on bipolar cells

combined responses arising from responses primarily from

photoreceptors and bipolar cells of amacrine cells
both the rod and cone systems; rod combined response with
dominated enhanced a-waves
reflecting photoreceptor
function

a-waves arise from cone a sensitive cone-pathway-driven response

photoreceptors and cone Off-
bipolar cells; the b-wave comes
from On- and Off-cone bipolar cells

http://www.iscev.org/standards
Lower ERG amplitudes and longer peak
times generally apply below 612 months
of age under dark-adapted conditions, and
below 23 months of age under light-
adapted conditions. Below 6 months of
age, the Dark-adapted 3 ERG may be poorly
defined in healthy infants; Dark-adapted
10 ERGs are usually well defined in infants
without retinal disease at all ages.
 PERG/ mfERG

ERG

PERG

mfERG
Standardization of ERG reporting is critical to the goal of having comparable data
worldwide.
EOG: Electrophysiology of the outer retina in dark and light.

There is a difference in electrical potential between the

front and back of the eye, sometimes called the corneo-
fundal potential or standing potential.
This potential is mainly derived from the retinal pigment
epithelium (RPE), and it changes in response to background
levels of retinal illumination.
The potential decreases for 810 min after switching to
darkness. Subsequent retinal illumination causes an initial
fall in the standing potential over 6075 s (the fast
oscillation), followed by a slow but larger rise over 714
min (the light response).
These phenomena arise from ion permeability changes
across ion channels in the basal RPE membrane that are
controlled (at least in part) by the bestrophin gene.

Arden ratios <1.5 are generally reported as

abnormally low, and those >2.0 are generally
reported as normal; ratios between 1.5 and
2.0 may be reported as borderline.
 Abnormal pattern VEP

PERG

Normal PERG Abnormal PERG

Normal P50/
Abnormal P50
Abnormal N95

ERG

Normal ERG Abnormal ERG

Optic nerf dysfunction Macular dysfunction Retinal dysfunction

Distrofias retinianas
evolutivas
El problema de la gran heterogeneidad
gentica y fenotpica
 Htrognit gntique
Un phnotype = plusieurs gnes responsables

62 gnes de RP :
(50% des cas muts)

24 AD
RHO : 20-30%

36 AR
USH2A : 10-15%
ABCA4 : 2-5%

2 LX
 Amaurose congnitale de Leber NOL
1869/ Theodor Karl Gustav von Leber/ Allemagne
phnotype + svre et prcoce de DR, congnital
Dg: 1er. Anne de vie
Origine gntique: AR, affect. Rare
Htrognit gntique (22 gnes/2015) et phnotypique
TC: AV , nystagmus, RPMs alt / absents, signe oculo- digitale de Franceschetti,
photophobie, hypermtropie majeure, kratocne
FO: normal / poivre et sel/ RP, etc
Corrlation G/Ph: colobome maculaire: AIPL1, RDH12, NMNATI1,
dpts punctiformes blanchtres et atrophie maculaire stellaire
RPE65, preserved para-arteriolar RPE CRB1
ERG: / absence totale de rponses
 ACL

NMNAT1
Koenekoop et al. (2012) reexamined affected individuals from 8 families with Leber congenital amaurosis in whom they had identified
mutations in the NMNAT1 gene (608700), which is ubiquitously expressed. All individuals with biallelic NMNAT1 mutations had severe
LCA but otherwise normal physical and mental health. However, in addition to the typical LCA phenotype all patients were found to have a
peculiar, prominent retinal feature termed 'macular coloboma,' which consists of an atrophic lesion in the central retina with a pigmented
border, signifying complete loss of neural tissue in the fovea, including photoreceptors, bipolar cells, and ganglion cells. Based on these
findings, Koenekoop et al. (2012) suggested that NMNAT1 mutations are associated with severe and rapid foveal degeneration.
ACL

RD3

Friedman et al. (2006) found that mouse Rd3 is preferentially expressed in the retina and
exhibits increasing expression through early postnatal development
 ACL
RDH12

ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100

1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS]
Vm 2. 0
viD

Vm 2. 0
viD

-0.4 -0.4

0.4 0.4 0.4 0.4 100 100 100 100

-0.2 -0.2
O1 O2 O1 O2
0 0

0.2 0.2 0.2 0.2 0.2 0.2 50 50 50 50

0.4 0.4
b
0 0 3-OP [OD] 4-OP [OS] 0 0 0 0 0 b 0
b b
ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100 b b Peak
Peak
a a a a a
a Trough Trough
Vm 2. 0
viD

Vm 2. 0
viD

-0.4 -0.4
-0.2 -0.2 -0.2 -0.2 -50 -50 -50 -50
-0.2 -0.2
a ba
b
0 0
-0.4 -0.4 -0.4 -0.4 -100 -100 -100 -100
0.2 0.2
0.2mV

0.2mV

0.4 0.4
0.2mV

0.2mV

50V

50V

50V

50V
Div

Div

Div

Div

Div

Div
Div

Div

1 [OD] 2 [OS]
ms 0 50 100 150 200 ms 0 50 100 150 200 ms 0 50 100 150 200 ms 0 50 100 150 200 ms 0 20 40 60 80 100 ms 0 20 40 60 80 100 ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100
 CEP290

1-Chan 1 [OS]

40

20

0 1(OS)
2(OS)
B
B
A A

-20

-40
20V
Div

ms 0 50 100 150 200

 1-Chan 1 [OS] 1-Chan 1 [OS]
0.4 1-Chan 1 [OS]

200 0.2
0 200
-0.2 B
0.2mV

100 A
100
-0.4
Div

0 A ms 0 50 100 150 200 250 0 B

2-Chan 2 [OD]
0.4
-100 -100
0.2
0
-200 -0.2 B -200
A
100V

0.2mV

A
100V

-0.4
Div
Div

Div

ms 0 50 100 150 200 250ms 0 50 100 150 200 250 ms 0 50 100 150 200 250
2-Chan 2 [OD] 3-Virt.Chan1 [OS] 2-Chan 2 [OD]
100
200 50
200
0
-50
100 100
50V

-100
Div

0 B
ms 0 50 100 150 200 250 0 B
A 4-Virt.Chan2 [OD]
100
-100 50 -100
0 A
-200 -50 -200
100V

100V
50V

-100
Div
Div

Div

ms 0 50 100 150 200 250ms 0 50 100 150 200 250 ms 0 50 100 150 200 250

Mutacion CRB1 / A.R

This gene encodes a protein which is similar to the Drosophila crumbs protein and localizes to the inner segment of mammalian
photoreceptors. In Drosophila crumbs localizes to the stalk of the fly photoreceptor and may be a component of the molecular scaffold that
controls proper development of polarity in the eye. Mutations in this gene are associated with a severe form of retinitis pigmentosa and with
Leber congenital amaurosis. Alternate splicing results in multiple transcript variants, some protein coding and some non-protein coding.
MFRP-related oculopathy
Rtinopathie pigmentaire
Rod-cone dystrophy
2014 2015
 1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS]
1-Chan 1 [OS]

0.4 200 100

200

100 0.2 100 50

B
0 1(OS) 0 1(OS)
0 1(OS) 0 1(OS) B
B
A A
B A
-100 -0.2 A
-100 -50

-200 -0.4 -200 -100

0.2mV

100V
100V

50V
Div

Div
Div
Div
ms 0 50 100 150 200 250ms 0
2-Chan 2 [OD]
50 100 150 200 ms 0 250 50 100 150 200 250 ms 0 25 50 75 100
2-Chan 2 [OD] 2-Chan 2 [OD] 2-Chan 2 [OD]

200 0.4 200 100

100 0.2 100 50

B
0 1(OD) 0 1(OD)
0 1(OD) 0 1(OD) B
B
A A
B A
-100 -0.2 A
-100 -50

-200 -0.4 -200 -100

0.2mV
100V

100V

50V
Div
Div

Div
Div
ms 0 50 100 150 200 250ms 0 50 100 150 200 ms 0 250 50 100 150 200 250 ms 0 25 50 75 100

