Impact of interdisciplinary counselling for parental decision-making in cases of pregnancies with prenatally diagnosed CHD.

INTRODUCTION: Parental counselling after antenatal diagnosis of a congenital heart defect requires a high degree of professional and emotional competence and ultimately a sense of responsibility on the part of the consulting physicians. However, little is known about parents` perceptions and evaluation of these consultations. MATERIAL/METHODS: Survey on 425 women who received interdisciplinary counselling after antenatal diagnosis of a complex fetal congenital heart defect in a specialized prenatal outpatient clinic with an affiliated paediatric heart centre. Two questionnaires were used to retrospectively evaluate the parental perception and impact on counselling, particularly on decision-making. Questionnaires differed between women conceiving the child and women who terminated the pregnancy. RESULTS: 400 women continued, 25 women terminated the pregnancy after diagnosis and counselling. Good quality of life was reported for 68% of the children, 15% died postnatally in the further course. 95% rated the counselling as good or very good regardless of the child´s outcome. 73% described the counselling as highly important for their subsequent decision. The possibility of termination of pregnancy was discussed with 37% of the respondents, 22% of them found it outrageous or very distressing. Of all respondents, one woman would have made a different decision regarding continuation of the pregnancy in retrospect. CONCLUSION: Retrospectively, parents rate prenatal counselling extremely positively, irrespective of the severity of the child´s heart defect. It can be assumed that the consistent joint interdisciplinary consultation and the high reputation of the cooperating heart centre have had an influence on the below-average rate of termination of pregnancy.

Natural history of pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (CPS) and prediction of outcome.

OBJECTIVES: To analyse prenatal parameters predicting biventricular (BV) outcome in pulmonary atresia with intact ventricular septum/critical pulmonary stenosis (PAIVS/CPS). METHODS: We evaluated 82 foetuses from 01/08 to 10/18 in 3 centres in intervals 1 (< 24 weeks), 2 (24-30 weeks) and 3 (> 30 weeks). RESULTS: 61/82 (74.4%) were livebirths, 5 (8.2%) lost for follow-up, 3 (4.9%) had compassionate care leaving 53 (64.6% of the whole cohort and 86.9% of livebirths) with intention to treat. 9 died, 44/53 (83.0%) survived. 24/38 (63.2%) with information on postnatal outcome had BV outcome, 14 (36.8%) non-BV outcome (2 × 1.5 circulation). One with BV outcome had prenatal valvuloplasty. Best single parameter for BV outcome was tricuspid/mitral valve (TV/MV) ratio (AUC 0.93) in intervals 2 and 3 (AUC 0.92). Ventriculo-coronary-arterial communications (VCAC) were present in 11 (78.6%) in non-BV outcome group vs. 2 (8.3%) in BV outcome group (p < 0.001). Tricuspid insufficiency (TI)-Vmax > 2.5 m/s was present in BV outcome group in75.0% (18/24) vs. 14.3% (2/14) in non-BV outcome group. Including the most predictive markers (VCAC presence, TI- Vmax < 2.5 m/s, TV/MV ratio < cutoff) to a score, non-BV outcome was correctly predicted when > 1 criterion was fulfilled in all cases. After recently published criteria for foetal intervention, only 4/9 (44.4%) and 5/14 (35.7%) in our interval 2 + 3 with predicted non-BV outcome would have been candidates for intervention. Two (1 × intrauterine intervention) in interval 2, two in interval 3 reached BV outcome and one 1.5 circulation without intervention. CONCLUSION: TV/MV ratio as simple parameter has high predictive value. After our score, non-BV outcome was correctly predicted in all cases. Criteria for foetal intervention must further be evaluated.

Prenatal Diagnosis and Postnatal Outcome of Fetuses with Pulmonary Atresia and Ventricular Septal Defect.

