Waardenburg Syndrome Research Articles

Establishment of an iPSC line (JTUi002-A) from a patient with Waardenburg syndrome caused by a SOX10 mutation and carrying a GJB2 mutation.

Waardenburg syndrome (WS) is an inherited auditory-pigmentary syndrome characterized by deafness and pigment abnormalities. Here, we generated an induced pluripotent stem cell (iPSC) line using episomal plasmid vectors from the fibroblasts of an 8-year-old boy affected with WS, caused by a novel mutation in the SOX10 gene (NM_006941.3: c.937_947del; p.Tyr313Argfs*85), with a concurrent hotspot mutation in the GJB2 gene (NM_004004.5:c.235delC; p.Leu79Cysfs*3). The expression of pluripotency markers of the iPSC cell line was verified at both the mRNA and protein levels and the pluripotency state of the cell line was demonstrated by the capability to differentiate into all three germ layers.

Hearing Impairment Overview in Africa: the Case of Cameroon.

The incidence of hearing impairment (HI) is higher in low- and middle-income countries when compared to high-income countries. There is therefore a necessity to estimate the burden of this condition in developing world. The aim of our study was to use a systematic approach to provide summarized data on the prevalence, etiologies, clinical patterns and genetics of HI in Cameroon. We searched PubMed, Scopus, African Journals Online, AFROLIB and African Index Medicus to identify relevant studies on HI in Cameroon, published from inception to 31 October, 2019, with no language restrictions. Reference lists of included studies were also scrutinized, and data were summarized narratively. This study is registered with PROSPERO, number CRD42019142788. We screened 333 records, of which 17 studies were finally included in the review. The prevalence of HI in Cameroon ranges from 0.9% to 3.6% in population-based studies and increases with age. Environmental factors contribute to 52.6% to 62.2% of HI cases, with meningitis, impacted wax and age-related disorder being the most common ones. Hereditary HI comprises 0.8% to 14.8% of all cases. In 32.6% to 37% of HI cases, the origin remains unknown. Non-syndromic hearing impairment (NSHI) is the most frequent clinical entity and accounts for 86.1% to 92.5% of cases of HI of genetic origin. Waardenburg and Usher syndromes account for 50% to 57.14% and 8.9% to 42.9% of genetic syndromic cases, respectively. No pathogenic mutation was described in GJB6 gene, and the prevalence of pathogenic mutations in GJB2 gene ranged from 0% to 0.5%. The prevalence of pathogenic mutations in other known NSHI genes was <10% in Cameroonian probands. Environmental factors are the leading etiology of HI in Cameroon, and mutations in most important HI genes are infrequent in Cameroon. Whole genome sequencing therefore appears as the most effective way to identify variants associated with HI in Cameroon and sub-Saharan Africa in general.

Congenital Hypogonadotropic Hypogonadism with Anosmia and Gorlin Features Caused by a PTCH1 Mutation Reveals a New Candidate Gene for Kallmann Syndrome

