Waardenburg Syndrome Symptoms, Causes, Treatment

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Simon Doyle
Waardenburg Syndrome Symptoms, Causes, Treatment

The Waardenburg syndrome (SW) it is a pathology of genetic origin classified as a type of neuropathy. Its clinical characteristics are defined by the presence of deafness or hearing loss, abnormal pigmentation of the eyes, hair or skin, and various facial alterations.

This pathology is characterized by its wide symptomatic variability, which is why several types are distinguished: Type I, Type II, Type III (Klein-Waardenburg syndrome or psudo Waardenburg) and Type IV.

At the etiological level, Waardenburg syndrome has an autosomal dominant inheritance pattern. It is usually associated with specific mutations in the EDN3, EDNRB, PAX3, SOX10, SNAI2, and MIT genes..

The diagnosis is made on the basis of various major and minor clinical criteria. However, it is necessary to perform various complementary laboratory tests. There is no specific cure or treatment for Waardenburg syndrome..

The intervention with this pathology usually focuses on the treatment of hearing disorders (surgical procedures, cochlear implants, etc.), speech therapy and neuropsychological rehabilitation, as well as psychological.

Article index

  • 1 History and discovery
  • 2 Characteristics of Waardenburg syndrome
  • 3 Statistics
  • 4 Signs and symptoms
    • 4.1 Cranio-facial alterations
    • 4.2 Pigment abnormalities
    • 4.3 Congenital deafness
  • 5 Do you have different clinical courses?
  • 6 Causes
  • 7 Diagnosis
    • 7.1 Major criteria
    • 7.2 Minor criteria
  • 8 Treatment
  • 9 References

History and discovery

This syndrome was initially described by the Dutch geneticist and ophthalmologist Petrus Johannes Waardenburg in 1848. In his clinical report he referred to the main clinical characteristics:

  • Cantorum dystopia
  • Nasal hyperplasia
  • Ocular pigment disorders
  • Variable deafness
  • Anonadáis pigmentation hair

Subsequent analyzes identified a large clinical variability in Waardenbur syndrome. In addition, Mckusick associated this syndrome with other similar clinical courses, such as Hirschsprung's disease..

At present, it is considered a rare pathology, which occurs with a variable degree of hearing impairment that can cause important learning and subsequent development disorders of the affected person..

The prognosis for Waardenburg syndrome is favorable, although it may be associated with significant morbidity and mortality related to medical complications, especially intestinal.

Characteristics of Waardenburg syndrome

Waardenburg syndrome is a congenital genetic disorder whose signs and symptoms tend to vary widely among those affected..

The most common features include distinctive facial abnormalities, altered pigmentation of the skin, eyes, or hair, and deafness..

In the medical literature, this syndrome is often considered a type of genodermatosis or neuropathy. The term genodermatosis refers to a broad set of diseases characterized by the presence of skin abnormalities and alterations of genetic origin..

On the other hand, the term neuropathy refers to a group of pathologies derived from the development of anomalies and defective processes during the migration and differentiation of the cells of the neural crest during gestation..

The neural crest is an embryonic structure made up of a broad set of undifferentiated cells whose development will lead to the formation of the craniofacial structure and the neuronal and glial cells that will form a large part of the nervous system..

Between week 8 and 10 of gestation, the migration process of the cells that make up the neural crest usually begins. When various pathological factors or genetic abnormalities interfere in this process, significant cognitive and / or physical abnormalities may appear, such as Waardenburg syndrome..

Statistics

Girl with Waardenburg syndrome.

The prevalence of Waardenbur syndrome is estimated to be 1 case in 40,000 people worldwide. Since its discovery, some 1,400 different cases have been described in the medical and experimental literature..

It seems to affect men and women equally. No associations have been identified with particular geographic regions or ethnic and racial groups..

Waardenbug syndrome represents 2-5% of all diagnosed cases of congenital hearing loss.

Although various clinical courses have been identified, type I and II are the most common. Type III and IV are rare.

