Prenatal diagnosis and management of monozygotic twins discordant for severe fetal abnormalities.

OBJECTIVE: We present prenatal diagnosis and management of monozygotic (MZ) twins discordant for severe fetal abnormalities. CASE REPORT: A 36-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, and hydrops fetalis, a giant cystic hygroma of 5 × 3.5 cm and left hydronephrosis in a co-twin. The other co-twin was structurally normal. Amniocentesis revealed a karyotype of 46,XY in both co-twins. Simultaneous polymorphic DNA marker analysis using the DNAs extracted from maternal blood and uncultured amniocytes confirmed MZ twinning. The woman underwent a successful selective fetal reduction by radiofrequency ablation at 22 weeks of gestation. At 28 weeks of gestation, premature rupture of membranes occurred, and a 1280-g normal male baby and a 275-g dead malformed co-twin were delivered. The normal co-twin was phenotypically normal and was doing well at age seven weeks. CONCLUSIONS: Prenatal diagnosis of MZ twins discordant for structural abnormalities should include a differential diagnosis of MZ twinning, and a zygosity test is necessary under such a circumstance.

First-trimester cystic hygroma and neurodevelopmental disorders: The association to remember.

OBJECTIVE: We present two prenatal cases of first-trimester cystic hygroma who are later found to suffer from rare genetic syndromes. CASE REPORT: Both of the two pregnant women were showed to have fetal cystic hygroma on ultrasound at the first trimester. Fetal microarray result was normal. Follow-up sonographic examinations showed no structural anomalies. The two pregnancies continued uncomplicatedly to term. However, the two infants developed early neurodevelopmental syndrome within two years of age. Exome sequencing confirmed that one child had Mental retardation, autosomal dominant 23 (MRD23) with a c.646delC (p.Q216Sfs∗35) variant in SETD5 gene, and the other child had Smith-Magenis syndrome with a c.3103dupC (Q1035Pfs∗31) variant in RAI1 gene. CONCLUSION: Clinicians have to be vigilant when counseling the patient whose fetus has a first-trimester cystic hygroma even with a normal array result and normal sonographic scans. Although they are rare, monogenetic syndromes are possible outcomes.

Congenital cystic neck masses: embryology and imaging appearances, with clinicopathological correlation.

Congenital cystic masses of the neck are uncommon and can present in any age group. Diagnosis of these lesions can be sometimes challenging. Many of these have characteristic locations and imaging findings. The most common of all congenital cystic neck masses is the thyroglossal duct cyst. The other congenital cystic neck masses are branchial cleft cyst, cystic hygroma (lymphangioma), cervical thymic and bronchogenic cysts, and the floor of the mouth lesions including dermoid and epidermoid cysts. In this review, we illustrate the common congenital cystic neck masses including embryology, clinical findings, imaging features, and histopathological findings.

Retroperitoneal lymphatic malformation in child with horseshoe kidney.

We describe a 12-year-old girl with a retroperitoneal lymphatic malformation (LM) and horseshoe kidney. The imaging characteristics of the lesions are reported. Retroperitoneal LM coexisting with horseshoe kidney is extremely rare. We hypothesized that they might share the similar etiologic factors. Imaging examinations are helpful in the definition of the 2 lesions and the relationship between them, but no characteristic findings are available to diagnose retroperitoneal LM before surgery. Surgical excision is ideal to treat LM, and the prognosis is good. Although asymptomatic horseshoe kidney need not be treated, it is important for patients to receive regular follow-up because of the propensity for various complications.

Synchronous ipsilateral Bochdalek and Morgagni diaphragmatic hernias: a case report.

The etiology of congenital diaphragmatic hernia (CDH) is unknown. Phenotypic patterns of CDH defects provide clues about normal diaphragm development and the pathophysiology of CDH. We report a case of a patient who was diagnosed with CDH postnatally and was found on imaging to have simultaneous Bochdalek and Morgagni hernias on the right side. During the operative repair of these defects, an additional left-sided Morgagni-type defect was also found. To the best of our knowledge, this form of CDH has not been previously reported.

