Somatic Mosaicism for Paternal Uniparental Disomy of 11p15.5 Region in Adrenal and Liver Tissues in a Newborn with Atypical Beckwith–Wiedemann Syndrome

Abstract Beckwith–Wiedemann syndrome (BWS) is characterized by overgrowth and increased risk of embryonic tumors. It results from alterations in genes controlled by imprinting centers H19DMR (Imprinting Center [IC] 1) and KvDMR (IC2). Strategies for diagnostic confirmation include methylation analysis and CDKN1C sequencing. We present a newborn with placentomegaly, hyperinsulinism and adrenal cytomegaly, but no typical external features of BWS. The patient had normal genetic studies in blood. However, adrenal and liver tissues showed hypermethylation of IC1 and hypomethylation of IC2. Microsatellite analysis confirmed mosaic paternal uniparental disomy. This study demonstrates the importance of analyzing additional tissues to reduce underdiagnosis of somatic mosaicism in BWS.

[1]  J. Kalish,et al.  Longitudinal Monitoring of Alpha-Fetoprotein by Dried Blood Spot for Hepatoblastoma Screening in Beckwith–Wiedemann Syndrome , 2019, Cancers.

[2]  R. Hennekam,et al.  Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith–Wiedemann syndrome: an international consensus statement , 2018, Nature Reviews Endocrinology.

[3]  G. Ferrero,et al.  Cancer Risk in Beckwith-Wiedemann Syndrome: A Systematic Review and Meta-Analysis Outlining a Novel (Epi)Genotype Specific Histotype Targeted Screening Protocol. , 2016, The Journal of pediatrics.

[4]  M. Maghnie,et al.  A multi-method approach to the molecular diagnosis of overt and borderline 11p15.5 defects underlying Silver–Russell and Beckwith–Wiedemann syndromes , 2016, Clinical Epigenetics.

[5]  R. Brusati,et al.  Recommendations of the Scientific Committee of the Italian Beckwith-Wiedemann Syndrome Association on the diagnosis, management and follow-up of the syndrome. , 2016, European journal of medical genetics.

[6]  V. Mitev,et al.  Different methylation patterns in BWS/SRS cases clarified by MS-MLPA , 2012, Molecular Biology Reports.

[7]  M. CarlosAspillaga,et al.  Recomendación sobre Curvas de Crecimiento Intrauterino , 2010 .

[8]  N. Niikawa,et al.  Japanese and North American/European patients with Beckwith–Wiedemann syndrome have different frequencies of some epigenetic and genetic alterations , 2007, European Journal of Human Genetics.

[9]  A. Reeve,et al.  Proportion of cells with paternal 11p15 uniparental disomy correlates with organ enlargement in Wiedemann-beckwith syndrome. , 2000, American journal of medical genetics.

[10]  Markus Schuelke,et al.  An economic method for the fluorescent labeling of PCR fragments , 2000, Nature Biotechnology.

[11]  Nan Faion T. Wu,et al.  The Beckwith-Wiedemann Syndrome , 1974, Clinical pediatrics.