ABSTRACT
Waardenburg syndrome (WS), also known as auditory-pigmentary syndrome, is the most common cause of syndromic hearing loss (HL), which accounts for approximately 2-5% of all patients with congenital hearing loss. WS is classified into four subtypes depending on the clinical phenotypes. Currently, pathogenic mutations of PAX3, MITF, SOX10, EDN3, EDNRB or SNAI2 are associated with different subtypes of WS. Although supportive techniques like hearing aids, cochlear implants, or other assistive listening devices can alleviate the HL symptom, there is no cure for WS to date. Recently major progress has been achieved in preclinical studies of genetic HL in animal models, including gene delivery and stem cell replacement therapies. This review focuses on the current understandings of pathogenic mechanisms and potential biological therapeutic approaches for HL in WS, providing strategies and directions for implementing WS biological therapies, as well as possible problems to be faced, in the future.
Subject(s)
Deafness , Waardenburg Syndrome , Animals , Microphthalmia-Associated Transcription Factor/genetics , Mutation , PAX3 Transcription Factor/genetics , Phenotype , SOXE Transcription Factors/genetics , Waardenburg Syndrome/diagnosis , Waardenburg Syndrome/genetics , Waardenburg Syndrome/therapyABSTRACT
Melanocyte development is orchestrated by a complex interconnecting regulatory network of genes and synergistic interactions. Piebaldism and Waardenburg syndrome are neurocristopathies that arise from mutations in genes involved in this complex network. Our understanding of melanocyte development, Piebaldism, and Waardenburg syndrome has improved dramatically over the past decade. The diagnosis and classification of Waardenburg syndrome, first proposed in 1992 and based on phenotype, have expanded over the past three decades to include genotype. This review focuses on the current understanding of human melanocyte development and the evaluation and management of Piebaldism and Waardenburg syndrome. Management is often challenging and requires a multidisciplinary approach.
Subject(s)
Melanocytes/physiology , Piebaldism/genetics , Waardenburg Syndrome/genetics , Diagnosis, Differential , Humans , Melanocytes/metabolism , Mutation , Phenotype , Piebaldism/diagnosis , Piebaldism/therapy , Waardenburg Syndrome/diagnosis , Waardenburg Syndrome/therapyABSTRACT
Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the development of neural crest cells, caused by an altered cellular migration during the embryonic phase. That alteration causes an association of different abnormalities such as pigmentary disturbances of the hair, iris, skin, stria vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We report a case of a 14-year-old Romanian male, with a family history of Waardenburg syndrome (mother) and Usher syndrome (father - congenitally sensorineural hearing loss and retinal degeneration). The case particularities are: the correlation between malocclusion and Waardenburg syndrome due to hypoplastic alae nasi and also factors that produced hearing loss, which could be Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X) gene mutation.
Subject(s)
Malocclusion/diagnosis , Malocclusion/therapy , Orthodontics/methods , Waardenburg Syndrome/diagnosis , Waardenburg Syndrome/therapy , Adolescent , Cell Movement , Cochlear Implantation , Connexin 26 , Connexins/genetics , Deafness/complications , Facies , Hair , Hearing Loss, Bilateral/complications , Humans , Male , Mutation , Neural Crest/pathology , Phenotype , Pigmentation , PrognosisABSTRACT
UNLABELLED: Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. OBJECTIVE: The aim of the article is to study the relative frequency of associations in 6 consecutive cases of SWS. METHODS: A review of 6 consecutive patients with SWS was performed to study the frequency of various components of the syndrome. RESULTS: Six patients had features of SWS. All patients had HD; of these, 3 had rectosigmoid HD, whereas 3 had extended HD. All patients had white forelock of hairs with skin depigmentation. One patient had sensorineural deafness, whereas other babies were less than 1 year, and thus, full evaluation of hearing deficiency was not assessed. Three patients had blue eyes, whereas other babies had normal iris pigmentation. Skin depigmentation was noted in 5 of the 6 patients. Three babies were seriously malnourished and showed higher association of enterocolitis. CONCLUSION: Shah-Waardenburg syndrome is an uncommon association of HD. Depigmentation with a white forelock and skin manifestations are common, whereas blue iris, long segment disease, and enterocolitis are present in nearly half of the patients.
