|Year : 2020 | Volume
| Issue : 2 | Page : 327-329
Case of waardenburg syndrome type 1 in a family with dental abnormalities
Chaitali Hambire1, Umesh Hambire2
1 Department of Pediatric Dentistry, Government Dental College and Hospital, Aurangabad, Maharashtra, India
2 Department of Mechanical Engineering, GECA, Aurangabad, Maharashtra, India
|Date of Submission||13-Mar-2020|
|Date of Acceptance||01-Jun-2020|
|Date of Web Publication||21-Dec-2020|
Dr. Chaitali Hambire
Government Dental College and Hospital, Aurangabad 431 001, Maharashtra
Source of Support: None, Conflict of Interest: None
Waardenburg syndrome type 1 (WS1; MIM #193500) is a rare autosomal-dominant auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and “dystopia canthorum.” The lateral displacement of the ocular inner canthi was caused by heterozygous mutation in the PAX3 gene on chromosome 2q36. This is the case report of a 7-year-old girl showing the characteristic features of WS1 with familial history. Four generations of the patient's family, comprising 32 members, were undertaken to determine the pattern of inheritance, expression of syndrome, and phenotypes. The clinical examination of the 32 family members (18 females, 14 males) showed that ten females (31.25%) and eight males (25%) were affected by WS1. The age of the patients ranged between 3 years and 76 years (mean 24.67 years). Out of 18 family members with WS1, ten members showed white forelock, six members showed dystopia canthorum, eight members had congenital sensorineural hearing loss, seven members had iris heterochromia, and three members had bilateral brilliant blue irises. Dental abnormalities were shown by nine family members including enamel hypoplasia, peg-shaped maxillary laterals, conical teeth, and class 3 malocclusion.
Keywords: Enamel hypoplasia, iris heterochromia, sensorineural hearing loss, Waardenburg syndrome
|How to cite this article:|
Hambire C, Hambire U. Case of waardenburg syndrome type 1 in a family with dental abnormalities. J Datta Meghe Inst Med Sci Univ 2020;15:327-9
| Introduction|| |
Waardenburg syndrome (WS) is a rare inherited disorder of various neural crest-derived tissues described in 1951 by a Dutch ophthalmologist named Petrus Johannes Waardenburg (W). The worldwide incidence of WS is estimated to be approximately 2/100,000. It is an autosomal disorder with clinical manifestations of sensorineural deafness and pigmentation defects of the skin, hair, and iris. The diagnosis of WS is positive when two major or one major plus two minor criteria are present [Table 1]. A first criterion is sensorineural hearing loss, followed by iris pigmentary abnormalities which are in the form of iris bicolor or characteristic brilliant blue iris, hair hypopigmentation (white forelock or white hairs at other sites on the body), and a midfacial alteration called dystopia canthorum which is lateral displacement of the inner eye corners. The W index is a biometric index based on interpupillary, inner canthi, and outer canthal distances. When the W index >1.95, it is considered positive for dystopia canthorum. The minor criterias of WS are the presence of skin hypopigmentation in the form of congenital leukoderma or white skin patches, medial eyebrow flare (synophrys), broad nasal root, hypoplasia alae nasi, and premature graying of the hair (before the age of 30). WS is classified into four types depending on the additional symptoms present: WS1, WS2, WS3, and WS4. Type I (WS1; OMIM #193500) is the classic form of WS with dystopia canthorum (lateral displacement of the inner canthi), whereas Type II (WS2; OMIM #193510) is characterized by the presence of unpigmented tissue and deafness with the absence of dystopia canthorum. Type III (WS3 or Klein–Waardenburg syndrome; OMIM #148820) is similar to Type 1 WS with additional musculoskeletal abnormalities, and Type IV (WS4 or Shah–Waardenburg syndrome or Waardenburg–Hirschsprung disease; OMIM #277580) is characterized by the presence of an aganglionic megacolon. A neurological variant of WS4 is a complex neurocristopathy comprised of four distinct syndromes: peripheral dysmyelination neuropathy, central dysmyelination, WS, and Hirschsprung disease (PCWH; OMIM 609136) and is a potentially fatal disease. WS is genetically heterogeneous. WS1 and WS3 are both caused by mutation in the paired box 3 (PAX3) gene.