PURPOSE: To assess the intrauterine course, associated conditions and postnatal outcome of fetuses with pulmonary atresia with ventricular septal defect (PAVSD). METHODS: All cases of PAVSD diagnosed prenatally over a period of 10 years with a minimum follow-up of 6.5 years were retrospectively collected in 3 tertiary referral centers. RESULTS: 50 cases of PAVSD were diagnosed prenatally. 44.0 % of fetuses had isolated PAVSD, 4.0 % had associated cardiac anomalies, 10.0 % had extra-cardiac anomalies, 38.0 % had chromosomal anomalies, 4.0 % had non-chromosomal syndromes. Among the 32 liveborn children, 56.3 % had reverse flow in the patent arterial duct, 25.0 % had major aortopulmonary collateral arteries (MAPCAs) with ductal agenesis and 18.7 % had a double supply. 17 pregnancies were terminated (34.0 %), there was 1 intrauterine fetal death (2.0 %), 1 neonatal death (2.0 %), and 6 deaths (12.0 %) in infancy. 25 of 30 (83.3 %) liveborn children with an intention to treat were alive at the latest follow-up. The mean follow-up among survivors was 10.0 years (range 6.5-15.1). 56.0 % of infants underwent staged repair, 44.0 % had one-stage complete repair. After exclusion of infants with additional chromosomal or syndromal anomalies, 88.9 % were healthy, and 11.1 % had mild limitations. The presence of MAPCAs did not differ significantly between survivors and non-survivors (p = 0.360), between one-stage or staged repair (p = 0.656) and healthy and impaired infants (p = 0.319). CONCLUSION: The prognosis in cases without chromosomal or syndromal anomalies is good. MAPCAs did not influence prognosis or postoperative health. The incidence of repeat interventions due to recurrent stenoses is significantly higher after staged compared with single-stage repair.

Absent pulmonary valve syndrome - diagnosis, associations, and outcome in 71 prenatally diagnosed cases.

OBJECTIVE: The objective of this study was to analyze the spectrum of prenatally diagnosed absent pulmonary valve syndrome (APVS) and the outcome from diagnosis onwards. Fetuses with APVS and tetralogy of Fallot (TOF/APVS) and with APVS and intact ventricular septum (APVS/IVS) were included. METHOD: Multicenter retrospective study of the International Prenatal Cardiology Collaboration Group. Clinical and echocardiographic databases of nine referral centers were reviewed from 2012-2016. RESULTS: The cohort included 71 cases, 59 with TOF/APVS and 12 with APVS/IVS. In 18.3% of cases, diagnosis was achieved within first trimester. Association with hydrops fetalis was high within first trimester (69%). No fetus with known outcome survived after first trimester diagnosis. Karyotype anomalies occurred in 45% of cases with known karyotype. Intrauterine fetal demise occurred in 14.3%. Overall survival after initial diagnosis in the total cohort was 28.1% (28.8% TOF/APVS and 25.0% APVS/IVS). Survival to birth was 50% in TOF/APVS and 44.4% in APVS/IVS. Survival of subjects born alive beyond neonatal period was 84.6% in TOF/APVS and 100% in APVS/IVS. CONCLUSION: Diagnosis of APVS is feasible within first trimester. Outcomes remain guarded, especially if first trimester diagnosis is included into the analysis because of associated karyotypic anomalies, the presence of hydrops fetalis, and patent ductus arteriosus. © 2017 John Wiley & Sons, Ltd.

Fetal Cardiac Axis in Fetuses with Conotruncal Anomalies.