Background: Two loci (CHD7 and SOX10) underlying Kallmann syndrome (KS) were discovered through clinical and genetic analysis of CHARGE and Waardenburg syndromes, conditions that include congenital anosmia caused by olfactory bulb (CA/OBs) defects and congenital hypogonadotropic hypogonadism (CHH). We hypothesized that other candidate genes for KS could be discovered by analyzing rare syndromes presenting with these signs. Study Design, Size, Duration: We first investigated a family with Gorlin-Goltz syndrome (GGS) in which affected members exhibited clinical signs suggesting KS. Participants/Materials, Methods: Proband and family members underwent detailed clinical assessment. The proband received detailed neuroendocrine evaluation. Genetic analyses included sequencing the PTCH1 gene at diagnosis, followed by exome analyses of causative or candidate KS/CHH genes, in order to exclude contribution to the phenotypes of additional mutations. Exome analyses in additional 124 patients with KS/CHH probands with no additional GGS signs. Results: The proband exhibited CA, absent OBs on magnetic resonance imaging, and had CHH with unilateral cryptorchidism, consistent with KS. Pulsatile Gonadotropin-releasing hormone (GnRH) therapy normalized serum gonadotropins and increased testosterone levels, supporting GnRH deficiency. Genetic studies revealed 3 affected family members harbor a novel mutation of PTCH1 (c.838G> T; p.Glu280*). This unreported nonsense deleterious mutation results in either a putative truncated Ptch1 protein or in an absence of translated Ptch1 protein related to nonsense mediated messenger RNA decay. This heterozygous mutation cosegregates in the pedigree with GGS and CA with OBs aplasia/hypoplasia and with CHH in the proband suggesting a genetic linkage and an autosomal dominant mode of inheritance. No pathogenic rare variants in other KS/CHH genes cosegregated with these phenotypes. In additional 124 KS/CHH patients, 3 additional heterozygous, rare missense variants were found and predicted in silico to be damaging: p.Ser1203Arg, p.Arg1192Ser, and p.Ile108Met. Conclusion: This family suggests that the 2 main signs of KS can be included in GGS associated with PTCH1 mutations. Our data combined with mice models suggest that PTCH1 could be a novel candidate gene for KS/CHH and reinforce the role of the Hedgehog signaling pathway in pathophysiology of KS and GnRH neuron migration.

Waardenburg-Shah syndrome (WS type IV): a rare case from Pakistan

Waardenburg-Shah syndrome is a rare autosomal recessive [AR] inherited disorder characterized by the presence of Hirschsprung’s disease with a high likelihood of aganglionic megacolon, due to which the mortality is high. The management of the condition involves surgical intervention for the removal of the aganglionic segment of the colon. Here, we report a neonate that presented with a white forelock, white eyelashes, iris hypopigmentation, and sensorineural deafness associated with bilious vomiting, refusal to feed, and failure to pass meconium indicating intestinal obstruction.

Identification of six novel variants in Waardenburg syndrome type II by next-generation sequencing.

BackgroundWaardenburg syndrome (WS) is a dominantly inherited, genetically heterogeneous auditory‐pigmentary syndrome characterized by nonprogressive sensorineural hearing loss and iris discoloration. This study aimed to investigate the underlying molecular pathology in Chinese WS families.MethodsA total of 13 patients with Waardenburg syndrome type II (WS2) from six unrelated Chinese families were enrolled. We investigated the mutation profile of genes related to congenital deafness in these families through a targeted sequencing technology and validated the candidate variants by Sanger sequencing.ResultsWe identified six novel variants in microphthalmia‐associated transcription factor (MITF) and SRY‐box 10 (SOX10), which were predicted to be disease causing by in silico analysis. Our results showed that mutations in SOX10 and MITF are two major causes of deafness associated with WS, and de novo mutations were frequently found in probands with SOX10 mutations but not in those with MITF mutations.ConclusionResults showed that targeted next‐generation sequencing (NGS) enabled us to detect disease‐causing mutations with high accuracy, stability, speed and throughput. Our study extends the pathogenic mutation spectrum of MITF and SOX10.

Genetic study of a family with affected members with Waardenburg syndrome type 4 without Hirschsprung disease

Introduction. Waardenburg syndrome (WS) is an autosomally inherited disorder with the most common state compounding pigmentary abnormality and sensorineural deafness. The rarest type of the disease is WS4 with the general characteristic discriminated from other types by the attendance of Hirschsprung disease (HD). Among the several genes, one of the causative genes in WS4 is endothelin 3 (EDN3) with both autosomal recessive and dominant inheritance. Aim. The intention of the present study is to report a pathogenic mutation as the genetic cause of WS in an Iranian family with four patients without any segregation criteria for the type of the disease. Material and methods. In order to detect of causing gene or genes related to the disease, Whole exome sequencing (WES) technique in proband’s sample was done. To confirm the detected mutation in proband and some family members with or without the disease direct sequencing of END3 gene was performed using Sanger method. Results. Pedigree analysis suggested segregation of WS as an autosomal recessive trait in the family. WES analysis suggested a gene (EDN3) related to WS type 4B. DNA sequencing confirmed a pathogenic missense mutation c.293C&gt;T, p.T98M in EDN3 gene in all of the four patients. Conclusion. Determination of WS can usually be missed owing to the lack of some attributes in every sufferer and also conventional clinical variance, in spite of several affected members in a single family. So, Genetic counseling is pivotal for families with multiple members influenced. We detected c.293C&gt;T, p.T98K mutation in EDN3 gene as a pathogenic variant which has been known as a likely pathogenic state in the American College of Medical Genetics and Genomics (ACMG) guidelines, despite one prior report. It will be helpful in genetic diagnosis of affected persons and increases the mutation spectrum of EDN3 gene.

