LeFort III/I for Beckwith-Wiedemann Syndrome: A Case Report.

This case presents a facially mature patient with Beckwith-Wiedemann Syndrome (BWS) who presented with severe class III malocclusion. Computed tomography imaging revealed an anterior crossbite of 19 mm and a narrow pharyngeal airway at the level of the tongue base precluding mandibular setback surgery. The patient was indicated for a LeFort III combined with a LeFort I advancement, each of 10 mm, for a 20 mm combined advancement. Stable, functional occlusion was achieved without airway compromise. This novel use of the combined LeFort III/I can restore stable class I occlusion in patients with BWS at risk for tongue base airway compromise.

Kagami-Ogata syndrome: an important differential diagnosis to Beckwith-Wiedemann syndrome.

We report the case of a fetus with sonographic characteristics of Beckwith-Wiedemann syndrome (BWS). A 30-year-old gravida 2 para 1 was referred to our fetal medicine unit with an omphalocele. Fetal macrosomia, organomegaly, and polyhydramnios but no macroglossia were detected and BWS was suspected. Genetic testing for BWS did not confirm the suspected diagnosis as the karyotype was normal. Symptomatic polyhydramnios led to repeated amnioreductions. At 35 + 5 weeks of gestation, a female neonate of 3660 g was delivered with APGAR scores of 6/7/8, after 1/5/10 min, respectively. The abnormal shape of the thorax, facial dysmorphism, need for ventilation, and generalized muscular hypotonia led to the suspicion of Kagami-Ogata syndrome (KOS), which was confirmed by genetic testing. KOS in our patient was caused by a large deletion in the MEG3-region on chromosome 14q32 affecting the maternal allele. In this report, we highlight the notion that when sonographic signs suggestive of BWS such as macrosomia, polyhydramnios, and omphalocele are present and genetic testing does not confirm the suspected diagnosis, KOS should be tested for.

Prenatal imaging throughout gestation in Beckwith-Wiedemann syndrome.

PURPOSE: Prenatal occurrence and timing of appearance of associated features in Beckwith-Wiedemann syndrome (BWS) are unknown. We reviewed our BWS patients with serial fetal imaging and correlated these with postnatal findings. METHODS: All BWS patients with fetal ultrasound (US) or magnetic resonance imaging (MRI) from 2000 to 2016 were reviewed to determine the presence of polyhydramnios, placentamegaly, macrosomia, macroglossia, retrognathia, omphalocele, visceromegaly, and hemihypertrophy. These observations were correlated with postnatal findings. Data were analyzed by Mann-Whitney U test. RESULTS: Nine BWS patients underwent 42 fetal imaging studies with median of five (range of two to six) studies per patient between 13 and 35 weeks gestation. All prenatal findings were confirmed postnatally with complete concordance. All patients with omphalocele were detected early in gestation but other postnatal findings less predictably so. All omphaloceles were small, and were found significantly earlier in gestation than macrosomia (P = 0.004) and macroglossia (P = 0.012). Visceromegaly and retrognathia were less frequent, with no significant differences in median gestational age from omphalocele when prenatally identified. CONCLUSIONS: In BWS, omphalocele is the most common prenatal finding and routinely observed in early gestation with 100% accuracy. Associated findings of macrosomia, macroglossia, visceromegaly, and retrognathia, when present, are detected later in gestation. Imaging in later gestation may reveal additional abnormalities that support a BWS diagnosis.

[Placental mesenchymal dysplasia]. / Mezenkhimal'naia displaziia platsenty.

OBJECTIVE: To carry out a clinical and morphological analysis of 6 cases of placental mesenchymal dysplasia (PMD) that is not associated with Beckwith-Wiedemann syndrome. MATERIAL AND METHODS: Medical records, placental macroscopic and microscopic changes, histochemical (MSB staining) and immunohistochemical studies of placental tissue with antibodies against p57, CD34, smooth muscle actin, desmin, and Ki-67 were analyzed. RESULTS: Vascular anomalies in the chorionic plate and stem villi, the increased size and edema of the stem villi during normal formation of the terminal branches of the villous tree, the lack of proliferation of villous trophoblast were the typical signs of PMD and were noted in all cases. Comparison of the results of ultrasonography with the morphological pattern of the disease suggested that there were ultrasound signs that were typical of PMD. The characteristics of the course and outcomes of pregnancy in PMD were given. The features of morphological changes in the presence of PMD concurrent with preeclampsia were found. Significant variability in p57 expression in PMD was shown and variants of changes given. There were no substantial features of the expression of desmin and smooth muscle actin in PMD. CONCLUSION: MDP has typical morphological and ultrasound signs. The significant variability in the levels of chorionic gonadotropin and alpha-fetoprotein and in the expression of p57 does not allow their use in the differential diagnosis of PMD. The high incidence of thrombotic events in the intervillous space and fetal vessels, as well as intrauterine growth restriction, intrauterine hypoxia, and an impaired neonatal adaptation period in PMD should be taken into account when determining the management tactics for female patients and newborns.