Purpose The purpose of this study was to assess the cardiac axis in fetuses with conotruncal anomalies during four-chamber view scanning. Materials and Methods We retrospectively evaluated the cardiac axis of 150 fetuses with conotruncal anomalies within the second and third trimester between October 2008 and August 2014. The cardiac axis was obtained by the angle of two lines in a transverse view of the fetal thorax at the level of the four-chamber view. The first line divided the thorax into two equal halves starting from the spine posteriorly ending at the sternum. The second line was placed through the interventricular septum of the fetal heart. The angle was calculated using OsiriX software. Results 23 had double outlet right ventricle (DORV), 17 had truncus arteriosus communis (TAC), 36 had tetralogy of Fallot (TOF), and 74 had complete transposition of the great arteries (d-TGA). In fetuses with DORV ≤ 24 + 6 weeks of gestation (wks), the mean cardiac axis was 52.5° (p = 0.005), at ≥ 25 + 0 wks it was 51.1° (p = 0.0003). In fetuses with TAC ≤ 24 + 6 wks, the mean cardiac axis was 56.8° (p = 0.01), at ≥ 25 + 0 wks it was 50.0° (p = 0.05). In fetuses with TOF ≤ 24 + 6 wks, the mean cardiac axis was 67.5° (p < 0.0001), at ≥ 25 + 0 wks it was 63.8° (p < 0.0001). In fetuses with d-TGA ≤ 24 + 6 wks, the mean cardiac axis was 45.6°, at ≥ 25 + 0 wks it was 45.4° (not significant). Throughout gestation, the cardiac axis did not show a difference in the two separate examinations. Conclusion In fetuses with DORV, TAC and TOF, the cardiac axis is significantly different from the normal axis, but in fetuses with TGA there is no significant difference compared to the normal axis. Therefore, analysis of the heart axis could be useful for screening for conotruncal anomalies.

Ebstein's Anomaly of the Tricuspid Valve in the Fetus - A Multicenter Experience.

Purpose To assess the spectrum of associated anomalies, the intrauterine course, the outcome and possible prognostic markers in prenatally diagnosed Ebstein's anomaly (EA). Materials and Methods All cases of EA diagnosed over a period of 13 years with a minimum follow-up of 1 year were retrospectively collected in 4 tertiary referral centers in Germany. Results In the study period 76 cases of EA were prenatally diagnosed. The mean gestational age at diagnosis was 25.0 weeks (range: 13 - 35). 41 (53.9 %) cases were isolated and 35 (46.1 %) had other cardiac and/or extracardiac anomalies. 19 (25.0 %) pregnant women opted for termination of pregnancy, intrauterine fetal death occurred in 7 cases (9.2 %), neonatal death in 14 cases (18.4 %), death in infancy or childhood in 9 cases (11.8 %) and 27 children (35.5 %) were alive at the last follow-up. After exclusion of terminations, the only parameter inversely correlated with intrauterine survival was hydrops fetalis. Prognostic parameters significantly associated with postnatal non-survival were an abnormal Celermajer index (right atrium/heart ratio > 0.7), cardiomegaly (cardiothoracic circumference ratio > 0.5), absence of antegrade flow over the pulmonary valve and earlier diagnosis in pregnancy. Conclusion Prenatally diagnosed EA has a high morbidity and mortality with the highest loss rate in the intrauterine and neonatal period. In our study, hydrops fetalis was the only parameter significantly associated with intrauterine demise, while other prenatal markers were only significantly associated with postnatal mortality.

Prenatal diagnosis of functionally univentricular heart, associations and perinatal outcomes.

OBJECTIVE: Functionally univentricular hearts (UVHs) represent cardiac anomalies in which either the pulmonary or systemic circulation cannot be supported independently. The purpose of our study was to determine perinatal outcomes after prenatal diagnosis of functionally UVH. METHODS: We retrospectively evaluated patients who presented between 2008 and June 2015 in our centre and in prenatal practice praenatal.de in Cologne. We included double inlet left ventricle (DILV), tricuspid valve atresia (TA), pulmonary valve atresia and intact ventricular septum (PA:IVS), unbalanced atrioventricular septal defect (AVSD), heterotaxy, hypoplastic left heart syndrome (HLHS) and hypoplastic left heart complex (HLHC). RESULTS: Of initially 155 patients, 128 were liveborn (82.6%). Ten neonates (7.8%) were lost to follow-up, in three (2.5%) neonates, parents decided for compassionate care. Overall survival after prenatal diagnosis of functionally UVH was 67.1%, and 90.4% on an intention-to-treat basis. Survival after surgery reached 93.7%. The majority of deaths occurred within the group of dominant RV (10/74, 13.5%). High risk HLHS with restrictive foramen ovale was associated with the lowest survival rate (13/17, 76.5%) with significant difference compared to survival rate in dominant LV (40/41, 97.6%, p < 0.05). CONCLUSION: These results should be explained to parents to ensure informed decisions and counselling. © 2016 John Wiley & Sons, Ltd.

