Journal of Pediatric Ophthalmology and Strabismus

Letters to the Editors 

Delayed Presentation of Children with Waardenburg Syndrome

Mridula Mehta, MS, DNB; Sumita Sethi, MS; Neelam Pushker, MD; Mandeep S. Bajaj, MD; Supriyo Ghose, MD, MNAMS

Abstract

To the Editors:

Waardenburg syndrome (WS), named after the Dutch ophthalmologist Petrus Johannes Waardenburg, is a rare hereditary disorder with ocular and systemic involvements.1,2 Based on genotypic and phenotypic variations, four different types of WS have been described, of which types 1 and 2 are the most common. According to the diagnostic criteria proposed by the WS Consortium, the major criteria are congenital sensorineural hearing loss (SNHL), pigmentary disturbances of the iris and hair, affected first-degree relative, dystopia canthorum, and W index that exceeds 1.95 [The W index (significant if more than 1.95) is calculated using the following formula: X = (2a-0.2119c-3.909)/c Y = (2a-0.2479b–3.909)/b W = X + Y + a/b, where - (a) inner canthal distance, (b) the interpupillary distance, and (c) the outer canthal distance, in mm.] The minor criteria are congenital vitiligo, synophrys, broad high nasal root, hypoplasia of alae nasi, and premature graying of hair. Individuals are considered to have WS type 1 if they fulfill two major (including dystopia canthorum) or one major and two minor criteria from the list. Individuals having other features but not dystopia canthorum are considered to have WS type 2. WS type 3 (or Klein–Waardenburg syndrome) and WS type 4 (or Waardenburg–Shah syndrome) are similar to WS type 1 but include skeletal muscle contractures and Hirschsprung’s disease, respectively.1–3

Abstract

To the Editors:

Waardenburg syndrome (WS), named after the Dutch ophthalmologist Petrus Johannes Waardenburg, is a rare hereditary disorder with ocular and systemic involvements.1,2 Based on genotypic and phenotypic variations, four different types of WS have been described, of which types 1 and 2 are the most common. According to the diagnostic criteria proposed by the WS Consortium, the major criteria are congenital sensorineural hearing loss (SNHL), pigmentary disturbances of the iris and hair, affected first-degree relative, dystopia canthorum, and W index that exceeds 1.95 [The W index (significant if more than 1.95) is calculated using the following formula: X = (2a-0.2119c-3.909)/c Y = (2a-0.2479b–3.909)/b W = X + Y + a/b, where - (a) inner canthal distance, (b) the interpupillary distance, and (c) the outer canthal distance, in mm.] The minor criteria are congenital vitiligo, synophrys, broad high nasal root, hypoplasia of alae nasi, and premature graying of hair. Individuals are considered to have WS type 1 if they fulfill two major (including dystopia canthorum) or one major and two minor criteria from the list. Individuals having other features but not dystopia canthorum are considered to have WS type 2. WS type 3 (or Klein–Waardenburg syndrome) and WS type 4 (or Waardenburg–Shah syndrome) are similar to WS type 1 but include skeletal muscle contractures and Hirschsprung’s disease, respectively.1–3

To the Editors:

Waardenburg syndrome (WS), named after the Dutch ophthalmologist Petrus Johannes Waardenburg, is a rare hereditary disorder with ocular and systemic involvements.1,2 Based on genotypic and phenotypic variations, four different types of WS have been described, of which types 1 and 2 are the most common. According to the diagnostic criteria proposed by the WS Consortium, the major criteria are congenital sensorineural hearing loss (SNHL), pigmentary disturbances of the iris and hair, affected first-degree relative, dystopia canthorum, and W index that exceeds 1.95 [The W index (significant if more than 1.95) is calculated using the following formula: X = (2a-0.2119c-3.909)/c Y = (2a-0.2479b–3.909)/b W = X + Y + a/b, where - (a) inner canthal distance, (b) the interpupillary distance, and (c) the outer canthal distance, in mm.] The minor criteria are congenital vitiligo, synophrys, broad high nasal root, hypoplasia of alae nasi, and premature graying of hair. Individuals are considered to have WS type 1 if they fulfill two major (including dystopia canthorum) or one major and two minor criteria from the list. Individuals having other features but not dystopia canthorum are considered to have WS type 2. WS type 3 (or Klein–Waardenburg syndrome) and WS type 4 (or Waardenburg–Shah syndrome) are similar to WS type 1 but include skeletal muscle contractures and Hirschsprung’s disease, respectively.1–3

We report a case series of six children (2 to 6 years old) who presented with characteristic manifestations of WS, with an emphasis on late presentation and hence improper development of speech and language skills. The most common presenting complaint was inability to speak and hear, followed by difference in eye color.

