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Beckwith-Wiedemann-Syndrom

Beckwith-Wiedemann syndrome

Zusammenfassung

Das Beckwith-Wiedemann-Syndrom (BWS) ist ein pädiatrisches Überwuchssyndrom mit variablem klinischem Erscheinungsbild. Obwohl die betroffenen Kinder mit zunehmendem Alter immer normaler aussehen, ist es wichtig, die Diagnose BWS zu stellen. Gründe sind mögliche syndromspezifische Komplikationen, insbesondere ein 400-fach erhöhtes Risiko der Patienten, an bestimmten embryonalen Tumoren – Nephroblastome (Wilms-Tumoren), Hepatoblastome u. a. – innerhalb der ersten Lebensjahre zu erkranken. Klinisch überlappt das BWS mit anderen Krankheitsentitäten, sodass eine eindeutige molekulargenetische Diagnostik zur Risikoabschätzung und adäquaten Therapie wünschenswert ist. Molekular ist das BWS mit der Chromosomenregion 11p15.5 assoziiert, einer Region in der es 2 Cluster von Genen gibt, die dem genomischen Imprinting unterliegen. Bei den Patienten lassen sich Sequenzabweichungen in bestimmten Genen finden, die Mehrzahl weisen aber DNA-Methylierungsveränderungen auf, welche die Gendosis der funktionell zur Verfügung stehenden, monoallelisch aktiven 11p15.5-Gene pathogen beeinflussen. Zurzeit existiert nur eine sehr unvollständige Genotyp-Phänotyp-Korrelation. Aktuelle Forschungsarbeiten liefern Ansätze, die Ätiopathogenese des Syndroms molekular besser zu verstehen. So werden beispielsweise Interaktionspartner identifiziert, die das Imprinting der 11p15.5-Gene modifizieren und epigenetisch regulieren.

Abstract

The Beckwith-Wiedemann syndrome (BWS) is a pediatric overgrowth syndrome with a variable clinical appearance. The phenotype normalizes with age but the diagnosis of BWS is important as syndrome-specific complications may develop, in particular as a result of a 400-fold increased risk of patients developing certain tumor entities, predominantly nephroblastomas (Wilms’ tumors) and hepatoblastomas, within the first years of life. BWS displays a clinical overlap with other syndromes so that an unambiguous molecular diagnostic is required for risk assessment and appropriate therapy. At the molecular level BWS is associated with the chromosomal region 11p15.5, where two clusters with imprinted genes are located. In patients both genetic mutations and in most cases aberrant DNA methylation can be observed, which pathogenically affect the gene dosage of functionally available monoallelically expressed 11p15.5 genes. Currently only a very incomplete genotype-phenotype correlation exists for BWS. Current research projects provide insights in the molecular etiopathogenesis of the syndrome by identifying interacting partners which modify the epigenetic regulation of imprinted 11p15.5-genes.

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Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht. Gefördert aus Mitteln des BMBF-Verbundprojekts: Netzwerk Imprintingerkrankungen, Teilprojekt 5 (Förderkennzeichen 01GM0885) für D.P.

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Prawitt, D., Enklaar, T. & Zabel, B. Beckwith-Wiedemann-Syndrom. medgen 22, 399–404 (2010). https://doi.org/10.1007/s11825-010-0245-9

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Schlüsselwörter

  • Beckwith-Wiedemann-Syndrom
  • Überwuchs
  • Wilms-Tumor-Gene
  • Humanes IGF2-Protein
  • Genomisches Imprinting

Keywords

  • Beckwith-Wiedemann syndrome
  • Gigantism
  • Wilms’ tumor genes
  • IGF2 protein, human
  • Genomic imprinting