Case Report
A 22 years old male came to our department for regular check up. History was given by his mother as he was congenitally deaf and mute. As per the mother, he had no visual complaints. She gave history of premature greying of hair in the boy and white areas of hypopigmentation over the forearms. He was the first of two children, born out of a non-consanguinous marriage with the sibling being healthy. His birth history and development history were insignificant. On being asked, she revealed history of dissimilar coloration of eyes in maternal grandmother as well as premature greying of eyelashes in herself.
On examination, visual acuity was 6/6, N6 in both eyes. Pupillary reactions were normal. Extraocular movements were normal and full in both eyes. Systemic examination revealed a white forelock of hair in the left frontal area with generalised premature greying of hair. There was a bunch of white hair seen in left eyebrow along with rows of hair joining the two eyebrows. There was a broad nasal root with hypoplastic alae nasi. There were multiple hypopigmented patches along with white hair on both the forearms. On ocular examination, the horizontal palpebral fissure was 25 mm in both eyes along with lateral displacement of canthi. There was dystopia canthorum with interpupillary distance of 55 mm and inner canthal distance of 40mm. Medially sclera was visible to a lesser extent giving an impression of convergent squint, however Hirschberg test revealed a central corneal reflex. Brilliant blue irides were noted bilaterally. Rest of the anterior segment examination was normal in both the eyes. The fundus in both eyes showed hypopigmentation at the posterior pole.
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Figure 1: Characteristic brilliant blue irides, synophrys, dystopia canthorum, hypoplastic alae nasi, premature greying of hair |
Figure 2: Hypopigmented patches on the skin and white hair on the forearms |
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Figure 3: Hypopigmentation at the posterior pole in both eyes. |
Discussion
Waardenburg Syndrome is a unique disease characterized by varying degrees of deafness combined with oculocutaneous pigmentary anomalies and defects of neural crest-derived tissues. It has four clinical subtypes and in an early report of the Waardenburg consortium, published in 1992, the diagnostic criteria were laid down to distinguish between the various types.[1] A person was labelled as Waardenburg syndrome Type I if he satisfied two major or one major plus two minor criteria. The five major criteria described, include sensorineural hearing loss, iris pigmentary abnormalities i.e. heterochromia iridis, heterochromia iridum or characteristic brilliant blue iris, hypopigmentation of hair, dystopia canthorum defined as lateral displacement of inner canthi, and the presence of a first-degree relative previously diagnosed with Waardenburg syndrome. The five minor criteria are skin hypopigmentation, medial eyebrow flare or synophrys, broad nasal root or dystopia canthorum, hypoplasia of alae nasi, and premature graying of hair. Absence of dystopia canthorum is a characteristic feature of Type II. Type III shows all the features above but it is associated with upper limb defects and is heralded as the rarest form of the four. Type IV is associated with Hirschsprung disease.[2] The case we report satisfies 4 major and all 5 minor criterias and can be thus classified as Type I.
As is clear, dystopia canthorum is a pivotal component for diagnosing Waardenburg Syndrome Type I and differentiating it from Type II. It is confirmed by calculating W index (in mm). W index is calculated as follows[3]:
W = X + Y + a/b where X = (2a – (0.2119c + 3.909))/c, Y = (2a – (0.2479b + 3.909))/b
Here, a=Inner canthal distance, b=interpupillary distance, c= outer canthal distance; W index of more than 1.95 is considered abnormal and it was found to be 2.497 in this case.
The mode of inheritance in Waardenburg syndrome has been typically described as autosomal dominant. While most cases of Type I and Type III Waardenburg syndrome are attributed to abnormalities in PAX3 gene, several other genes have recently been implicated.[4] These include, MITF (microphthalmia associated transcription factor) that is the suspected gene in Type II, [5] and EDN3 (endothelin 3) that has been linked to Type IV.
We found hypopigmentation at the posterior pole while past authors have reported hyperpigmentation. There is a need to further explore this aspect of the disease and describe the various possible retinal pictures of the disease. Fundus picture has not been given due importance in literature while describing this condition and has not been considered as a major or minor criteria.
Conclusion:
A timely diagnosis of this striking syndrome could facilitate improvement in speech discrimination in these patients, by cochlear implantation, hence leading to a better quality of life.[6] It would also prove useful in genetic counselling of expectant mothers in such families.
References
- Farrer LA, Grundfast KM, Amos J, Arnos KS, Asher JH Jr, Beighton P et al. Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: First report of the WS consortium. Am J Hum Genet 1992;50:902-13.
- Kliegman RM, Behraman RE, Jenson HB, Stanton BF. Nelson Text Book of Pediatrics. 18th ed. Vol. 2. W.B Saunders Company; 2007. Jun, p. 2683
- Arias S, Mota M. Apparent non-penetrance for dystopia in Waardenburg syndrome type I, with some hints on the diagnosis of dystopia canthorum. J Genet Hum. 1978;26:103-131.
- Baldwin CT, Hoth CF, Amos JA, da-Silva EO, Milunsky A. An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome. Nature. 1992 Feb 13; 355(6361):637-8.
- Tassabehji M, Newton VE, Read AP. Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. Nat Genet. 1994 Nov; 8(3):251-5.
- Deka RC, Sika K, Chaturvedy G, Singh CA, Venkat Karthikeyan C, Kumar R, Agarwal S. Cochlear implantation in Waardenburg syndrome: The Indian scenario. Acta Otolaryngol. 2010;130(10):1097-100
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