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Waardenburg Syndrome
Introduction
Waardenburg syndrome refers to a group of genetic conditions typically inherited in an autosomal dominant pattern. Named after Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg, the condition was first described in 1951.[1] During embryogenesis, pathogenic mutations disrupt neural crest cell migration and division. Since melanocytes originate from the neural crest, affected individuals demonstrate abnormal melanocyte distribution, leading to patchy depigmentation.
This rare disorder involves loss of pigment-producing cells in the eyes, skin, hair, and the stria vascularis of the cochlea.[2] Clinical presentation varies, but hallmark features include a broad nasal root, hypertelorism with dystopia of the lacrimal puncta, heterochromia or hypopigmented irides, medial eyebrow hypertrichosis, a white forelock, and congenital sensorineural hearing loss (SNHL).[3]
Although no curative therapy exists, supportive care includes cochlear implantation and surgical management of associated conditions such as Hirschsprung disease. Genetic counseling facilitates early diagnosis, risk assessment, and informed family planning.[4]
Etiology
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Etiology
Waardenburg syndrome follows an autosomal dominant inheritance pattern in most cases. Multiple gene mutations, including insertions, deletions, frameshifts, missense, and nonsense variants, disrupt the migration and differentiation of neural crest cells during embryogenesis, leading to characteristic clinical features.[5] Penetrance and expressivity vary depending on the specific gene involved.
Four clinical subtypes have been identified. Type 1, one of the most common forms, results from mutations in the PAX3 gene and typically presents with congenital SNHL, dystopia canthorum (lateral displacement of the inner canthi), neural tube defects, cleft lip or palate, and patchy depigmentation of the skin and hair.[6] Ocular pigmentary abnormalities frequently accompany these features. Type 2 Waardenburg syndrome, also common, arises from mutations in the MITF gene.[7] Although individuals with type 2 lack dystopia canthorum, they share other clinical features with type 1.
Type 3 represents a more severe variant of type 1, with additional musculoskeletal abnormalities involving the upper limbs.[8] Type 4, caused by mutations in EDNRB or EDN3 (which encode endothelin receptor type B and endothelin-3, respectively), is typically inherited in an autosomal recessive manner and may present with Hirschsprung disease due to enteric nervous system involvement.[9]
Epidemiology
The prevalence of Waardenburg syndrome varies geographically. In the Netherlands, the estimated incidence is approximately 1 in 212,000 individuals, with low penetrance observed in about 20% of cases. Globally, the estimated prevalence is approximately 1 in 42,000 individuals. Types 1 and 2 are the most frequently reported subtypes worldwide, whereas type 3 remains exceedingly rare.[10] Type 4 accounts for approximately 19% of all reported cases.[11] Among individuals with deaf-mutism, Waardenburg syndrome occurs in 0.9% to 2.8%. The condition affects all racial and ethnic groups equally and demonstrates no sex predilection. While diagnosis is often made at birth based on characteristic physical features, some pigmentary changes may become more apparent with age.