Systemic examination revealed presence of hypopigmented patches on skin (cases 1, 2, and 4) and hypopigmented hair (cases 1 and 2). Ocular examination revealed heterochromia iridum in four cases and heterochromia iridis in two cases (Figs. 1A, 1B, and 1D). Pure tone audiometry revealed varying severity of SNHL in all six children. Magnetic resonance imaging three-dimensional reconstruction of inner ear (in one child with severe SNHL) revealed bilateral hypoplasia of cochlear cells (Fig. 1C). Considering the parental concerns, a trial of hearing aid was given and the parents were counseled for cochlear implant.

(A) Child with Waardenburg Syndrome Type 1 Showing Heterochromia Iridum, Dystopia, and Synophrys (case 1). (B) Child with Waardenburg Syndrome Type 2 Showing Hypochromic Iris in the Right Eye, Heterochromia Iridis in the Left Eye, Synophrys, and White Forelock (case 2). (C) Magnetic Resonance Imaging Three-Dimensional Reconstruction of Case 2 Showing Right-Sided Hypoplastic Cochlea. (D) Child with Waardenburg Syndrome Type 1 Showing Hypochromic Iris in the Left Eye, Heterochromia Iridis in the Right Eye, Dystopia, and Synophrys (case 3). (E) Father of Case 3 Having Similar Dystopic and Eyebrow Features but with Isochromic Iris.

Figure. (A) Child with Waardenburg Syndrome Type 1 Showing Heterochromia Iridum, Dystopia, and Synophrys (case 1). (B) Child with Waardenburg Syndrome Type 2 Showing Hypochromic Iris in the Right Eye, Heterochromia Iridis in the Left Eye, Synophrys, and White Forelock (case 2). (C) Magnetic Resonance Imaging Three-Dimensional Reconstruction of Case 2 Showing Right-Sided Hypoplastic Cochlea. (D) Child with Waardenburg Syndrome Type 1 Showing Hypochromic Iris in the Left Eye, Heterochromia Iridis in the Right Eye, Dystopia, and Synophrys (case 3). (E) Father of Case 3 Having Similar Dystopic and Eyebrow Features but with Isochromic Iris.

In WS, the auditory defects and pigmentary abnormalities are explained by improper differentiation of the melanocytes, secondary to mutations of various genes (PAX3, MITF, EDNRB, and SOX10).2 Tissues derived from the neural crest and involved in the pathogenesis of WS are the cochlear striae vascularis, frontal bone, limb muscles, and enteric ganglia.

In newborns and infants, WS may be detected by pigmentary abnormalities and by hearing screening. There are two specific modalities for newborn hearing screening (ie, the transient otoacoustic emission or brain stem electric response audiometry).4 Treatment consists of auditory rehabilitation in the form of hearing aids and cochlear implant, where possible.5

In the current case series, the difference in eye color had been noticed by the parents since birth, but they did not consider it serious enough and presented later with SNHL. It is important to identify such children early in life to ensure complete evaluation and comprehensive management in the form of amplification, appropriate educational intervention, and cochlear implant where possible to assist adequate development of speech and language skills in the affected children.

Mridula Mehta, MS, DNB
Sumita Sethi, MS
Neelam Pushker, MD
Mandeep S. Bajaj, MD
Supriyo Ghose, MD, MNAMS
Pediatric Ophthalmology Services
Dr. Rajendra Prasad Centre for
Ophthalmic Sciences
All India Institute of Medical Sciences
New Delhi, India

References

  1. Duke-Elder S. Systems of Ophthalmology; Vol III, Pt 2. Congenital Deformities of the Eye. London: Henry Kimpton; 1969:813–814, 879, 1141–1144.
  2. Bondurand N, Dastot-Le Moal F, Stanchina L, et al. Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4. Am J Hum Genet. 2007;81:1169–1185. doi:10.1086/522090 [CrossRef]
  3. Liu XZ, Newton VE, Read AP. Waardenburg syndrome type II: phenotypic findings and diagnostic criteria. Am J Med Genet. 1995;55:95–100. doi:10.1002/ajmg.1320550123 [CrossRef]
  4. Alberti PW, Hyde ML, Riko K, Corbin H, Abramovich S. An evaluation of BERA for hearing screening in high-risk neonates. Laryngoscope. 1983;93:1115–1121. doi:10.1288/00005537-198309000-00001 [CrossRef]
  5. Daneshi A, Hassanzadeh S, Farhadi M. Cochlear implantation in children with Waardenburg syndrome. J Laryngol Otol. 2005;119:719–723. doi:10.1258/0022215054797943 [CrossRef]

10.3928/01913913-20101104-07

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