The 'Radiant Effect': Recent Sonographic Image-Enhancing Technique and Its Impact on Nuchal Translucency Measurements.

Background: This study assesses the effects of the 'Radiant' image enhancement technique on fetal nuchal translucency (NT) measurements during first-trimester sonographic exams. Methods: A retrospective analysis of 263 ultrasound images of first-trimester midsagittal sections was conducted. NT measurements were obtained using a semi-automatic tool. Statistical methods were applied to compare NT measurements with and without 'Radiant' enhancement. An in vitro setup with predefined line distances provided additional data. Results: Incremental increases in NT measurements were observed with varying levels of 'Radiant' application: an average increase of 0.19 mm with 'Radiant min', 0.24 mm with 'Radiant mid', and 0.30 mm with 'Radiant max.' The in vitro results supported these findings, showing consistent effects on line thickness and measurement accuracy, with the smallest mean deviation occurring at the 'Radiant mid' setting. Conclusions: 'Radiant' image enhancement leads to significant increases in NT measurements. To avoid systematic biases in clinical assessments, it is advisable to disable 'Radiant' during NT measurement procedures. Further studies are necessary to corroborate these findings and to consider updates to the NT reference tables based on this technology.

Nine new twin pairs with esophageal atresia: a review of the literature and performance of a twin study of the disorder.

BACKGROUND: Isolated esophageal atresia (EA) is a rare congenital malformation whose etiology remains largely unknown. Nine twin pairs with EA were identified from our clinical service, prompting the performance of a systematic review of the literature and the first reported twin study of isolated EA. METHODS: A total of 330 twin pairs with EA were identified from the literature. The zygosity, concordance, and malformation (isolated vs. nonisolated) status of all 339 twin pairs were evaluated. A total of 72 twin pairs (4 of 9 / 68 of 330) fulfilled the criteria for inclusion in a classic twin study of isolated EA. RESULTS: The pairwise concordance rates were 50% (95% confidence interval [CI], 34-66%) for monozygous (MZ) twin pairs and 26% (95% CI, 15-42%) for dizygous (DZ) twin pairs (p = 0.033). The probandwise concordance rates were 67% (95% CI, 53-78%) for MZ twin pairs and 42% (95% CI, 29-56%) for DZ twin pairs (p = 0.011). The MZ/DZ ratios were 1.9 for pairwise analysis and 1.6 for probandwise analysis. The familial risk ratios for MZ and DZ twin pairs were 1700 and 900, respectively. CONCLUSION: The observation of higher concordance rates for MZ compared to DZ twin pairs indicates that genetic factors contribute to isolated EA.

Right- versus left-sided congenital diaphragmatic hernia: postnatal outcome at a specialized tertiary care center.