Ex-utero intrapartum treatment procedure for giant neck masses--fetal and maternal outcomes.

BACKGROUND/PURPOSE: For fetuses with giant neck masses and tracheal obstruction, an ex-utero intrapartum treatment (EXIT) procedure allows for safe nonemergent airway management while on placental support. Our objective was to examine fetal and maternal outcomes after EXIT procedure specifically for giant neck masses. METHODS: The medical records of all patients referred to a comprehensive fetal center for a giant neck mass between 2001 and 2010 were reviewed retrospectively. RESULTS: Among 24 patients referred, an EXIT procedure was performed in 12 with evidence of tracheal compression. An EXIT procedure was not performed because of minimal tracheal involvement (n = 8), elective abortion (n = 2), fetal demise (n = 1), or obstetric complication (n = 1). In all fetuses, the airway was successfully secured; tracheal intubation was achieved with rigid bronchoscopy (n = 10), direct laryngoscopy (n = 1), and tracheostomy (n = 1). Eleven patients survived to discharge, whereas 1 patient with significant pulmonary hypoplasia died 8 days after emergency EXIT procedure. Of 11 surviving infants, 10 are neurodevelopmentally intact. All mothers who desired future pregnancies have subsequently had uncomplicated deliveries (n = 6). CONCLUSIONS: Ex-utero intrapartum treatment procedure for giant neck mass can be performed safely for both mother and child. Most fetuses can be orotracheally intubated with minimal long-term morbidity. The potential for future pregnancies is preserved.

Nuchal translucency and cystic hygroma colli in screening for fetal major congenital heart defects in a series of 12,910 euploid pregnancies.

OBJECTIVE: Many studies have shown that an increased nuchal translucency (NT) may be a good marker of fetal heart malformation, but the extent to which NT is suitable for identifying the population at risk remains unclear. We aimed to determine the value of NT measurement and of the presence of cystic hygroma colli in the screening of euploid fetuses for congenital heart defects (CHD). METHODS: We carried out a retrospective analysis of 12 910 euploid pregnancies examined between January 1995 and August 2007 at our institution. The screening performance of NT measurements in identifying fetuses with CHD was assessed, with comparison between the use of cut-offs defined as absolute values, multiples of the median (MoM) and percentiles. The presence of cystic hygroma colli was also assessed in the prediction of CHD. RESULTS: The incidence of major CHD was 3.4 per thousand (44/12 910). The sensitivity of NT measurement in screening for major CHD was 54.5% if the threshold was set at the 95(th) percentile, 45.4% if it was set at 3 mm, 27.3% for 3.5 mm, 50.0% for 1.5 MoM and 45.5% for 1.75 MoM. The false-positive rates for these thresholds were 8.4, 6.6, 1.7, 8.9 and 6.3%, respectively. The incidence of major CHD was 1.2% (10/813) in cases of thick NT (> 95(th) centile) and 4.3% (13/304) in cases of hygroma colli. CONCLUSIONS: NT measurement during the first trimester is potentially useful for screening for fetal major CHD. Screening performance is consistent whether NT values are expressed as MoMs, percentiles or absolute values. The incidence of major CHD seems to be higher in cases of cystic hygroma colli.

Application of transcervical hysterofetoscopy and cord blood collection at first trimester termination of pregnancy for fetal abnormalities.

