Waardenburg Syndrome: Symptoms, Causes, Treatment

He Waardenburg syndrome (SW) Is a pathology of genetic origin classified as a type of neurocristopathy (Llalliré, Young Park, Pasarelli, Petuaud, Raffo, Rodríguez Álvarez and Virguez, 2010).

Its clinical characteristics are defined by the presence of deafness or hearing loss, anomalies in pigmentation of the eyes, hair or skin and various facial alterations (Vázquez Rueda, Blesa Sánchez, Núñez Núñez and Galán Gómez, 1998).

Waardenburg syndrome

This pathology is characterized by its wide symptom variability, which makes it possible to distinguish several types: Type I, Type II, Type III (Klein-Waardenburg syndrome or Waardenburg syndrome) and Type IV (Shah-Waardenburg syndrome) (Parpar Tena, 2016 ).

At the etiologic level, Waardenburg syndrome has an autosomal dominant inheritance pattern (Lattig and Tamayo, 1999). It is usually associated with specific mutations in the genes EDN3, EDNRB, PAX3, SOX10, SNAI2 and MIT (Genetics Home Reference, 2016).

The diagnosis is made based on several major and minor clinical criteria. However, it is necessary to perform various complementary laboratory tests (Lalliré et al., 2010).

There is no cure or specific treatment for Waardenburg syndrome (Lalliré et al., 2010).

The intervention with this pathology usually focuses on the treatment of auditory alterations (surgical procedures, cochlear implants, etc.), logopedical rehabilitation and Neuropsychological , As well as psychological (Castro Pérez, Sanabria Negrín, Torres Capote, IvirucU Tielves and González Serrano, 2012; Parpar Tena, 2016).

Characteristics of Waardenburg's syndrome

Waardenburg syndrome is a congenital genetic disorder whose signs and symptoms tend to vary widely among those affected (National Organization for Rare Disorders, 2015).

The most frequent features include distinctive facial abnormalities, altered pigmentation of the skin, eyes or hair and deafness (National Organization for Rare Disorders, 2015).

In the medical literature, this syndrome is usually considered a type of Genodermatosis or Neurocristopathy (Touraine, 2008).

The term genodermatosis refers to a broad set of diseases characterized by the presence of abnormalities and cutaneous alterations of genetic origin (Falcón Lincheta, 2016).

On the other hand, the term neurocristopathy refers to a group of pathologies derived from the development of abnormalities and defective processes during the migration and differentiation of neural crest cells during gestation (Espinosa and Alonso Calderón, 2009).

The Neural crest Is an embryonic structure made up of a large set of undifferentiated cells whose development will lead to the formation of the craniofacial structure and neuronal cells and Glial That formed a large part of the nervous system (Díaz Hernández and Méndez Herrera, 2016).

Between weeks 8 and 10 of gestation, the process of migration of the cells that make up the neural crest usually begins (Vázquez Rueda et al., 1998).

When various pathological factors or genetic abnormalities interfere in this process, important cognitive and / or physical abnormalities can occur, as is the case of Waardenburg syndrome (Vázquez Rueda et al., 1998).

This syndrome was initially described by the Dutch geneticist and ophthalmologist Petrus Johannes Waardenburg In 1848 (Castro Perez, Ledesma Vega, Ivis Otaño Placencia, Ramírez Sosa and Ramos Cruz, 2011).

In his clinical report he referred to the main clinical characteristics (Parpar Tena, 2016):

  • Dystopia cantorum
  • Nasal hyperplasia
  • Ocular Pigmentary Alterations
  • Variable deafness
  • Pigmentary hair anonadáis

Further analyzes identified a large clinical variability in Waardenbur syndrome. In addition, Mckusick associated this syndrome with other similar clinical courses, such as Hirschsprung disease (Vázquez Rueda et al., 1998).

At present, it is considered a rare pathology, which presents with a variable degree of hearing impairment that can cause important alterations in the learning and subsequent development of the person affected (Castro Pérez et al., 2011).

The prognosis of Waardenburg syndrome is favorable, although it may be associated with significant morbidity and mortality related to medical complications, especially intestinal (National Organization for Rare Disorders, 2016).

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Waardenburg Syndrome: Symptoms, Causes, Treatment Girl with Waardenburg syndrome.

The prevalence of Waardenburg syndrome is estimated at 1 case per 40,000 people worldwide (Genetics Home Reference, 2016).

Since its discovery, some 1,400 different cases have been described in the medical and experimental literature (National Organization for Rare Disorders, 2016).

It seems to affect men and women alike. No associations have been identified with geographic regions or particular ethnic and racial groups (National Organization for Rare Disorders, 2016).

Waardenburg syndrome accounts for 2-5% of all diagnosed cases of congenital hearing loss (Genetics Home Reference, 2016).

Although several clinical courses have been identified, type I and II are the most common. Type III and IV are rare (Genetics Home Reference, 2016).

Signs and symptoms

Waardenburg Syndrome: Symptoms, Causes, Treatment 1

Waardenburg syndrome is characterized by three fundamental alterations: craniofacial alterations, pigment abnormalities and deafness (National Organization for Rare Disorders, 2016; Lalliré et al., 2010; Lattig and Tamayo, 1999):

Cranio-facial alterations

  • Dystopia cantorum: The internal angle of the eyes usually presents an offset arrangement towards the lateral area.
  • Hypertelorism : The distance between both eyes is usually greater than usual.
  • Harelip: Fissure or cleft located in one or more areas of the upper lip.
  • Sinofridia: The eyebrows usually present a continuous development, without any separation or area free of hair.
  • Nasal hypoplasia: The bridge of the nose usually presents a wide structure, with some underdeveloped areas or some type of malformation.

