Waardenburg syndrome: causes, symptoms and treatment

This disorder of genetic causes produces physical and psychological alterations.

There are a large number of different disorders and conditions that can damage and impair our health. Many of them are well known to most of the population, especially when they are relatively prevalent or dangerous. Influenza, cancer, AIDS, Diabetes or Alzheimer's disease are just a few examples. Occasionally, some diseases that are not widely considered 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 rare diseases or a large number of genetic disorders. One of them is Waardenburg syndrome, which we will talk about along these lines..

Waardenburg syndrome: main symptoms

Waardenburg syndrome is a rare disease of genetic originThe Waardenburg syndrome is a rare disease of genetic origin, which is estimated to be suffered by one in forty thousand people and which is classified as one of the neurochristopathies, disorders generated as a consequence of alterations in the development of the neural crest.

This disease is characterized by the presence of alterations in facial morphologyThe presence of dystopia cantorum or displacement of the side of the inner canthus of the eye, pigmentation problems both at skin and eye level that causes them to have a light coloration (it is not uncommon to have eyes of a characteristic intense blue or heterochromia, and that part of the hair is white) and some level of hearing loss or even deafness at congenital level. It is not uncommon for vision problems to appear, although it is not one of the critical symptoms for diagnosis.

In addition, other digestive system other affectations linked to the digestive system, the movement or even the intellectual capacity may also appear.. The hair may also appear gray or even with white locks, as well as light spots on the skin. Nevertheless, this syndrome is characterized by being highly heterogeneous, having different types of symptomatological presentation.

Types of Waardenburg syndrome

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

Waardenburg syndrome type 1

Waardenburg syndrome type 1 is one of the most common. In this type of presentation of the syndrome, all of the above symptoms are present: morphofacial alterations and pigmentary problems, along with possible deafness.The presence of congenital deafness (although it only occurs in about 1 in 4 cases) is very common.

The presence of one eye of each color or heterochromia is observed with great frequency.It is very often observed the presence of one eye of each color or heterochromia, the light tonality of eyes (generally 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 internal canthus 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 average (although in some cases hypertelorism may also appear).

Waardenburg syndrome type 2

Waardenburg syndrome types 1 and 2 share almost all diagnostic criteria and the symptoms are almost identical. The main difference lies in the fact that in type 2 dystopia cantorum does not occur (if it did, it would be a Waardenburg syndrome). is not present in type 2 (if it did, it would be Waardenburg syndrome type 1).

In addition to this, in this presentation of the syndrome the facial morphological alterations are usually somewhat less marked than in comparison to type 1, while the deafness presented is usually somewhat more evident and frequent, being the majority (it appears in 70% of cases). Spina bifida or lack of genital development may also occur.

Klein-Waardenburg Syndrome or type 3

This type of disorder is characterized because in addition to the previous symptoms (it is generally closer to type 1), there are usually malformations in the upper extremities and neurological alterations. Also, it is usually more correlated with movement problems, muscular tension, cephalorachidian alterations or functional diversity at the intellectual level.. Eyelid drooping in at least one of the eyes, a symptom called ptosis, is also frequent, despite the absence of dystopia cantorum.

Waardenburg-Shah or type 4 syndrome

Very similar in symptomatology to Waardenburg syndrome type 2, but with the addition of alterations in the enteric and gastrointestinal system. which causes a lower number of neurons managing the intestines and is usually correlated with constipation and other digestive problems such as Hirschsprung's disease or congenital megacolon, in which feces are not expelled normally due to problems with the neuronal ganglia of the enteric system and there is an enlargement of the intestine and colon as a result of its obstruction.

Causes of this alteration

Waardenburg syndrome is a disease of genetic origin, which can be inherited or appear due to 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 in an autosomal dominant pattern. The problems seem to arise from an altered neuronal migration during development, which generates the symptomatology and a lack of melanocytes (causing the pigmentation alterations).

One of the genes that is most associated with the disorder in its most common typologies in types 1 and 3 is PAX3 (it is considered that 90% of type 1 patients have mutations in this gene). But it is not the only one. Type 2 is more associated with the MITF gene, and type 4 with an association of genes including EDN3, EDNRB and SOX10.

Treatment

Waardenburg syndrome is a genetic disorder, which does not have at least at this time any curative treatment. However, many of the difficulties caused by the syndrome are treatable, with a rather symptom-focused approach. rather focused on specific symptoms and complications depending on the dysfunction or risk it may pose to the patient. or risk it may pose to the patient.

The most common type of intervention is that related to possible deafness or hypoacusis, in which techniques such as cochlear implantation could be used.. The surveillance and prevention of the appearance of tumors (e.g. melanomas) is also something to be taken into account and if they appear they should also be properly treated. Some alterations of the skin and facial morphology may also require surgery, although this is not so frequent. Finally, if eye problems appear, they should also be treated.

For the most part, Waardenburg syndrome does not generate or usually present major complications in its most common forms, type 1 and type 2, so that sufferers are usually able to lead a typical life. This does not mean that they do not have difficulties, but the prognosis is generally positive for a good quality of life.

In the case of subtypes 3 and 4, the number of complications may be greater. In the case of subtype 4, the megacolon can lead to life-threatening alterations in the patient's life.. The latter is the case of megacolon, if not properly treated.

The treatment of these complications may require surgery to correct the megacolon or to improve the functionality of the upper extremities (for example, reconstructing the extremities and separating the fingers). In case of intellectual disability, it may also be necessary to apply educational guidelines that take into account the possible problems arising from In the case of intellectual disability, it may also be necessary to apply educational guidelines that take into account the possible problems derived from it, such as an individualized plan in the educational environment (although intellectual disability is usually mild).

It is also necessary to assess the possible psychological impact: the presence of morphological anomalies can trigger problems of anxiety, self-esteem and depression derived from self-image. If necessary, psychological therapy can be of great help.

Referencias bibliográficas:

• Duque, G.A.;Ramírez-Cheyne, J. & Saldarriaga-Gil, W. (2016). Síndrome de Waardenburg tipo 1 en gemelos monocigóticos y su familia. Revista de la Facultad de Medicina, 64 (2): 365-371.
• Santana, E.E. y Tamayo, V.J. (2015). Síndrome Waardenburg, Presentación de una familia afectada. Gaceta Médica Espirituana, 17 (3). Cuba.
• Waardenburg, P.J. (1951). A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary of the iris and head hair and with congenital deafness. Amer. Jour. Hum. Genet.,3 (3): 195-201.