Table 3.

Beckwith-Wiedemann Syndrome: Frequency of Select Tumors by Molecular Mechanism

Tumor typeMolecular Mechanism 1Estimated Tumor Risk
Overall risk for
all types of tumors 		Loss of methylation at IC2 (maternal)2.6%
Gain of methylation at IC1 (maternal)28.1%
Paternal UPD16%
Heterozygous maternal CDKN1C pathogenic variants5.6%
Classic BWS phenotype w/normal molecular genetic testing6.2%
Wilms tumor Loss of methylation at IC2 (maternal)0.2%
Gain of methylation at IC1 (maternal)24%
Paternal UPD7.9%
Heterozygous maternal CDKN1C pathogenic variantsNot increased 2
Classic BWS phenotype w/normal molecular genetic testing4.1%
Hepatoblastoma Loss of methylation at IC2 (maternal)0.7%
Gain of methylation at IC1 (maternal)Unknown; rare
Paternal UPD3.5%
Heterozygous maternal CDKN1C pathogenic variantsNot increased 2
Classic BWS phenotype w/normal molecular genetic testing0.3%
Neuroblastoma Paternal UPD1.4%
Heterozygous maternal CDKN1C pathogenic variants4.2%
Adrenocortical carcinoma Paternal UPD1.1%

Adapted from Brioude et al [2018] Supplementary Table 3 (which also includes risks below 1% for neuroblastoma, rhabdomyosarcoma, and adrenocortical carcinoma)

BWS = Beckwith-Wiedemann syndrome; IC1 = imprinting center 2; IC2 = imprinting center 2; UPD = uniparental disomy

1.

Molecular test results undertaken on blood sampling should be used cautiously when applied to tumor risk determination given that tissue-specific mosaicism is known to impact test results and molecular changes may vary by the tissue tested [Brzezinski et al 2017, Duffy et al 2021].

2.

The risks for Wilms tumor and for hepatoblastoma are not increased compared to the general population.

From: Beckwith-Wiedemann Syndrome

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