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Indian Journal of Clinical and Experimental Ophthalmology 2023;9(1):125–127
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Indian Journal of Clinical and Experimental Ophthalmology
Journal homepage: www.ijceo.org
Case Report
A rare genetic mutation case report: Waardenburg syndrome type I
Gagandeep Kaur1, Anureet Kaur1, Mandeep Kaur1,*, Haramritpal Singh2,
Charu Chadha1
1Dept. of Ophthalmology, Guru Gobind Singh Medical College, Faridkot, Punjab, India
2Dept. of Pediatrics, Gobind Singh Medical College, Faridkot, Punjab, India
ARTICLE INFO
Article history:
Received 04-01-2023
Accepted 14-01-2023
Available online 30-03-2023
Keywords:
Waardenburg syndrome
Auditory- pigmentary abnormalities
Sensorineural hearing loss
Heterochromia iridis
ABSTRACT
Waardenburg syndrome is a rare genetically inherited disorder well-known for its classical auditory-
pigmentary abnormalities. Various other minor systemic defects can also occur in structures developing
from neural crest cells during embryogenesis. We are reporting a case of a 7-year old girl who presented to
our OPD with bilateral sensorineural hearing loss and heterochromia iridis.
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1. Introduction
Waardenburg syndrome (WS) is an uncommon autosomally
inherited disorder described first time by a Dutch
ophthalmologist, P. J. Waardenburg in 1951.1It is
a heterogeneous genetic disorder characterized by
sensorineural deafness along with depigmentary changes
and defects in derivatives of neural crest cells. Clinical
changes in skin, hair, and eye occur due to the physical
absence of melanocytes.2
1.1. Genetics
The estimated incidence of WS is 2 per 1 lac without any
predilection for race or sex.3In about 20% of cases, WS
is expressed in the incomplete form.4Different genetic
mutations like insertion, deletion, frameshift, missense,
and nonsense disrupting the normal development of
melanocytes. Mutations in the PAX3 gene on chromosome
2q37 are present in WS1 and WS 3. MITF on chromosome
3p12 in WS 2 whereas SOX 10 and Endothelin B receptors
* Corresponding author.
E-mail address:mandeepkaurdeo@gmail.com (M. Kaur).
(EDNRB) gene is mutated in WS 4 respectively.5,6
1.2. Classification
WS is divided into four different physical types. WS type
I and II are the most common forms.7
Type I WS: Wide space between inner canthus of eyes
along with hearing loss (up to 20%).
Type II WS: No wide space between the inner canthus of
the eyes but the presence of other characteristic features of
WS along with hearing loss (up to 50%).
Type III WS: Also known as Klein- WS. Patients will
have limb abnormalities along with other features. The
rarest form of WS.8
Type IV WS: Also known as Shah- WS. Patients will
have Hirschsprung disease with other features.9
1.3. Diagnostic criteria
Criteria were proposed by the Waardenburg consortium and
according to this criteria, 2 major or 1 major plus 2 minor
symptoms should be present to be diagnosed as a case of
WS Type I.10
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126 Kaur et al. / Indian Journal of Clinical and Experimental Ophthalmology 2023;9(1):125–127
1.4. Major criteria
1. Sensorineural hearing loss
2. Iris pigmentary abnormalities
3. Hair hypopigmentation
4. Dystopia canthorum
5. Presence of WS in first-degree relative
1.5. Minor criteria
1. Skin hypopigmentation
2. Medial eyebrow flare
3. Broad nasal root
4. Hypoplasia of ala nasi
5. Premature graying of hair (<30 years)
2. Case Report
A 7year old girl child, presented to eye OPD with a
complaint of continuous watering for 4 years. The patient
had no other ocular or physical complaints (as per the
patient). On ocular examination, visual acuity was 6/6 in
both eyes. Periorbital erythema was present due to watering
along with dystopia canthi. Blue iris in left eye present
(Figure 1). On direct ophthalmoscopy, a bright red fundal
reflex was seen in both eyes. On indirect ophthalmoscopy,
macula and optic disc were within normal limits. No
choroidal and peripheral fundal pigmentary abnormalities
were seen.
Fig. 1: Morphological features like periorbital erythema, dystopia
canthi and heterochromia iridis
General physical examination revealed bilateral
sensorineural hearing loss and a cochlear implant was
present in the place (Figure 2). A depressed nasal bridge
was also seen. As per history given by the mother she was
having a white forelock of hair at birth and shed off by 2
years of age. No relevant family history was present and the
younger male sibling was normal. The patient had no other
complaints like any mental, limbal or gastrointestinal tract
abnormalities.
