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 Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 19  |  Issue : 1  |  Page : 64-67

Waardenburg syndrome type 1 in a Hausa/Fulani child: Implications for genetic counseling


1 Department of Otorhinolaryngology, Bayero University, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria
2 Department of Ophthalmology, Bayero University, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria

Date of Web Publication17-Dec-2015

Correspondence Address:
Abdulazeez O Ahmed
PO Box - 14529, Main Post Office, Kano, Kano State
Nigeria
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DOI: 10.4103/1119-0388.172069

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  Abstract 

Waardenburg syndrome (WS) is associated with hearing loss and is an autosomal inherited disorder with genetic heterogeneity. WS types 1 and 2 depict a high degree of inter- and intrafamilial variabilities, with type 1 being less common than type 2. In Northern Nigeria, due to cultural and religious inclinations, consanguineous marriages are quite common; thus, inheritable genes are easily passed on from one generation to the next. Following the paucity of reports of this syndrome in Northern Nigeria and its rarity worldwide, we report this case of WS type 1 with familial variability from a consanguineous marriage. We posit that with the availability of genetic counseling, it is possible to avoid the risk of passing on the Waardenburg gene to an unborn child and help to avoid untold hardship and societal stigma to both the child and the parent.

Keywords: Consanguineous, familial variability, genetic counseling, Waardenburg syndrome


How to cite this article:
Ahmed AO, Kolo ES, Bello-Muhammad N, Hassan S. Waardenburg syndrome type 1 in a Hausa/Fulani child: Implications for genetic counseling. Trop J Med Res 2016;19:64-7

How to cite this URL:
Ahmed AO, Kolo ES, Bello-Muhammad N, Hassan S. Waardenburg syndrome type 1 in a Hausa/Fulani child: Implications for genetic counseling. Trop J Med Res [serial online] 2016 [cited 2019 Oct 17];19:64-7. Available from: http://www.tjmrjournal.org/text.asp?2016/19/1/64/172069


  Introduction Top


It is estimated that about one in 1,000 children is born deaf or becomes deaf in early childhood.[1] About 50% of childhood deafness can be attributed to genetic causes, of which 30% occurs with other features as a recognizable syndrome while in 70% of cases, deafness occurs as an isolated feature (nonsyndromic).[1] Researchers/geneticists have typed and mapped genes for several of these syndromes associated with hearing loss that are now recognized globally, namely, Waardenburg syndrome (WS), Pendred syndrome, branchio-oto-renal syndrome, Usher syndrome, and Jervell and Lange-Nielsen syndrome to mention but a few. World wide data reports show that WS is rare, accounting for 2-5% of cases of congenital hearing loss with occasional incomplete penetrance and a prevalence of one case per 42,000 persons.[2] It is an autosomal inherited disorder with genetic heterogeneity characterized by congenital sensorineural hearing loss; pigmentary discoloration of the hair, the iris, and the skin; and dystopia canthorum. This is due to the absence of melanocytes from the stria vascularis of the cochlea, the hair, the eyes, and the skin. WS has no ethnic or racial predilection.

WS has four clinical subtypes, namely, WS 1-4; WS 1 is classified as type 1 with features of hearing loss, dystopia canthorum (lateral displacement of both medial canthi and lacrimal punctae), pigmentary abnormalities of the eye, the skin, and the hair; WS type 2 includes all of the above features without dystopia canthorum; WS type 3 (Klein-Waardenburg) includes features of WS types 1 and 2 in association with severe musculoskeletal contractures; WS type 4 (Waardenburg-Shah) includes features of WS types 1 and 2 in association with Hirschsprung's disease. Types 1 and 2 are autosomal dominant that are transmitted with inter- and intrafamilial variabilities, although type 1 is said to be less common than type 2.[3] As a disability, hearing loss is highly heterogenic and, therefore, it is quite difficult to pool data from the families for linkage analysis research, more so where these are available; in Sub-Saharan Africa, this is almost a mirage at this time; but large families with a strong single gene effect can be identified and genetically isolated to establish a “founder effect.”