Case of waardenburg syndrome type 1 in a family with dental abnormalities

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.

Different rate of retinal degenerations in mice with two distinct mutations in the Mitf gene

AbstractPurposeThe microphthalmia‐associated transcription factor (Mitf) gene is crucial for development of the retinal pigment epithelium (RPE) and photoreceptors. Loss of function mutations in this gene can cause ocular hypopigmentation, microphthalmia and blindness. Mice heterozygous for the Mitfmi‐wh/+ mutation have been used as a model for Waardenburg and Tietz syndromes in humans. The compound heterozygote Mitfmi‐wh/Mitfmi has two different mutant alleles in the Mitf gene each of which have quite severe effects on the phenotype. The purpose of this study was to examine changes over time in retinal function and structure in these mice, between 1 and 5 months of age, to elucidate the rate of progression of the retinal degenerations.MethodsB6‐Mitfmi‐wh/+ and B6‐Mitfmi‐wh/Mitfmi mice were examined and compared to C5BL/6J mice as control. Mice were anesthetized by an intraperitoneal injection of 40 mg/kg‐1 Ketamine and 4 mg/kg‐1 Xylazine. Fundus and optical coherence tomography (OCT) images were obtained with a Micron IV. Flash electroretinography (ERG) from mice with a corneal electrode was used to determine retinal function.ResultsFundus images from all mutant mice show hypopigmentation at 1 month, with large non‐pigmented areas forming at later stages. Mitfmi‐wh/+ mice are either blind or not at 1 month, with the ERG normal in amplitude in some animals and absent in others. The Mitfmi‐wh/+ mice with ERG responses at 1 month show slow retinal degeneration, with reduced responses at 5 months. Mitfmi‐wh/Mitfmi mice show either abnormal ERG responses at 1 month, or a flat ERG. The ERG responses in some of the Mitfmi‐wh/Mitfmi mice decrease with time, and at 4 months is flat. OCT images reveal that retinal layers in animals with flat ERG are thinner than in mice showing reduced ERG, but abnormally thin in both.ConclusionsWe conclude that Mitfmi‐wh/Mitfmi mutant mice show evidence of fast retinal degeneration. The Mitfmi‐wh/+ mutant mice are either blind at 1 month or show evidence of slow degeneration. Mice with these Mitf mutations may serve as models of retinal degenerations progressing at different rates, due to mutations in a gene expressed in the RPE.

The clinical and genetic research of Waardenburg syndrome type I and II in Chinese families

ObjectiveWaardenburg Syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance and highly genetic heterogeneity. To date, mutations of PAX3, SOX10, MITF, EDNRB, EDN3 and SNAI2 have been implicated in the pathogenesis of WS. In this study, we aimed to identify pathogenic genes among WS families and to analyze the pathogenic relationship between genotypes and phenotypes. MethodsIn this study, all six families studied were from Hubei province, China.WS patients underwent screening for all deafness genes including PAX3, SOX10, MITF, EDNRB, EDN3 and SNAI2 using Massively Parallel Sequencing (MPS) and validation of mutations using Sanger sequencing. ResultsClinical evaluation revealed prominent phenotypic variability in Hubei WS patients. Two WS1 families and four WS2 families were diagnosed in six families. Sensorineural hearing loss was the most common, followed by iris pigmentary abnormality. Molecular genetic analysis of the WS genes for six families revealed five novel heterozygous mutations. Two mutations occurred in the PAX3 gene: one nonsense mutation c.667C > T(p.Arg223Ter) and one missense mutation c.220C > T(p.Arg74Cys).One missense mutation c.331T > C (p.Phe111Leu) and one nonsense mutation c.346C > T(p.Gln116Ter) were detected in the SOX10 gene. Two mutations were detected in the MITF gene: one splice site mutation c.859-1G > A and one nonsense mutation c.859G > T(p.Glu287Ter). Among them, the mutations (SOX10 c.331T > C and MITF c.859G > T) were de novo mutations. ConclusionIn this study, six mutations were found to be associated with the phenotype of patients. Our data helped illuminate the phenotypic and genotypic spectrum of WS in Hubei province and could have implications for the genetic counseling of WS in Hubei province.