Spinal adrenal cortical adenoma associated with Beckwith-Wiedemann syndrome: case report and review of the literature.

PURPOSE: Ectopic adrenal cortical adenoma in the spinal region is extremely rare. The majority of cases of ectopic adrenocortical tissue are found along the path of embryonic migration within the urogenital tract. Beckwith-Wiedemann syndrome (BWS) is a pediatric overgrowth disorder involving a predisposition to tumor development, including adrenal lesions. To date, only eight spinal cases have been reported. This is the third reported case in pediatric population, the first one associated with genetic syndrome and the first benign to recur. We review the current literature on this topic. CASE DESCRIPTION: We present a 2-year-old boy affected by Beckwith-Wiedemann syndrome who developed a tumor at L4-L5 level. He underwent a gross total resection with MRI post-surgery demonstrating non-residual tumor. Histology disclosed an ectopic adrenal cortical adenoma with oncocytic features. Immunohistochemically was positive for inhibin-alpha, synaptophysin, and melan-A. It was negative for chromogranin A, GFAP, S-100, and other markers. One year later, he developed a recurrence at the same level being necessary a second surgery leaving a small sheet of residual tumor. CONCLUSION: Spinal adrenocortical adenomas are exceptional, and its behavior could be related to other conditions such as BWS. Gross total resection can be curative but a tight follow-up is needed. Immunohistochemical studies that include inhibin-alpha, synaptophysin, and melan-A can be useful in differential diagnosis as ultrastructural study. The decision on how to treat these patients is difficult given the low number of cases.

Beckwith-Wiedemann Syndrome and Primary Lymphedema of the Lower Extremity.

Beckwith-Wiedemann syndrome is the most common genetic overgrowth syndrome. Patients with Beckwith-Wiedemann syndrome may have hemihypertrophy, but their lymphatic vasculature is intact. We present a child with Beckwith-Wiedemann syndrome and lower extremity enlargement thought to be due to hemihypertrophy that was instead diagnosed with primary lymphedema. There are many causes of leg overgrowth in the pediatric population and misdiagnosis is common. While extremity enlargement secondary to hemihypertrophy may occur in 15% of patients with Beckwith-Wiedemann syndrome, progression and pitting edema only occur in primary lymphedema. This report highlights the importance of ensuring an accurate diagnosis so that patients are managed appropriately.

Novel fetal and maternal sonographic findings in confirmed cases of Beckwith-Wiedemann syndrome.

OBJECTIVE: The objective of the study was to examine the prenatal anomalies in fetuses with Beckwith-Wiedemann syndrome (BWS). METHODS: The study included a retrospective assessment of 12 pregnancies that were seen at three tertiary referral centres (Universities of Tübingen, Bonn, and Cologne/Germany). The genetic mutation, the results of the second trimester ultrasound examination, and the outcome of the pregnancies are shown. Biometric data were transformed into z-values. RESULTS: Median gestational age at the time of examination was 22.6 (range 19.0-29.7) weeks of gestation. In all cases, the head circumference (HC) and the femur length (FL) were within the normal range, but the HC-FL ratio was above the 95th centile in 75% of the cases. An exomphalos, macroglossia, and visceromegaly were observed in 67%, 50%, and 83% of the cases, and in 58% and 83%, there were polyhydramnios and placentamegaly respectively. The fetal pancreas was identified in three quarters of the cases. A third of the women had large, overstimulation-like ovaries, although each pregnancy was conceived naturally. In four cases, beta-human chorionic gonadotropin (hCG) levels were measured and mean hCG levels were 498 106 IU/L. DISCUSSION: Besides exomphalos, BWS should be considered if there is macroglossia, a distinct growth pattern, pancreatic hyperplasia, placentamegaly, and substantially increased levels of beta-hCG. © 2015 John Wiley & Sons, Ltd.

