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Background  Beckwith-Wiedemann syndrome (BWS) is a rare pediatric overgrowth disorder with a variable clinical phenotype caused by deregulation affecting imprinted genes in the chromosomal region 11p15. Alterations of the imprinting control region 1 (ICR1) at the  IGF2/H19  locus resulting in biallelic expression of  IGF2  and biallelic silencing of  H19  account for approximately 10% of patients with BWS. The majority of these patients have epimutations of the ICR1 without detectable DNA sequence changes. Only a few patients were found to have deletions. Most of these deletions are small affecting different parts of the ICR1 differentially methylated region (ICR1-DMR) removing target sequences for CTCF. Only a very few deletions reported so far include the  H19  gene in addition to the CTCF binding sites. None of these deletions include  IGF2 .    Case presentation  A male patient was born with hypotonia, facial dysmorphisms and hypoglycemia suggestive of Beckwith-Wiedemann syndrome. Using methylation-specific (MS)-MLPA (Multiplex ligation-dependent probe amplification) we have identified a maternally inherited large deletion of the ICR1 region in a patient and his mother. The deletion results in a variable clinical expression with a classical BWS in the mother and a more severe presentation of BWS in her son. By genome-wide SNP array analysis the deletion was found to span ~100 kb genomic DNA including the ICR1DMR,  H19 , two adjacent non-imprinted genes and two of three predicted enhancer elements downstream to  H19 . Methylation analysis by deep bisulfite next generation sequencing revealed hypermethylation of the maternal allele at the  IGF2  locus in both, mother and child, although  IGF2  is not affected by the deletion.    Conclusions  We here report on a novel large familial deletion of the ICR1 region in a BWS family. Due to the deletion of the ICR1-DMR CTCF binding cannot take place and the residual enhancer elements have access to the  IGF2  promoters. The aberrant methylation (hypermethylation) of the maternal  IGF2  allele in both affected family members may reflect the active state of the normally silenced maternal  IGF2  copy and can be a consequence of the deletion. The deletion results in a variable clinical phenotype and expression.    Electronic supplementary material  The online version of this article (doi:10.1186/s12881-015-0173-2) contains supplementary material, which is available to authorized users.

A novel large deletion of the ICR1 region including H19 and putative enhancer elements