Pathophysiology
Waardenburg syndrome is a genetic disorder most often inherited in an autosomal dominant pattern. Several hypotheses have been proposed to explain its pathogenesis and the diverse clinical subtypes. The most widely accepted explanation is the neural crest theory, which attributes the condition to abnormalities in the differentiation and migration of neural crest cells during embryogenesis. This theory also explains the association between Waardenburg syndrome and Hirschsprung syndrome, as both conditions involve disrupted neural crest cell development. First arch syndrome, a condition resulting from the failure of neural crest cells to migrate into the 1st pharyngeal arch, shares overlapping clinical features with Waardenburg syndrome.[12][13]
In type 1 Waardenburg syndrome, mutations occur in the PAX3 gene, which is located on chromosome 2q36.1. This gene encodes a transcription factor that primarily functions as a transcriptional activator but can also act as a repressor for certain targets.[14] During embryonic development, PAX3 is expressed in progenitor cells that contribute to the skeletal muscle, nervous system, and the lateral margins of the neural plate—regions that give rise to neural crest cells.[15][16] As development progresses, PAX3 expression appears in melanoblasts, Schwann cell precursors, and components of the inner ear and mandible. Translation of this gene also plays a role in defining the location of the nasion.[16][17]
In type 2 Waardenburg syndrome, mutations affect the MITF gene on chromosome 3p13. This gene encodes a transcription factor expressed in melanocytes, osteoclasts, and mast cells.[18] The MITF protein is essential for melanin production, DNA repair, mitotic regulation, membrane trafficking, and mitochondrial function. These diverse roles explain the pigmentation defects and SNHL seen in type 2 Waardenburg syndrome, as well as its involvement in other conditions such as Tietz syndrome and melanoma.[19][20][21][19]
Type 3, the rarest variant of Waardenburg syndrome, arises from mutations in the PAX3 gene, similar to type 1.[22] Diagnosis is clinical, based on characteristic features of hypopigmentation and SNHL in combination with limb anomalies.[23] Upper limb involvement is more frequent and may include hypoplasia and flexion contractures. Homozygous PAX3 mutations typically result in more severe musculoskeletal manifestations than heterozygous mutations.[24] Type 3 is also referred to as Klein-Waardenburg syndrome.[25]
Type 4 combines the classic pigmentary abnormalities and SNHL seen in Waardenburg syndrome with aganglionic megacolon, consistent with Hirschsprung disease.[26] This subtype, also known as Waardenburg-Hirschsprung syndrome or Waardenburg-Shah syndrome, includes 3 genetically distinct forms.[27] Type 4A results from mutations in the EDNRB gene on chromosome 13q22.3, which encodes the endothelin B receptor.[28] Type 4B involves mutations in the EDN3 gene on chromosome 20q13.32, which encodes an endothelin receptor ligand. Type 4C arises from mutations in the SOX10 gene on chromosome 22q13.1, which encodes a transcription factor critical for neural crest development.[29]
Individuals with heterozygous mutations in types 4A and 4B may remain asymptomatic or present with mild disease. In contrast, truncating mutations in SOX10 associated with type 4C often result in severe clinical phenotypes, frequently accompanied by additional neurologic abnormalities.[30]
Several etiologic theories have been proposed to explain Waardenburg syndrome, including intrauterine necrosis and associations with status dysraphicus. However, none fully account for the syndrome’s diverse clinical features. Inherited forms of deafness contribute to approximately 50% of congenital hearing loss, with around 70% of these cases involving mutations in single genes that directly impair auditory function. Syndromic deafness, including that seen in Waardenburg syndrome, often coexists with other developmental anomalies. In Waardenburg syndrome, hearing loss results from mutations in MITF and PAX3 in types 2 and 1, respectively. Type 4 involves mutations in genes encoding the endothelin B receptor (EDNRB) or its ligand endothelin 3 (EDN3).
Histopathology
The characteristic histopathological feature of Waardenburg syndrome is the absence or severe reduction of melanocytes, although residual dihydroxyphenylalanine-positive cells may be present. In hypopigmented skin, melanosomes or indeterminate dendritic cells may be seen within keratinocytes. Langerhans cells remain normal in the epidermis. The density of pigment cells is reduced at the margins of depigmented areas, with notable nuclear and cytoplasmic abnormalities. Vacuolated cells may contain a clear halo surrounded by melanosomes.[31] Histopathologic examination of the inner ear at autopsy demonstrates spiral ganglion atrophy and reduced numbers of nerve fibers, along with the absence of the organ of Corti.[32]
History and Physical
Clinically, Waardenburg syndrome may be identified by characteristic morphological features that manifest after birth. A detailed physical examination and comprehensive family history form the foundation of the diagnostic evaluation. Typical features include a white forelock, broad nasal root, and heterochromia irides (difference in eye color). Some children may fail initial newborn hearing screening, if conducted, while others may raise concerns later due to a lack of auditory responsiveness. Not every individual with Waardenburg syndrome exhibits all clinical features. Based on genetic mutations and clinical presentation, 4 distinct types of Waardenburg syndrome have been described.