Signs and symptoms

Waardenburg syndrome is characterized by three fundamental alterations: craniofacial alterations, pigmentary abnormalities and deafness:

Craniofacial alterations

  • Cantorum dystopia: the internal angle of the eyes is usually displaced 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 type of separation or free area of ​​hair.
  • Nasal hypoplasia: the bridge of the nose usually has a wide structure, with some underdeveloped areas or some type of malformation.

Pigment abnormalities

  • Eyes: they usually present a significant decrease in their coloration or pigmentation. It is common for one or both to have a very light bluish hue. It is also possible to identify a variable heterochromia, resulting in different shades between both eyes..
  • Hair: it is characterized by the premature development of gray hair or loss of pigmentation. The hair on the head, eyebrows or eyelashes turns white. Often a localized tuft or area of ​​white hair is seen (poliosis).
  • Skin: Although it is rare, in some individuals it is possible to observe discolored areas on the skin with a white appearance (vitiligo). Abnormalities in the development of connective tissue may also appear.

Congenital deafness

Another of the central medical findings of Waardenburg syndrome is the 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 hearing capacity derived from internal injuries related to the nerve endings that conduct auditory information from the inner ear to the brain centers..

Do you have different clinical courses?

Waardenburg syndrome is classified into 4 basic types based on the clinical course and the specific symptoms that are present in affected people:

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

Causes

Waardenbuug syndrome has a congenital origin associated with various genetic alterations.

The analysis of cases has allowed to locate these anomalies in the genes: EDN3, EDNRB, PAX3, SOX10, SNAI2 and MIT.

This set of genes seems to be involved in the development and formation of various types of cells, including those responsible for the production of melanocytes.

Melanocytes are responsible for generating melanin, a pigment that contributes to the coloring of the eyes, hair or skin.

Depending on the different clinical courses, we can identify different genetic alterations:

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

Diagnosis

As we pointed out in the initial description, the diagnosis of Waardenbug syndrome is made based on several major and minor criteria:

Major criteria

  • Hearing loss associated with sensorineural deafness.
  • Alteration of pigmentation and coloration of the eyes: blue iris, bicolor iris and / or heterochromia.
  • Alteration of hair pigmentation: white hair on the head, eyebrows, eyelashes, etc..
  • Harelip.
  • Cantorum dystopia.

Minor criteria

  • Alteration of skin pigmentation.
  • Premature development of gray hair.
  • Continuous brow development.
  • Abnormally wide nasal bridge.

To establish a definitive diagnosis, it is essential to identify the presence of two major criteria or at least one major and two minor. In addition, it is necessary to use some complementary tests: biopsy, audiometry or genetic tests.

Treatment

There is no cure for Waardenbug syndrome, although symptomatic approaches can be used..

Treatment of the most common signs and symptoms usually requires medical intervention from 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 therapy and neuropsychological intervention..

References

  1. Espinosa, R., & Alonso Calderón, J. (2009). Neurocristopathies and Hirschsprung's disease. Cir. Pediatr, 25-28.
  2. Genetics Home Reference. (2016). Waardenburg syndrome. Obtained from Genetics Home Reference.
  3. Lattig, M., & Tamayo, M. (1999). Waardenburg syndrome.
  4. Llaliré, J., Young Park, K., Passarelli, M., Petuaud, G., Raffo, G., Rodríguez Álvarez, G., & Virguez, E. (2010). Waardenbug syndrome. Arch. Oftal. B. Aires. .
  5. NIH. (2016). Waardenburg syndrome. Retrieved from MedlinePlus.
  6. NORD. (2016). Waardenburg Syndrome. Obtained from National Organization for Rare Disorders.
  7. Parpar Tena, S. (2016). Waardenburg syndrome. Presentation of a case with pigmentary glaucoma. Rev. Mex. Ophthalmol.
  8. Touraine, R. (2008). Waardenburg-Shah syndrome. Obtained from Orphanet.

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