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BeckwithWiedemann and RussellSilver Syndromes: from new molecular insights to the comprehension of imprinting regulation

Azzi, Salaha,b,c; Abi Habib, Walida,b,c; Netchine, Irenea,b,c

Current Opinion in Endocrinology, Diabetes & Obesity:
doi: 10.1097/MED.0000000000000037
GROWTH AND DEVELOPMENT: Edited by Lynne L. Levitsky
Abstract

Purpose of review: The imprinted human 11p15.5 region encompasses two imprinted domains important for the control of fetal growth: the H19/IGF2 domain in the telomeric region and the KCNQ1OT1/CDKN1C domain in the centromeric region. These two domains are differentially methylated and each is regulated by its own imprinting control region (ICR): ICR1 in the telomeric region and ICR2 in the centromeric region. Aberrant methylation of the 11p15.5 imprinted region, through genetic or epigenetic mechanisms, leads to two clinical syndromes, with opposite growth phenotypes: Russell–Silver Syndrome (RSS; with severe fetal and postnatal growth retardation) and Beckwith–Wiedemann Syndrome (BWS; an overgrowth syndrome).

Recent findings: In this review, we discuss the recently identified molecular abnormalities at 11p15.5 involved in RSS and BWS, which have led to the identification of cis-acting elements and trans-acting regulatory factors involved in the regulation of imprinting in this region. We also discuss the multilocus imprinting disorders identified in various human syndromes, their clinical outcomes and their impact on commonly identified metabolism disorders.

Summary: These new findings and progress in this field will have direct consequence for diagnostic and predictive tools, risk assessment and genetic counseling for these syndromes.

Author Information

aAP-HP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes

bUPMC Paris 6, UMR_S938, Centre de Recherche de Saint-Antoine

cINSERM, UMR_S938, Centre de Recherche de Saint-Antoine, Paris, France

Correspondence to Irène Netchine, Explorations Fonctionnelles Endocriniennes, Hôpital Armand Trousseau, Pierre & Marie Curie School of Medicine, INSERM UMR-S938, 26 Av du Dr Arnold Netter, 75012, France. Tel.: +33 144736448;. fax: +33 144736621; e-mail: irene.netchine@trs.aphp.fr

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins