Beckwith-Wiedemann syndrome

Classification according to ICD-10
Q87.3	Congenital malformation syndromes with increased tissue growth in early childhood - Wiedemann-Beckwith syndrome
ICD-10 online (WHO version 2019)

The Beckwith-Wiedemann syndrome , also under the definition Wiedemann-Beckwith syndrome , Wiedemann syndrome and exomphalos-macroglossia-gigantism syndrome ( EMG Syndrome ), is a genetically conditional overgrowth syndrome , which with malformation and tumors and responsive to a Gene mutation is due.

frequency

In 1964, Hans-Rudolf Wiedemann reported for the first time on a familial form of an umbilical cord break ( omphalocele ) with an enlarged tongue ( macroglossia ) in Germany and differentiated it from other syndromes. In 1969 J. Bruce Beckwith described the same shape. Therefore, the syndrome that Wiedemann first called EMG syndrome is now called Beckwith-Wiedemann syndrome. It occurs at a frequency of 1 in 12,000 to 1 in 15,000. Today more than 500 case studies have been documented, 15% of which were family-related. A slightly increased frequency was observed with artificial insemination using ICSI ( Intracytoplasmic Sperm Injection ).

Symptoms

The birth weight and length of birth of infants with this peculiarity are usually larger than usual and it can happen that the growth in height is asymmetrical .

A Viszeromegalie shows in a liver - spleen - or kidney enlargement , there is often an enlarged tongue ( macroglossia ) before.

Other symptoms include malformations of the abdominal wall , such as umbilical hernias (umbilical hernias ) or umbilical cord breaks ( omphalocele ), as well as abnormal kidneys ( kidney cysts , multicystic kidney dysplasia or a so-called congestive kidney ( hydronephrosis )).

In the first days of life, severe hypoglycaemia ( drop in glucose levels below the normal value) can occur.

In the head area an unusually small skull trained (falls microcephaly ) on. Also characteristic are protruding eyes ( exophthalmos ), a midface hypoplasia and indentations on the dorsal helical edge of the ears ( notched ears ).

Embryonic tumors, especially Wilms tumors , are more likely to occur depending on the genetic causes. Other types of tumors that can occur include the hepatoblastoma and adrenal gland tumors (e.g. neuroblastoma ). According to current knowledge, this increased likelihood of the development of tumors only exists up to around the age of 8.

For this reason, children with Beckwith-Wiedemann syndrome up to the age of 8 should have their kidneys, adrenal glands, liver and the entire abdomen regularly examined using ultrasound and magnetic resonance imaging. Regular blood and urine tests are also advisable.

Genetic cause

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

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

Ten out of 100 children have a paternal uniparental disomy (both chromosomes 11 are inherited from the father, none from the mother).

Hypermethylation of H19 in connection with the biallelic expression of IGF-2 can be demonstrated in five to ten out of 100 children . As a result, tumors (e.g. Wilms tumors) occur more frequently.

In up to 20 out of 100 children, the genetic cause cannot yet be clarified.

The two genes IGF2 and H19 are controlled by a common enhancer . Usually, the effect of the enhancer on IGF2 is blocked by an isolator on the maternal side, so that only H19 is maternally expressed. Both genes are expressed paternally (on the paternal side), as the isolator cannot work here due to the methylation of H19.

Through mutations may lead to increased methylation and unusual expression of the genes, leading to the emergence of Beckwith-Wiedemann syndrome.

Differential diagnosis

A distinction must be made between Simpson-Golabi-Behmel syndrome and Perlman syndrome .

Individual evidence

↑ Lentze, Schaub, Schulte, Spranger and Heyne: Pediatrics: Basics and Practice. 2nd edition 2003, Springer-Verlag
↑ Alexander Strauss: Ultrasound Practice. 2nd edition, Springer, Berlin 2008, pp. 68-69, ISBN 978-3-540-78252-0

literature

Robert J Ferry Jr: Beckwith-Wiedemann Syndrome. Medscape
A. Schinzel: Newly discovered structural chromosome aberrations in well-known syndromes, associations and sequences . In: Results of Internal Medicine and Paediatrics / Advances in Internal Medicine and Pediatrics Volume 57, 1988, pp. 57-75.
Regine Witkowski , Otto Prokop , Eva Ullrich: Lexicon of Syndromes and Malformations: Causes, Genetics, Risks . Springer, Berlin 2003, ISBN 3-540-44305-3 .