The Beckwith-Wiedemann Syndrome, also under the synonyms Wiedemann-Beckwith syndrome, Wiedemann Syndrome and Exomphalos macroglossia gigantism syndrome (EMG syndrome) is a genetic syndrome of tall stature associated with malformations and tumors and caused by a gene mutation.
Frequency
In 1964, Hans-Rudolf Wiedemann reported for the first time on a familial form of umbilical cord hernia (omphalocele) with an enlarged tongue (macroglossia) in Germany and distinguished it from other syndromes. In 1969, J described. Bruce Beckwith the same form. Therefore, the syndrome, which Wiedemann first called EMG syndrome, is now referred to as Beckwith-Wiedemann syndrome. It occurs with a frequency of 1:12.000 to 1:15.000 on. [1] Today, more than 500 case histories are documented, of which 15 % were family related. A slightly increased frequency was observed in artificial inseminations by ICSI (intracytoplasmic sperm injection).
Symptoms
The birth weight and length of infants with this condition tend to be larger than usual, and size growth may be asymmetrical.
Visceromegaly is manifested by enlargement of the liver, spleen or kidneys, often there is an enlarged tongue (macroglossia).
Other symptoms include malformations of the abdominal wall, such as umbilical hernias (umbilical hernias) or umbilical cord hernia (omphalocele), as well as kidney abnormalities (kidney cysts or a so-called congested kidney (hydronephrosis)).
In the first days of life, severe hypoglycemia (glucose levels dropping below normal) can occur.
In the head region, an unusually small skull (microcephaly) is noticeable. Characteristic are also protruding eyes (exophthalmos), midface hypoplasia and depressions at the dorsal helix edge of the ears (notch ears).
Embryonal tumors, especially Wilms tumors, occur with increased probability depending on the genetic causes. Other types of tumors that can occur are u. a. hepatoblastoma as well as adrenal tumors (z.B. Neuroblastoma). According to current findings, this increased likelihood of developing tumors exists only up to about age 8. year of life.
For this reason, children with Beckwith-Wiedemann syndrome should be screened by age 8. The kidneys, adrenal glands, liver and the entire abdominal cavity are regularly examined with ultrasound and magnetic resonance imaging before the age of 16. Regular blood and urine tests are still advisable. [2]
Genetic cause
The genetic cause is a direct alteration of the genes IGF-2 (insulin-like growth factor 2) and H19, which are located on band 11p15.5 of chromosome 11.
In most children with this syndrome, IGF2 is expressed paternally (on the father’s side) and maternally (on the mother’s side), d. h. both alleles carrying IGF2 also express it.
Ten out of 100 children have paternal uniparental disomy (both chromosomes 11 inherited from father, none from mother).
In five to ten out of 100 children, hypermethylation of H19 associated with biallelic expression of IGF-2 can be detected. As a result, there is an increased incidence of tumors (z. B. Wilms tumors).
In up to 20 out of 100 children, the genetic cause cannot yet be determined.
The two genes IGF2 and H19 are controlled by a common enhancer. Usually, the effect of the enhancer on IGF2 is blocked maternally by an isolator, so that only H19 is expressed maternally. Paternally, both genes are expressed, since the isolator cannot act here due to a methylation of H19.
Mutations can lead to increased methylation and abnormal expression of genes, resulting in Beckwith-Wiedemann syndrome.