Beckwith-Wiedemann-Syndrom (BWS): Aktueller Stand der Diagnostik und des klinischen Managements

Zusammenfassung

Die vorliegenden Empfehlungen der internationalen Beckwith-Wiedemann-Syndrom (BWS/BWSp)-Konsensus-Gruppe stellen einen Rahmen für die Verbesserung der Diagnostik und der klinischen Begleitung bei Patienten des BWSp dar. Hierbei ist den komplexen genetischen Basismechanismen und den variablen Multisystem-Phänotypen des BWSp dahingehend Rechnung zu tragen, dass ein verantwortlicher klinischer Ansprechpartner die notwendige Koordination der unterschiedlichen Aspekte für den einzelnen Patienten übernimmt. Die vorgeschlagenen diagnostischen und medizinischen Empfehlungen sollen hierbei praktikabel und kosten-effektiv gestaltet sein. Nichtsdestotrotz sind auf dem Hintergrund der sehr unterschiedlichen Gesundheitssysteme und medizinrechtlichen Vorgaben weitere Datenerhebungen wichtig, um tatsächlich auf lange Sicht die besten Strategien, z. B. in der Tumorfrüherkennnung, allgemein gültig empfehlen zu können. Daher müssen die hier gegebenen Konsensus-Empfehlungen im Rahmen prospektiver Studien evaluiert und weiteren zukünftigen Konsensus-Initiativen zur Evidenz-basierten Überprüfung vorgelegt werden.

Abstract

Beckwith-Wiedemann syndrome (BWS) belongs to the group of imprinting disorders and is characterized by variable clinical features, including overgrowth, macroglossia, abdominal wall defect, neonatal hypoglycemia, body asymmetry and an increased risk for embryonal tumors. In the majority of cases, molecular alterations of the Imprinting Center (IC) regions in the chromosomal region 11p15.5 can be detected, and a correlation of single clinical features with specific genomic and epigenetic changes is obvious. Therefore, the detailed molecular diagnosis is a prerequisite for a precise prediction of the tumor risk and the tumor spectrum. Furthermore, it is the basis for a well-directed genetic counselling of the families. Despite a huge number of comprehensive studies based on a large number of cases, standardized diagnostic criteria and advices for therapeutic management were missing. In the following, the recently published first international consensus guidelines drafted by 41 experts in the field of BWS from 11 European countries and the USA are summarized. Patients support groups had been included as well. In total, 72 consented recommendations for clinical and molecular diagnosis as well as for the clinical management of BWS have been published. They refer both to patients with the classical BWS phenotype and to those with “atypical” phenotypes which are summarized as BWS spectrum (BWSp). A modified clinical scoring system is now suggested, which represents the basis to initiate molecular diagnostics. Therapeutic recommendations comprise the major clinical questions in BWS/BWSp, i. e. early monitoring of an increased tumor risk, treatment of the macroglossia and the abdominal wall defects, and therapeutic interventions for hypoglycemia. However, though there was a broad consensus on the majority of therapeutic interventions, discussions on tumor monitoring are foreseeable. Thus, prospective studies to evaluate the consensus guidelines and their use are planned.

Schlüsselwörter

Konsensus-Empfehlungen - Imprinting-Erkrankung - Tumorüberwachung - Diagnostik - Beckwith-Wiedemann-Syndrom

Key words

Imprinting Disorder - Consensus Guidelines - Tumour surveillance - Diagnostics - Beckwith-Wiedemann syndrome

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