“Parental imprinting” refers to an epigenetic marking of genes that results in monoallelic expression. This phenomenon plays a critical role in embryogenesis and development. The epigenetic modification of the genome involves methylation changes and the remodeling of chromatin-associated proteins (Li 2002). Imprints are established during the development of germ cells, and the reprogramming of imprinting occurs within the first days after fertilization (Reik and Walter 2001). The alteration of normal imprinting patterns is implicated in a number of human genetic diseases. Among them, the Beckwith-Wiedemann syndrome (BWS [MIM 130650]) is an overgrowth syndrome secondary to the dysregulation of the imprinted 11p15 region (Maher and Reik 2000). Numerous mechanisms are involved in BWS, and∼ 70% of cases of BWS are related to epigenetic abnormalities at the 11p15 locus, mostly demethylation of the KvDMR1 region of the KCNQ1OT (previously called “LIT1”) gene (MIM 604115)(Engel et al. 2000; Bliek et al. 2001; Gaston et al. 2001; Weksberg et al. 2001; DeBaun et al. 2002). KCNQ1OT encodes a noncoding antisense transcript within intron 10 of the KCNQ1 gene (MIM 192500)(Lee et al. 1999; Mitsuya et al. 1999; Smilinich et al. 1999) and might be involved in the regulation of parental imprinting of the centromeric domain of the 11p15 region (Fitzpatrick et al. 2002). In sheep and cattle, epigenetic abnormalities have been shown to be involved in large offspring syndrome (LOS)(Young et al. 1998). Affected animals exhibit various phenotypes, including large size at birth. In both species, the syndrome is caused by the in vitro exposure of embryos, between fertilization and the blastocyst stage, to various unusual environments. LOS is related to the loss of imprinting of the IGF2 receptor gene (MIM 147280), which ensures internalization and degradation of IGF2 and displays an antiproliferative function (Young et al. 2001). In vitro preimplantation procedures in mice are also responsible for overgrowth, owing to the abnormal expression of various imprinted genes, particularly the genes located at distal chromosome 7 (h19 [MIM 103280] and igf2 [MIM 147470] genes), orthologous to the human 11p15 region (Humpherys et al. 2001; Rideout et al. 2001). In humans, a case of BWS was recently described after in vitro fertilization (IVF)(Olivennes et al. 2001). Moreover, two recent papers (DeBaun et al. 2003; Maher et al. 2003) described an increase in prevalence of assisted reproductive technologies (ART) in patients with BWS. De Baun et al.(2003) reported a sixfold increase (4.6% vs. 0.76% in the general population) and showed that four of the six patients for whom DNA was available exhibited an isolated demethylation of KvDMR1 in the KCNQ1OT gene. Maher et al.(2003) reported a threefold increase (4% vs. 0.997% in the general population) and demonstrated that two of the six patients on whom molecular analysis could be done also exhibited an isolated demethylation of KvDMR1. Our department is a reference center in France for molecular diagnosis of BWS, and patients are referred from various medical departments (neonatology, pediatrics, genetics, and fetopathology). We studied a series of 149 patients referred for overgrowth syndromes and diagnosed as BWS, since all of them exhibited genetic or epigenetic defects at the 11p15 locus. According to the inclusion criteria described elsewhere (Gaston et al. 2001), 102 patients exhibited a complete form of BWS, and 47 exhibited an incomplete form of BWS. The techniques used to analyze the 11p15 region have been described elsewhere (Gaston et al. 2000, 2001). Epigenetic …