Fetal growth patterns in Beckwith–Wiedemann syndrome

Abstract

We provide data on fetal growth pattern on the molecular subtypes of Beckwith-Wiedemann syndrome (BWS): IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age-corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1-GoM (n = 21), UPD (n = 87), IC2-LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1-GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1-GoM patients, lowest in IC2-LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2-LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1-GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2-LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2-LoM, but manifest a body mass disproportion rather similar to that seen in IC1-GoM cases.

Esophageal atresia and Beckwith–Wiedemann syndrome in one of the naturally conceived discordant newborn twins: first report

“…The high frequency of severe abdominal wall defects in centromeric cases is consistent with the hypothesis that genes expressed by the centromeric domain (IC2), containing also KCNQ1OT1 and hypomethylated in the newborn here described, are involved in normal midline development [2,3,15,16]. The incidence of WBS is increased in MT, particularly in the female ones [12,17], due to the ART pregnancies [2][3][4]18]. An increased rate of EA with or without tracheoesophageal fistula in twins is reported in several studies [9].…”

“…Our results point out the role of KCNQ1OT1 in developing the severe BWS phenotype of the affected twin, although additional genomic as well as epigenetic changes cannot be excluded . The high frequency of severe abdominal wall defects in centromeric cases is consistent with the hypothesis that genes expressed by the centromeric domain (IC2), containing also KCNQ1OT1 and hypomethylated in the newborn here described, are involved in normal midline development . The incidence of WBS is increased in MT, particularly in the female ones , due to the ART pregnancies .…”

Prenatal imaging throughout gestation in Beckwith‐Wiedemann syndrome

“…A review by Williams et al proposed prenatal diagnostic guidelines based on the presence of two major criteria (abdominal wall defect, macroglossia, macrosomia) or one major plus two minor criteria (nephromegaly/dysgenesis, adrenal cytomegaly, aneuploidy/abnormal loci, polyhydramnios) . Studies suggest that prenatal findings of BWS appear in the second or third trimester, but no study to date has specifically examined the temporal progression of the phenotype throughout gestation.…”

“…Although the majority of cases are diagnosed postnatally, many of its clinical manifestations can be detected prenatally on fetal imaging. 4 Studies suggest that prenatal findings of BWS appear in the second or third trimester, [4][5][6][7][8][9] but no study to date has specifically examined the temporal progression of the phenotype throughout gestation.…”

Early Therapeutic Intervention in a Child with Beckwith–Wiedemann Syndrome in Inpatient and Outpatient Conditions — Case Report

“…Children with BWS are characterized by hypoglycaemia in infanthood period, asymmetric regional body overgrowth, specific facial dysmorphic features, and predisposition to embryonic malignancies, particularly to Wilms tumour or hepatoblastoma [3,[7][8][9].…”