Beckwith–Wiedemann syndrome

The Beckwith- Wiedemann syndrome, also under the synonyms of Beckwith-Wiedemann syndrome, Wiedemann syndrome and exomphalos - macroglossia - gigantism syndrome (EMG syndrome ), is a genetic condition overgrowth syndrome, which is associated with malformations and tumors and due to a gene mutation is.

Frequency

1964 Hans- Rudolf Wiedemann reported for the first time a familial form of umbilical cord rupture ( omphalocele ) with enlarged tongue ( macroglossia ) in Germany and excluded them from other syndromes. 1969 described Bruce J. Beckwith the same shape. Therefore, the syndrome, which Wiedemann initially designated as having EMG syndrome, now known as Beckwith -Wiedemann syndrome. It occurs with an incidence of 1:12,000 to 1:15,000. Today, more than 500 case studies are documented, of which 15 % occurred on family history. For artificial insemination by ICSI (intracytoplasmic sperm injection), a slightly increased incidence was observed.

Symptoms

Birth weight and birth length of infants with this feature are usually larger than usual and it can happen that the size growth is asymmetric.

A visceromegaly seen in liver, spleen or kidney enlargement, often is an enlarged tongue ( macroglossia ) ago.

Other symptoms include abnormalities of the abdominal wall, such as umbilical hernias ( umbilical hernia ) or umbilical cord rupture ( omphalocele ) and kidney problems ( renal cysts or a so-called stasis ( hydronephrosis ) ).

In the first days of life may lead to severe hypoglycemia (glucose level lowered below the normal range ).

In the head region an unusually small trained skull falls on ( microcephaly ). Characteristic are also bulging eyes ( exophthalmos ), a midface and indentations on the dorsal helical rim of the ear (notch ears).

Embryonal tumors, particularly Wilms' tumors, occur as a function of the genetic causes of an increased probability. Other types of tumors that can occur include the hepatoblastoma, and adrenal tumors (eg, neuroblastoma ). This increased probability for the formation of tumors is according to recent findings, only up to about the age of 8.

For this reason, should kidneys, adrenal glands, liver, and the entire abdomen with ultrasound and magnetic resonance imaging are investigated with the Beckwith- Wiedemann syndrome up to 8 years regularly in children. Furthermore, regular blood and urine tests are advisable.

Genetic cause

The genetic cause is an immediate change in genes IGF -2 ( insulin -like growth factor 2) and H19, which are on the band 11p15.5 of chromosome 11.

In most children with this syndrome paternal IGF2 ( paternal ) and maternal ( mother's side) is expressed, that is, both alleles carry the IGF2 express it well.

In ten out of 100 children with a paternal uniparental disomy is present ( both chromosomes 11 are inherited from the father, no one from the mother ).

Five to ten out of 100 children hypermethylation of the H19 in the context of biallelic expression of IGF -2 is demonstrated. As a result, it is more common to the development of tumors (eg Wilms' tumors).

With up to 20 out of 100 children, the genetic cause is not yet clarified.

Both IGF2 and H19 genes are controlled by a common enhancer. Usually maternal ( mother's side) is blocked the effect of the enhancer on IGF2 by an insulator, so that only maternally expressed H19. Paternal ( father's side) both genes are expressed, since the insulator here due to methylation of H19 can not act.

Mutations can lead to increased methylation and unusual expression of the genes leading to the formation of the Beckwith -Wiedemann syndrome.

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