Waardenburg syndrome - A case report

Abstract

Waardenburg syndrome is a rare genetic disorder characterized by varying degree of deafness associated with pigmentary anomaly and defects of neural crest cell derived structures. Four subtypes (I-IV) with variable penetrance and gene expression of different clinical features have been described. We report a patient showing constellation of complete heterochromia, dystopia canthorum, white forelock, and synophrys. Other affected family relatives with heterochromia have been depicted in pedigree.

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Bansal
Y,
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Waardenburg
syndrome
–
A
case
report.
Contact
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Anterior
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(2012),
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Case
report
Waardenburg
syndrome
–
A
case
report
Yuvika
Bansal, Parul
Jain∗,
Gaurav
Goyal,
Malvika
Singh,
Chittranjan
Mishra
Guru
Nanak
Eye
Centre,
New
Delhi,
India
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
21
June
2012
Received
in
revised
form
7
October
2012
Accepted
11
October
2012
Keywords:
Waardenburg
syndrome
Heterochromia
a
b
s
t
r
a
c
t
Waardenburg
syndrome
is
a
rare
genetic
disorder
characterized
by
varying
degree
of
deafness
associated
with
pigmentary
anomaly
and
defects
of
neural
crest
cell
derived
structures.
Four
subtypes
(I–IV)
with
variable
penetrance
and
gene
expression
of
different
clinical
features
have
been
described.
We
report
a
patient
showing
constellation
of
complete
heterochromia,
dystopia
canthorum,
white
forelock,
and
synophrys.
Other
affected
family
relatives
with
heterochromia
have
been
depicted
in
pedigree.
© 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1.
Introduction
Waardenburg
syndrome
(WS),
was
originally
described
as
a
syndrome
with
six
characteristic
features;
lateral
displacement
of
the
medial
canthi,
broad
and
high
nasal
root,
hypertrichosis
of
medial
part
of
eyebrows,
partial
or
total
heterochromia
iridis,
white
forelock
and
congenital
deaf-mutism.
The
condition
described
orig-
inally
is
now
categorized
as
WS
type
1.
Since
then,
four
subtypes
(I–IV)
with
variable
penetrance
of
different
clinical
features
have
been
described
[1].
Out
of
five
major
and
five
minor
criteria
of
Waardenburg
syn-
drome,
either
two
major
or
one
major
plus
two
minor
criteria
must
be
present
for
diagnosing
WS
1
[2].
WS
III
is
similar
to
type
I
with
additional
musculoskeletal
abnormalities.
WS
IV
is
associated
with
Hirschsprung
disease
[1,3].
We
report
a
case
of
a
young
girl
showing
features
of
WS
with
her
pedigree
chart
showing
variable
penetrance
of
features
and
hence
marked
intrafamilial
variation
of
expression
of
WS.
2.
Case
report
A
12-year
old
girl
presented
to
the
outpatient
department
of
our
tertiary
eye
care
hospital
with
chief
complaints
of
difference
in
colour
of
her
eyes
with
decreased
vision
in
left
eye
(Fig.
1).
Her
unaided
visual
acuity
at
presentation
was
20/20
OD
and
20/60
OS
improving
to
20/20
OS
with
−1.25
DSph.
She
was
the
second
child
∗Corresponding
author
at:
E
8/3
Sector
13
R
K
Puram,
New
Delhi
110066,
India.
Tel.:
+91
9971927902.
E-mail
addresses:
bansal.yuvi@gmail.com
(Y.
Bansal),
pjain811@gmail.com
(P.
Jain),
dr.gaurav.mamc@gmail.com
(G.
Goyal),
malvika.singh.12935@facebook.com
(M.
Singh),
drchitaranjan.gnec@gmail.com (C.
Mishra).
of
a
non-consanguinous
marriage
with
healthy
siblings
(2
brothers
and
1
sister).
Her
birth
and
developmental
history
did
not
reveal
anything
significant.
On
systemic
examination,
she
was
moderately
built
with
an
average
height,
weight
and
normal
IQ.
She
had
centrally
placed
white
forelock
in
frontal
area
(artificially
dyed
for
cosmetic
rea-
sons)
without
any
associated
depigmentation
of
scalp
or
elsewhere
on
the
body.
Her
ENT
and
abdominal
examinations
were
normal.
On
ocular
examination,
the
horizontal
palpebral
fissure
was
smaller
in
both
the
eyes
(25
mm)
along
with
lateral
displace-
ment
of
canthi.
She
also
had
broad
nasal
root,
dystopia
canthorum
with
interpupillary
distance
of
50
mm
and
inner
canthal
distance
of
35
mm.
Medially
sclera
was
visible
to
lesser
extent
however
Hirschberg
corneal
reflex
was
central.
Lacrimal
system
was
patent
on
syringing.
Complete
heterochromia
with
blue
hypoplastic
iris
was
noted
in
left
eye
(Fig.
2).
Rest
of
the
anterior
segment
examination
was
nor-
mal
in
both
the
eyes.
Pupillary
reactions
were
normal.
Right
fundus
was
normal
whereas
left
fundus
was
albinotic
showing
hypopig-
mentation
(Fig.
3).
Pedigree
of
index
case
was
traced
by
interviewing
her
grand-
mother
as
depicted
by
symbols.
It
appeared
to
be
an
autosomal
recessive
inheritance
with
variable
expressivity
for
heterochromia
(Fig.
4).
3.
Discussion
Waardenburg
syndrome
is
a
rare
disease
characterized
by
deaf-
ness
in
association
with
pigmentary
anomalies
and
defects
of
neural
crest-derived
tissues.
It
is
characterized
by
clinical
man-
ifestations
of
oculocutaneous
anomalous
pigmentation,
deafness
of
varying
degree,
dystopia
canthorum
and
broad
nasal
root.
There
are
four
clinical
subtypes
of
Waardenburg
depending
on
the
presence
of
various
clinical
features.
There
are
five
major
1367-0484/$
–
see
front
matter ©
2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.clae.2012.10.083

