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.

[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.

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.

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.

[Beckwith-Wiedemann syndrome: What do you search in prenatal diagnosis? About 14 cases]. / Le syndrome de Beckwith-Wiedemann : que faut-il rechercher en anténatal? À propos d'une série de 14 cas.

OBJECTIVES: Beckwith-Wiedemann syndrome (BWS) is the most common overgrowth syndrome and has an incidence of 1/13,700. The majority of the cases are diagnosed after birth. Patients with BWS have an increased risk of neonatal hypoglycemia and embryonal tumors development in childhood. We wanted to identify the ultrasound signs that must alert physicians to prepare best perinatal management strategies. METHODS: We conducted a retrospective study of a population of 14 cases of BWS diagnosed in perinatal period; four of them were detected prenatally by ultrasound. The anomalies signs described in prenatal were analyzed and compared with the clinical features of the postnatal period. RESULTS: The major features reported were represented by macrosomia for 71.4% with an increase of abdominal circumference, and macroglossia for 78.6%. The minor features were various with 64% of visceromegaly (nephromegaly and/or hepatomegaly), 50% of hydramnios and for 80% of male children a genital anomaly (crytorchidism and/or hypospadias). CONCLUSION: This study identified some prenatal ultrasound signs that should alert the clinician to the possibility of BWS. A genetic conseling, after confirmation by molecular diagnosis, could be proposed in a near future in prenatal, and could improve postnatal management strategies for these affected children at high postnatal risk.

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.

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.

Sonographic assessment of renal growth in patients with Beckwith-Wiedemann syndrome: the Beckwith-Wiedemann syndrome renal nomogram.

BACKGROUND: Beckwith-Wiedemann syndrome is a disorder of somatic overgrowth. Evidence of kidney overgrowth is a diagnostic criterion that may be used to help identify those patients who are at the greatest risk of developing Wilms tumors. In such subjects, kidney size is typically larger than that of age-matched normal controls. OBJECTIVE: The purpose of our study was to generate a nomogram that could be used to measure renal dimensions in children with Beckwith-Wiedemann syndrome in a clinical setting. MATERIALS & METHODS: All of the Beckwith-Wiedemann syndrome patients followed at our institution from 1996 to 2004 were eligible for inclusion in our study. Renal length was measured with a curvilinear transducer and with the patient supine. Renal lengths were measured for both kidneys using real-time ultrasound for all patients. Their data were compared with those of age-matched controls reported in the 1984 study by Rosenbaum et al. RESULTS: Ninety-six children with Beckwith-Wiedemann syndrome were followed from 1996 to 2004. Forty-three of these patients met our criteria for inclusion in the study: 28 girls (65%) and 15 boys (35%). We identified a linear relationship between kidney length and patient age. No statistically significant differences in renal length were found between boys and girls (p=0.2153) or between the kidneys on either side of the body (p=0.9613). CONCLUSION: Our study provides a practical, simple renal growth chart that offers a reasonable, sensitive method for evaluating kidney size in children with Beckwith-Wiedemann syndrome.

Bilateral hemorrhagic adrenal cysts in an incomplete form of Beckwith-Wiedemann syndrome: MRI and prenatal US findings.

Benign hemorrhagic adrenal cysts are a cause of subdiaphragmatic mass in the fetus and neonate with Beckwith-Wiedemann syndrome. Characteristic imaging features on ultrasonography, color Doppler, and magnetic resonance imaging help differentiate adrenal hemorrhage from neonatal neuroblastoma and help avoid unnecessary surgery in these patients. Bilateral adrenal hemorrhage is self-limiting, and spontaneous resolution is the usual outcome. This report presents this rare condition with prenatal ultrasonographic and magnetic resonance imaging findings and reviews the differential diagnosis of neonatal adrenal masses.

Beckwith-Wiedemann syndrome and bilateral adrenal pheochromocytoma: sonography and MRI findings.

Beckwith-Wiedemann syndrome is characterized by a group of clinical abnormalities, the most frequent of which are omphalocele, macroglossia, gigantism, neonatal hypoglycemia and umbilical hernia. The association of this syndrome with malignant tumors is well documented. We report a child with this syndrome associated with bilateral adrenal pheochromocytoma.