Dental manifestations in the form of dental agenesis, cleft lip and/or palate, tooth enamel malformations, and fissured tongue have been described. This is a case report of four generations of an Indian family affected with WS1 and dental phenotypes, not commonly, associated with this disorder.
| Case Report|| |
The proposita 7-year-old female child reported to the Department of Pediatric and Preventive Dentistry Department, Government Dental College and Hospital Aurangabad, accompanied by her aunt, with a chief complaint of carious teeth. The child suffered from bilateral congenital sensorineural hearing loss. Extraoral examination revealed a unilateral brilliant blue iris, dystopia canthorum, broad nasal root, hypoplastic alae of the nose, and protrusion of the lower lip in relation to the upper lip (Korkhaus lip step). The child had dolichocephalic head and leptoprosopic face. The facial profile was straight with an inclination toward class 3 malocclusion [Figure 1] and [Figure 2]. Dental examination revealed conical mandibular central incisors and canines along with peg-shaped maxillary lateral incisors. She had dental crossbite with spacing in anterior teeth [Figure 3]. The W index was 1.98 in our child confirming the diagnosis of WS1.
Four generations of the patient's family, comprising 32 members, were undertaken to determine the pattern of inheritance, expression of syndrome, and phenotypes. The clinical examination of the 32 family members (18 females, 14 males) showed that ten females (31.25%) and eight males (25%) were affected by WS 1. The age of the patients ranged between 3 years and 76 years (mean 24.67 years). Out of 18 family members with WS1, ten members showed white forelock, six members showed dystopia canthorum, eight members had congenital sensorineural hearing loss, seven members had iris heterochromia, and three members had bilateral brilliant blue irises. Dental abnormalities were shown by nine family members including enamel hypoplasia, peg-shaped maxillary laterals, conical teeth, and class 3 malocclusion.
| Discussion|| |
WS has autosomal-dominant inheritance, as reported in our case, affecting nine members of four generations. The etiopathogenesis of WS lies in the mutations in the endothelin 3, endothelin receptor type B (EDNRB), microphthalmia-associated transcription factor (MITF), PAX3, snail homolog 2, and SOX10 (encoding the Sry bOX10 transcription factor) genes, which impairs the normal development, survival, and function of melanocytes resulting in their physical absence from the skin, hair, eyes, or the stria vascularis of the cochlea.
The neural crest cell-derived melanoblasts migrate through different pathways to different destinations such as the inner parts of the ears, skin, and the choroids and iris of the eyes. These melanoblasts undergo differentiation to form the cells producing melanin. These provide protection from ultraviolet radiations and decide the individual's skin color. Piebaldism is a disorder characterized by the patches of white skin and hair due to the absence of melanocytes in the depigmented areas. The association of such pigmentary disturbance with deafness in WS is thought to be due to the lack of melanoblast-derived intermediate cells of the stria vascularis, a small cochlear structure that plays an important role in the production of endolymph. A lack of strial intermediate cells leads to degeneration of the organ of Corti, and thus hearing loss, in several animal models. Studies have shown that the TF PAX3 and SOX10 cooperate upon binding to the MITF promoter to modulate its expression. Recently, SOX10 was also described as able to regulate expression during melanocyte development. Finally, epistatic relationships between the ET3/ETB pathway and MITF were recently described. ET3/ETB signaling regulates MITF in two ways: (1) direct phosphorylation through mitogen-activated protein kinase and (2) upregulation of MITF gene expression. MITF is also associated with feedback loop of EDNRB expression. The MITF mutations are present in WS2 with autosomal-dominant transmission in 15% of cases. The autosomal-dominant transmission with neurological involvement is found in association with mutations of SOX10 in 15% WS2 and 50% of cases of WS4.
In our case, all the family members were showing the characteristic features of WS-white forelock with eyebrow hyperplasia along with other extracutaneous characters such as heterochromia irides, broad nasal root, and deafness. They were also exhibiting dental malformations such as conical-shaped incisors and dental crossbite. The mandibular prognathism was also found in patients previously reported in the literature by other authors.
| Conclusion|| |
A multidisciplinary team of medical professionals including an otolaryngologist, audiologist, speech therapist, geneticist, genetic counselor, ophthalmologist, dermatologist, gastroenterologist, and dentist is required for the optimal management of the WS patients. Genetic counseling is a must to confirm the diagnosis as well as the type of WS. In the future, more researches with larger number of cases are required for better understanding of the mechanisms involved in the clinical manifestations of this rare syndrome and other gene mutations associated with it.
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]