OBJECTIVE: To systematically investigate the impact of the location of the defect in congenital diaphragmatic hernia on neonatal mortality and morbidity with a special focus on survival at discharge, extracorporeal membrane oxygenation requirement, and the development of chronic lung disease. DESIGN: Retrospective tertiary care center study with a matched-pair analysis of all fetuses that were treated for congenital diaphragmatic hernia between 2004 and 2009. SETTING: A specialized tertiary care center for fetuses with congenital diaphragmatic hernia. PATIENTS: Complete sets of data were available for 106 patients with congenital diaphragmatic hernia. For 17 of 18 infants with right-sided congenital diaphragmatic hernia we were able to allocate infants with left-sided congenital diaphragmatic hernia with no relevant difference in previously described prognostic factors, such as pulmonary hypoplasia and liver herniation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There was a strong trend toward better survival in infants with right-sided congenital diaphragmatic hernia than with left-sided congenital diaphragmatic hernia (94% vs. 70%; p = .07). More neonates with left-sided congenital diaphragmatic hernia died of severe pulmonary hypertension despite extracorporeal membrane oxygenation. Fewer neonates with right-sided congenital diaphragmatic hernia died, yet higher degrees of pulmonary hypoplasia and oxygen requirement were observed despite extracorporeal membrane oxygenation. CONCLUSIONS: In congenital diaphragmatic hernia, the location of the defect has a substantial impact on postnatal survival and the development of chronic lung disease. In left-sided congenital diaphragmatic hernia, pulmonary hypertension resistant to therapeutic management, including extracorporeal membrane oxygenation, is more common and is associated with a higher rate of neonatal demise. Right-sided congenital diaphragmatic hernia infants have an increased benefit from extracorporeal membrane oxygenation but the better survival entails a higher rate of chronic lung disease.

Macroscopic and histopathologic findings in a laparoschisis model in fetal sheep: comparisons with gastroschisis in human fetuses and implications for prenatal interventions.

PURPOSE: In order to further define the challenges, minimally invasive fetal surgery will have to overcome human fetuses with gastroschisis. The purpose of this study was to compare macroscopic and histopathologic characteristics of experimental laparoschisis in sheep fetuses with actual cases of gastroschisis from a postmortem series of human fetuses. METHODS: Employing fetoscopy, we created a laparoschisis model in eight fetal sheep between 74 and 92 days of gestation (median 86.5 days). Twenty to 31 days after fetoscopic creation of fetal laparoschisis, six surviving fetuses were harvested for macroscopic and histopathologic assessments of the experimental lesion. These findings were compared to those of ten human fetuses with gastroschisis after termination of pregnancy. RESULTS: In the six sheep fetuses, both macroscopic and histopathologic intestinal changes achieved by this animal model resembled those of the human fetuses with gastroschisis. The surface of the intestine, liver and stomach exposed to the amniotic fluid was covered by a thick pseudocapsule made up of reactive fibroblasts and a dense capillary network. Parts of the capsule showed a foreign body-type reaction. CONCLUSIONS: Macroscopic and histopathological findings in a new minimally invasive laparoschisis model in sheep resemble those found in human fetuses with gastroschisis. The new model seems therefore suitable for assessing the potential of prenatal minimally invasive fetoscopic interventions in this condition.

A classic twin study of isolated gastroschisis.

The etiology of gastroschisis remains elusive. A classic twin study was used to assess the relative contribution of environmental and genetic factors in its development. Screening of 4872 twin pregnancies identified three unreported twin pairs comprising two monozygous and one dizygous discordant pair of twins. Review of the literature identified an additional 21 twin pairs. We observed lower pair- and proband-wise concordance rates for monozygotic compared to dizygotic twin pairs, pair- and proband-wise concordance ratios below 1.0. Our results suggest environmental to play a greater role than genetic factors in the development of gastroschisis.

Partial amniotic carbon dioxide insufflation (PACI) during minimally invasive fetoscopic surgery: early clinical experience in humans.

