Waardenburg syndrome: causes, symptoms and treatment

There are many different disorders and conditions that can affect our health. Many of them are well known to most of the population, especially when they are relatively widespread or dangerous. Flu, cancer, AIDS, diabetes or Alzheimer’s disease are just a few examples. Sometimes some that are not well regarded by the majority of the population also come to the fore in epidemics or awareness campaigns, such as Ebola, chronic obstructive pulmonary disease (COPD) or amyotrophic lateral sclerosis (ALS).

But there are many diseases that we have hardly ever heard of, such as those considered rare or a large number of genetic disorders. One of them is Waardenburg syndrome, which we will talk about in this sense.

    Waardenburg syndrome: main symptoms

    Waardenburg syndrome is a strange disease of genetic origin, Which is estimated to be in one in forty thousand people and is classified as neurocristopathy, disorders caused by alterations in the development of the neural crest.

    This disease is characterized by the presence of changes in facial morphology, Showing the presence of dystopia cantorum or displacement on the side of the inner corner of the eye, problems with pigmentation of the skin and eyes which give them a distinct coloring (it is not uncommon for the eyes to appear a characteristic intense blue or that appears heterochromia, and that leaves the hair is white) and certain level of hypoacusía or even deafness at the congenital level. It is also not uncommon for vision problems to appear, although this is not one of the critical symptoms for diagnosis.

    They can also appear other impairments related to the digestive system, movement or even intellectual abilities. Hair can also appear with white hair or even with white flakes, as well as light spots on the skin. Despite this, this syndrome is characterized by being very heterogeneous, having different types of symptomatic presentation.

    Types of Waardenburg syndrome

    Waardenburg syndrome, as we have said, does not have one way of presenting itself, but different subtypes of this syndrome can be distinguished. Among them, the most important are four, the first two being more frequent (in rare diseases) and the second two less frequent.

    Waardenburg syndrome type 1

    One of the most common is Waardenburg syndrome type 1. In this type of syndrome presentation, all of the symptoms mentioned above occur: morphofacial changes and pigmentation problems, With possible congenital deafness (although it only occurs in about 1 in 4 cases).

    The presence of one eye of each color or heterochromia is observed very frequently, The clear tone of the eyes (usually with a tendency to blue) and skin and, one of the characteristic symptoms of this type, the presence of dystopia cantorum or displacement of the inner corner of the eye. This type of symptom is reminiscent of hypertelorism, with the difference that in reality the distance between the eyes is not greater than the average (although in some cases hypertelorism may also appear).

    Waardenburg syndrome type 2

    Waardenburg syndrome types 1 and 2 almost entirely share the diagnostic criteria, the symptoms being virtually identical. The main difference is that in type 2 cantorum dystopia does not occur (If we did, we would be dealing with Waardenburg syndrome type 1).

    In addition, in this presentation of the syndrome, the facial morphological changes are generally a little less marked than compared to type 1, while the deafness presented is generally a little more obvious and frequent, being the majority (appears in 70% of cases). Spina bifida or lack of genital development can also occur.

    Klein-Waardenburg syndrome or type 3

    This type of disorder is characterized by the fact that in addition to the above symptoms (it is usually closer to type 1), there are usually upper limb malformations and neurological alterations. It is also generally more correlated with movement problems, muscle tension, cerebrospinal disorders or functional diversity at the intellectual level. The eyelid also droops in at least one of the eyes, a symptom called ptosis, despite the absence of dystopia cantorum.

    Waardenburg-Shah syndrome type 4

    Very similar in symptomatology to Waardenburg syndrome type 2, but adding more alterations of the enteric and gastrointestinal system which cause fewer neurons running the intestines and which often correlate with constipation and other digestive problems such as Hirschsprung’s disease or congenital megacolon, in which feces are not normally expelled due to problems with the neuronal ganglia of the enteric system and there is an enlarged intestine and colon product of its obstruction.

    Causes of this alteration

    Waardenburg syndrome is a disease of genetic origin that it can be inherited or appear due to a de novo mutation. The heritability of this disorder depends on the type we are analyzing.

    Types 1 and 2 are transmitted by an autosomal dominant pattern. The problems appear to result from altered neuronal migration during development, which generates symptomatology and a lack of melanocytes (Causes of pigmentation disorders).

    One of the genes most associated with the disease in its most common typologies in types 1 and 3 is PAX3 (90% of types 1 are said to have mutations in this gene). But he is not the only one. Type 2 is most associated with the Mitf gene and type 4 with a combination of genes including EDN3, EDNRB and SOX10.


      Waardenburg syndrome is a genetic disease that currently has no cure. However, many of the difficulties that the syndrome generates, in the process of being realized, are treatable. an approach rather focused on specific symptoms and complications based on dysfunction or risk it may present to the patient.

      The most common type of procedure is related to deafness or possible hearing loss, in which techniques such as cochlear implantation could be used. Monitoring and preventing the occurrence of tumors (eg melanoma) should also be kept in mind and if they do appear, they should also be properly treated. Certain alterations in the morphology of the skin and face may also require surgery, although this is not as common. Finally, eye problems will also need to be treated.

      For the most part, Waardenburg syndrome does not usually cause or have major complications in its most common modalities, type 1 and type 2, so those who do can usually lead typical lives. This does not mean that they do not have difficulties, but in general the prognosis is positive in terms of having a good quality of life.

      In the case of subtypes 3 and 4, complications, the number of complications may be greater. In the case of the 4th the megacolon suffers it can lead to alterations that endanger the lives of those who suffer from it. The latter is the case with megacolon, if it is not properly treated.

      Treatment of these complications may require surgery to correct megacolon or improve upper limb functionality (eg, reconstruction of the extremities and separation of the fingers). In the case of intellectual disability, the application of educational guidelines may also be necessary that take into account the possible problems that arise from it, such as an individualized plan in the field of education (although in general the intellectual disability is generally slight).

      It is also necessary to assess the possible psychological impact: the presence of morphological abnormalities can trigger anxiety, self-esteem and depression problems related to self-image. If necessary, psychological therapy can be very helpful.

      Bibliographic references:

      • Duke, GA; Ramírez-Cheyne, J. and Saldarriaga-Gil, W. (2016). Waardenburg syndrome type 1 in monozygotic twins and their families. Journal of the Faculty of Medicine, 64 (2): 365-371.
      • Santana, EE and Tamayo, VJ (2015). Waardenburg syndrome, Presentation of an affected family. Spiritual Medical Gazette, 17 (3). Cuba.
      • Waardenburg, PJ (1951). A new syndrome that combines abnormalities in the development of the eyelids, eyebrows and the root of the nose with pigmentation of the iris and head and congenital deafness. Bitter. Day. Buzzing. Genet., 3 (3): 195-201.

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