Waardenburg syndrome is a congenital condition that medical science classifies under leucism and divides into four different types. Typical signs include deafness, malformations, and pigmentary abnormalities. Because Waardenburg syndrome is a genetic disorder, it is not causally treatable.
What is Waardenburg syndrome?
Waardenburg syndrome is a type of leucism that lay people often confuse with albinism. Both leucism and albinism are characterized by a lack of pigment. Waardenburg syndrome owes its name to Petrus Johannes von Waardenburg, who first described the condition in 1951. A person with leucism has no melanocytes, skin cells that produce pigment. The majority of melanocytes are located in the epidermis and around the hair follicles. Pigments are found not only in the skin, but also in the eyes, where the retina and iris also form pigments. They serve not only for optical design. They protect the skin or the cells of the eye from excessive exposure to light. The pigment melanin can be either brown to black or yellow to reddish. As a rule, mixtures of both variants are present, which form the characteristic color image of the pigment cells.
Causes
Waardenburg syndrome results from a mutation in the genetic material. In this case, the deoxyribonucleic acid (DNA) shows deviations compared to a healthy DNA. Depending on the affected gene, the disease manifests itself in different ways. Type I and type III (Klein-Waardenburg syndrome) are caused by a mutation in the gene PAX, at gene locus 2Q35. In type II, the MITF gene is responsible for the inheritance of the syndrome. Different gene segments can be mutated there. Sometimes medicine therefore differentiates type III even further into subtypes A, B, C and D. Externally, however, the subtypes hardly seem to differ from each other. For type IV, different gene segments on the endothelin-3 gene or the endothelin-B receptor gene are also possible mutation sites. All four types of Waardenburg syndrome are autosomal, meaning they are located on one of the autosomes, not on the X or Y chromosome. Types I, II, and III are recessive: only when the double set of chromosomes has two disease-bearing genes does the syndrome manifest. However, if a person has not only one mutated but also one healthy gene segment, the disease does not break out. Such a person can still pass on Waardenburg syndrome to his or her children.
Symptoms, complaints, and signs
The most noticeable symptom of Waardenburg syndrome is pigmentary disturbance, which is mainly reflected in three areas. The forelock is colorless in people with Waardenburg syndrome and therefore appears white. The eyes have different colors because the iris of both eyes does not produce pigment in each area. Areas that do not contain pigments appear blue in the iris. The remaining areas form the pigments as they are genetically predetermined. Medicine also refers to this phenomenon as iris heterochromia. In addition to white forelock and iris heterochromia, Waardenburg syndrome type I also manifests white spot disease or checkered skin (vitiligo). This is the term used by physicians to describe the lack of pigment in the skin, which is most apparent on the hands, neck, face, and anogenital area. In addition, hearing loss and facial deformities manifest themselves: a high and broad nasal bridge are characteristic, as are tissues or organs that form in the wrong place (dystopia canthorum). Dystopia canthorum does not occur in type II of Waardenburg syndrome, although type II otherwise corresponds to type I. In type III, all the symptoms of type I are present; in addition, malformations of the arms occur. The most severe manifestation of Waardenburg syndrome is seen in type IV, which often results in the death of the affected person. The differentiation of certain neurons is also disturbed in this form of the disease, which also leads to the development of Hirschsprung’s disease (congenital megacolon). This intestinal disease manifests itself, among other things, in the narrowing of the colon.
Diagnosis and course of the disease
Waardenburg syndrome is congenital. Early in the child’s development in the womb, the mutation interferes with proper development, resulting in the various symptoms.Doctors can diagnose Waardenburg syndrome not only on the basis of external features: They can gain clarity on whether any of the mutations that cause the syndrome are present by genetic testing.
Complications
Waardenburg syndrome can lead to several complications. A typical consequence of the disease is the characteristic pigmentary abnormality. This noticeable blemish results in serious psychological problems, depending on how severe it is and at what age it first appears. Those affected often develop social anxiety or even full-blown depression. In Waardenburg syndrome type I, white spot disease also occurs, which can exacerbate the mental suffering mentioned above. Furthermore, hearing loss and facial deformities may occur in the course of the disease. A possible secondary disease of Waardenburg syndrome is Hirschsprung’s disease. This intestinal disease is associated with narrowing of the colon. Serious gastrointestinal symptoms can occur, which may result in constipation or even intestinal obstruction. Because the syndrome is hereditary, there are few treatment options, and the disease often takes a severe course that is associated with permanent cognitive and aesthetic impairment for those affected. Symptomatic therapy is also not without risk. For example, the administration of cortisone can lead to skin irritation and other side effects. Surgical procedures, such as those performed in the treatment of bowel disorders, are always associated with a risk of infection and injury.