Type 1 is defined by dystopia canthorum, broad nasal root, short philtrum, and a short retropositional maxilla. Type 2 presents with normally positioned canthi, SNHL, and heterochromia irides. Type 3, also known as Klein-Waardenburg syndrome, shares features with type 1 but includes prominent musculoskeletal abnormalities, such as underdeveloped carpal bones, aplasia of the 1st and 2nd ribs, sacral cysts, limb anomalies, and hypoplasia of muscles with syndactyly. In some cases, type 3 includes the full spectrum of primary features along with severe skeletal deformities, microcephaly, and intellectual disability. Type 4, also referred to as "Shah-Waardenburg syndrome," resembles type 2 clinically but includes congenital aganglionic megacolon consistent with Hirschsprung disease.
Pigmentary changes in Waardenburg syndrome affect the skin, hair, and eyes. Skin findings include achromic spots and hyperpigmented macules over normally pigmented areas. Ocular abnormalities include heterochromia irides and bilateral isohypochromia. Diagnosis is primarily clinical and based on established major and minor diagnostic criteria (see Table. Major and Minor Criteria for the Diagnosis of Waardenburg Syndrome).[33] The clinical diagnosis of type 1 Waardenburg syndrome requires either 2 major criteria or 1 major plus 2 minor criteria.[34]
Table. Major and Minor Criteria for the Diagnosis of Waardenburg Syndrome
|
Major Criteria |
Minor Criteria |
|
Heterochromia irides SNHL White forelock Lateral displacement of inner canthi 1st-degree relative |
Broad nasal root White macules or patches on the skin Synophrys Premature greying Hypoplasia of the nasal alae |
Evaluation
Type 1 and Type 3 Waardenburg syndrome are the most common variants, and the point mutations responsible may be detected using multiplex ligation-dependent probe amplification in specific genes. Formal measurements of the interpupillary and intercanthal distances may be taken and compared with normative charts if uncertainty exists regarding the presence of hypertelorism versus telecanthus. A comprehensive audiogram is essential, and depending on the patient’s age, an auditory brainstem response may be the most thorough test available.[35]
No specific radiological tests are recommended for evaluating Waardenburg syndrome. However, imaging of the middle ear structures and cochlea may be necessary, depending on the genetic and clinical findings. High-resolution computed tomography or, occasionally, magnetic resonance imaging may be used to assess cases requiring imaging.[36]
Treatment / Management
Waardenburg syndrome is a genetic disorder without a definitive treatment.[37] In affected children, early recognition and intervention for hearing abnormalities are essential to support optimal language development, comprehension, and social inclusion. Hearing aids may provide benefits depending on the severity of hearing loss, while cochlear implantation is often necessary for congenital deafness. Sun protection is recommended for hypopigmented skin patches due to increased susceptibility to ultraviolet damage.[38] Genetic counseling plays a critical role in the care of individuals with this condition.
Differential Diagnosis
Several conditions may present with overlapping features and should be considered in the differential diagnosis of Waardenburg syndrome. These disorders often involve pigmentary changes, auditory abnormalities, or other systemic manifestations that require careful clinical distinction.
- Piebaldism: A genetic disorder marked by congenital depigmentation of the skin and hair, typically with a stable, nonprogressive course.[39]
- Tietz syndrome: A rare genetic condition associated with profound congenital deafness and generalized hypopigmentation; musculoskeletal abnormalities may also occur.
- Oculocutaneous albinism: A group of disorders resulting from impaired melanin synthesis, characterized by diffuse depigmentation of the skin, hair, and eyes.
- Vogt-Koyanagi-Harada disease: An autoimmune condition that affects the skin, eyes, inner ear, and central nervous system, often presenting with uveitis, vitiligo, and hearing loss.
- Vitiligo: An acquired condition that presents with progressive depigmented macules on the skin and, occasionally, hair.
