REVIEW ARTICLE Prenatal Sonographic Features of Beckwith-Wiedemann Syndrome Chih-Ping Chen1,2,3*, Shu-Chin Chien4 Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome, charac- terized by macrosomia, macroglossia, organomegaly, abdominal wall defects, hemihy- pertrophy, ear creases/pits, neonatal hypoglycemia, adrenocortical cytomegaly, abdominal wall defects, and an increased frequency of embryonal tumors. It is known to be the result of genetic and epigenetic alterations on chromosome 11p15.5. Most of the affected cases are diagnosed after birth and it is difficult to diagnose prenatally. Currently, ultra- sound is viewed as a useful tool in the prenatal detection of affected cases. This article provides an overview of the prenatal sonographic features of BWS, including polyhydram- nios, macrosomia, macroglossia, omphalocele, an enlarged placenta, urinary anomalies, gastrointestinal anomalies, fetal hydrops and other rare anomalies. Several diseases may have phenotypic overlaps with BWS including Sotos syndrome, Weaver syndrome, Simpson- Golabi-Behmel syndrome, diabetes in pregnancy complicated with macrosomia, and infantile polycystic kidney disease. Increasing awareness and knowledge of various fetal malformations of BWS on prenatal ultrasound will be helpful in the early detection through- out the gestation. Prenatal diagnosis of fetuses with BWS could help obstetricians and pedi- atricians in the decision-making process for prenatal, perinatal and postnatal care. KEY WORDS — Beckwith-Wiedemann syndrome, prenatal ultrasound ■ J Med Ultrasound 2009;17(2):98–106 ■ Introduction autosomal inheritance with variable expressions [3]. It is the most common congenital overgrowth con- Beckwith-Wiedemann syndrome (BWS, MIM dition with typical features in neonates, including 130650), reported by Beckwith [1] in 1963 and macrosomia, macroglossia, organomegaly, abdom- Wiedemann [2] in 1964 respectively, is known as an inal wall defects, hemihypertrophy, ear creases/pits, Received: May 5, 2008 Accepted: May 19, 2009 1Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, 2Department of Medical Research, Mackay Memorial Hospital, Taipei, 3Department of Biotechnology and Bioinformatics, Asia University, Taichung, 4Departments of Medical Genetics and Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan. *Address correspondence to: Chih-Ping Chen, MD, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan. E-mail: [email protected] 98 J Med Ultrasound 2009 • Vol 17 • No 2 ©Elsevier & CTSUM. All rights reserved. Prenatal Sonography of Beckwith-Wiedemann Syndrome neonatal hypoglycemia, adrenocortical cytomegaly, Prenatal Sonographic Features and an increased risk of pediatric neoplasia. Clini- cal diagnosis of BWS in the neonatal period was The first prenatal diagnosis of BWS was in 1980 based on the presence of either three major fea- [8]. The prenatal sonographic features of published tures (omphalocele, macroglossia, gigantism), or BWS cases are summarized in Table 1 [8–40]. two major features plus three minor features (nephromegaly, ear creases/pits, facial nevus flam- meus, hypoglycemia, congenital cardiac defects, Increased Amniotic Fluid Amount or hemihypertrophy) [4]. Mental retardation seems to be associated with untreated and profound The most consistent ultrasound finding in the neonatal hypoglycemia [4]. The incidence of BWS reported cases was polyhydramnios (Table 1). It can is reported to be approximately in 1 in 13,500 live be evident from the second trimester. The cause births [5]. The overall risk for development of em- for the development of polyhydramnios in associa- bryonal malignancies such as Wilms’ tumor, hepa- tion with BWS is unclear at present. toblastoma, neuroblastoma, rhabdomyosarcoma and adrenal carcinoma in BWS children is 5–10% [6,7]. The syndrome is known to come from a Fetal Overgrowth (Macrosomia) range of genetic and epigenetic alterations on chromosome 11p15.5 and these alterations can More than one half of BWS cases were prenatally be easily analyzed by molecular tests in the mod- detected with macorsomia (Table 1). Although 87% ern era. of individuals with BWS have pre- or postnatal over- Most BWS cases are sporadic and cytogeneti- growth, it is unknown about the timing of the onset cally normal. Currently, they are diagnosed post- of overgrowth [4]. Evaluation of the head circum- natally on the basis of physical features and there ference, abdominal circumference, and estimated is still a lack of fixed criteria for early detection of fetal weight percentiles of six BWS fetuses demon- affected fetuses without a positive family history. strated that affected fetuses may exhibit acceler- At present, ultrasound is thought to be a valuable ated growth as early as 25–30 weeks’ gestation, but tool in the prenatal detection of characteristic find- may exceed the 90th percentile only after 36 weeks’ ings associated with BWS. Here, we review the asso- gestation [25]. Prenatal detection of polyhydram- ciated sonographic features in fetuses with BWS nios and overgrowth beginning between 25–36 and the reported prenatal sonographic findings weeks’ gestation, even without omphalocele, should include polyhydramnios, macrosomia, macroglossia, alert the clinical physicians to the possibility of BWS omphalocele, an enlarged placenta, urinary anom- [25,30]. alies, gastrointestinal anomalies, fetal hydrops and other rare anomalies. Early diagnosis of fetuses with BWS is significantly beneficial for prenatal counsel- Facial Anomaly ing, perinatal management such as the mode and time of delivery planning, and postnatal care The reported facial anomaly associated with BWS for neonatal hypoglycemia, respiratory distress is macroglossia. Neonatal macroglossia may result and the risk of malignancy. In addition, differential in airway obstruction, which requires surgical resec- diagnosis including Sotos syndrome, Weaver syn- tion. Macroglossia is shown to be the most com- drome, Simpson-Golabi-Behmel syndrome, dia- mon clinical feature in the BWS patients with the betes in pregnancy complicated by macrosomia, incidence of approximately 82–98% [7,41]. Based and infantile polycystic kidney disease is discussed on Table 1, the detection rate in the prenatal period here. is less than in the postnatal period because either J Med Ultrasound 2009 • Vol 17 • No 2 99 100 J MedUltrasound 2009 • 17 Vol • No2 Table 1. Literature review of reported prenatal sonographic features with BWS (A) Enlarged placentas Urinary anomalies Gastrointestinal anomalies Poly- Macro- Macro- Ompha- Nephro- Fetal Placento- Renal Pyelec- Adrenal Adreno- Hepato- Enlarged Pancreatic Pancreato- Others hydramnios somia glossia locele PMD megaly hydrops megaly cysts tasis tumor megaly megaly pancreas cyst blastoma 1980 Weinstein and (+)(+)(+)(+) Anderson 1982 Shapiro et al. (+)(+) 1983 Nivelon-Chevallier (+)(+)(+) Family history et al. Nivelon-Chevallier (+)(+)(+) Family history et al. 1985 Grundy et al. (+)(+)(+)(+) 1986 Koontz et al. (+)(+) 1986 Winter et al. (+)(+) 1988 Cobellis et al (+)(+) Family history 1989 Lodeiro et al. (+)(+)(+)(+)(+) 1989 Meizner et al. (+)(+)(+)(+) 1989 Wieacker et al. (+)(+)(+)(+)(+) 1990 Shah and Metlay (+)(+)(+) 1991 Viljoen et al. (+)(+)(+)(+)(+) 1994 Hewitt and Bankier (+)(+)(+)(+) 1994 Whisson et al. (+)(+)(+)(+)(+) 1994 Nowotny et al. (+)(+)(+)(+) Cardiomegaly 1996 Drut and Drut (+)(+)(+) (+) Drut and Drut (+)(+)(+) (+) 1997 Harker et al. (+)(+)(+)(+)(+) 1997 Ranzini et al. (+)(+) Ranzini et al. (+)(+)(+)(+) Ranzini et al. (+)(+) Ranzini et al. (+) Table 1. Literature review of reported prenatal sonographic features with BWS (B) Enlarged placentas Urinary anomalies Gastrointestinal anomalies Poly- Macro- Macro- Ompha- Nephro- Fetal Placento- Renal Pyelec- Adrenal Adreno- Hepato- Enlarged Pancreatic Pancreato- Others hydramnios somia glossia locele PMD megaly hydrops megaly cysts tasis tumor megaly megaly pancreas cyst blastoma Ranzini et al. (+) (+)(+) Ranzini et al. (+) Ranzini et al. (+)(+)(+)(+) Family history 1997 Fremond et al. (+)(+)(+) 2000 Fert-Ferrer et al. (+)(+)(+) (+) Fert-Ferrer et al. (+) (+) 2001 Hamada et al. (+)(+)(+)(+) (+) Single umbilical artery 2001 Benzacken et al. (+)(+) 2002 Reish et al. (+)(+)(+)(+) Reish et al. (+)(+)(+) Reish et al. (+)(+)(+)(+)(+) 2002 O’Connor and (+) Levine 2002 Weinstein and (+)(+)(+) Goldstein 2003 Pelizzo et al. (+) (+) 2004 Le Caignec et al. (+)(+) 2004 Mulik V et al. (+)(+)(+)(+) 2005 Williams et al. (+)(+)(+) Williams et al. (+)(+)(+)(+) J MedUltrasound 2005 Izbizky et al. (+)(+)(+)(+) 2007 Grati et al. (+) Grati et al. (+) 2007 Aagaard-Tillery Single et al. umbilical artery Prominent 2009 • 17 Vol • No2 maternal ovaries PMD = placental mesenchymal dysplasia. 101 C.P. Chen, S.C. Chien macroglossia may not develop until late fetal life or Urinary Anomalies even after birth [42] or information about the face was neglected on prenatal ultrasound [12]. The reported urinary anomalies in association with BWS include nephromegaly, pyelectasis, and adre- nal cysts. Several fetuses with BWS were reported Abdominal Wall Defect to have had hepatomegaly (Table 1). A right hem- orrhagic adrenal cyst was reported in a fetus with Omphalocele can be a characteristic prenatal sono- incomplete BWS at 21 gestational weeks [53]. Bi- graphic feature of BWS. Several fetuses with BWS lateral hemorrhagic adrenal cysts were reported were reported to have had omphalocele (Table