Prenatally detected cystic adrenal mass associated with Beckwith-Wiedemann syndrome.

We report a case of a right-sided cystic adrenal mass, detected after the 21st week of gestation, associated with fetal macrosomia. The diagnosis of Beckwith-Wiedemann syndrome was evoked. Prenatal sonography and magnetic resonance imaging did not allow establishing the origin of the suprarenal mass. The differential diagnosis of cystic neuroblastoma, pseudocystic adrenal haemorrhage, and adrenocortical macrocysts was discussed. A laparotomy was performed 2 weeks after birth due to the increasing size of the tumour and due to its possible malignant origin. Histological findings were haemorrhagic lesions without evidence of malignancy and adrenal cortical cytomegaly. The diagnosis of an adrenocortical macrocyst component of Beckwith-Wiedemann syndrome was established.

Bilateral benign haemorrhagic adrenal cysts in Beckwith-Wiedemann syndrome: case report.

Beckwith-Wiedemann syndrome is the most common overgrowth malformation syndrome. The classical features include macrosomia, macroglossia, omphalocele and ear lobe anomalies. Among the associated adrenal anomalies, foetal cortical cytomegaly, outer cortical haemorrhage and unilateral benign cysts are well described. A term neonate was admitted with typical features of the syndrome. Radiological evaluation revealed a rare association of bilateral benign hamorrhagic adrenal cysts. Serial sonography confirmed hamorrhage into benign cysts and ruled out neoplasms. Only one similar case has been documented in the literature previously.

Sonographic findings in Beckwith-Wiedemann syndrome related to H19 hypermethylation.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with congenital malformations and tumour predisposition. BWS results from variable mutations or epigenetic modifications of imprinted genes in the 11p15 chromosomal region. We present a fetus with mild general overgrowth and bilateral enlarged echogenic kidneys with loss of the corticomedullary differentiation in which prenatal diagnosis of BWS was suspected. The rest of the fetal anatomy and the amniotic fluid volume appeared normal. After termination of the pregnancy, molecular analysis confirmed the diagnosis of BWS by showing an isolated hypermethylation of the H19 gene.

Antenatal manifestation of congenital pancreatoblastoma in a fetus with Beckwith-Wiedemann syndrome.

Antenatal detection of an isolated abdominal cyst was found to be a pancreatoblastoma in a female fetus with Beckwith-Wiedemann syndrome. Prenatal and post-natal features and management of this very rare tumour are discussed. Molecular investigation disclosed a mosaic paternal 11p15 uniparental disomy in the tumoral cells. The prognosis of a congenital pancreatoblastoma is good if complete surgical excision is achieved. However, the association with Beckwith-Wiedemann syndrome requires a prolonged follow-up because of the increased risk of developing malignant tumours.

Wiedemann-Beckwith syndrome: further prenatal characterization of the condition.

We describe three unrelated cases of Wiedemann-Beckwith syndrome (WBS). Two of them were diagnosed postnatally while the third was detected during pregnancy that resulted in elective termination. Amniotic karyotypes were normal in all. PCR amplification of polymorphic loci mapping to 11p15.5 region documented partial trisomy of 11p15.5 due to paternal translocation in one, and segmental and mosaic segmental unipaternal disomy (UPD) in the second and third cases, respectively. Based on findings documented in these cases and the literature, we tabulated the anomalies that might be detected prenatally by ultrasound and that may suggest the syndrome. Constant findings included fetal overgrowth, polyhydramios, enlarged placenta, and specifically a distended abdomen. As most described signs developed after 22 weeks of gestation, a careful follow-up should be carried on until late stages of pregnancy. An amniotic karyotype might not detect subtle chromosomal rearrangements. We therefore recommend utilizing PCR of polymorphic loci on 11p15.5, in addition to conventional cytogenetic analysis of the fetus and both parents to detect possible maternal deletions or inversions, paternal duplications, and UPD that may account for the largest subset of sporadic WBS reaching 25% of cases. An early diagnosis of WBS is important for counseling the parents concerning potential risk for developing embryonic tumors, selection of the mode of delivery due to potential adrenal cysts that might bleed during labor, and prevention of neonatal hypoglycemia.