Accurate diagnosis relies on a detailed clinical history, physical examination, and genetic testing when appropriate. Differentiating Waardenburg syndrome from these conditions is essential for guiding management, prognosis, and genetic counseling.
Prognosis
Waardenburg syndrome is a chronic condition, but life expectancy in affected children remains normal. Morbidity arises from abnormalities in neural crest-derived tissues and may include intellectual disability, deafness, ocular disorders such as cataracts, skeletal anomalies, and psychiatric conditions.[40] These clinical features reflect the underlying genetic mutations responsible for the disease. Homozygous mutations often result in more severe manifestations than heterozygous mutations, and certain variants, particularly Type 4, are typically associated with greater severity.
Complications
The complications of Waardenburg syndrome vary by subtype. Type 1 may be associated with blepharophimosis, while Type 2 is frequently characterized by SNHL, which occurs in approximately 70% of cases. Type 3 is marked by skeletal anomalies, and in more severe presentations, intellectual disability and microcephaly. The primary complication of Type 4 is congenital aganglionic megacolon, also known as Hirschsprung disease.[41]
Consultations
Consultation with a geneticist plays a critical role in managing Waardenburg syndrome, especially since Type 1 follows an autosomal dominant inheritance pattern and often occurs in families. Although prenatal testing can identify pathogenic gene mutations, it cannot reliably predict clinical severity. Effective management requires an interprofessional team, including audiologists, dermatologists, ophthalmologists, and surgeons. Coordinated care supports early intervention and comprehensive treatment of the syndrome’s multisystem complications.
Deterrence and Patient Education
Life expectancy is typically normal in children with Waardenburg syndrome. Genetic counseling remains essential, as a single affected gene can transmit the condition to future generations. In the absence of definitive treatment, educating families and patients about symptom-based management is critical. Morbidity stems from defects in neural crest-derived tissues.[42]
Enhancing Healthcare Team Outcomes
Waardenburg syndrome presents complex challenges and is best managed by an interprofessional team that can address its wide range of complications. Psychosocial functioning and quality of life may be significantly affected, particularly when psychiatric conditions are also present. Management often requires collaboration among dermatologists, psychiatrists, ophthalmologists, neurologists, and rheumatologists. Nurses trained in dermatology play a critical role in patient education, support, treatment guidance, and monitoring for complications. Close communication across the care team is essential to optimize patient outcomes.[43]
References
Sil A, Panigrahi A. Visual Dermatology: Waardenburg Syndrome Type II. Journal of cutaneous medicine and surgery. 2020 May/Jun:24(3):305. doi: 10.1177/1203475420902048. Epub [PubMed PMID: 32421428]
Tan J, Duron A, Sucov HM, Makita T. Placode and neural crest origins of congenital deafness in mouse models of Waardenburg-Shah syndrome. iScience. 2025 Jan 17:28(1):111680. doi: 10.1016/j.isci.2024.111680. Epub 2024 Dec 24 [PubMed PMID: 39868048]
