The syndrome describes a genetic mutation-related disease that belongs to the group of large-growth syndromes. It is associated with congenital malformations and a predisposition to tumors. The growth of various organs is asymmetric.
Patients' organs begin to grow at a disproportionately fast rate in the second half of pregnancy and the first few years of life, with normal size in adulthood. This so-called visceromegaly increasingly affects internal organs, such as the spleen, liver, kidneys, pancreas, and tongue. Furthermore, malformations of the head and defects of the abdominal wall are common. Clinically, severe hypoglycemia can occur in the first few days of life.
Even in the embryonic phase tumors occur frequently, especially hamartomas and angiomas affect the embryo and the placenta.
The inheritance is sporadic in 85% of the cases and thus unknown and in 15% familial autosomal dominant. Cause are several genetic defects (IGF-2 and H19 gene) on chromosome 11 at the genome 11p15.5. In BWS, different cytogenetic and molecular genetic changes are observed in this gene region.
The gene H19 regulates the activity of IGF-2. In the case of the Beckwith-Wiedemann syndrome, both the allele of the IGF-2 gene is active, which originates from the paternal as well as the maternal chromosome 11. The activity of IGF-2 comes about through the methylation of H19.
Thus, the cause of the unbalanced growth, accompanied by tumors and hypoglycaemias, is the overproduction of the growth factor IGF-2 resulting from the gene mutation. It has a similar structure to insulin, has a mitogenic, anti-apoptotic and growth-stimulating effect.
IGF-2 has, on a small scale, the ability to dock on insulin receptors, lowering the blood sugar levels. The increased IGF-2 concentration promotes cell division, stimulates growth and at the same time prevents the destruction of diseased cells. Thus, it partially replaces the role of insulin.