GJB2 and GJB6 Mutations in Hereditary Recessive Non-Syndromic Hearing Impairment in Cameroon.

This study aimed to investigate GJB2 (connexin 26) and GJB6 (connexin 30) mutations associated with familial non-syndromic childhood hearing impairment (HI) in Cameroon. We selected only families segregating HI, with at least two affected individuals and with strong evidence of non-environmental causes. DNA was extracted from peripheral blood, and the entire coding region of GJB2 was interrogated using Sanger sequencing. Multiplex PCR and Sanger sequencing were used to analyze the prevalence of the GJB6-D3S1830 deletion. A total of 93 patients, belonging to 41 families, were included in the analysis. Hearing impairment was sensorineural in 51 out of 54 (94.4%) patients. Pedigree analysis suggested autosomal recessive inheritance in 85.4% (35/41) of families. Hearing impairment was inherited in an autosomal dominant and mitochondrial mode in 12.2% (5/41) and 2.4% (1/41) of families, respectively. Most HI participants were non-syndromic (92.5%; 86/93). Four patients from two families presented with type 2 Waardenburg syndrome, and three cases of type 2 Usher syndrome were identified in one family. No GJB2 mutations were found in any of the 29 families with non-syndromic HI. Additionally, the GJB6-D3S1830 deletion was not identified in any of the HI patients. This study confirms that mutations in the GJB2 gene and the del(GJB6-D13S1830) mutation do not contribute to familial HI in Cameroon.

Waardenburg syndrome: a rare genetic disorder in four generations of a family

Waardenburg Syndrome (WS) is a rare autosomal dominant disorder manifesting with sensorineural deafness, pigmentation defects of the skin, hair and iris and various defects of neural crest derived tissues. A primigravida mother delivered a full term, appropriate for gestational age, 2530 gm female child, by emergency LSCS. Baby was admitted in the NICU in view of features suggestive of Waardenburg syndrome, like white forelock of hair, broad nasal root and hypopigmented patches on the skin for further work up and management. Several members in the family were affected in the last 4 consecutive generations. Our baby was feeding well and discharged home after an uneventful hospital stay. Early diagnosis, detection of findings of hearing loss and the characteristic ophthalmic findings as well as regular follow up is necessary to enable the patient to lead a better quality of life.

Delineating the role of MITF isoforms in pigmentation and tissue homeostasis.

MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, encodes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini. It is not completely understood how these isoforms influence pigmentation in different tissues and how the expression of these independent isoforms of MITF is regulated. Here, we show that melanocytes express two isoforms of MITF, MITF-A and MITF-M. The expression of MITF-A is partially regulated by a newly identified retinoid enhancer element located upstream of the MITF-A promoter. Mitf-A knockout mice have only subtle changes in melanin accumulation in the hair and reduced Tyr expression in the eye. In contrast, Mitf-M-null mice have enlarged kidneys, lack neural crest-derived melanocytes in the skin, choroid, and iris stroma, yet maintain pigmentation within the retinal pigment epithelium and iris pigment epithelium of the eye. Taken together, these studies identify a critical role for MITF-M in melanocytes, a minor role for MITF-A in regulating pigmentation in the hair and Tyr expression in the eye, and a novel role for MITF-M in size control of the kidney.

Waardenburg syndrome and seizures - Is there an association?