1-Chan 1 [OS] 1-Chan 1 [OS]

200 200

100 100

In RP, the rod-driven (scotopic) responses are 0

-100
1(OS) 0

-100
1(OS)

A
B

-200 -200

equally or more severely reduced than cone-

100V
100V

Div
Div
ms 0 50 100 150 200 250 ms 0 50 100 150 200 250
2-Chan 2 [OD] 2-Chan 2 [OD]

driven (photopic) responses, whereas in early

200 200

100 100

0 1(OD) 0 1(OD)

CRD there are normal rod responses and -100

-200
-100

-200
A
B

100V
100V

Div
Div

substantially reduced cone responses,

1-Chan 1 [OS] 1-Chan 1 [OS]

ms
200
0 50 100 150 100
200 250 ms 0 50 100 150 200 250

100 50

0 1(OS) 0 1(OS) B
B
A A

although rod responses will deteriorate as

-100 -50

-200 -100
100V

50V
Div

Div
ms 0 50 100 150 200 250 ms 0 25 50 75 100
2-Chan 2 [OD] 2-Chan 2 [OD]

the disease progresses.

200 100

100 50

0 1(OD)
0 1(OD)
B
A B
A
-100 -50

-200 -100
100V

50V
Div

Div
ms 0 50 100 150 200 250 ms 0 25 50 75 100
 RP lie lX

XY XX
RPGR
RP2

XY XY
 II II

II II
EMC y RP
RP sans pigment
 Dbut des signes 13 ans
AV : OD 4/10e P10; OG 10/10e P1,5
 ERG : teint droite et normal gauche.
 Dystrophie de cnes avec hyper- rponse des btonnes

KCNV2 /A.R

1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS]
1 [OD] 2 [OS] 1 [OD] 2 [OS]
0.4
B
200 300 200 0.2 200 B
B 0 B

100 200 100 -0.2 100

0.2mV

-0.4 A 100 100 100 100

Div

0 100 0 0
B ms 0 50 100 150 200 250
2-Chan 2 [OD]
-100 0 -100 0.4 -100
A 0.2 50 50 50 50
A
-200 -100 -200 0 B
-200
100V
100V

-0.2 b
100V

100V
0.2mV

1(OS)
Div
Div

b
-0.4 A 1(OD)
Div

A 3A(OD)
Div

2(OD) 3A(OS)
Div

2(OS)
ms 0 50 100 150 200 250
ms 0 50 100 150 200 ms
250 2-Chan 2 0[OD] 50 100 150 200 250 Peak Peak 2(OS)
250 ms 0 50 100 150 200 250 0 0 0 1(OD) 0 3A(OS)
2-Chan 2 [OD] 2-Chan 2 [OD] ms 0 50 100 150 200 2-Chan 2 [OD]
3A(OD)
2(OD) 1(OS)
3-Virt.Chan1 [OS]
100
200 300 200 B B Trough a
50 200 Trough a
0
100 200 100 -50 -50 -50 -50 -50
B 100
50V

-100
Div

0 100 0
B 0
ms 0 50 100 150 200 250
-100 0 -100 4-Virt.Chan2 [OD]
A 100 -100 -100 -100 -100 -100
A
50
-200 -100 -200 0
100V

-200
100V
100V

-50
100V
Div

Div
Div

50V

50V

50V

50V

50V
-100 A
Div
Div

Div

Div

Div

Div
ms 0 50 100 150 200 250 ms 0 50 100 150 200 250
ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0
ms 0 50 100 150 200 250 20 40 60 80 100 ms 0 20 40 60 80 ms
100-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100
 ABCA4
Stargardt
 II II
RDS