Grewal PS, Knight H, Michaelides M. Asymmetric choroidal hypopigmentation in a Son and mother with Waardenburg syndrome type I. Ophthalmic genetics. 2020 Jun:41(3):284-287. doi: 10.1080/13816810.2020.1750037. Epub 2020 Apr 13 [PubMed PMID: 32281454]
Yu Y, Liu W, Chen M, Yang Y, Yang Y, Hong E, Lu J, Zheng J, Ni X, Guo Y, Zhang J. Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome. Molecular genetics & genomic medicine. 2020 May:8(5):e1217. doi: 10.1002/mgg3.1217. Epub 2020 Mar 13 [PubMed PMID: 32168437]
Alehabib E, Alinaghi S, Pourfatemi F, Darvish H. Incomplete penetrance of MITF gene c.943C}T mutation in an extended family with Waardenburg syndrome type II. International journal of pediatric otorhinolaryngology. 2020 Aug:135():110014. doi: 10.1016/j.ijporl.2020.110014. Epub 2020 Apr 21 [PubMed PMID: 32422366]
Agrawal R, Walia S. Waardenburg Syndrome Type 1. Indian journal of ophthalmology. 2022 Jul:70(7):2679-2681. doi: 10.4103/ijo.IJO_3003_21. Epub [PubMed PMID: 35791202]
Ren SM, Kong XD, Wu QH, Jiao ZH, Chen C, Qin ZB. [Analysis of genetic variation in patients with Waardenburg syndrome type Ⅱ by next generation sequencing]. Zhonghua yi xue za zhi. 2020 Mar 24:100(11):853-858. doi: 10.3760/cma.j.cn112137-20190730-01692. Epub [PubMed PMID: 32234158]
Level 2 (mid-level) evidenceTekin M, Bodurtha JN, Nance WE, Pandya A. Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome? Clinical genetics. 2001 Oct:60(4):301-4 [PubMed PMID: 11683776]
Chandra Mohan SLN. Case of Waardenburg Shah syndrome in a family with review of literature. Journal of otology. 2018 Sep:13(3):105-110. doi: 10.1016/j.joto.2018.05.005. Epub 2018 Jun 8 [PubMed PMID: 30559775]
Level 3 (low-level) evidenceApaydin F, Bereketoglu M, Turan O, Hribar K, Maassen MM, Günhan O, Zenner HP, Pfister M. [Waardenburg syndrome. A heterogenic disorder with variable penetrance]. HNO. 2004 Jun:52(6):533-7 [PubMed PMID: 15029423]
Song J, Feng Y, Acke FR, Coucke P, Vleminckx K, Dhooge IJ. Hearing loss in Waardenburg syndrome: a systematic review. Clinical genetics. 2016 Apr:89(4):416-425. doi: 10.1111/cge.12631. Epub 2015 Jul 17 [PubMed PMID: 26100139]
Level 1 (high-level) evidenceLi S, Guo M, Ruan B, Liu Y, Cui X, Han W, Li R. A Novel PAX3 Mutation in a Chinese Family with Waardenburg Syndrome Type 1. Genetic testing and molecular biomarkers. 2020 May:24(5):249-255. doi: 10.1089/gtmb.2019.0231. Epub 2020 Apr 3 [PubMed PMID: 32250160]
Johnson JM, Moonis G, Green GE, Carmody R, Burbank HN. Syndromes of the first and second branchial arches, part 1: embryology and characteristic defects. AJNR. American journal of neuroradiology. 2011 Jan:32(1):14-9. doi: 10.3174/ajnr.A2072. Epub 2010 Mar 18 [PubMed PMID: 20299437]
Mayanil CS, George D, Freilich L, Miljan EJ, Mania-Farnell B, McLone DG, Bremer EG. Microarray analysis detects novel Pax3 downstream target genes. The Journal of biological chemistry. 2001 Dec 28:276(52):49299-309 [PubMed PMID: 11590174]
Buckingham M, Relaix F. The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions. Annual review of cell and developmental biology. 2007:23():645-73 [PubMed PMID: 17506689]
Monsoro-Burq AH. PAX transcription factors in neural crest development. Seminars in cell & developmental biology. 2015 Aug:44():87-96. doi: 10.1016/j.semcdb.2015.09.015. Epub 2015 Sep 26 [PubMed PMID: 26410165]