When should you see a doctor?
Since Waardenburg syndrome cannot heal on its own, the affected person should see a doctor. In this regard, early detection and subsequent treatment of the disease always has a very positive effect on the further course and can also prevent further complications. Therefore, a medical professional should be contacted at the first signs and symptoms of the syndrome. A doctor should be consulted if the affected person suffers from a severe pigment disorder. This often results in completely colorless skin, which appears very white. Likewise, white patches may form on the skin. Most patients also suffer from hearing loss due to Waardenburg syndrome, which does not disappear on its own. Likewise, the organs in the body are misaligned, so severe complications can occur. Waardenburg syndrome can be detected by a pediatrician or by a general practitioner. Further treatment depends very much on the type and severity of the symptoms, so that no general prediction can be made about the further course of the disease. Since the syndrome can often also lead to psychological upsets, a visit to a psychologist is also very useful.
Treatment and therapy
Because Waardenburg syndrome is a hereditary disease, causal treatment is not possible. It may be possible to take measures to alleviate the hearing loss. However, the exact procedure depends on the individual initial situation. In the more severe type IV, physicians must also treat Hirschsprung disease.
Prevention
Specific prevention is not possible for Waardenburg syndrome because it is a hereditary disease. Type IV of Waardenburg syndrome follows an autosomal recessive inheritance. The disease therefore manifests itself only if the child inherits one disease-bearing allele from each of the two parents. However, if the genetic material contains only one diseased and one healthy allele, Waardenburg syndrome does not break out. Inheritance of types I-III, on the other hand, is autosomal dominant: if a person has one mutant and one healthy gene, the disease manifests. However, this person does not necessarily have to pass on Waardenburg syndrome to his or her child, since he or she can also inherit the healthy gene. Chance determines whether a parent passes the disease-bearing gene or the healthy gene to their child.
Follow-up
Waardenburg syndrome requires extensive follow-up care. Because it is a congenital disorder, causative treatment is not possible. Follow-up care focuses on counseling the patient regarding further therapeutic measures. The pigmentary disorders and sensorineural hearing loss need to be evaluated by a physician at regular intervals. Follow-up care consists of a patient interview and a physical examination.During the anamnesis, the physician first obtains a picture of the current symptoms. Complaints that have largely subsided do not require further follow-up. Pigment disorders and hearing loss are chronic conditions that need to be checked regularly. If necessary, new therapeutic measures may emerge for the patient between check-ups. The patient should keep a diary and note down any unusual symptoms. With the help of the notes, regular follow-up care can be optimally aligned with the symptom picture. Depending on the nature of the symptoms, therapeutic help may also be required. Since the syndrome can run very differently, the measures must be determined individually.
What you can do yourself
Medical treatment of Waardenburg syndrome can be supported by various self-help measures. The typical sensorineural hearing loss can be compensated by wearing a hearing aid. Relatives must speak loudly and clearly and turn toward the patient when speaking so that the patient can lip-read. To avoid misunderstandings, it is recommended to be open about the hearing loss. This also applies to other symptoms of the disease, such as pigmentary disorders and visual disturbances, which can develop in the course of life. Sufferers should inform themselves in detail about the ptosis-epicanthus syndrome and decide together with the doctor which remedies help against the individual symptoms. In most cases, very different complaints occur, which can sometimes also represent a psychological burden. Therapeutic support is just as important for patients as physical treatment, especially in the case of depressive moods or anxiety disorders. Parents of children suffering from Waardenburg syndrome should arrange for genetic testing. Often, the trigger of the hereditary disease can be determined, making it easier to plan for further children. If the symptoms have a strong negative impact on well-being, it may also be useful to visit a self-help group. The Leona e.V. association provides those affected with further points of contact.