Systematic review of sonographic findings of placental mesenchymal dysplasia and subsequent pregnancy outcome.

OBJECTIVE: To describe the sonographic features and pregnancy outcomes of placental mesenchymal dysplasia (PMD), an entity often misdiagnosed as molar pregnancy. METHODS: We reviewed PMD cases from our institution and performed a systematic review of the existing literature. Inclusion criteria for the review were diagnosis of PMD as defined by placental pathology, description of placental morphology on antenatal ultrasound and reporting of pregnancy outcomes. RESULTS: We found three cases of PMD at our institution. Patient 1 had elevated human chorionic gonadotropin (hCG) and an enlarged, hydropic placenta at 13 weeks, suggestive of a molar pregnancy. Patient 2 also had elevated hCG with large, vascular placental lakes on ultrasound suggesting placenta accreta or molar pregnancy. Case 3 involved placentomegaly and fetal anomalies suggestive of Beckwith-Wiedemann syndrome. From the literature review, 61 cases met the inclusion criteria. The most common sonographic features included enlarged (50%) and cystic (80%) placenta with dilated chorionic vessels. Biochemical aneuploidy screening abnormalities were relatively common as were fetal anomalies, Beckwith-Wiedemann syndrome and other genetic abnormalities. Pregnancy complications included intrauterine growth restriction (IUGR; 33%), intrauterine fetal death (IUFD; 13%), and preterm labor (33%). Pregnancies without fetal anomalies, IUGR, IUFD or preterm labor had normal neonatal outcomes despite PMD (9%). CONCLUSIONS: The differential diagnosis of PMD includes molar pregnancy and other placental vascular anomalies. PMD is associated with adverse pregnancy outcome, so heightened surveillance with genetic evaluation, serial growth scans and third-trimester assessment of wellbeing should be considered. PMD must be differentiated from gestational trophoblastic disease because management and outcomes differ.

Beckwith-Wiedemann syndrome with placental chorangioma due to H19-differentially methylated region hypermethylation: a case report.

Beckwith-Wiedemann syndrome (BWS) is a common overgrowth syndrome that involves abdominal wall defects, macroglossia, and gigantism. It is sometimes complicated by placental tumor and polyhydramnios. We report a case of BWS, prenatally diagnosed with ultrasonography. A large and well-circumscribed tumor also existed on the fetal surface of the placenta, which was histologically diagnosed as chorangioma after delivery. Polyhydramnios was obvious and the fetal heart enlarged progressively during pregnancy. Because the biophysical profiling score dropped to 4 points at 33 weeks of gestation, we carried out cesarean section. By epigenetic analysis, H19-differentially methylated region hypermethylation was observed in the placental tumor, normal placental tissue, and cord blood mononuclear cells. This is the first report of BWS with placental tumor due to H19-differentially methylated region hypermethylation.

Familial Beckwith-Wiedemann syndrome: Prenatal manifestation and a possible expansion of the phenotype.

We describe a case of Beckwith-Wiedemann syndrome (BWS) demonstrating pre- and post-natal intra-familial variability. Our first encounter with the family occurred in the 1990s following the birth of 3 affected offspring. The first two pregnancies presented with exomphalos and elevated second trimester maternal serum alpha-fetoprotein (msAFP, 3.43 and 4.01 MOM, respectively) as well as elevated maternal human chorionic gonadotrophin (mhCG, 4.33 and 8.8 MOM, respectively). The diagnosis of BWS was confirmed postnatally in both cases. The third ongoing pregnancy presented only with elevated mhCG (7.09 MOM) and no malformation. Nonetheless BWS was suspected. The diagnosis was confirmed postnatally with clinical manifestations including macroglossia and cleft palate. Two affected female siblings were also diagnosed with Mullerian agenesis in adulthood. Suspecting a common genetic etiology, sequencing of the CDKN1C gene revealed a maternally inherited, likely pathogenic variant (NM_000076.2: c.367_385del; p.(Ala123Serfs*143)) causative of BWS. Chromosomal microarray and whole exome sequencing did not reveal any other pathogenic variant that would explain the Mullerian agenesis. One of the affected females underwent successful preimplantation genetic testing (PGT) with a surrogate and gave birth to a healthy female. To the best of our knowledge, this is the first report of Mullerian agenesis as a possible rare expansion of the BWS phenotype. In addition, this case highlights the potential role of abnormal second trimester biochemical markers (msAFP, mHCG) as possible indicators of BWS, especially in familial cases.