OBJECTIVE: To examine the applicability of hysterofetoscopy and cord blood collection at first trimester termination of pregnancy for fetal abnormalities. METHODS: From 2004 to 2007, transcervical hysterofetoscopy was performed in seven patients at the same operation setting of surgical termination of pregnancy. The findings were compared with prenatal diagnosis. Feasibility of cord blood collection was also examined. RESULTS: Out of these seven patients, six of them had prenatal ultrasound diagnosis of cystic hygroma. All of them had chromosomal abnormalities. Subcutaneous oedema was confirmed by hysterofetoscopy with good view. Another pregnancy was complicated by homozygous alpha thalassaemia and the diagnosis was confirmed by electrophoresis of fetal haemoglobin collected from umbilical cord vessel. Cord blood collection was also attempted in two other patients yielding fetal blood with minimal maternal contamination. CONCLUSION: Transcervical hysterofetoscopy is a feasible tool in confirming external fetal structural abnormalities before surgical termination of pregnancy. It can be performed under either general anaesthesia or conscious sedation. Umbilical cord blood collection can facilitate confirmation of genetic diseases. It may also allow the potential of isolating fetal mesenchymal stem cell in first trimester.

Prenatal diagnosis of posterior mediastinal lymphangioma by two- and three-dimensional ultrasonography.

Lymphangioma is a rare benign tumor characterized by proliferating lymph vessels and composed of large cyst spaces with endothelium-lined channels of varying dimensions. The incidence of lymphangioma is approximately one in 6000 pregnancies. Less than 1% of lymphangiomas are purely mediastinal. The great majority of cases are of cystic lymphangioma, but very rarely there is a mixed lesion consisting of multiple cysts of dilated capillary and lymph vessels. We report a case of posterior mediastinal lymphangioma diagnosed at 28 weeks' gestation, in which three-dimensional ultrasonography was helpful in determining the precise location of the tumor. A Cesarean section was performed at 39 weeks and the tumor was resected on the 5(th) day postdelivery; histological examination revealed a mixed cystic lymphangioma.

Jugular lymphatic maldevelopment in Turner syndrome and trisomy 21: different anomalies leading to nuchal edema.

Increased nuchal translucency (NT), morphologically known as nuchal edema, is an ultrasound marker for aneuploidy. Turner syndrome presents with massive NT, called cystic hygroma. Conflicting data exist as to whether cystic hygroma and increased NT are different entities. Both are associated with jugular lymphatic distension. The authors investigated jugular lymphatics of trisomy 21, Turner syndrome, and normal karyotype fetuses. Fetuses were investigated using immunohistochemistry for blood vascular, lymphatic, and smooth muscle cell markers. Trisomy 21 fetuses showed nuchal cavities within the mesenchymal edema negative for endothelial markers. These were extremely large in Turner fetuses, showing similar characteristics. The skin showed numerous dilated lymphatics in the case of trisomy 21 and scanty small lymphatics in Turner fetuses. A jugular lymphatic sac was present in control and trisomy 21 fetuses and was enlarged in trisomy 21 cases. In Turner fetuses, no jugular lymphatic sac was observed. Nuchal edema in trisomy 21 and Turner syndrome appears to be a similar entity caused by different lymphatic abnormalities.

[EXIT procedure in the management of severe foetal airway obstruction. the paediatric otolaryngologist's perspective]. / Procedimiento EXIT en el manejo de fetos con severo compromiso respiratorio. La perspectiva del otorrinolaringólogo pediátrico.

The ex-utero intrapartum treatment (EXIT) procedure is a technique designed to allow partial foetal delivery via caesarean section with establishment of a safe foetal airway by either intubation, bronchoscopy, or tracheostomy while foetal oxygenation is maintained through utero-placental circulation. The most common indication for the EXIT procedure is the presence of foetal airway obstruction, which is usually caused by a prenatal diagnosed neck mass. We report three cases of head and neck tumours with airway obstruction treated by means of EXIT and with different solutions in the management of the airway. With the involvement of Paediatric Otolaryngologists in EXIT, new indications and select variations from the standard EXIT protocol should be considered.

Characteristics and outcome of fetal cystic hygroma diagnosed in the first trimester.

