TY - JOUR
T1 - Phenotype, cancer risk, and surveillance in Beckwith–Wiedemann syndrome depending on molecular genetic subgroups
AU - Maas, Saskia M.
AU - Vansenne, Fleur
AU - Kadouch, Daniel J.M.
AU - Ibrahim, Abdulla
AU - Bliek, Jet
AU - Hopman, Saskia
AU - Mannens, Marcel M.
AU - Merks, Johannes H.M.
AU - Maher, Eamonn R.
AU - Hennekam, Raoul C.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Patients with Beckwith–Wiedemann syndrome (BWS) have an increased risk to develop cancer in childhood, especially Wilms tumor and hepatoblastoma. The risk varies depending on the cause of BWS. We obtained clinical and molecular data in our cohort of children with BWS, including tumor occurrences, and correlated phenotype and genotype. We obtained similar data from larger cohorts reported in the literature. Phenotype, genotype and tumor occurrence were available in 229 of our own patients. Minor differences in phenotype existed depending on genotype/epigenotype, similar to earlier studies. By adding patients from the literature, we obtained data on genotype and tumor occurrence of in total 1,971 BWS patients. Tumor risks were highest in the IC1 (H19/IGF2:IG-DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS-DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and the group in whom no molecular defect was detectable (6.7%). Wilms tumors (median age 24 months) were frequent in the IC1 (24%) and pUPD (7.9%) subgroups. Hepatoblastoma occurred mostly in the pUPD (3.5%) and IC2 (0.7%) subgroups, never in the IC1 and CDKN1C subgroups, and always before 30 months of age. In the CDKN1C subgroup 2.8% of patients developed neuroblastoma. We conclude tumor risks in BWS differ markedly depending on molecular background. We propose a differentiated surveillance protocol, based on tumor risks in the various molecular subgroups causing BWS.
AB - Patients with Beckwith–Wiedemann syndrome (BWS) have an increased risk to develop cancer in childhood, especially Wilms tumor and hepatoblastoma. The risk varies depending on the cause of BWS. We obtained clinical and molecular data in our cohort of children with BWS, including tumor occurrences, and correlated phenotype and genotype. We obtained similar data from larger cohorts reported in the literature. Phenotype, genotype and tumor occurrence were available in 229 of our own patients. Minor differences in phenotype existed depending on genotype/epigenotype, similar to earlier studies. By adding patients from the literature, we obtained data on genotype and tumor occurrence of in total 1,971 BWS patients. Tumor risks were highest in the IC1 (H19/IGF2:IG-DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS-DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and the group in whom no molecular defect was detectable (6.7%). Wilms tumors (median age 24 months) were frequent in the IC1 (24%) and pUPD (7.9%) subgroups. Hepatoblastoma occurred mostly in the pUPD (3.5%) and IC2 (0.7%) subgroups, never in the IC1 and CDKN1C subgroups, and always before 30 months of age. In the CDKN1C subgroup 2.8% of patients developed neuroblastoma. We conclude tumor risks in BWS differ markedly depending on molecular background. We propose a differentiated surveillance protocol, based on tumor risks in the various molecular subgroups causing BWS.
KW - genotype–phenotype correlation
KW - hepatoblastoma
KW - neuroblastoma
KW - Wiedemann–Beckwith syndrome
KW - Wilms tumor
UR - http://www.scopus.com/inward/record.url?scp=84982124257&partnerID=8YFLogxK
UR - https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.37801
U2 - 10.1002/ajmg.a.37801
DO - 10.1002/ajmg.a.37801
M3 - Article
C2 - 27419809
AN - SCOPUS:84982124257
SN - 1552-4825
VL - 170
SP - 2248
EP - 2260
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 9
ER -