Abstract
Objectives
To report a phenotypic series of eight patients of Beckwith-Wiedemann Syndrome (BWS) with abnormalities of 11p15.5 region to highlight the spectrum of phenotypic manifestations.
Methods
All the cases were evaluated using Methylation Specific Multiplex Ligation Dependent Probe Amplification (MS-MLPA) of 11p15.5 region to detect the abnormal methylation status of ICR1 (H19DR) and ICR2 (KvDMR) regions.
Results
The median age at diagnosis was 5.7 mo (range 1.5–13 mo) with female preponderance. Macroglossia, ear creases and abdominal wall defects were the major features. Hypomethylation at ICR2 and hypermethylation at ICR1 was observed in 6/8 and 2/8 patients respectively. No specific genotype and phenotype correlation was observed.
Conclusions
This report highlights the major clinical features of BWS that should prompt pediatricians to offer genetic testing to evaluate the epigenetic abnormalities using MS-MLPA, as it not only helps in appropriate counseling but also provides further guidance about the tumor risk surveillance.
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References
Mussa A, Russo S, De Crescenzo A, et al. Prevalence of Beckwith-Wiedemann syndrome in north west of Italy. Am J Med Genet A. 2013;161A:2481–6.
Thorburn MJ, Wright ES, Miller CG, Smith-Read EH. Exomphalos-macroglossia-gigantism syndrome in Jamaican infants. Am J Dis Child. 1970;119:316–21.
Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2010;18:8–14.
DeBaun MR, Tucker MA. Risk of cancer during the first four years of life in children from the Beckwith-Wiedemann syndrome registry. J Pediatr. 1998;132:398–400.
Shuman C, Beckwith JB, Weksberg R. Beckwith-Wiedemann syndrome. 2000 Mar 3 [Updated 2016 Aug 11]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1394/.
Brioude F, Kalish JM, Mussa A, et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14:229–49.
Ibrahim A, Kirby G, Hardy C, et al. Methylation analysis and diagnostics of Beckwith-Wiedemann syndrome in 1,000 subjects. Clin Epigenetics. 2014;6:11.
Duffy KA, Sajorda BJ, Yu AC, et al. Beckwith–Wiedemann syndrome in diverse populations. Am J Med Genet Part A. 2019;179:525–33.
Mussa A, Russo S, Larizza L, Riccio A, Ferrero GB. (Epi)genotype-phenotype correlations in Beckwith-Wiedemann syndrome: a paradigm for genomic medicine. Clin Genet. 2016;89:403–15.
Maas SM, Vansenne F, Kadouch DJM, et al. Phenotype, cancer risk, and surveillance in Beckwith–Wiedemann syndrome depending on molecular genetic subgroups. Am J Med Genet Part A. 2016;170:2248–60.
Tan TY, Amor DJ. Tumour surveillance in Beckwith-Wiedemann syndrome and hemihyperplasia: a critical review of the evidence and suggested guidelines for local practice. J Paediatr Child Health. 2006;42:486–90.
Beckwith JB. Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am J Med Genet. 1998;79:268–73.
Acknowledgements
The authors are thankful to the patients and their families for their cooperation and Dr. Renu Saxena, Molecular Genetics, Sir Ganga Ram Hospital, New Delhi for doing molecular testing of patients.
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AREC was involved in the evaluation of the patients, collection of data, and analysis of the data. He drafted and edited the manuscript and revised it. PM was involved in the collection and analysis of the data. She drafted and edited the initial manuscript. MK was involved in the diagnosis, and management of the patients. She critically reviewed and revised the manuscript for important intellectual content. NG was involved in the diagnosis, and management of the patients. She conceptualized the study. She critically reviewed and revised the manuscript for important intellectual content. All the authors reviewed and approved the final manuscript. MK is the guarantor for this paper.
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Correa, A.R.E., Mishra, P., Kabra, M. et al. Epigenetic Abnormalities of 11p15.5 Region in Beckwith-Wiedemann Syndrome - A Report of Eight Indian Cases. Indian J Pediatr 87, 175–178 (2020). https://doi.org/10.1007/s12098-019-03148-3
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DOI: https://doi.org/10.1007/s12098-019-03148-3