Wu M, Li J, Engleka KA, Zhou B, Lu MM, Plotkin JB, Epstein JA. Persistent expression of Pax3 in the neural crest causes cleft palate and defective osteogenesis in mice. The Journal of clinical investigation. 2008 Jun:118(6):2076-87. doi: 10.1172/JCI33715. Epub [PubMed PMID: 18483623]
Hershey CL, Fisher DE. Mitf and Tfe3: members of a b-HLH-ZIP transcription factor family essential for osteoclast development and function. Bone. 2004 Apr:34(4):689-96 [PubMed PMID: 15050900]
Garraway LA, Sellers WR. Lineage dependency and lineage-survival oncogenes in human cancer. Nature reviews. Cancer. 2006 Aug:6(8):593-602 [PubMed PMID: 16862190]
Cheli Y, Ohanna M, Ballotti R, Bertolotto C. Fifteen-year quest for microphthalmia-associated transcription factor target genes. Pigment cell & melanoma research. 2010 Feb:23(1):27-40. doi: 10.1111/j.1755-148X.2009.00653.x. Epub 2009 Nov 25 [PubMed PMID: 19995375]
Smith SD, Kelley PM, Kenyon JB, Hoover D. Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF. Journal of medical genetics. 2000 Jun:37(6):446-8 [PubMed PMID: 10851256]
Li S, Qin M, Mao S, Mei L, Cai X, Feng Y, He C, Song J. A comprehensive genotype-phenotype evaluation of eight Chinese probands with Waardenburg syndrome. BMC medical genomics. 2022 Nov 3:15(1):230. doi: 10.1186/s12920-022-01379-6. Epub 2022 Nov 3 [PubMed PMID: 36329483]
Level 2 (mid-level) evidenceSomashekar PH, Upadhyai P, Narayanan DL, Kamath N, Bajaj S, Girisha KM, Shukla A. Phenotypic diversity and genetic complexity of PAX3-related Waardenburg syndrome. American journal of medical genetics. Part A. 2020 Dec:182(12):2951-2958. doi: 10.1002/ajmg.a.61893. Epub 2020 Sep 29 [PubMed PMID: 32990402]
Salah S, Meiner V, Abumayaleh A, Asafra A, Al-Sharif T, Al-Fallah O, Hasasneh B, Zlotogora J. Biallelic variants in PAX3 cause Klein syndrome. Clinical genetics. 2022 Sep:102(3):223-227. doi: 10.1111/cge.14167. Epub 2022 Jun 5 [PubMed PMID: 35607853]
Saberi M, Golchehre Z, Salmani H, Karamzade A, Tabatabaie SZ, Keramatipour M. First report of Klein-Waardenburg Syndrome in Iran and a novel pathogenic splice site variant in PAX3 gene. International journal of pediatric otorhinolaryngology. 2018 Oct:113():229-233. doi: 10.1016/j.ijporl.2018.08.009. Epub 2018 Aug 10 [PubMed PMID: 30173992]
Jabeen R, Babar ME, Ahmad J, Awan AR. Novel mutations of endothelin-B receptor gene in Pakistani patients with Waardenburg syndrome. Molecular biology reports. 2012 Jan:39(1):785-8. doi: 10.1007/s11033-011-0799-x. Epub 2011 May 6 [PubMed PMID: 21547364]
Read AP, Newton VE. Waardenburg syndrome. Journal of medical genetics. 1997 Aug:34(8):656-65 [PubMed PMID: 9279758]
Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. Review and update of mutations causing Waardenburg syndrome. Human mutation. 2010 Apr:31(4):391-406. doi: 10.1002/humu.21211. Epub [PubMed PMID: 20127975]
Fernández RM, Núñez-Ramos R, Enguix-Riego MV, Román-Rodríguez FJ, Galán-Gómez E, Blesa-Sánchez E, Antiñolo G, Núñez-Núñez R, Borrego S. Waardenburg syndrome type 4: report of two new cases caused by SOX10 mutations in Spain. American journal of medical genetics. Part A. 2014 Feb:164A(2):542-7. doi: 10.1002/ajmg.a.36302. Epub 2013 Dec 5 [PubMed PMID: 24311220]