RP

II II
 Rtinoschisis lie lX

RS1 is the only gene known to be

associated with X-linked juvenile
retinoschisis
Retinoschisin-Na/K ATPase-SARM1 complex. The binding of
retinoschisin to the Na/K ATPase 2-subunit induces oligomerization of
Na/K ATPase and the binding and/or activation of SARM1 to the
cytoplasmic side of the Na/K ATPase. This complex is postulated to be
important in maintaining cell and synaptic structure and function
possibly through its effect on the cytoskeletal elements in the cell. This
in turn can affect how cells interact with the extracellular matrix to
maintain retinal cell organization.
 Rtinoschisis lie lX

1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS]

0.4 0.4
200 200
200 200 0.2 0.2 100 100 100 100

0 0
100 100
b b
-0.2 -0.2
100 100 a
50 50 50 50
a
b
-0.4 -0.4
0.2mV

0.2mV

Peak Peak b b
0 0
Div

Div

0 0 ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100 0 0 0 0

a 3-OP [OD] 4-OP [OS]
b Trough
b Trough
a
40 40 -100 -100 a
a b
-100 -100 -50 -50 -50 -50
20 20

0 0
O1 O2 O1 O2
-200 -200
-200 -200 -20 -20 -100 -100 -100 -100
a

a
-40 -40
100V

100V
100V

100V

-300 -300
50V

50V

50V

50V
20V

20V

Div

Div

Div

Div
Div

Div
Div

Div

Div

Div

ms 0 50 100 150 200 ms 0 50 100 150 200 ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100 ms 0 50 100 150 200 ms 0 50 100 150 200 ms 0 20 40 60 80 100 ms 0 20 40 60 80 100 ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100
P/ I. Rtinoschisis lie lX
 Goldmann
Favre
NR2E3/ AR

Vitreoretinal dystrophy that manifests

with early onset of night blindness,
atypical pigmentary dystrophy of the
retina, degenerative changes in the
vitreous humor, peripheral and, less
often, central retinoschisis, lens
opacities, and an enhanced S-cone
response on electroretinography (ERG)
1-Chan 1 [OS] 1-Chan 1 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS]

200 200

100 100 100 100 100 100

0 0
A B

-100 B
-100 50 50
50 50
-200 -200 A b
100V

100V
Div

Div

ms 0 0
0 50 100 150 200 250 ms 0 50 100 150 200 250 0 0 b Peak
Peak
2-Chan 2 [OD] 2-Chan 2 [OD] Trough
Trough
200 200
a
a
100 -50 -50 -50 -50
100

0 0
A B

-100 -100
B
-100 -100 -100 -100

A
-200 -200
100V

100V

50V

50V
50V

50V
Div

Div

Div
Div

Div

Div

ms 0 50 100 150 200 250 ms ms 0 20 40 60 80 100 ms 0 20 40 60 80 100

0 50 100 150 200 250ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100
From: Expanded Clinical Spectrum of Enhanced S-Cone Syndrome

JAMA Ophthalmol. 2013;131(10):1324-1330. doi:10.1001/jamaophthalmol.2013.4349

Enhased S cone syndrome

The waveforms of the
scotopic
maximal response are
similar to those of the
transient photopic
response, except for reduced
amplitudes in the a- and b-
waves;

Copyright 2015 American Medical

Date of download: 9/16/2015
Association. All rights reserved.
NR2E3/ AR
 Choroderemie/ CHM gene/ Xq21.2

XY XX

XY XY
Bietti/CYP4V2/ 4q35.2/AR
Gyrate atrophy of choroid and
retina with or without
ornithinemia/ OAT/ 10q26.13
 Suspicion Sorsby

