Beckwith-Wiedemann syndrome is characterized by a genetically determined growth disorder of the child with uneven growth of the various organs. This maldevelopment begins intrauterine (in the uterus) and is often associated with tumor formation.
What is Beckwith-Wiedemann syndrome?
Beckwith-Wiedemann syndrome is a very rare genetic disorder and affects children up to the age of eight. This disorder has a 1 in 12000 to 1 in 15000 chance of occurring. Various organs, such as the liver, pancreas, spleen or kidneys grow disproportionately. The tongue also often enlarges to such an extent that it no longer fits in the mouth. This growth disorder is often accompanied by various benign and malignant tumors. Furthermore, hypoglycemic states (low blood sugar) occur during the first weeks of life. Other malformations affect the abdominal wall, often resulting in umbilical hernias. Kidney cysts are also common. After the age of eight, the growth-related symptoms of Beckwith-Wiedemann syndrome disappear, and the likelihood of cancer growth also decreases to normal.
Causes
The cause of this uneven growth is the genetically determined overproduction of the growth factor IGF-2 (insulin-like growth factor 2). This growth factor is structurally similar to insulin and has mitogenic (cell-dividing), antiapoptotic (prevents cell suicide), and growth-stimulating effects. It can also dock to insulin receptors to a small extent, thereby lowering blood glucose levels. Thus, the increased concentration of IGF-2 promotes cell division and thus stimulates growth. At the same time, however, it prevents the destruction of diseased and degenerated cells and also replaces the role of insulin to some extent. The result is unbalanced growth, which is accompanied by tumors and, in infancy, often by hypoglycemia. The genetic causes of the overproduction of the hormone IGM-2 are alterations in the genes IGF-2 and H19, which are located on chromosome 11. Normally, only the allele of the gene IGF-2 is active, which originates from the paternal chromosome 11. The corresponding allele of maternal chromosome 11 is usually inactive. The activity of IGF-2 is regulated by the action of the gene H19. However, if H19 is methylated, as in paternal (father’s) chromosome 11, the activity of IGF-2 comes into full play. Several mutations lead to Beckwith-Wiedemann syndrome. For example, hypermethylation may be present so that both alleles of IGH-2 are active. Furthermore, it is also possible that two paternal chromosomes 11 are inherited without a maternal chromosome 11 being present. In 20 percent of cases, the genetic cause of Beckwith-Wiedemann syndrome cannot be determined.
Symptoms, complaints, and signs
Infants born with Beckwith-Wiedemann syndrome are usually taller and heavier than healthy infants. The tall stature often affects the organs as well and may cause further growth disturbances in early childhood. Externally, the syndrome can also be recognized by the too small head and protruding eyeballs. The tongue is disproportionately large and leads to the typical speech disorders. Some children also suffer from malformations of the hands and feet or damage to the spine. Likewise, defects in the abdominal wall, disorders of the gastrointestinal tract and bone diseases may occur. Affected infants also suffer from tumors, which usually develop shortly after birth or in the first years of life and grow rapidly. In many affected individuals, the external abnormalities lead to psychological problems such as social anxiety or depression. If the syndrome is treated early, the symptoms can at least be reduced. However, some symptoms, such as the dwarfism of the skull or the protruding eyeballs, cannot always be treated. They cause physical and psychological problems throughout life. These include visual disturbances, circulatory problems, inflammation, bleeding, and a number of other symptoms that depend on the type and severity of the condition.
Diagnosis
Beckwith-Wiedemann syndrome can be diagnosed on the basis of typical growth disturbances. In 15 percent of cases, a positive family history is present. The other cases occur sporadically.If macrosomia (disproportionate size of organs and body parts), macroglossia (enlarged tongue), defects in the abdominal wall, at least one enlarged organ, and embryonal tumors are present, Beckwith-Wiedemann syndrome can be assumed. Molecular genetic testing should continue to be performed to confirm the diagnosis of Beckwith-Wiedemann syndrome.
Complications
In general, Beckwith-Wiedemann syndrome leads to the development of tumors, shortening life span if the disease is not treated properly or early. Often, the organs also do not grow evenly, resulting in growth failure in the patient. The organs in the patient are greatly enlarged, which can be seen especially in the tongue. Due to the enlarged tongue and the too small skull, speech defects may occur during the child’s development. Likewise, the eyeballs often protrude. Because of the unusual appearance, children can become victims of teasing and bullying in many cases. Beckwith-Wiedemann syndrome is treated only symptomatically, with no specific treatment of the symptom. Mainly the tumors are monitored and removed if necessary. Since the tumors grow relatively quickly, the affected person must undergo many surgical procedures. As a result, the life of the affected person is severely restricted and the quality of life decreases. Many patients also suffer from reduced self-esteem due to the altered appearance. If the removal of the tumors is successful, there are no further complications. In most cases, symptoms of Beckwith-Wiedemann syndrome occur only up to the age of eight years.