Waardenburg Syndrome (WS) is a rare genetic disorder characterized by hearing loss and other defects in structures arising from the neural crest. Here we present a patient with unexplained seizures and genetically-proven Waardenburg Syndrome Type 1 and review the possibility that seizures may be associated. We present the case of a 39 year old woman with facial features of WS presenting to the neurology clinic. A 39 year old woman presented with appearance notable for a broad nasal bridge with wide-set eyes and the dystopic canthorum characteristic of WS Type 1. She had poliosis, a forelock of white hair, and sectoral heterochromia of the eyes, an iris being of two distinct colors. Without an identifiable precipitant, the patient had a witnessed generalized tonic-clonic seizure at age 33. Subsequent workup revealed an unremarkable electroencephalogram (EEG) and brain magnetic resonance imaging (MRI.) However, her seizures recurred. Genetic testing was performed confirming a pathogenic mutation in the PAX3 gene, a gene important in embryonic development with activity in neural crest cells and a known association with Waardenburg Syndrome. There was no family history of seizures, however, her daughter had one febrile seizure at 18 months and another daughter died suddenly in her sleep at age 5. Although seizures in Waardenburg Syndrome are rare, this syndrome is a known neurocristopathy and defective migration of neural crest cells can manifest with a wide spectrum of known and not yet understood neurologic abnormalities. Perhaps additional cases of seizures in WS will be reported.

Waardenburg Syndrome: A Case Report

Waardenburg syndrome is an uncommon autosomal dominant or recessive disorder, distinguished by hypopigmentation of either skin or hairs or both, segmental, partial or complete heterochromia iridis or isohypochromia, hypertrichosis of eyebrow, synophrys, dystopia canthorum, broad and high nasal root and congenital deafness. The diagnostic criteria consist of major and minor criteria; major includes congenital sensorineural hearing loss, pigmentary abnormality in iris, segmental, partial or complete heterochromia iridis, isohypochromia, fore hair’s achromia, dystopia canthorum and affected first degree relative while minor criteria include congenital leukoderma, synophrys, broad and high nasal root, hypoplasia of nasal alae and premature graying of hair.&#x0D; Herein we report a case of two days old baby boy having uncommon pigmentation of hair and iris beside dystopia canthorum. He was diagnosed as a case of Waardenburg Syndrome type1 (WS1).

Whole genome genotyping mapped regions on chromosome 2 and 18 in a family segregating Waardenburg syndrome type II

ObjectivesWaardenburg syndrome is a rare genetic disorder. It is characterized by sensorineural hearing impairment and pigment defects of the skin, hair and iris. In some cases abnormalities in the tissues derived from neural crest have also been reported. Mutations in several genes have been reported as an underlying cause of Waardenburg syndrome. Objective of this study is to identify the chromosomal region(s) associated with Waardenburg syndrome in an extended Saudi family. MethodsGenomic DNA was extracted from fifteen individuals of a Saudi family segregating Waardenburg syndrome. Whole genome SNP genotyping was performed to identify common identity by descent chromosomal region(s) shared by affected individuals. ResultsPedigree analysis confirm autosomal dominant inheritance of Waardenburg syndrome type II in a family. Whole genome SNP genotypes were analyzed using AutoSNPa and DominantMapper tools. Shared identity by descent chromosomal regions were identified on chromosome 2 and chromosome 18. Regions were checked for known Waardenburg syndrome genes. No known gene is present in both regions. ConclusionsIn summary, we identified novel chromosomal regions associated with Waardenburg syndrome type II in a Saudi family. Deep sequencing of a complete candidate regions are required to identify the gene underlying Waardenburg syndrome in this family.

The heterozygous EDNRB mutation in a Chinese family with Waardenburg syndrome type I.

The genovariation of endothelin receptor type B (EDNRB) was identified in a Chinese family with Waardenburg syndrome type I (WS1) in the present study. WS1 was diagnosed in a 19-year-old young man, his older sister and aunt according to WS consortium criteria. After extracting genomic DNA from the peripheral blood samples, the coding exons and intronic regions of EDNRB were sequenced. A missense heterozygous mutation was found in the coding region of exon 2 in the EDNRB gene on chormosome 13q22.3 of the proband. The same mutation was detected in the proband's afflicted paternal aunt and first older sister. Subsequent polyphen analysis and three-dimensional modeling confirmed that the c.469A>G heterozygous mutation in EDNRB was possibly pathogenic. This is the first report of EDNRB mutation as a potential disease-causing mutation in Chinese patients with WS1.