In Northern Nigeria, due to cultural and religious inclinations, consanguineous marriages are quite common; thus, inheritable genes are easily passed on from one generation to the next. WS types 1 and 2 are inherited in an autosomal dominant fashion; therefore, an affected person has a 50% chance in each pregnancy of having an affected child. Although the symptoms may vary, there is no way of telling if an affected child will have less or more severe symptoms than his/her parent. In types 3 and 4, inheritance is complex and difficult to predict; but with genetic counseling, it is possible to assess the risk of passing on the Waardenburg gene to an unborn child and help to avoid untold hardship and societal stigma to both the child and the parent. Five genes have been implicated in the causation of this syndrome, i.e., paired box 3 (PAX3) gene found in most cases of WS types 1 and 3, microphthalmia-associated transcription factor (MITF) gene for WS type 2, endothelin-3 (EDN3) for WS type 4, although associated with mutations of this gene and its receptor endothelin receptor type B(EDNRB) gene, or in SRY (sex determining region Y)-box 10 (SOX10) gene.

Due to the paucity of reports of WS in Northern Nigeria and its rarity worldwide, we report this case of WS type 1 with familial variability in a consanguineous marriage.


  Case Report Top


An 18-month-old male child was presented by his parents on account of his inability to hear and respond to his mother; at 7 months of age, he did not startle to loud sounds and could not babble. Furthermore, he had hypopigmentation of the frontal hair (white forelock), with an abnormal eye color in one eye (heterochromia irides) since birth. This child was the fifth in a monogamous setting. Pregnancy was uneventful, he was delivered at term but at home with a cord around the neck that was promptly untwined; he, however, did not cry immediately after birth. The child passed meconium by the first day of life and no subsequent history to suggest bowel obstruction and musculoskeletal problems was recorded. Family history revealed hearing impairment in the elder sister and premature graying of the frontal hair with a broad nasal root in both the siblings and the mother. Also, there were variable degrees of hearing losses among the mother's siblings, altogether numbering 10, together with a white forelock; however, not all the siblings had a broad/high nasal root or widely spaced medial canthi (i.e. WS type 2) although two had died in early infancy. Similarly, some of her siblings also had premature graying of the frontal hair (white forelock). The father on the hand had no hearing loss or other associated pigmentary disturbances and was his wife's second degree relative (maternal cousin).

Physical examination revealed a white forelock on the frontal region of the head, with several areas of hypopigmented skin on the nasojugal folds bilaterally and on the right alar nasi. Dystopia canthorum was also noticed with a broad nasal root [Figure 1]. Distraction test was not heard in either ear.
Figure 1: An 18-month-old child with sensorineural hearing loss with other features of WS

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Ophthalmological examination showed good visual acuity bilaterally, dystopia canthorum, complete heterochromia irides; Fundoscopy revealed a reddish fundal glow, pink optic disc, widespread retinal changes and prominent choroidal vessels. The macular area of the fundus could not be visualized due to lack of cooperation from the child.

Audiometric assessment with free field audiometry and tympanometry revealed minimal residual hearing bilaterally, at 110 dBSPL, indicating profound hearing loss with bilateral flat tympanograms. However, acoustic reflexes were not reliably recorded because the child became uncooperative and started crying with his mouth open. We could not test with auditory brainstem response (ABR) audiometry or otoacoustic emission (OAE) due to the lack of these equipments in our center at the time of seeing this child.

Family audiograms were also recorded, which showed a wide variability and asymmetry. However, it was not possible to evaluate the child's grandparents who later refused to come for this assessment. The imaging investigations were also unremarkable.

Based on the above features and the criteria suggested by the WS consortia, a clinical impression of WS type 1 was made.


  Discussion Top


WS is a unique clinical entity divided into subtypes (WS 1-4), basically due to the variable penetrance and expression of its culprit genes. WS type 1 is an auditory-pigmentary disorder comprising sensorineural hearing loss and pigmentary disturbances in the eye, the skin, and the hair, along with dystopia canthorum.[4] It is also inherited in an autosomal dominant manner. Our case is particularly interesting in that the child's grandparents had initially resisted any effort to bring him to the hospital, since they have borne children with similar features who are doing well despite the stigma. This is, however, not surprising because in this region, health-seeking behavior leaves so much to be desired.