Experience with hemihyperplasia and Beckwith-Wiedemann syndrome surveillance protocol.

Beckwith-Wiedemann syndrome (BWS) and isolated hemihyperplasia (IHH) are two well known overgrowth conditions that are associated with cancer predisposition. Multiple surveillance protocols have been proposed to detect the most commonly reported tumor types Wilms tumor and hepatoblastoma. We reviewed the history of our patients who were part of this monitoring protocol. Information from 63 cases was collected retrospectively while another 63 control samples for AFP measurement were obtained prospectively. Twenty-five (40%) patients had an ultrasound abnormality, the most frequent being nephromegaly/size discrepancy. Two patients had well documented cases of tumors/tumor precursor (2/63:3.2%) detected by ultrasound images. Three hundred thirty-six separate AFP values were available with values above 50,000 ng/ml seen in three patients older than 2 months, one with hepatoblastoma and two other with hemangiomas/hemangioendotheliomas. There was no clear difference in the range of AFP values between previously reported controls, our own normal population and affected patients. In conclusion, ultrasound surveillance detected renal and liver pathology including benign and malignant lesions. The known variability of AFP in normal neonates and patients with BWS makes interpretation difficult in early infancy. Very high AFP values did seem to be correlated with risk for identifiable liver lesions. Determination of the natural changes in AFP levels over time will allow more appropriate comparison.

Isolated fetal omphalocele, Beckwith-Wiedemann syndrome, and assisted reproductive technologies.

OBJECTIVE: To assess the frequency of Beckwith-Wiedemann syndrome (BWS) among fetuses with an ultrasound diagnosis of isolated omphalocele and to examine relevant clinical variables, in particular route of conception. MATERIALS AND METHODS: An ultrasound and consultation database (1988-2007) was searched and cases were included that met the following criteria: omphalocele, no additional major structural anomaly or autosomal aneuploidy, and either newborn examination or molecular diagnostic studies for BWS. Medical records were reviewed and a nested case-control analysis matching day of birth assessed the route of conception, given the changing prevalence of assisted reproduction during the study period. RESULTS: Thirty cases of isolated omphalocele were identified. Beckwith-Wiedemann syndrome was diagnosed in six cases (6/30 [20.0%]); four by newborn examination (4/6) and two on prenatal molecular studies (2/6). Of note, one case of BWS had a karyotype of 47,XXX, the remainder was euploid. Compared with isolated omphaloceles, fetuses with BWS more often were twins (3/6 vs. 1/24; p < 0.001), had polyhydramnios (4/6 vs. 2/24; p < 0.001), were macrosomic at birth (3/6 vs. 4/24 p < 0.001), and had been conceived by assisted reproduction (3/6 vs. 2/22; p = 0.04). When compared with normal controls matched by date of birth, conception by assisted reproductive technique among BWS births was highly significant, (p < 0001). CONCLUSIONS: Beckwith-Wiedemann syndrome is present in a noteworthy portion of fetuses with isolated omphalocele on ultrasound, and prenatal molecular studies are warranted. Even among this small cohort, a recurring theme of conception by assisted reproduction exists.

Unilateral testicular enlargement in a teenager with Beckwith-Wiedemann syndrome: a case report.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a rare congenital overgrowth disorder. A major feature is lateralized overgrowth, which can variably involve a single body district up to the entire hemisome. Visceral asymmetrical involvement has been observed, commonly represented by enlargement of one kidney or adrenal gland, rather than one gonad. CASE PRESENTATION: We report the case of a pubertal boy affected by BWS, who developed a progressive testicular enlargement, ipsilateral to the pre-existing external body overgrowth. Asymptomatic unilateral testis enlargement started after regular pubertal onset and worsened over time, without any associated pathological findings in a long-term follow-up. Since biopsy is not indicated in case of benign macro-orchidism, we hypothesize that this asymmetric enlargement could be an expression of visceral lateralized overgrowth in BWS. CONCLUSIONS: At the best of our knowledge, this is the first detailed report of unilateral testicular overgrowth in BWS. We revised common causes of painless unilateral scrotal masses in the pediatric age. Considering both the overall frequency of neoplasia and the malignancies predisposition in BWS, a testicular cancer should be carefully ruled out through a close follow-up, before stating a benign condition. A normal ultrasound pattern, together with normal serum hormonal levels and negative tumor markers, make testicular neoplasms highly unlikely.