Phenotype Inheritance Phenotype Gene/Locus

Location Phenotype Gene/Locus
MIM number (in progress) mapping key MIM number

Sorsby fundus
22q12.3 136900 AD 3 TIMP3 188826
dystrophy
 TOPORS
Gene
AD

Mutations in TOPORS Cause Autosomal Dominant Retinitis Pigmentosa with Perivascular Retinal
Pigment Epithelium Atrophy
Christina F. Chakarova,* Myrto G. Papaioannou,* Hemant Khanna, Irma Lopez, Naushin Waseem, Amna Shah, Torsten Theis, James Friedman, Cecilia
Maubaret, Kinga Bujakowska, Brotati Veraitch, Mai M. Abd El-Aziz, De Quincy Prescott, Sunil K. Parapuram, Wendy A. Bickmore, Peter M. G. Munro,
Andreas Gal, Christian P. Hamel, Valeria Marigo, Chris P. Ponting, Bernd Wissinger, Eberhart Zrenner, Karl Matter, Anand Swaroop, Robert K.
Koenekoop, and Shomi S. Bhattacharya W
The American Journal of Human Genetics Volume 81 November 2007

CTRP5
(C1QTNF5) gene

Late-onset retinal degeneration

Dystrophies rtiniennes volutives
syndromiques
 S. de Joubert
Triade classique:
Signe de la dent molaire MRI / hypotonie
/ retard psychomoteur
Tachypne pisodique/ apne
Ataxie
Apraxie OM
Troubles cognitifs (variable)
Dystrophie rtinienne (RP prcoce), troubles rnaux
(nphronoptise, IRC), colobome, fibrose hpatique/ Ins hp,
Hamartomes buccaux, troubles endocriniens
AR, 19 gnes, li lX (OFD1), TTC21B mutation mono alllique
 S. de Bardet Biedl
Ciliopathie
Dystrophie rtinienne (Rod/Cone, Cone/Rod, CD)
Polydactylie post axiale
Obsit tronculaire
Troubles des apprentissages
Hypogonadisme (M)/ anomalies gnitales (F)
Anomalies rnales (IRC)
S. secondaires: retard du langage,
brachydactilye, syndactylie, troubles motionnelles,
lenteur didation, DM, anomalies cardiaques, anosmie,
etc
AR, 18 gnes
S pluridisciplinaire
 1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS]

0.4 0.4

200 200 0.2 0.2 200 200 100 100 100 100

0 b 0 b

b
-0.2 a -0.2 a
50 50 50 50
100 b 100 100 100
b
b
-0.4 -0.4
0.2mV

0.2mV

Peak Peak
Div

Div

0 0 ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100 0 b 0 0 0 0 0

a a 3-OP [OD] 4-OP [OS] b

40 40 Trough
Trough
-100 -100 -100 -100 -50 a -50 -50 -50
20 20
a
a a
0 0
O1 O2 O1 O2
-200 -200 -20 -20 -200 -200 -100 -100 -100 -100

-40 -40
100V

100V

100V

100V

50V

50V

50V

50V
20V

20V

Div

Div

Div

Div
Div

Div

Div

Div

Div

Div

ms 0 50 100 150 200 ms 0 50 100 150 ms

200-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100 ms 0 50 100 150 200 ms 0 50 100 150 200 ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100ms 0 20 40 60 80 100 ms 0 20 40 60 80 100
 S. de Alstrom
Dystrophie rtinienne prcoce, Cone/ rod, photophobie +++, 100%
(Dg Achromatopsie congnitale)
Nystagmus
Handicap visuel (1er dcennie)
Obsit tronculaire (12m) 98%
Petite taille 98%
Surdit de perception/ progressive 88%
Cardiomyopathie dilate ou restrictive 18%
S. de insulino- rsistance/ DM-T2 92% (4-30 ans)
Hypogonadisme hypogonadotropique 78% males
QI normal
Anomalies hpatiques 23 -92%
AR/ gne ALMS1
S. Pluridisciplinaire
 1 [OD] 2 [OS] 1 [OD] 2 [OS] 1 [OD] 2 [OS]