Pigmentary Abnormalities

  • Eyes: Usually exhibit a significant decrease in their coloration or pigmentation. It is common for one or both of them to have a very bluish hue. It is also possible to identify a variable heterochromia, resulting in different shades between both eyes.
  • Hair: Is characterized by the premature development of Canicie Or loss of pigmentation. The hair of the head, eyebrows or lashes acquires a white coloration. A tuft or localized area of ​​white hair (poliosis) is often observed.
  • Skin: Although it is rare, in some individuals it is possible to observe discolored areas on the skin with a white appearance ( Vitiligo ). Anomalies in the development of connective tissue may also appear.

Congenital Deafness

Another of the central medical findings of Waardenburg syndrome is loss of hearing ability and acuity.

The most common is to identify in those affected a variable degree of deafness or sensorineural hearing loss.

The term Sensorineural hearing loss Refers to a loss of auditory capacity derived from internal injuries related to the nerve terminals that conduct auditory information from the inner ear to the brain centers (National Institutes of Health, 2016).

Do you have different clinical courses?

Waardenburg Syndrome: Symptoms, Causes, Treatment 2

Waardenburg syndrome is classified into 4 basic types depending on the clinical course and the specific symptoms that are present in the affected individuals (Castro Pérez et al., 2011):

  • Type I: This subtype is defined by the presence of all alterations related to the cranial-facial and ocular pigment structure. Approximately 25% of those affected present some type of sensorineural deafness.
  • Type II: Facial and ocular abnormalities are less common in this subtype. More than 70% of those affected develop sensorineural deafness and do not present with cantorum dystopia.
  • Type III (Waardenburg-Klein syndrome): Its clinical course is similar to type I. In addition, those affected have some musculoskeletal and neurological abnormalities. It is often observed Microcephaly or Intellectual disability .
  • Type IV (Waardenburg-Shah Syndrome): The characteristics of type I are usually associated with the presence of other anomalies such as congenital megacolon.


Waardenburg syndrome has a congenital origin associated with various genetic alterations (Lattig and Tamayo, 1999).

Case analysis has allowed us to locate these anomalies in the genes: EDN3, EDNRB, PAX3, SOX10, SNAI2 and MIT (Genetics Home Reference, 2016).

This set of genes seems to be involved in the development and formation of various cell types, including those responsible for the production of Melanocytes (Genetics Home Reference, 2016).

Melanocytes are responsible for generating melanin , A pigment that contributes to the coloration of the eyes, hair or skin (Genectics Home Reference, 2016).

Depending on the different clinical courses, we can identify different genetic alterations (Genectics Home Reference, 2016):

  • Type I and Type III : PAX3 gene.
  • Type II : MITF and SNAI2 genes.
  • Type IV: SOX10, EDN3 and EDNRB.


As noted in the initial description, the diagnosis of Waardenbug syndrome is based on several major and minor criteria (Llalliré et al., 2010):

Major Criteria

  • Loss of hearing ability associated with sensorineural deafness.
  • Alteration of the pigmentation and coloration of the eyes: blue iris, bicolour iris and / or Heterochromia .
  • Alteration of hair pigmentation: white hair on the head, eyebrows, eyelashes, etc.
  • Harelip.
  • Dystopia cantorum.

Minor Criteria

  • Alteration of pigmentation of the skin.
  • Early development of gray hairs.
  • Continuous eyebrow development.
  • Abnormally wide nasal bridge.

To establish a definitive diagnosis it is fundamental to identify the presence of two major criteria or at least one major and two minor criteria.

In addition, it is necessary to use some complementary tests: biopsy, audiometry or genetic tests (Lalliré et al., 2010).


There is no cure for Waardenburg syndrome, although symptomatic approaches may be employed.

The treatment of the most frequent signs and symptoms usually requires the medical intervention of dermatologists and ophthalmologists.

On the other hand, in the case of the treatment of sensorineural deafness, a cochlear implant can be performed, accompanied by a speech and neuropsychological intervention.


  1. Castro Perez, F., Ledesma Vega, Y., Ivis Otaño Placencia, C., Ramírez Sosa, P., & Ramos Cruz, M. (2011). Waardeburg's syndrome. Variability in a family in Sandino, Pinar del Río, Cuba. Rev. Medical Sciences .
  2. Castro Pérez, F., Sanabria Negrín, J., Torres Capote, M., Iviricu Tielvez, R., & González Serrano, H. (2012). Waardenburg syndrome: disabilities and physical appearance, its linkage to academic performance and social relationships. Rev. Medical Sciences .
  3. Espinosa, R., & Alonso Calderón, J. (2009). Neurocristopathies and Hirschsprung's disease. Cir. Pediatr , 25-28.
  4. Genetics Home Reference. (2016). Waardenburg syndrome . Retrieved from the Genetics Home Reference.
  5. Lattig, M., & Tamayo, M. (1999). Waardenburg syndrome.
  6. Llaliré, J., Young Park, K., Passarelli, M., Petuaud, G., Raffo, G., Rodríguez Álvarez, G., & Virguez, E. (2010). Waardenbug syndrome. Arch. Oftal. B. Aires. .
  7. NIH. (2016). Waardenburg syndrome . Obtained from MedlinePlus.
  8. NORD. (2016). Waardenburg Syndrome . Retrieved from the National Organization for Rare Disorders.
  9. Parpar Tena, S. (2016). Waardenburg syndrome. Presentation of a case with pigmentary glaucoma. Rev. Mex. Oftalmol .
  10. Touraine, R. (2008). Waardenburg-Shah syndrome . Obtained from Orphanet.
  11. Vázquez Rueda, F., Blesa Sánchez, E., Núñez Núñez, R., & Galán Gómez, E. (1998). Waardenbug syndrome and Hirschsprung's disease. An Esp Pediatr .

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