OBJECTIVE: The aim of this study was to determine the course of pregnancy and the neonatal outcome of fetuses with cystic hygroma diagnosed at 10-14 weeks' gestation. METHODS: Maternal and fetal data (nuchal translucency, karyotype, pregnancy outcome) in cases of fetal cystic hygroma, admitted or referred to our antenatal diagnostic centre, were prospectively entered into a computer database. Paediatric outcome was analysed when relevant. RESULTS: Some 72 fetuses had cystic hygroma. The mean size of the cystic hygroma was 7.9 mm. Chromosomal abnormalities were present in 52.7% of cases (38/72), including 14 cases (36.8%) of Down syndrome. A total of 34 chromosomally normal pregnancies gave rise to 18 live births (52.9%), with no visible serious structural abnormalities. The outcome of pregnancy was unfavourable (miscarriage, elective termination, serious structural abnormalities) in 77.7% of cases (56/72). The 18 live-born infants were followed up for 17-98 months. Sixteen infants developed normally, while 1 developed Noonan's syndrome and 1 had a urinary tract abnormality (pyelo-ureteral junction; PUJ). CONCLUSION: These data suggest that the prognosis of fetal cystic hygroma detected during the first trimester is poor, and show that sonographic evaluation of fetal nuchal translucency thickness in the first trimester is crucial.

Cystic hygroma and lymphangioma: associated findings, perinatal outcome and prognostic factors in live-born infants.

OBJECTIVES: We aimed to determine associated ultrasonographic findings, chromosome abnormalities and the prognostic factors of cystic hygromas in live-born infants. METHODS: We reported a series of 57 cystic hygroma cases, who were diagnosed in the first and the second trimester of pregnancy by means of the ultrasonographic morphology of cystic hygroma, associated structural abnormalities, karyotype analysis and the autopsy findings. Survivors were followed for their fetal outcome and prognosis. RESULTS: There were 57 new cases of cystic hygroma among 8,155 screenings (0.7%). 35 of the cases (61.4%) were nonseptated and 22 of the cases (38.6%) were septated cystic hygroma. Chromosomal abnormalities were found in 23 of the cases (40.3%). The most common abnormality in nonseptated cystic hygroma was trisomy 21 (8 cases, 25%) and in septated cystic hygroma was Turner syndrome (4 cases, 21.1%). The most common associated structural malformations were cardiac abnormalities (in 7 cases, 20%) in nonseptated cystic hygroma cases and nonimmune hydrops (in 12 cases, 54.5%) in septated cystic hygroma cases. Overall survival was poor; only one case of septated cystic hygroma with axillary location and seven cases of nonseptated cystic hygroma, of whom two died in the neonatal period, were alive (10.5%). This study had 80% power to detect 0.03% difference in diagnosis cystic hygroma (alpha = 0.05, beta = 0.80). CONCLUSION: Fetuses with cystic hygroma are at high risk for adverse outcome. Prenatal diagnosis with invasive procedures should be done in order to inform the parents in detail. Axillary location of the hygroma and the depth of invasion had prognostic importance.

Gastroschisis with fetal chromosomal abnormality: a case report.

Gastroschisis is a rare anomaly and it is usually not associated with other syndromic or nonsyndromic anomalies. The first case of gastroschisis with aneuploidy (Turner syndrome) is presented. A fetal huge cystic hygroma was diagnosed by prenatal sonography at 12 weeks of pregnancy and chorionic villi sampling (CVS) was performed. Cytogenetic analysis revealed 45, X0. The pregnancy was terminated by induction of labor at 16 weeks of pregnancy. The female fetus had a big membrane of cystic hygroma surrounding the fetal neck. Additionally, a full abdominal thickness defect with multiple loops of bowel outside the abdomen, which could not be diagnosed on prenatal ultrasound scan, was detected on postnatal examination.

Prenatal diagnosis of an unexpected interstitial 22q11.2 deletion causing truncus arteriosus and thymic hypoplasia in a ring 22 chromosome derived from a maternally inherited paracentric inversion.

