|Year : 2021 | Volume
| Issue : 3 | Page : 144-147
Waardenburg syndrome: About seven cases
Houda Mounji, Malika Benfdil, Youssef Lakhdar, Mohamed Chehbouni, Youssef Rochdi, Hassan Nouri, Abdelaziz Raji
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Mohammed VI, Marrakech, Morocco
|Date of Submission||10-Feb-2020|
|Date of Acceptance||20-May-2020|
|Date of Web Publication||16-Dec-2021|
Dr. Houda Mounji
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Mohammed VI, Marrakech
Source of Support: None, Conflict of Interest: None
Background: Waardenburg syndrome (WS) is an autosomal dominant inherited genetic condition that manifests with sensorineural deafness and pigmentation defects of the skin, hair, and iris. This genetically and clinically heterogeneous disease accounts for 2% of the congenitally deaf population. Objectives: The aim of our study is to determine epidemiological and clinical characteristics of this group to improve the management, especially for the hearing impairment. Methods: Seven cases were diagnosed during the examination of children with suspected congenital deafness. Results: The age of our children ranged from 1.3 to 5 years, with a median age of 3.6 years, with female predominance; no consanguineous marriage and fetal or perinatal history have been reported; there was family history of premature greying in four cases and deafness in two cases. Two patients had WS Type 1 with a dystopia canthorum, while four cases had WS Type 2. There was one patient with Waardenburg Klein or Shah syndrome. The otoscopy was normal in all children. Evoked auditory potentials, otoacoustic emissions, and tonal audiometry were performed; they had shown a congenital, sensorineural bilateral, and profound hearing loss >100 dB in all cases. All children had received a cochlear implantation followed by speech reeducation. A genetic consultation was carried out for all our children. Conclusion: WS is a relatively common genetic cause of sensorineural hearing loss. Early diagnosis and improvement of hearing impairment are most important for psychological and intellectual development of the children with WS.
Keywords: Children, cochlear implant, hearing loss, heterochromia, Waardenburg
|How to cite this article:|
Mounji H, Benfdil M, Lakhdar Y, Chehbouni M, Rochdi Y, Nouri H, Raji A. Waardenburg syndrome: About seven cases. Indian J Otol 2021;27:144-7
| Introduction|| |
Waardenburg syndrome (WS) is a rare disease characterized by sensorineural deafness in association with pigmentary defects. Petrus Johannes Waardenburg first described it in 1951 and the countenance as described includes lateral displacement of the medial canthi, heterochromia iris, white forelock of hair, and deaf mutism. The incidence of WS is estimated at 2/100,000 worldwide. The international distribution of this disease can be observed without preference for race or gender. Four distinct types of WS have been described, depending on the presence of other abnormalities. Types 1 and 2 can be clinically distinguished only by dystopia canthorum, which is the characteristic of WS Type 1 and absent in WS Type 2. Type 3 has the same symptoms as Type 1 with musculoskeletal limb abnormalities. Type 4 is called Shah–WS with only a few cases of it being reported in the literature. It is associated with Hirschsprung's disease, its most defining feature being the aganglionic megacolon. Our aim is to determine epidemiological and clinical characteristics of this group to improve the management, especially for the hearing impairment.
| Methods|| |
We report seven cases of WS who were diagnosed during the examination of children with suspected congenital deafness in the ENT Department of Mohamed VI University Hospital of Marrakech and in collaboration of the Department of Ophthalmology in a period of 11 years between December 2008 and January 2019.
| Results|| |
The age of our children ranged from 1.3 to 6.3 years, with a median age of 3.9 years, with female predominance.
No consanguineous marriage and fetal or perinatal history have been reported. There was a family history of premature greying in four cases, an iris heterochromia (maternal grandfather, maternal grandmother, and paternal uncle) in three children, and a family history of deafness in two cases.
All patients had clinical features consistent with WS; two of them had WS Type 1 with a dystopia canthorum, and four cases had WS Type 2. There was one case with a Waardenburg Shah syndrome (Type 4). We noted clinical manifestations as follows [Table 1]: white distinct forelock of hair in three cases, a broad nasal root in three cases, one case of medial hypertrichosis; we have noticed two cases of complete iris heterochromia, two cases of a sectorial iris heterochromia, and two cases of a very pale blue eyes. One child had not iris depigmentation [Figure 1].
|Figure 1: The different clinical features found in the physical examination of our cases|
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A congenital leukoderma was present in three cases.
The ophthalmic examination has shown bright red fundal reflex with choroidal depigmentation in four cases.
