Waardenburg Syndrome, Type 4

Last update 01 Nov 2024

Basic Info

Synonyms

Hirschsprung disease with pigmentary anomaly, SHAH-WAARDENBURG SYNDROME, Shah Waardenburg syndrome

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Introduction

A rare, autosomal dominant or autosomal recessive syndrome caused by mutations in the SOX10, EDN3, or EDNRB genes. It is characterized by pigmentary abnormalities of the hair, skin, and eyes, congenital sensorineural hearing loss, and Hirschsprung disease.

100 Clinical Results associated with Waardenburg Syndrome, Type 4

100 Translational Medicine associated with Waardenburg Syndrome, Type 4

0 Patents (Medical) associated with Waardenburg Syndrome, Type 4

166

Literatures (Medical) associated with Waardenburg Syndrome, Type 4

08 May 2024·Cureus

Clinical Insights Into Waardenburg-Shah Syndrome: A Case Series and Literature Review

Article

Author: Nimal, Simran ; Mahalingam, Akhshaya ; Reshie, Aisha ; Duggineni, Dileep ; Kankipati, Sri Meghana ; Fayaz, Falah

Researching Waardenburg syndrome (WS) underscores its rarity and complex symptomatology, presenting as a congenital disorder predominantly inherited in an autosomal dominant pattern. It exhibits incomplete penetrance, which results in a wide range of clinical manifestations, with variable phenotypic presentations within the same family as well. The most commonly found features are facial abnormalities, hypopigmentation of the skin, heterochromia iridis, and conductive deafness. Adding to the eccentricities of this syndrome are its four subtypes, each presenting with its specific clinical features, which helps in delineating the subtype. A mutated paired box 3 (PAX3) gene manifests as type 1 Waardenburg, which is characterized by sideways displacement of the inner angles of the eyes (i.e., dystopia canthorum), widely spaced eyes, congenital sensorineural hearing impairment, and patchy pigmentation of the iris, skin, and hair. Due to insufficient research, it has been difficult to isolate all the genetic mutations responsible for type 2, but its phenotype is very similar to type 1 with minor differences. Type 3 is characterized by musculoskeletal abnormalities. Waardenburg-Shah syndrome (type 4), which is associated with Hirschsprung disease, is the rarest subtype and is caused by genetic mutations in the endothelin receptor type B (EDNRB), endothelin-3 (EDN3), or sex-determining region Y (SRY) box 10 (SOX10) gene. We present a case series of this unique subtype that presented with a typical history of constipation due to Hirschsprung disease and had phenotypic manifestations of white forelock, heterochromia iridis, and bilateral sensorineural hearing loss (SNHL). In parallel with a positive 1° family history of a white forelock, we reflect on the fundamentals of this unique syndrome, as well as its management protocols, highlighting the importance of genetic counseling and cultivation of a high index of suspicion for its diagnosis.

26 Jun 2023·BMC medical genomics

A novel variant of the SOX10 gene associated with Waardenburg syndrome type IV.

Article

Author: Zhang, Pai ; Zang, Weiwei ; Chai, Yuqiong ; Wang, Yanan

BACKGROUNDWaardenburg syndrome (WS) is a rare genetic disorder characterized by varying degrees of sensorineural hearing loss and accumulated pigmentation in the skin, hair and iris. The syndrome is classified into four types (WS1, WS2, WS3, and WS4), each with different clinical phenotypes and underlying genetic causes. The aim of this study was to identify the pathogenic variant in a Chinese family with Waardenburg syndrome type IV.METHODSThe patient and his parents underwent a thorough medical examination. We applied whole exome sequencing to identify the causal variant on the patient and other family members.RESULTSThe patient presented with iris pigmentary abnormality, congenital megacolon and sensorineural hearing loss. The clinical diagnosis of the patient was WS4. The whole exome sequencing (WES) revealed a novel variant (c.452_456dup) in the SOX10 gene, which could be responsible for the observed pathogenic of WS4 in this patient. Our analysis suggests that this variant produces a truncated protein that contributes to the development of the disease. The genetic test confirmed the diagnosis of WS4 in the patient from the studied pedigree.CONCLUSIONSThis present study demonstrated that genetic test based on WES, an effective alternative to regular clinical examinations, helps diagnose WS4. The newly identified SOX10 gene variant can expand the understanding of WS4.

01 Dec 2022·Journal of Medical Case Reports

Waardenburg syndrome type 4 coexisting with open-angle glaucoma: a case report

Article

Author: Wang, Ningli ; Wan, Yue ; Zhang, Li

AbstractBackgroundWaardenburg syndrome is an autosomal dominant disorder with varying degrees of sensorineural hearing loss as well as abnormal pigmentation in hair, skin, and iris. There are four types of Waardenburg syndrome (1–4) with different characteristics. Mutations in six genes have been identified to be associated with the various types. Herein, we describe a case of Waardenburg syndrome type 4 combined with open-angle glaucoma.Case presentationA 43-year-old Han Chinese man had undergone trabeculectomy due to progression of visual field impairment and unstable intraocular pressure in both eyes. Slit-lamp examination revealed diffuse iris hypopigmentation in the left eye and hypopigmentation of part of the iris in the right eye. Fundus examination showed red, sunset-like fundus due to a lack of pigmentation in the retinal pigment epithelium layer, diffuse loss of the nerve fiber layer, and an excavated optic nerve head with advanced-stage glaucoma. Imaging was performed using anterior segment optical coherence tomography to detect the iris configuration. In the heterochromic iris portion, the normal part of the iris showed a clear hyperreflective signal of the anterior border layer, while atrophy of the pigmented anterior border layer showed a hyporeflective area of the anterior surface resulting in reduced light absorption. Two mutations of the endothelin receptor type B gene were recognized in this study. The first (c.1111G>A on exon 7) leads to an amino acid change from glycine to serine at codon 371. Sanger verification revealed that this mutation is inherited from the mother. The other mutation (c.553G>A) leads to an amino acid change from valine to methionine at codon 185. Sanger verification showed that this mutation was inherited from the father.ConclusionWaardenburg syndrome shows a remarkable diversity in clinical presentation and morphology. This disease can also present with open-angle glaucoma. Sequencing analysis revealed two heterozygous mutations in the EDNRB gene in this patient, inherited from his mother and father, respectively. These two sites constitute a compound heterozygous variation.

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Waardenburg Syndrome, Type 4

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