OBJECTIVE: To present the prenatal diagnosis of an interstitial 22q11.2 deletion involving a ring 22 chromosome associated with truncus arteriosus and a hypoplastic thymus. CASE: Following the sonographic diagnosis of a cystic hygroma at 12 weeks of gestation, chromosome analysis revealed a ring 22 chromosome. RESULTS: Ring chromosomes typically result in the deletion of genetic material from the distal long and short arms of the affected chromosome. The presence of an interstitial deletion in a ring chromosome is therefore unusual. FISH analysis revealed an unexpected deletion involving the TUPLE1 gene in the DiGeorge/Velocardiofacial syndrome region in 22q11.2. Maternal chromosome analysis revealed the cause of the apparent interstitial deletion, a paracentric inversion in the long arm of chromosome 22, resulting in the distal long arm of 22q being located adjacent to the centromere and the proximal end being located near the telomere. The fetus was subsequently diagnosed with truncus arteriosus and a hypoplastic thymus, consistent with DiGeorge syndrome. CONCLUSION: The ring chromosome 22 found in the fetus appears to have been derived from a rearrangement of the mother's inverted 22, resulting in ring formation and loss of the end of the distal long arm of the inverted 22, including the TUPLE1 locus, causing DiGeorge syndrome in the fetus. The apparent interstitial deletion was actually a terminal deletion in a maternally inherited rearranged chromosome 22.

[Increased nuchal translucency and cystic hygroma in the first trimester: prenatal diagnosis and neonatal outcome]. / Hyperclarté nucale et hygroma cervical au premier trimestre de la grossesse: diagnostic prénatal et devenir néonatal.

OBJECTIVE: A prospective study of pregnancy outcome in fetuses with increased nuchal translucency above the 95th centile (group NT) or cystic hygroma (group CH) at 10 to 14 weeks of gestation was performed. PATIENTS AND METHODS: Maternal and fetal data (nuchal translucency, caryotype, pregnancy outcome) and infant follow-up of 223 fetuses with first trimester nuchal translucency thickness (183 NT and 40 CH) were analysed. RESULTS: The measurement of nuchal translucency thickness shows a significant difference between group CH and NT (7.4+/-2.9 mm compared 3.7+/-0.8 mm). Chromosomal abnormalities were present in 55% (22/40) in group CH, with 9 cases/22 (40.9%) of Turner syndrome, compared with 14.2% (26/183) in group NT with trisomy 21 in 15 cases/26 (57.7%) (P<0.05). The rate of unfavourable outcome of pregnancy (spontaneous abortion, elective termination of pregnancy, serious structural anomalies) was 80% (32/40) in group CH compared with 18% (33/183) in group NT (P<0.05). In chromosomally normal pregnancies, the rate of fetus with no visible serious structural anomalies was 44.4% (8/18) in group CH compared with 93% (146/157) in group NT (P<0.05). DISCUSSION AND CONCLUSION: Our data show ultrasonographic evaluation of the fetal nuchal translucency thickness at the first trimester is actually indispensable. Neonatal outcome and malformation rate in fetuses with increased nuchal translucency or cystic hygroma are different, even with normal karyotype.

Prenatal DNA diagnosis of Noonan syndrome in a fetus with massive hygroma colli, pleural effusion and ascites.

Prenatal molecular genetic diagnosis for Noonan syndrome I is reported. Noonan syndrome was suspected because of large cystic hygroma colli, massive pleural effusion and ascites at 23 weeks of gestation and normal karyotype (46,XX). DNA was prepared from amnion cells and screened for mutations in the PTPN11 gene. In exon 8, a missense mutation (S285F) was found. Delivery was induced at 33 weeks of gestation because of silent cardiotocography (CTG). Despite immediate drainage of the hydrothorax, mechanical ventilation was insufficient and the child died 9 h after birth due to severe pulmonary hypoplasia. Pleural punctate was enriched for small lymphocytes and thus was characterized as chylus. Prenatal ultrasound findings in Noonan syndrome usually are unspecific and rarely lead to a diagnosis. However, with the combination of cystic hygroma, pleural effusion, ascites and normal karyotype Noonan syndrome should be considered and DNA testing for PTPN11 mutations may be appropriate. Malformations of lymphatic vessels and/or chylothorax in Noonan syndrome seem to be more frequent than usually anticipated.