The otoscopy was normal in all children. Evoked auditory potentials, otoacoustic emissions, and tonal audiometry were performed; they had shown a congenital, sensorineural bilateral, and profound hearing loss >100 dB in all cases. Computed tomographic scan and magnetic resonance imaging of the temporal bone were normal in all cases. All children had received unilateral cochlear implantation [Figure 2]. Speech reeducation has been started with good outcomes with an average follow-up of 4 years.
|Figure 2: A right cochlear implantation in patients with Waardenburg syndrome|
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The molecular genetic testing, in our context, is not available because of the high cost of genetic methods. Nevertheless, a genetic consultation was carried out for all our children [Figure 3].
| Discussion|| |
WS is a rare dominantly inherited genetically heterogeneous auditory–pigmentary syndrome, with an estimated prevalence of 1/42,000. It is a relatively common genetic cause of sensorineural hearing loss (SNHL) and is estimated to be responsible for 2%–5% of cases of congenital hearing loss. It has no racial or ethnic predilection and has an equal male-to-female ratio.
It is characterized by nonprogressive SNHL and iris discoloration, caused by physical absence of melanocytes from the skin, hair, eyes, or the stria vascularis of the cochlea. Absence of melanocytes could be caused by a failure of differentiation in the neural crest, a failure of melanoblasts to migrate, or a failure to terminally differentiate and survive in their final location.
To diagnose WS, five major and five minor diagnostic criteria have to be established. The major criteria include SNHL, white forelock, pigmentary disturbance of the iris, dystopia canthorum (lateral displacement of the inner eye corners), and first-degree relatives diagnosed with WS. Minor criteria include congenitally hypopigmentation of the skin, medial eyebrow flare (synophrys), hypoplastic alae nasi, prominent broad nasal root, and early graying of hair before the age of 30. The clinical diagnosis of WS requires at least two major criteria or one major and two minor criteria.,,,,,
Four different types of WS have been described based on genotypic and phenotypic variations; WS Type 1 and Type 2 are more common than Type 3 and Type 4., Type 1 and 2 have similar features; although people with Type 1 almost always have canthorum dystopia, this sign is missing in Type 2. Type 3, called Klein-WS, includes abnormalities of the limbs and Type 4 also known as Waardenburg-Shah syndrome has signs of both WS and Hirschsprung's disease.,,,,,
In our cases, one child underwent a surgery for Hirschsprung's disease. Nevertheless, no musculoskeletal limb abnormalities were found.
WS I and II are autosomal dominant in most of cases. WS III is usually sporadic; however, when it occurs in families, inheritance is autosomal dominant. Type IV is probably autosomal recessive.,,
Several gene mutations may result in WS; these genes are involved in the development of melanocytes: mutations in the PAX3 gene (encoding the paired box 3 transcription factor), result in WS Type 1 and Type 3, while mutation in the MITF gene (microphthalmia-associated transcription factor) is responsible for Type 2 WS. Mutations in the SOX10, EDN3 (endothelin 3), SNAI2 (snail homolog 2), or EDNRB (endothelin receptor Type B) genes are responsible for WS Type 4 and recently reported KITLG mutation gene (encoding KIT ligand).,,
Hearing loss in WS has a congenital, sensorineural character, and it is usually nonprogressive, varying from slight to profound.,,
In most affected individuals with WS, congenital SNHL is in both ears. However, in rare cases, only one side may be affected. Evidence suggests that congenital SNHL is more frequently associated with WS2 than WS1.,,,,
In our study, all cases have bilateral congenital profound SNHL which was proven by evoked auditory potentials.
Management of the hearing loss depends on its severity; cochlear implantation has been successfully used in all our children.
If the family-specific PAX3 pathogenic variant is known, molecular genetic testing of relatives at risk allows for early screening of those at risk for hearing loss. Folic acid supplementation in pregnancy is recommended for women at increased risk of having a child with WS Type 1 because of possibly increased risk for neural tube defects in association with WS Type 1.,
A genetic consultation was carried out for all our children, however, unfortunately; we could not have done the molecular genetic testing due to financial constraints.
| Conclusion|| |
WS is found in 2%–3% of patients with congenital deafness. Due to its varying clinical presentations, it may be difficult to diagnose it at an early stage; however, when the typical pigmentary disturbances are present, then diagnosis is easy. All features of WS I and II, except SNHL, are essentially benign and cosmetic in nature and do not necessitate active intervention, but deafness, if severe, can be a major handicap; thus, an early diagnosis will help in better management of the patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]