When should you see a doctor?
Beckwith-Wiedemann syndrome can usually be diagnosed promptly after the child is born. The doctor, an obstetrician or the parents will usually notice the typical deformities immediately and arrange for a diagnosis. Further treatment should be given as soon as possible. Prompt action – usually monitoring the tumors first and removing them if necessary – can at least reduce further complications. However, the changes in appearance can only be treated symptomatically. In most cases, certain deformities remain, which can lead to psychological problems later in life. If the changed appearance leads to exclusion and consequently to a reduced self-esteem, a therapist must be consulted. Accompanying counseling sessions with specialists and self-help groups with other affected persons are available to patients. Further medical measures are not necessary insofar as Beckwith-Wiedemann syndrome resolves as usual. However, if symptoms persist well beyond the age of eight, the treating physician should be consulted again.
Treatment and therapy
Beckwith-Wiedemann syndrome can only be treated symptomatically because it is genetic. Especially from early childhood until the age of eight, this disease requires a lot of treatment. In infancy, blood glucose levels must be monitored to avoid hypoglycemia. If this occurs too frequently, it can also lead to brain development disorders. Furthermore, tumor development, such as Wilms tumor, hepatoblastoma, neuroblastoma and rhabdomyosarcoma, must be constantly checked. These tumors grow very rapidly and must be surgically removed. In order to control tumor development, it is necessary to perform blood tests every six to twelve weeks until 4 years of age and ultrasound examinations of the abdomen every three months until 8 years of age. Then, at the age of eight years, the symptoms of Beckwith-Wiedemann syndrome disappear.
Outlook and prognosis
Beckwith-Wiedemann syndrome has an unfavorable disease course. The prognosis of the genetic disorder is considered very poor, as there are no adequate treatment options for permanent recovery. For legal reasons, intervention and modification of human genetics has not been permitted to date. This limits the medical profession’s options and allows only symptomatic treatment. Despite great efforts, scientists and researchers have not yet been able to achieve a lasting cure or minimize the symptoms. Children are particularly at risk. The risk of premature death within the first 8 years of life is significantly increased.It additionally increases sharply if no medical treatment is used. In addition to disturbances in growth, tumors repeatedly form in various parts of the body. These often have a malignant course of disease and rapid growth. The child must undergo regular examinations so that the formation of a tumor can be detected at an early stage. Several operations are performed during childhood. The growth disorders are corrected as best as possible and the tumors are removed. Each surgical intervention is associated with the usual risks and side effects. When the patient reaches adulthood, tumor formation normally decreases. However, an increased risk of death remains.
Prevention
Prevention of Beckwith-Wiedemann syndrome is not possible because it is genetic. However, up to the age of eight, the child requires constant medical monitoring to prevent life-threatening maldevelopment.
Prevention
Beckwith-Wiedemann syndrome requires lifelong treatment because the malformations and tumors often cause long-term consequences. Follow-up care focuses on the measures that need to be taken after surgery. In the case of tumors, alternative means must be considered in addition to conservative therapeutic measures. Especially during aftercare, methods from Chinese medicine can provide pain relief and an improved sense of well-being. The doctor in charge can support patients in finding a suitable alternative medicine practitioner and provide further tips for a healthy lifestyle adapted to the condition. In addition, the usual progress controls must be taken up. Depending on the patient’s health, these checkups may be weekly, monthly or yearly. After surgery, any wounds must be checked. Follow-up care after chemotherapy or radiation therapy also includes ultrasound examinations, measurements of blood values, and patient consultations. Genetic counseling is also part of the aftercare. During the consultation with a specialist in genetic diseases, the risk of recurrence is assessed, among other things. If the patient is expecting offspring, the risk of disease in the child must be weighed. In some circumstances, an ultrasound examination can provide information about the child’s health.
Here’s what you can do yourself
Parents of children with the disease should inform themselves comprehensively about Beckwith-Wiedemann syndrome at an early stage so that they know what to expect after the birth of their child and can take the necessary organizational measures in good time. Care places for infants in need of care are extremely scarce. Parents should therefore make arrangements for their child’s placement as early as possible. However, it is to be expected that not both parents will be able to return to their jobs promptly or full time, as the care of a child suffering from Beckwith-Wiedemann syndrome is very costly, especially up to the age of eight. The children usually suffer from a large number of tumors and cysts that require constant monitoring and medical supervision, so that regular visits to the doctor and hospital must be integrated into the family’s daily routine. Affected families learn best from people in similar situations how this can be accomplished. Since Beckwith-Wiedemann syndrome is very rare, there are no disease-specific support groups, but parents can join groups for conditions with similar symptoms. As children age, they themselves also suffer from the limitations associated with their disease. Because of their striking external appearance, they are often teased or bullied by their peers. To cope better with this situation, parents should consult a child psychologist in good time.
