Fetal growth patterns in Beckwith-Wiedemann syndrome

• Published in: Clinical genetics Vol. 90; no. 1; pp. 21 - 27
• Main Authors: Mussa, A., Russo, S., de Crescenzo, A., Freschi, A., Calzari, L., Maitz, S., Macchiaiolo, M., Molinatto, C., Baldassarre, G., Mariani, M., Tarani, L., Bedeschi, M.F., Milani, D., Melis, D., Bartuli, A., Cubellis, M.V., Selicorni, A., Silengo, M.C., Larizza, L., Riccio, A., Ferrero, G.B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-07-2016
• Subjects: Anthropometry; Beckwith-Wiedemann; Beckwith-Wiedemann Syndrome - classification; Beckwith-Wiedemann Syndrome - diagnosis; Beckwith-Wiedemann Syndrome - genetics; Beckwith-Wiedemann Syndrome - pathology; Chromosomes, Human, Pair 11 - chemistry; Cyclin-Dependent Kinase Inhibitor p57 - genetics; DNA Methylation; Fetal Development - genetics; fetal growth; Fetus; Gene Expression; Genetic disorders; Genomic Imprinting; Genotype; Gestational Age; Growth disorders; Health risk assessment; Humans; Infant, Newborn; Mutation; overgrowth; Phenotype; Premature Birth; Rodents; Uniparental Disomy; phenotype; Beckwith-Wiedemann; fetal growth; overgrowth; genotype
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.12759

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.