BACKGROUND: The technical performance of minimally invasive fetoscopic surgery may be severely hindered by poor visualization of intra-amniotic contents. Partial amniotic carbon dioxide insufflation (PACI) allows the visual limitations of operating within the fluid environment to be overcome. PATIENTS AND METHODS: When amniotic fluid exchange failed to improve fetoscopic visualization, PACI was attempted during 37 fetoscopic procedures between 17 + 5 and 33 + 2 weeks of gestation. PACI was attempted with filtered carbon dioxide using a commercially available insufflator via one to three trocars that were percutaneously introduced into the amniotic cavity. The maximum pressure during PACI was limited by the maximum insufflation pressure (30 mmHg) generated by the insufflator. Improvement of fetoscopic visualization as well as technical, maternal, and fetal safety aspects surrounding PACI were analyzed. RESULTS: PACI could successfully be instituted in 36 of the 37 procedures. In one case, when in the presence of increased uterine tone the opening pressure exceeded the maximum insufflation pressure of the insufflator, the strategy was abandoned. In all cases where PACI could be instituted successfully, the approach offered far superior visualization of the fetoscopic procedure than would have been possible within amniotic fluid. Acute or chronic maternal or fetal complications were observed in only one case (intraoperative membrane rupture). CONCLUSION: PACI greatly improves fetal visualization during fetoscopic interventions when fetoscopy within fluid meets with difficulties. Continued assessment of its benefits, risks, and safety margins at specialist centers is required.

Life-saving effects of fetal tracheal occlusion on pulmonary hypoplasia from preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes before 22 weeks of gestation may result in severe fetal pulmonary hypoplasia. Fetoscopic tracheal balloon occlusion might result in catch-up pulmonary growth. CASE: After preterm premature rupture of membranes at 16 weeks of gestation, magnetic resonance imaging at 26 0/7 weeks showed a fetal lung volume of 13 mL and pulmonary blood flow hardly could be detected. Fetoscopic tracheal balloon occlusion was performed at 27 6/7 weeks; within 6 days, fetal lung volume increased to 70 mL and lung blood flow normalized. The fetus was delivered electively at 28 6/7 weeks. Six hours after delivery, the neonate required only 21% oxygen and was extubated after 55 hours. CONCLUSION: Short-term fetoscopic tracheal balloon occlusion may result in rapid normalization of fetal lung volume and blood flow in fetuses with life-threatening pulmonary hypoplasia from preterm premature rupture of membranes before 22 weeks of gestation.

Is there a therapeutic role for fetoscopic surgery in the prenatal treatment of gastroschisis? A feasibility study in sheep.

BACKGROUND/PURPOSE: Gastroschisis is a malformation of the anterior abdominal wall that consists of a right paraumbilical defect with bowel loops bathed in the amniotic fluid. The prognosis relies mainly on morbidity attributable to intrauterine bowel loss or postpartum bowel dysfunction. The purpose of this study was to evaluate a potential role for fetoscopic surgery in severely affected fetuses with this condition. METHODS: Employing fetoscopy, we created a laparoschisis model in eight fetal sheep between 74-92 days of gestation; median 86.5 days). Twenty to 31 days after fetoscopic creation of fetal laparoschisis, a second procedure was scheduled in six survivors of the first surgery with the goal of assessing the potential for fetoscopic intervention in this condition. RESULTS: In the six survivors, macroscopic intestinal changes achieved by this animal model resembled those of human fetuses with gastroschisis. Whereas fetoscopic enlargement of the defect within the abdominal wall was feasible, in none of the fetuses was return of herniated abdominal viscera followed by abdominal closure possible using fetoscopic instrumentation. Furthermore, any attempt to return the herniated viscera into the fetal abdomen resulted in immediate and severe hemodynamic compromise of the fetoplacental circulation by stretching of the intra-abdominal umbilical arteries and vein. CONCLUSION: Minimally invasive fetoscopic enlargement of the defect within the abdominal wall is feasible in sheep fetuses with iatrogenic laparoschisis. This approach might benefit human fetuses with gastroschisis considered at high risk for bowel loss by constriction at the defect site. In contrast, return of herniated abdominal viscera followed by abdominal closure is limited by physiological constraints and seems currently not feasible with current fetoscopic instrumentation.

Percutaneous fetoscopic patch closure of human spina bifida aperta: advances in fetal surgical techniques may obviate the need for early postnatal neurosurgical intervention.