Comprehensive analysis of syndromic hearing loss patients in Japan

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

Identification of Waardenburg Syndrome and the Management of Hearing Loss and Associated Sequelae: A Review for the Pediatric Nurse Practitioner.

Waardenburg syndrome (WS) is a rare genetic disorder that is further divided into four subtypes with distinguishing clinical manifestations, categorized by phenotypic variations based on activation or deactivation of six specific gene types. The criteria for clinical diagnosis are established based on these phenotypic variants. While key clinical features may cause suspicion of WS, genetic testing confirms the diagnosis. Pigmentary defects are one of the hallmark features of WS while some individuals may exhibit sensorineural hearing loss, which can be progressive. Audiological treatment is essential to mitigate hearing loss and to minimize speech and language deficits as well as behavior and socioemotional development. Associated complications include musculoskeletal abnormalities and Hirschsprung disease. This article aims to discuss the role of the pediatric nurse practitioner in the early identification, diagnosis, treatment, and long-term management of affected children in the primary care setting.

Waardenburg syndrome: characteristics and long-term outcomes of paediatric cochlear implant recipients

Objective: To assess the long-term outcomes after cochlear implantation in children under 3 years of age with Waardenburg syndrome (WS), concerning preoperative radiological imaging, intraoperative surgical findings and postoperative auditory and speech performance.Material and methods: A retrospective analytical study conducted on the young WS children with bilateral profound sensorineural hearing loss (SNHL) who underwent the cochlear implantation. Postoperative outcomes were confronted with results obtained by aged-matched peers without additional disabilities. The auditory performance was assessed with the MAIS and CAP. The speech and language development were evaluated with the MUSS and SIR. Radiological evaluation was performed with the MRI and HRCT scans.Results: There were 22 children with WS, who received a multichannel implant at a mean age of 23.5 months of age (SD 7.5, range: 12–36 months). WS group outperformed non-syndromic (NS) children in SIR (4.7, 95%, SD 0.8 vs. 4.3, 95%, SD 0.8) and MUSS (35.6, 95%, SD 3.4 vs. 30.3, 95%, SD 7.6). Auditory performance assessed in MAIS/IT-MAIS improved similarly in both groups (34.8, 95%, SD 1.8 in WS vs. 35, 95%, SD 2.5 in NS children). The reference group gained significantly higher scores in CAP (6.2, 95%, SD 0.7 vs. 5.8, 95%, SD 1.8). Additional anomalies of the inner ear were observed including the enlarged vestibular aqueduct (EVA), common cavity deformity (CCD), incomplete partition type II (IP-II). Two cases presented various forms of mental retardation.Conclusion: The study demonstrated that cochlear implantation in young children with WS is a beneficial method treating profound SNHL. The most beneficial outcomes may be achieved thanks to the early implantation, parental involvement and comprehensive care from speech therapists, preferably implemented altogether. The detailed radiological examination and psychological assessment should be considered before the implantation. The results support the concept of early cochlear implantation in children with genetic disorders.

Waardenburg Syndrome Type 1 in an Infant Diagnosed with Congenital Hypothyroidism

Waardenburg syndrome type 1 is a rare autosomal dominant auditory-pigmentary syndrome characterised by pigmentary abnormalities of the hair, skin, and eyes associated with congenital non-progressive sensorineural hearing loss. Diagnosis is usually clinical and based on the characteristic clinical features which constitute major and minor criteria. Though hypothyroidism has been described among family members of children with Waardenburg syndrome type 1 there is no reported existence of the two conditions in the same patient. Here we report Waardenburg Syndrome Type 1 in an infant who was already diagnosed to have congenital hypothyroidism and whether it would be a co incidental finding or an association needs further evaluation.