Brief Communication
Waardenburg Syndrome Type II

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Joginder Pal Chugh, *Prachi Jain, Rajender Singh Chauhan, Ashok Rathi
Regional Institute of Ophthalmology, 
Pt. B.D Sharma Post Graduate Institute of Medical Sciences, 
Rohtak (Haryana), India- 124001.

Corresponding Author
Prachi Jain
Regional Institute of Ophthalmology, 
Pt. B.D Sharma Post Graduate Institute of Medical Sciences, 
Rohtak (Haryana), India- 124001


Dear Editor, 

This is in reference to case report of Waardenburg Syndrome reported by Yuvika Bansal et al.[1] We are reporting another case of Waardenburg Syndrome, showing bilateral pigmentary disturbance of iris and retina along with sensorineural hearing loss in contrary to previously reported case with unilateral ocular manifestations, prominent dystopia canthorum and lack of hearing abnormlities. Presence of dystopia canthorum in previously reported case clearly differentiates type I from type II Waardenburg syndrome. An effort has been made to address varied presentation and spectrum of the same disease through this article

Waardenburg syndrome was first described by Dutch ophthalmologist, Petrus Johannes Waardenburg in 1947.[2] It is a rare disorder characterized by sensorineural hearing deficit, pigmentary disturbances and abnormalities of neural crest derivatives. Clinical manifestations are because of lack of melanocytes in the cochlea, skin, eyes and hair. Reported prevalence is 1 in 42,000.[2] Four clinical types of Waardenburg syndrome (WS) have been recognized. 

Here is a case report of Type II Waardenburg syndrome showing typical features of the disease.

A 14 year old male child was admitted in medicine ward for febrile illness. On examination, he was found to have bilateral, profound sensorineural hearing loss since childhood. Associated ocular findings were – bilateral isohypochromia irides (Figure 1) along with pigmentary abnormalities of retina. Right fundus was diffusely depigmented while left fundus was partially depigmented with normal pigmentation temporal to fovea (Figure 2). Gonioscopy revealed bilateral open, normal angles with sparsely pigmented trabecular meshwork. Retinoscopy did not reveal any gross refractive error. IOP with Goldmann’s applanation tonometry was 14 mmHg in both eyes. Inter-inner canthal , inter-outer canthal and interpupillary distances were 32mm, 105mm and 62mm respectively, which were within normal limits for Indian population. OCT revealed bilateral macular thickness of 243 microns with normal retinal structure. Other systemic findings in this patient were- flat nasal bridge, premature graying of hairs, patchy hyperpigmented spots over face and trunk, discoloured nails (melanonychia), mild splenomegaly with evidence of megaloblastic anemia on peripheral blood smear. Bowel habits were normal and no evidence of musculoskeletal involvement was found. No family history of similar features was found. Observing the ocular and systemic findings, diagnosis of Type II Waardenburg Syndrome was made. No active intervention from ophthalmic perspective is required in such cases.

WS is characterized by sensorineural hearing loss, dystopia canthorum (lateral displacement of medial canthi), partial or complete heterochromia irides or isohypochromia irides, synophrys, pigmentary changes in skin and hairs, broad nasal root and hypoplasia of nasal septum. Not every case manifests the complete spectrum of clinical features and marked variability is observed even within families.

Four subtypes of WS have been recognized. WS type I expresses full symptomatology of the disease with dystopia canthorum as the most prominent and consistent feature.[2] WS type II may have all features of WS except dystopia canthorum. Sensorineural hearing loss (77%) and heterochromia or isohypochromia irides (47%) are most important diagnostic features of this type.[3,4] WS type III, also known as Klein-Waardenburg syndrome has additional musculoskeletal abnormalities like limb muscle hypolplasia, syndactyly and Sprengel shoulder.[5] WS type IV, also known as Waardenburg-Shah syndrome, is characterized by the association of disease with congenital aganglionic megacolon.[6]

WS type I and III have autosomal dominant inheritance while type IV has autosomal recessive inheritance. Type II may have both autosomal dominant as well as autosomal recessive mode of inheritance. WS may also arise secondary to de novo mutations. Point mutations involving PAX3 gene (2q35) were found in WS type I and III patients. WS type II is associated with point mutations in MITF which has role in melanocyte differentiation. WS type IV occurs secondary to involvement of Endothelin-3(EDN3) or Endothelin-B receptor (EDNRB) genes.[7]

Diagnosis is usually clinical. Differential diagnoses include albinism, piebaldism, vitiligo and Vogt-Koyanagi-Harada disease. Persons with Waardenburg syndrome have normal life expectancy and no effective treatment is available for such persons. Early diagnosis and improvement of hearing defect along with psychological support helps in social rehabilitation of such persons.

Considering the sensorineural hearing loss with ocular, skin and hair findings along with lack of dystopia canthorum, musculoskeletal and gastrointestinal abnormalities, diagnosis of Waardenburg syndrome type II was made. Association with megaloblastic anemia is not reported in literature to the best of our knowledge and megaloblastic anemia can be an incidental finding. 

  1. Waardenburg Syndrome: Case report. Bansal Y, Jain P, Goyal G, Singh M, Mishra C. Del J Ophthalmol 2012; 23:125-6.
  2. Waardenburg PJ. A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet 1951; 3:195-253.
  3. Oysu C, Baserer N, Tinaz M. Audiometric manifestations of Waardenburg’s    syndrome. Ear Nose Throat J 2000; 79:704-9.
  4. Tagra   S, Talwar AK, Walia RL, Sidhu P. Waardenburg syndrome. Indian J Dermatol Venereol Leprol 2006; 72:326.
  5. Klein D. Historical background and evidence for dominant inheritance of the Klein-Waardenburg syndrome (type III). Am J Med Genet 1983; 14:231-39.
  6. Shim WK, Derieg M, Powell BR, Hsia YE. Near-total intestinal aganglionosis in the Waardenburg-Shah syndrome. J Pediatr Surg 1999; 34:1853-5.
  7. Edery P, Attie T, Amiel J et al. Mutation of the endothelin-3 gene in the Waardenburg-Hirschprung disease (Shah-Waardenburg syndrome). Nature Genetics 1996; 12:442-44.