200 200 200 200 100 100

100 100 100 100 50 50

0 0 0 0 0 0

-100 -100 -100 -100 -50 -50

-200 -200 -200 -200 -100 -100

100V

100V

100V

100V

50V

50V
Div

Div

Div

Div
Div

Div

ms 0 50 100 150 200 ms 0 50 100 150 200 ms 0 50 100 150 200 ms 0 50 100 150 200 ms 0 20 40 60 80 100 ms 0 20 40 60 80 100
Cockayne syndrome (CS) is characterized by growth failure and multisystemic degeneration, with a variable
age of onset and rate of progression
ERCC6
ERCC8
Both play important roles in transcription-coupled
nucleotide excision repair (TC-NER), a DNA repair
process that preferentially removes UV-induced
pyrimidine dimers and other transcription-blocking
lesions from the transcribed strands of active
genes

Major criteria
Postnatal growth failure (height and weight <5th centile by age 2 years)
Progressive microcephaly and neurologic dysfunction manifested as early
developmental delay in most individuals, followed by progressive behavioral and
intellectual deterioration in all individuals; brain MRI reveals leukodystrophy
[Boltshauser et al 1989, Sugita et al 1992]. Intracranial calcifications are seen in some
individuals.
Minor criteria
Cutaneous photosensitivity with or without thin or dry skin or hair (~75%)
Demyelinating peripheral neuropathy diagnosed by electromyography, nerve
conduction testing, and/or nerve biopsy
Pigmentary retinopathy (~55%) and/or cataracts (~36%)
Sensorineural hearing loss (~60%)
Dental anomalies, including dental caries (~86%), enamel hypoplasia, anomalies of
tooth number and anomalies of tooth size and shape
A characteristic physical appearance of "cachectic dwarfism" with thinning of the
skin and hair, sunken eyes, and a stooped standing posture
Characteristic radiographic findings of thickening of the calvarium, sclerotic
epiphyses, vertebral and pelvic abnormalities
Usher syndrome type I is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia,
and adolescent-onset retinitis pigmentosa. Unless fitted with a cochlear implant, individuals do not typically develop
speech. MYO7A (USH1B), USH1C, CDH23 (USH1D), PCDH15 (USH1F), USH1G, and CIB2 (USH1J)

Usher syndrome type II is characterized by congenital (i.e., prelingual) bilateral sensorineural hearing loss that is mild to
moderate in the low frequencies and severe to profound in the higher frequencies, intact vestibular responses, and
retinitis pigmentosa (RP). USH2A (accounting for up to 80% of cases), GPR98 (VLGR1), and DFNB31.

Usher syndrome type III (USH3). USH3 is characterized by postlingual progressive sensorineural hearing loss, late-onset
RP, and variable impairment of vestibular function [Plantinga et al 2005]. Mutation of CLRN1 or HARS is causative [Joensuu
et al 2001, Vstinsalo et al 2011, Puffenberger et al 2012]. Persons with USH3 may have symptoms that mimic USH2,
especially early in the progression of the disease [Pennings et al 2003].
 Enf. de Refsum
Anosmie
RP prcoce
Neuropathie Sensorielle/motrice
Surdit de perception
Ataxie
Ichtyose
Cardiomyopathie
Dg +: clinique/ biologique: concentration plasmatique de Ac.
phitanique 200 mol/L
AR/ 2 gnes PHYH et PEX7
 S. Dltion de lADNm
Kearn Sayre S. (KSS)/ Pearson S./
ophtalmoplgie externe progressive (PEO)
KSS
Pathologie multi systmique
Triade: dbut < 20a, RP, ptosis, PEO (paralysies de
MExO)
1+ : troubles de la conduction cardiaque, ataxie
crbelleuse, protinorachie > 100 mg/dl
Kearn Sayre Syndrome
S. de Jalili Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis
imperfecta. Am J Hum Genet. 2009 Feb;84(2):266-73. doi: 10.1016/j.ajhg.2009.01.009. Epub 2009 Feb 5.

