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Isolated‐ and Beckwith‐Wiedemann syndrome related‐ lateralised overgrowth (hemihypertrophy): Clinical and molecular correlations in 94 individuals
Author(s) -
Radley Jessica A.,
Connolly Melissa,
Sabir Ataf,
Kanani Farah,
Carley Helena,
Jones Rachel L.,
Hyder Zerin,
Gompertz Lianne,
Reardon Willie,
Richardson Ruth,
McClelland Louise,
Maher Eamonn R.
Publication year - 2021
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13997
Subject(s) - hemihypertrophy , beckwith–wiedemann syndrome , multiplex ligation dependent probe amplification , cohort , imprinting (psychology) , medicine , genetics , pathology , biology , dna methylation , gene , gene expression , exon
The congenital imprinting disorder, Beckwith‐Wiedemann syndrome (BWS) is associated with variable clinical features including hemihypertrophy/lateralised overgrowth (LO) and embryonal tumour predisposition. BWS‐associated (epi)genetic alterations occur in a subset of patients with isolated LO (ILO), leading to the concept of BWS spectrum disorder (BWSp). We investigated the relationship between clinical features and molecular diagnostic results in a cohort with LO using the BWSp international consensus group (BWSICG) clinical scoring system. Clinical/molecular findings in 94 previously‐unreported patients with LO referred for BWSp molecular studies were reviewed retrospectively. The BWSICG score was assigned and diagnostic rate calculated. BWSp‐associated (epi)genetic alteration was identified in 15/94 (16%). The molecular diagnostic rate by MS‐MLPA (blood DNA) for BWS‐related molecular findings in patients with LO was positively correlated with the BWSICG score. 3/48 with ILO had a molecular alteration. No individuals with ILO had developed an embryonal tumour at last follow up. Among a cohort of individuals with LO referred for BWSp molecular testing, the BWSICG score correlated with diagnostic yield. The embryonal tumour risk in children with ILO and negative molecular testing appeared very low, however longer‐ and more complete follow up is required to better define tumour risks in this group.