BACKGROUND: A percutaneous minimally invasive fetoscopic approach was attempted for closure of a spina bifida aperta in two fetuses with L5 lesions. The goal was to obviate the need for postnatal neurosurgery to manage this condition. METHODS AND RESULTS: The percutaneous fetoscopic procedures were performed by a two-layer approach at respectively 22+/-2 and 22+/-4 weeks of gestation. The fetuses were delivered respectively at 32+/-6 and 32+3 weeks of gestation. Their neural cords were completely covered although in small areas skin closure was incomplete. Postnatally, complete skin closure occurred beneath an occlusive draping within 2 to 3 weeks such that neurosurgical intervention was not required. Both neonates showed reversal of hindbrain herniation, near-normal leg function, and satisfactory bladder and bowel function. For one of the two fetuses, ventriculoperitoneal shunt insertion was not required. CONCLUSIONS: Percutaneous minimally invasive fetoscopic patch closure of spina bifida aperta offers a substantially less maternal trauma than open fetal surgical repair and currently may even obviate the need for postnatal neurosurgical repair. With a little further improvement in surgical techniques and a better understanding of incorporating surgical patches into the fetus, complete skin closure seems possible in the near future.

Percutaneous fetoscopic laser decompression of congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia via a single trocar--current technical constraints and potential solutions for future interventions.

OBJECTIVE: To alleviate congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia by percutaneous minimally-invasive fetoscopic tracheal decompression using laser. METHODS: The procedure was performed via one trocar under general maternofetal anesthesia in a human fetus with CHAOS from laryngeal atresia at 21+6 weeks of gestation. RESULTS: Normalization of the lung-heart size relationship was observed within days after the procedure. The fetus was delivered by ex utero intrapartum treatment (EXIT) in order to perform a tracheotomy at 31+1 weeks of gestation and survived hospital treatment to discharge. CONCLUSIONS: Percutaneous minimally-invasive fetoscopic decompression of the fetal trachea via a single trocar is feasible in human fetuses with CHAOS from laryngeal atresia.

Three unusual but cytogenetically similar cases with up to five different cell lines involving structural and numerical abnormalities of chromosome 18.

We report two prenatal and two postnatal diagnosed cases (the latter monozygotic twins) with ring chromosomes after GTG banding. All four, de novo r(18), cases turned out to be more complex after application of high-resolution molecular cytogenetics techniques such as use of fluorescence in situ hybridization, centromeric probes, multicolor banding, and locus-specific probes for chromosome 18. All four cases are mosaics involving chromosome 18 in up to five different cell lines, including 46,r(18); 46,dr(18); 47,r(18)x2; 46,mar(18); and 45,-18. Mosaicism sharing both numerical and structural anomalies is rare, but rings often appear as mosaics due to their mitotic instability. Overall, patients with ring chromosome 18 usually share clinical features of 18q- syndrome and, less frequently, those of 18p- syndrome. High-resolution molecular cytogenetics techniques were useful in the characterization of cases with dynamic mosaicism and in establishing the relationship between loss or gain of chromosomal material and the phenotype.

VATER/VACTERL association: identification of seven new twin pairs, a systematic review of the literature, and a classical twin analysis.

The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. The identification of 14 twin pairs with an initial diagnosis of VATER/VACTERL association at our clinical centers led to the performance of a classical twin study. This involved a thorough evaluation of these 14 twin pairs and a further 55 twin pairs identified from a systematic review of the literature. The zygosity, concordance, and malformation status of all 69 twin pairs were evaluated. Twenty-four twin pairs fulfilled the criteria for inclusion in a comparison of the concordance rates between monozygous (MZ) and dizygous (DZ) twin pairs. The pairwise concordance rates were 15% [95% confidence interval (CI) 4-42%] for MZ and 18% (95% CI 5-48%) for DZ twin pairs (P=0.53). The probandwise concordance rates were 27% (95% CI 11-52%) for MZ and 31% (95% CI 13-58%) for DZ twin pairs (P=0.40). Although based on a limited number of twin pairs, the findings of the present study are consistent with the low number of familial cases reported to date, and suggest that the role of inherited genetic factors in the majority of VATER/VACTERL cases is limited.