II II

II II
 Infrared RE Infrared LE

FAF RE

FAF LE
 Jalili Syndrome
1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS]
0.4
200 0.2 0.4 200 200
B 0 B
-0.2
100 100 100

0.2mV
A 0.2
-0.4

Div
0 ms 0 50 100 150 200 250 0 B 0 0
B B
A 2-Chan 2 [OD] A A
0.4
-100 -0.2 -100 -100
0.2 A
0 B
-200 -0.2 -0.4 -200 -200
100V

100V

100V
0.2mV

0.2mV
A
-0.4

Div
Div

Div

Div
Div
ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 25 50 75 100 ms 0 50 100 150 200 250
2-Chan 2 [OD] 3-Virt.Chan1 [OS] 2-Chan 2 [OD] 2-Chan 2 [OD] 2-Chan 2 [OD]
100
200 50 0.4 200 200
B
0
-50
100 0.2 100 100

50V
-100

Div
0 ms 0 50 100 150 200 250 0 B 0 0
4-Virt.Chan2 [OD] A B A B
A 100
-100 -0.2 -100 -100
50 A
0

1a -200 -50 -0.4 -200 -200

100V

100V

100V
0.2mV
50V

-100
Div
Div

Div

Div
Div
ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 25 50 75 100 ms 0 50 100 150 200 250

Dark-adapted 3 ERG
Dark-adapted
Dark-adapted 0,01 ERG oscillatory potentials Dark-adapted 10 ERG Light- adapted 3 ERG Light- adapted 31,25 Hz Flicker ERG
ERG
1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS]
0.4
400 0.2 0.2
200 200
B 0 1(OS) B B
300 -0.2 0 1(OS)
0.2mV

100 100
-0.4
Div

A B B
200 -0.2 2(OS)
ms 0 50 100 150 200 250 0 1(OS) 0
2-Chan 2 [OD]
100 0.4 -0.4 A A
A -100 -100
0.2
0 1(OS) 0 1(OD) B
-0.6
-0.2 -200 -200
100V

0.2mV

100V

100V
0.2mV

A -0.4
Div

-100 -0.8
Div

Div

Div

Div
A

ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 25 50 75 100 ms 0 50 100 150 200 250
2-Chan 2 [OD] 3-Virt.Chan1 [OS] 2-Chan 2 [OD] 2-Chan 2 [OD] 2-Chan 2 [OD]
100
400 B 50 0.2
200 200
0 1(OS) B
300 -50 0 1(OD)
100 B 100
50V

-100
Div

2(OD) B
200 -0.2
ms 0 50 100 150 200 250 0 1(OD) 0
4-Virt.Chan2 [OD]
100 100 -0.4 A
50 -100 A -100
A
0

1b
1(OD)
0 1(OD) -0.6
-50 -200 -200
100V

100V

100V
0.2mV
50V

A -100
Div

-100 -0.8
Div

Div

Div

Div
ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 25 50 75 100 ms 0 50 100 150 200 250

Full field ERG (ISCEV protocols) showed mild reduced rod-driven response. Marqued reduction of cone
system response was present at light adapted ERG. ERG confirmed the diagnosis of cone-rod dystrophy
classically associated in the context of Jalili Syndrome.
1a Jalili patient ERG, 1b normal ERG
 Pas tjs gntique.

1-Chan 1 [OS] 1-Chan 1 [OS] 1-Chan 1 [OS] 1 [OD] 2 [OS]

1 [OD] 2 [OS]
0.4
200 0.2 200
0 1(OS)
-0.2 A B
100
100
0.2mV

100 100
-0.4 100 100
Div

0 1(OS)
ms 0 1(OS) B
B
0 50 100 150 200 250
A 2-Chan 2 [OD] A
-100 0.4 -100
0.2 50 50
50 50
0 1(OD)
-200 -200
-0.2 B b
100V

A
100V

b
0.2mV

-0.4

CAR
Div
Div

Peak
Div

Peak
0 0
ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0
2-Chan 2 [OD]
50 100 150 200 250 0 0
2-Chan 2 [OD] 3-Virt.Chan1 [OS]
100 a a

200 50 200 Trough

Trough
0 1(OS)
-50 -50
100 -50 100 -50 -50
50V

-100
Div

0 1(OD) 0 1(OD)
B ms 0 50 100 150 200 250 B
A 4-Virt.Chan2 [OD] A
100 -100 -100 -100
-100 -100 -100
50
0 1(OD) -200
-200
100V