Fig. 2: Cochlear implant over left ear
As per diagnostic criteria, she was having 4 major and 1
minor feature making her a case of WS type I.
3. Discussion
WS type I, II, and IV are inherited in autosomal dominant
fashion with variable penetrance and expressivity whereas
WS type III is autosomal recessive.11 Dysgenesis of the
auditory-pigmentary complex leads to changes in skin, hair,
and stria vascularis of cochlea giving the typical physical
and morphological appearance to the patient along with
SNHL.4These neurocristopathies sometimes also cause
defects in the frontal bone, limbal muscles, and enteric
ganglia as they are also derived from neural crest cells.12
Variable penetrance of WS may lead to different
physical characteristics even among individuals having
the same type of WS. Most patients present with an
ocular manifestation called dystopia canthorum. Dystopia
canthorum is morphologically the most penetrating sign
of WS with reported penetrance even up to >95%.12 The
patient will have a typical appearance of blepharophimosis
and increased inner canthal distance with laterally displaced
lacrimal punctae (even up to cornea).4,13 Waardenburg
index (WI) is used to distinguish between WS type I and
WS type II on basis of dystopia canthorum.11 Different
measurements required to calculate WI using caliper are
inner canthal distance, interpupillary distance, and outer
canthal distance.14 Waardenburg index (WI) of >1.95 is a
reliable and practical measure of dystopia canthorum.13,15
Ocular pigmentary changes in an anterior segment like
partial or complete heterochromia iridis are reported in
>25% of cases whereas hypoplastic iridis is seen in >40%
of patients. Posterior segment changes like albinotic or
Kaur et al. / Indian Journal of Clinical and Experimental Ophthalmology 2023;9(1):125–127 127
peripheral funds mottling are also noticed occasionally.4
The differential diagnosis for congenital heterochromia
iridis includes Benign heterochromia, WS, Piebaldism,
Congenital Horner’s syndrome, Sturge Weber syndrome,
Neurofibromatosis type 1, Tuberous sclerosis, Hirschsprung
disease, Bloch-Sulzberger syndrome, Bourneville disease,
and Parry-Romberg syndrome.16
Bilateral SNHL is not a universal but most serious
feature of WS but penetrance is seen in >65% of WS type
I and >85% of WS type II cases. It is the most common
type of hearing loss associated with WS. The hearing
loss is typically non-progressive and may be unilateral or
bilateral.14,17
Pigmentary defects of skin can occur in up to 50% of
cases. Hypopigmented as well as hyperpigmented patches
can be seen anywhere on the body like the face, trunk,
and limbs. Usually, the forehead region shows hair changes
like white forelock but can involve any part of the scalp.
Classic white forelock is observed in >40% of cases and is
the most common hair pigmentary defect associated with
WS I. Premature graying (i.e < 30 years of age) of the
scalp, eyebrows, cilia, or body hair is reported in >5% of
cases.4,12,18
4. Conclusion
Currently, no definitive treatment is available for WS.
The role of prenatal diagnosis and genetic counseling is
also variable due to an incomplete understanding of the
molecular and genetic basis of disease. Team efforts of
specialist medical professionals like ophthalmologists,
dermatologists, otolaryngologists, and physicians are
required to manage a case of WS. Early diagnosis of
SNHL, any bony abnormalities, and Hirschsprung disease
is important and can significantly improve quality of life by
treatment and also prevent related complications. A child
presenting with blue iris and white forelock of hair should
be checked for any hearing loss if not done already. Timely
diagnosis of SNHL can be treated by cochlear implants
and regular speech therapy later. Vocational and social
training should be given as early as possible to prevent any
developmental delay in these children.
5. Source of Funding
None.
6. Conflict of Interest
None.
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Author biography
Gagandeep Kaur, Assistant Professor
Anureet Kaur, Senior Resident
Mandeep Kaur, Senior Resident
Haramritpal Singh, Junior Resident
Charu Chadha, Senior Resident
Cite this article: Kaur G, Kaur A, Kaur M, Singh H, Chadha C. A rare
genetic mutation case report: Waardenburg syndrome type I. Indian J
Clin Exp Ophthalmol 2023;9(1):125-127.
