Abstract
Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are two imprinting disorders associated with opposite molecular alterations in the 11p15.5 imprinting centres. Their clinical diagnosis is confirmed by molecular testing in 50-70% of patients. The authors from different reference centres for BWS and SRS have identified single patients with unexpected and even contradictory molecular findings in respect to the clinical diagnosis. These patients clinically do not fit the characteristic phenotypes of SRS or BWS, but illustrate their clinical heterogeneity. Thus, comprehensive molecular testing is essential for accurate diagnosis and appropriate management, to avoid premature clinical diagnosis and anxiety for the families.
Highlights
Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are congenital imprinting disorders, associated with oppositely altered parent of origin-specific expression of two neighbouring clusters of imprinted genes on Chr11p15.5 (Soellner et al, 2017 b) (Figure 1)
Over 50% of SRS cases are caused by loss of paternal allele methylation (LOM) of imprinting centre 1 (IC1 or H19/IGF2:IG-DMR), whereas gain of maternal allelic methylation at IC1 (GOM) can be identified in 5–10% of BWS cases
By considering the clinical data and the reason for referral and the molecular findings, we suggest to categorize these cases into three groups
Summary
Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are congenital imprinting disorders, associated with oppositely altered parent of origin-specific expression of two neighbouring clusters of imprinted genes on Chr11p15.5 (Soellner et al, 2017 b) (Figure 1). SRS affects approximately 1:50,000 individuals, with characteristic features including pre- and post-natal growth restriction, relative macrocephaly and prominent forehead, early feeding difficulties, and body asymmetry (Wakeling et al, 2016). To identify the major molecular changes, first-line testing for BWS and SRS is recommended to include DNA methylation analysis of IC1 and IC2 (Eggermann et al, 2016).
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