Beckwith Wiedemann syndrome: A population-based study on prevalence, prenatal diagnosis, associated anomalies and survival in Europe.

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49.2% and 43.3% of preterm males and females, respectively. Of term newborns, 41.1% of males and 24% of females were macrosomic. Out of 353 cases with known time of diagnosis, 39.9% were suspected prenatally, 36.3% at birth, 7.6% were diagnosed in the first week of life, and 16.2% in the first year of life. The mean gestational age at prenatal diagnosis by obstetric ultrasound was 19.8 ±â€¯6.2 (11-39) gestational weeks. The mean prenatal diagnosis of cases where parents opted for termination of pregnancy was 15.3 ±â€¯2.4 (11-22) gestational weeks, and the mean gestational age at termination was 19.3 ±â€¯4.1 (13-26) gestational weeks. The prenatal detection rate was 64.1% (141/220) with no significant change over time. There were 12.7% of familial cases. The study confirmed the association of assisted reproductive technologies with Beckwith Wiedemann syndrome, as 7.2% (13/181) of patients were conceived by one of the methods of assisted reproductive technologies, which was three times higher compared to the general population of the countries included in the study. Twin pregnancies of undetermined zygosity were recorded in 5.7% (21/365) cases, and were on average three to four times more common than in European countries that participated in the study. The estimated mean prevalence of classical Beckwith Wiedemann syndrome in Europe was 3.8 per 100,000 births or 1:26,000 births.

18F-FDG PET/CT for Molecular Imaging of Hepatoblastoma in Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is a rare congenital overgrowth disorder variably characterized by macrosomia, macroglossia, congenital hypoglycemia, and hemihyperplasia. The BWS predisposes affected individuals to embryonal tumors during childhood. The BWS is caused by abnormal gene regulation in a particular region of chromosome 11. We present the case of a 1-year-old boy with BWS who underwent an F-FDG PET/CT scan for restaging of hepatoblastoma. On the F-FDG PET scan, increased tracer accumulation was observed in hepatoblastoma lesions. In addition, marked hemihyperplasia was noted. This case highlights the usefulness of F-FDG PET/CT for restaging of hepatoblastoma in BWS.

Urological Findings in Beckwith-Wiedemann Syndrome With Chromosomal Duplications of 11p15.5: Evaluation and Management.

Beckwith-Wiedemann Syndrome (BWS) is an overgrowth disorder with various congenital anomalies. Although the most classic constellation includes macrosomia, macroglossia, and omphalocele, nephrourological findings are commonly associated with BWS. Clinical presentation is highly variable because of its complex molecular heterogeneity, which involves changes in DNA methylation and disruption of growth regulatory genes. We report 3 pediatric patients, ages 13 months to 3 years old, who presented with clinical features consistent with BWS. A variety of nephrourological abnormalities were also noted, including posterior urethral valves, hydroureteronephrosis, and undescended testes. Genetic testing for all 3 patients revealed duplication of the region chromosome 11p15.5.

[Prenatal diagnosis of Beckwith-Wiedemann syndrome in third trimester]. / Prenatalne rozpoznanie zespolu beckwith'a-- wiedemann'a w III trymestrze ciazy.

AIM OF THE STUDY: The aim of the study was to analyze prenatally recognized cases of Beckwith-Wiedemann syndrome (BWS) and further follow-up. We report the most common features which can help in prenatal diagnosing of that condition. MATERIAL AND METHODS: 3 fetuses diagnosed with BWS, referred for echocardiographic evaluation had been examined in referral centre from 2003-2005. RESULTS: Mean gestational age at the diagnosis was 31 week. During ultrasound evaluation characteristic features were recognized: macrosomy, macroglossia, nephromegaly in all cases, polyhydramnion was associated in 2 cases. No congenital heart defect and any functional changes were found during ECHO. In one case prenatal karyotyping was performed and revealed normal karyotype. Postnatal karyotyping in remain two cases was normal in one and abnormal in second case (Moz 46XX (13/46XX-18, +MAR5). CONCLUSIONS: 1. Prenatal diagnosis of Beckwith-Wiedemann syndrome can be obtained based on characteristic ultrasound features in the third trimester. 2. Most common features of BWS diagnosed in prenatal ultrasound included: macrosomy, macroglossia, visceromegaly and polyhydramnios. 3. In utero diagnosis is important for further mode and time of delivery planning, also neonates' clinical condition directly after delivery and long-term postnatal prognosis. 4. Karyotyping is recommened in all cases of BWS.