Level 3 (low-level) evidencePingault V, Zerad L, Bertani-Torres W, Bondurand N. SOX10: 20 years of phenotypic plurality and current understanding of its developmental function. Journal of medical genetics. 2022 Feb:59(2):105-114. doi: 10.1136/jmedgenet-2021-108105. Epub 2021 Oct 19 [PubMed PMID: 34667088]
Level 3 (low-level) evidenceEz-Zahraoui M, Lezrek O, Cherkaoui O. [Waardenburg syndrome type 1]. Journal francais d'ophtalmologie. 2019 Jan:42(1):94-95. doi: 10.1016/j.jfo.2018.03.028. Epub 2018 Dec 13 [PubMed PMID: 30554874]
Brizzolara A, Torre M, Favre A, Pini Prato A, Bocciardi R, Martucciello G. Histochemical study of Dom mouse: A model for Waardenburg-Hirschsprung's phenotype. Journal of pediatric surgery. 2004 Jul:39(7):1098-103 [PubMed PMID: 15213907]
Astakhov YS, Tultseva SN, Lisochkina AB, Takhtaev YV, Astakhov SY, Shakhnazarova AA. [Ophthalmologic manifestations of Waardenburg syndrome]. Vestnik oftalmologii. 2019:135(6):91-99. doi: 10.17116/oftalma201913506191. Epub [PubMed PMID: 32015313]
Gowda VK, Srinivas S, Srinivasan VM. Waardenburg Syndrome Type I. Indian journal of pediatrics. 2020 Mar:87(3):244. doi: 10.1007/s12098-019-03170-5. Epub 2020 Jan 27 [PubMed PMID: 31989460]
Fan W, Ni K, Chen F, Li X. Hearing characteristics and cochlear implant effects in children with Waardenburg syndrome: a case series. Translational pediatrics. 2022 Jul:11(7):1234-1241. doi: 10.21037/tp-22-271. Epub [PubMed PMID: 35958009]
Level 2 (mid-level) evidenceKontorinis G, Goetz F, Lanfermann H, Luytenski S, Giesemann AM. Inner ear anatomy in Waardenburg syndrome: radiological assessment and comparison with normative data. International journal of pediatric otorhinolaryngology. 2014 Aug:78(8):1320-6. doi: 10.1016/j.ijporl.2014.05.020. Epub 2014 May 24 [PubMed PMID: 24882458]
Ren S, Chen X, Kong X, Chen Y, Wu Q, Jiao Z, Shi H. Identification of six novel variants in Waardenburg syndrome type II by next-generation sequencing. Molecular genetics & genomic medicine. 2020 Mar:8(3):e1128. doi: 10.1002/mgg3.1128. Epub 2020 Jan 20 [PubMed PMID: 31960627]
Wallis KE, Blum NJ, Waryasz SA, Augustyn M. Bilateral Cochlear Implants: Maximizing Expected Outcomes. Journal of developmental and behavioral pediatrics : JDBP. 2018 Feb/Mar:39(2):177-179. doi: 10.1097/DBP.0000000000000547. Epub [PubMed PMID: 29324475]
Shah M, Patton E, Zedek D. Piebaldism. StatPearls. 2025 Jan:(): [PubMed PMID: 31334958]
Minami SB, Nara K, Mutai H, Morimoto N, Sakamoto H, Takiguchi T, Kaga K, Matsunaga T. A clinical and genetic study of 16 Japanese families with Waardenburg syndrome. Gene. 2019 Jul 1:704():86-90. doi: 10.1016/j.gene.2019.04.023. Epub 2019 Apr 10 [PubMed PMID: 30978479]
Raissi D, Christie A, Applegate K. Waardenburg Syndrome and Left Persistent Superior Vena Cava. Journal of clinical imaging science. 2018:8():44. doi: 10.4103/jcis.JCIS_31_18. Epub 2018 Nov 15 [PubMed PMID: 30546928]
Boutkhil M, Benchekroun Belabess S, El Ikhloufi M, Taouri N, Cherkaoui O. [Waardenburg syndrome, a family story]. Journal francais d'ophtalmologie. 2019 Sep:42(7):e319-e324. doi: 10.1016/j.jfo.2018.12.026. Epub 2019 May 24 [PubMed PMID: 31130388]
Shrinkhal, Singh A, Mittal SK, Agrawal A, Verma R, Yadav P. Waardenburg syndrome with dry eyes: A rare association. Taiwan journal of ophthalmology. 2019 Jul-Sep:9(3):198-201. doi: 10.4103/tjo.tjo_103_18. Epub 2019 Sep 12 [PubMed PMID: 31572658]