Please
cite
this
article
in
press
as:
Bansal
Y,
et
al.
Waardenburg
syndrome
–
A
case
report.
Contact
Lens
Anterior
Eye
(2012),
http://dx.doi.org/10.1016/j.clae.2012.10.083
ARTICLE IN PRESS
G
Model
CLAE-580;
No.
of
Pages
3
2Y.
Bansal
et
al.
/
Contact
Lens
&
Anterior
Eye
xxx (2012) xxx–
xxx
Fig.
1.
Showing
facial
features.
Fig.
2.
Slit
lamp
photograph
(a)
right
eye.
(b)
Left
eye
with
heterochromia.
and
five
minor
criteria
for
Waardenburg
syndrome.
Major
crite-
ria
include
sensorineural
hearing
loss,
iris
pigmentary
abnormality,
hair
hypopigmentation,
dystopia
canthorum
and
first-degree
rel-
ative
previously
diagnosed
with
Waardenburg
syndrome
[1–4].
Minor
criteria
include
skin
hypopigmentation,
medial
eyebrow
flare
(synophrys),
broad
nasal
root,
hypoplasia
alae
nasi,
and
pre-
mature
greying
of
the
hair.
As
per
the
diagnostic
criteria
proposed
by
Waardenburg
con-
sortium
for
diagnosing
WS
I,
two
major
or
one
major
plus
two
minor
criteria
should
be
present.
WS
III
is
similar
to
type
I
with
Fig.
3.
(a)
Fundus
photo
right
eye.
(b)
Fundus
photo
left
eye.
additional
musculoskeletal
abnormalities.
People
who
present
with
type
3
(Klein–Waardenburg
syndrome)
present
with
hypoplastic
muscles
and
contractures
of
the
upper
limbs
in
addition
to
WS
type
1
features.
WS
IV
is
associated
with
Hirschsprung
disease.
WS
II
is
characterized
by
more
frequent
occurrence
of
sensorineu-
ral
hearing
loss
and
heterochromia
iridis
but
absence
of
dystopia
canthorum.
Liu
et
al.
have
proposed
that
for
diagnosing
WS
II,
two
major
criteria
be
fulfilled
and
dystopia
canthorum
be
replaced
with
premature
greying
as
one
of
the
major
criteria.
Our
case
had
4
major
criteria
and
2
minor
criteria
of
Waarden-
burg
type
1.
Dystopia
canthorum
is
a
crucial
feature
for
diagnosing
WS
type
1
which
differentiates
it
from
WS2.
Dystopia
canthorum
is
confirmed
by
calculating
W
index
(in
mm).
W
index
is
calculated
as
follows:
W
=
X
+
Y
+
a
b
X
=2a
−
(0.2119c
+
3.909)
c
Y
=2a
−
(0.249b
+
3.9090)
b
Fig.
4.
Pedigree
chart.