Hearing loss is due to the lack of melanocytes in the stria vascularis of the cochlea. Congenital hearing loss is a major feature in most cases of WS and is usually sensorineural and nonprogressive, with a penetrance of 69% in WS type 1 and 87% in WS type 2.[5] This was the presenting feature in our case as well. This loss may be unilateral or bilateral and vary from mild to profound; our patient had bilateral and profound hearing loss, which also correlates well with a similar report in the region from a special school for the deaf.[6]

Other pigmentary abnormalities such as heterochromia, white forelock, dystopia canthorum, and skin changes (only on the face) were equally noted in this patient, which were also noted in his mother but were absent in his father. This agrees with the manner in which WS type 1 is inherited, i.e. autosomal dominant. This is because the PAX3 gene on chromosome 2q35 is a transcription factor that is necessary for embryogenesis; a majority of the patients have an affected parent, whereas minorities of them do not have an affected parent. Availability of genetic testing/sequencing would have been quite useful for the parents and other relatives regarding how to avoid similar occurrence in the future. This was, however, not possible as no geneticist or facility for doing this is available in the region. Furthermore, counseling of the grandparents ab initio may have reduced the impact of these disabilities, as majority of the children would have had some sort of amplification for hearing loss and advice for cosmetic options.

In addition, among the siblings of the mother, there was a lot of variability, with some lacking dystopia canthorum, some without white forelock, some without heterochromia, and a significant number who had no hypopigmented skin changes. This further emphasizes the intra- and interfamilial variabilities, as reported by some authors.[5],[7]

Some authors have reported radiological features in certain WS patients, such as the absence of the posterior semicircular canals bilaterally;[8] globally, this is not a common finding and we did not find it in our case or from the previous reports in this region.[6],[9] Similarly, a recent report showed an association of WS with laryngomalacia in a 45-day-old infant.[10] This is quite novel; though unusual, it is not impossible and the perinatal history of our patient did not reveal any such complaints. We hope that this may ginger efforts to establish genetic counseling units within the health facilities in the region and in the long term, after early and appropriate intervention to reduce the stigma associated with this syndrome in our society. Therefore, prevention by genetic counseling/testing is cost-effective as a preventive strategy and, therefore, highly advocated.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


  Acknowledgment Top


We want to thank our records department for their support in the compilation and retrieval of the case record for this report. Similarly, we would like to thank the patients' parents who graciously volunteered to be examined for the purpose of medical advancement.

 
  References Top

1.
Fortnum HM, Summerfield AQ, Marshall DH, Davis AC, Bamford JM. Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: Questionnaire based ascertainment study. BMJ 2001;323:536-40.  Back to cited text no. 1
    
2.
Nayak CS, Isaacson G. Worldwide distribution of Waardenburg syndrome. Ann Otol Rhinol Laryngol 2003;112:817-20.  Back to cited text no. 2
    
3.
Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. Review and update of mutations causing Waardenburg syndrome. Hum Mutat 2010;31:391-406.  Back to cited text no. 3
    
4.
Karaman A, Aliagaoglu C. Waardenburg syndrome type 1. Dermatol Online J 2006;12:21.  Back to cited text no. 4
    
5.
Newton V. Hearing loss and Waardenburg's syndrome: Implications for genetic counselling. J Laryngol Otol 1990;104:97-103.  Back to cited text no. 5
    
6.
Ahmed AO, Samaila E, Abah ER, Oladigbolu KK, Merali H, Abubakar A. Audiometric findings in Waardenburg's syndrome amongst the institutionalised deaf/blind in Kaduna- Nigeria. Niger J Med 2011;20:28-32.  Back to cited text no. 6
    
7.
Tamayo ML, Gelvez N, Rodriguez M, Florez S, Varon C, Medina D, et al. Screening program for Waardenburg syndrome in Colombia: Clinical definition and phenotypic variability. Am J Med Genet A 2008;146A: 1026-31.  Back to cited text no. 7
    
8.
Mahajan SM, Pithwa M, Chavan A, Pimple D. Absent posterior semicircular canal: HRCT feature of Waardenburg syndrome. Indian J Otol 2012;18:38-40.  Back to cited text no. 8
  Medknow Journal  
9.
Ahmed AO, Abah ER, Oladigbolu KK. Waardenburg syndrome [type 2] in a deaf/blind population in North-Western Nigeria: Series of four cases. Pyramid J Med 2011;1:14-7.  Back to cited text no. 9
    
10.
Thapa R, Mallick D, Ghosh A, Ghosh A. Waardenburg syndrome associated with laryngomalacia. Singapore Med J 2009;50:e401-3.  Back to cited text no. 10
    


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Acknowledgment
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