-50
100V

50V

50V
50V

Div

-100

50V

50V

Div

Div
Div

Div

Div

Div
ms 0 50 100 150 200 250 ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100
ms 0 50 100 150 200 250 ms 0 50 100 150 200 250 ms 0 20 40 60 80 100 ms 0 20 40 60 80 100

1-Chan 1 [OS] 1-Chan 1

1-Chan 1 [OS]
[OS] 1-Chan 1 [OS] 1 [OD] 2 [OS]
0.4 1 [OD] 2 [OS]
200 0.2
200 200
0
-0.2
100 AB 100
0.2mV

100 100 100

-0.4
Div

100 100
1(OS)
0 0
ms 0 50 100 150 200 250 0
A B 2-Chan 2 [OD]
0.4
-100 a B
-100
-100 A
B
0.2 50 50
0 50 50
b
-200 -200
-0.2 A B
-200
100V

100V
100V

0.2mV

-0.4
Div
Div
Div

a
ms 0 50 100 150 200 250 ms 0 50 100
100 150
150 200
200 250 ms
250 0 50 100 150 200 250 0 0
0 Peak 0 Peak
2-Chan 2 [OD] 2-Chan 2 [OD]
3-Virt.Chan1 [OS] 2-Chan 2 [OD]
Trough
100 Trough

200 50
200 200

MAR
0
-50 -50 -50 -50 -50
100 100 100
50V

-100 b
a
Div

0 0
ms
1(OD)
0 50 100 150 200 250 0
A B 4-Virt.Chan2 [OD]
100 -100 -100
-100 -100 a B -100 B -100 -100
50 A
0
-200 -200
-50 -200
100V

100V
100V

50V

50V

50V
-100
50V

50V
Div
Div

Div
Div

Div

Div
Div

Div

ms 0 50 100 150 200 250 ms 0 50 100

100 150
150 200
200 250
250 ms 0 50 100 150 200 250 ms 0 20 40 60 80 100 ms 0 20 40 60 80 100 ms-20 0 20 40 60 80 100 ms-20 0 20 40 60 80 100
Rtinopathie auto-immune:
No paranoplasique (probably more common )
Paranoplasique
1. CAR (more common than MAR)
2. MAR
Protines antigniques
Rtine spcifique: rcoverine (photorcepteurs)/ CAR, RAI
non paranoplasique
No rtine spcifique: enolasa/ CAR, RAI non
paranoplasique
Autres: auto Ac contre AHC, arrestine, transducine, TULP1, protine
neurofilament, photorecepteurs cell specific nuclear receptors (PNR), anti
muller cells, etc..

La prsence des Ac. anti-rtine circulants nest pas spcifique et ne suffit pas
pour faire le Dg.
(autres pathologies rtiniennes, maladies auto-immunes systmiques, sujets normaux)
 Baisse de lacuit visuel (+/- aigue)/ normal
Scotomes
PHOTOPSIES
Nyctalopie
photophobie
Dyschromatopsie
Fundus: normal/ EPR alt., pleur papillaire, vaisseaux grles
Bilatrale mais parfois asymtrique
Inflammation minime voir absente
No PNAR: femme, adulte (50-60 ans), sans antec. opht, photopsies,
scotomes, sans antc familial de RP, ERG pathologique, absence de cancer
associ
RP pri - vasculaire ?
 Champ visuel :
OD OG
 A retener
Pathologies rares, souvent sous diagnostiques
Handicap visuel ccit lgale
Impact familial
Impact multi-systmique
Avis ophtalmo gntique conseill
Phnotypage clinique et fonctionnel
Gnotypage/ conseil gntique appropri
Dg antnatal (primplantatoire ou prnatale)
Traitement spcifique non disponible
Prise en charge de lhandicap visuel
 Ttm pharmacologique
Cellules souches
Thrapie gnique
Implants rtiniens
Prise en charge multidisciplinaire
de formes syndromiques