Please
cite
this
article
in
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as:
Bansal
Y,
et
al.
Waardenburg
syndrome
–
A
case
report.
Contact
Lens
Anterior
Eye
(2012),
http://dx.doi.org/10.1016/j.clae.2012.10.083
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Model
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No.
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Y.
Bansal
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Contact
Lens
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Eye
xxx (2012) xxx–
xxx 3
Inner
canthal
distance
(a),
interpupillary
distance
(b),
and
outer
canthal
distance
(c).
W
index
greater
than
1.95
is
considered
abnor-
mal.
W
index
was
2.16
in
this
case.
Hearing
loss
which
is
a
major
criteria
was
not
present
in
this
case.
This
is
not
a
universal
fea-
ture
of
WS
but
penetrance
study
of
sensorineural
deafness
showed
69%
penetrance
in
WS1
and
87%
in
WS2.
This
patient
had
dystopia
canthorum,
heterochromia
and
an
albinotic
fundus.
Patients
with
WS
can
have
poor
vision
due
to
foveal
hypoplasia,
hypermetropic
amblyopia
and
few
cases
have
been
reported
of
recurrent
vitreous
haemorrhage
leading
to
poor
vision
associated
with
WS
[6].
WS
I
and
II
are
autosomal
dominant
in
most
of
cases.
WS
III
is
usually
sporadic
but
when
it
occurs
in
families,
inheritance
is
auto-
somal
dominant.
Type
IV
is
probably
autosomal
recessive
[1,3,5].
Multiple
genes
have
been
implicated
in
the
syndrome.
Abnormali-
ties
in
the
PAX3
gene
accounts
for
most
of
WS1
and
WS3
patients.
MITF
(microphthalmia
associated
transcription
factor)
gene
abnor-
mality
is
responsible
for
WS2.
WS4
is
heterogeneous,
with
reported
mutations
in
EDN3
(endothelin
3),
in
its
receptor
EDNRB
(endothe-
lin
receptor
type
B),
or
in
SOX10
(SRY-sex
determining
region
Y).
We
could
not
perform
PAX
3
sequence
but
it
appeared
to
be
an
autosomal
recessive
inheritance
with
variable
penetrance,
because
of
healthy
parents
but
some
family
members
with
the
disease.
The
genetic
evaluation
of
WS
has
not
yet
been
able
to
predict
the
final
outcome
that
can
be
expected
in
an
individual
showing
a
mutation
of
candidate
gene
thus
complicating
the
issue
of
genetic
counselling
and
limiting
the
scope
for
prenatal
diagnosis.
All
fea-
tures
of
WSI
and
II
except
sensorineural
hearing
loss
are
essentially
benign
and
cosmetic
in
nature
and
do
not
necessitate
active
inter-
vention
but
deafness,
if
severe,
can
be
a
major
handicap.
One
of
the
reasons
to
be
aware
of
the
clinical
features
of
WS
is
differentiation
from
other
pigment
disorders
like
oculocutaneous
albinism,
nevus
amenicus,
hypomelanosis
of
Ito,
piebalidism
and
vitiligo.
References
[1] Dourmishev
AL,
Dourmishev
LA,
Schwartz
RA,
Janniger
CK.
Waar-
denburg
syndrome.
International
Journal
of
Dermatology
1999;38:
656–63.
[2] Tagra
S,
Talwar
AK,
Walia
RS,
Sidhu
P.
Waardenburg
syndrome.
Indian
Journal
of
Dermatology,
Venereology
and
Leprology
2006;72:326.
[3]
Read
AP,
Newton
VE.
Waardenburg
syndrome.
Journal
of
Medical
Genetics
1997;34:656–65.
[4] Demirci
GT,
Atis
G,
Altunay
IK.
Waardenburg
syndrome
type
1:
a
case
report.
Dermatology
Online
Journal
2011;17(11):3.
[5]
Nayak
CS,
Isaacson
G.
Worldwide
distribution
of
Waardenburg
syndrome.
Annals
of
Otology,
Rhinology
and
Laryngology
2003;112:817–20.
[6] Ang
CS.
Haemorrhage
in
a
patient
with
Waardenburg
syndrome.
Asian
Journal
of
Ophthalmology
2002;4(4):13–4.