Prenatal diagnosis of ventricular septal defect and overriding aorta at 14 weeks' gestation,using trans vaginal sonography

Two fetuses with heart abnormalities were detected by transvaginal sonography at 14 weeks of gestation. In the first fetus, a ventricular septal defect and an overriding aorta were detected and a diagnosis of tetralogy of Fallot was suggested. In addition, cystic hygroma and omphalocoele were visualized and the cytogenetic study revealed trisomy 18. In the second fetus, ventricular septal defect, pericardial effusion, and omphalocoele were detected.     

Isolated right diaphragmatic eventration mimicking congenital heart disease in utero

Diaphragmatic eventration is the upward displacement of the abdominal viscera secondary to a thin or paralytic diaphragm. Its clinical presentations and radiographic pictures are similar to those of diaphragmatic hernia. Prenatal diagnosis of diaphragmatic eventration is extremely rare. A pregnant woman was referred to us because of abnormal cardiac findings noted at 20 weeks of gestation. A diagnosis of partial anomalous pulmonary venous connection was made on the basis of our findings of right atrial enlargement with an abnormal vascular channel drainage to it. The infant was born via cesarean section at 40 weeks and developed complications of cyanosis immediately after birth. Postnatal imaging studies and surgical findings disclosed right side diaphragmatic eventration with liver and associated vasculature upward displacement into the right pleural cavity. The cardiac structure was otherwise normal. We conclude that when an abnormal vessel tracing and unexplainable cardiac chamber asymmetry is encountered, diaphragmatic eventration should be considered as one of the differential diagnoses. Correct recognition and transferral to the hospital for neonatal assistance may lead to timely and appropriate management of these fetuses. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of Myhre syndrome with a heterozygous pathogenic variant in SMAD4 gene presented with thick nuchal translucency and cardiac abnormalities

Prenatal testing was performed in a 39-year-old Chinese pregnant woman referred for increased nuchal translucency measuring 5.7 mm. Non-invasive prenatal testing and SNP array study on amniotic fluid samples were normal. Whole exome sequencing (WES) was initiated further as the fetus had pericardial effusion of 1.2 mm, thickened myocardium over the right ventricular lateral wall and aberrant right subclavian artery. A detailed fetal echocardiogram also revealed persistent left superior vena cava and dilated coronary sinus at 20 weeks. From whole exome sequencing of the trio, a de novo heterozygous variant NM_005359.5(SMAD4): c.1499T>C (p.Ile500Thr) was detected. This pathogenic variant has been reported in the postnatal case cohort of Myhre syndrome. This condition is characterized by facial dysmorphism, intellectual disability, hearing loss, skeletal abnormalities and potential life threatening respiratory or cardiovascular manifestations. Termination of pregnancy was performed at 23 weeks. Small chins, pre-axial polydactyly, brachydactyly and clinodactyly were noted in the abortus. Ultrasound findings of increased nuchal translucency, thickened myocardium and pericardial effusion prompted further genetic evaluation for the prenatal diagnosis of Myhre syndrome by whole exome sequencing.     

Prenatal sonographic detection of intra-abdominal extralobar pulmonary sequestration: Report of three cases and literature review

Three cases of intra-abdominal extralobar pulmonary sequestration detected antenatally by ultrasound are reported. One case was associated with a large left diaphragmatic hernia. Sonographically, all the cases were found in the left supra-renal region presenting as a well-defined echogenic mass with cystic hypoechoic areas. The condition should be considered in the differential diagnosis of all antenatally detected upper abdominal echogenic masses, particularly when associated with a diaphragmatic hernia. Postnatal ultrasound-guided fine needle aspiration biopsy in one case yielded respiratory type epithelium and this procedure could provide a reasonably confident diagnosis of the lesion.     

Prenatal diagnosis of congenital diaphragmatic hernia: Timing of visceral herniation and outcome

Ultrasonographic prenatal diagnosis of congenital diaphragmatic hernia is well established, but the correlation of prenatal detection with clinical outcome remains unclear. We report our experience with 15 cases of prenatally diagnosed congenital diaphragmatic hernia. Seven fetuses were detected at 14–16 weeks' gestation; two with a normal sonographic study at 15 and 16 weeks' gestation showed visceral herniation at 21 and 23 weeks, respectively. In the remaining six cases, a diaphragmatic hernia was found at ultrasonography after 24 weeks' gestation, while previous sonographic studies had been normal. All seven fetuses in whom a diaphragmatic hernia was diagnosed before 16 weeks' gestation were aborted; four of them had severe malformations or karyotype abnormalities. The two neonates who were diagnosed at 21 and 23 weeks' gestation died after surgical repair. In contrast, all six infants whose visceral herniation was diagnosed after 24 weeks of gestation, and whose sonographic studies at 15–23 weeks had been normal, are alive and well after corrective surgery. The results of this series suggest that the timing of visceral herniation into the thoracic cavity is a major indicator of the prognosis of these fetuses and that herniation that occurs after 25 weeks of gestation carries a favourable clinical outcome. Normal sonographic studies during the first half of pregnancy do not exclude the subsequent development of congenital diaphragmatic hernia, raising questions about the advisability of repeat examinations at later stages of gestation.     

Intrapericardial teratoma with hydrops leading to in utero demise

We report a case of intrapericardial teratoma following in utero demise at 29 weeks with nonimmune hydrops. The diagnosis was strongly suggested by ultrasound findings and confirmed by fetopathology. The mechanism whereby intrapericardial teratomas may lead to hydrops and death is massive pericardial effusion responsible for compressive tamponade. When prenatal diagnosis is performed before this stage, in utero interventions can obtain decompression, and the birth can be planned with rapid and appropriate management of the neonate. Copyright © 2007 John Wiley & Sons, Ltd.     

Fetal diaphragmatic hernia and upper limb anomalies suggest Brachmann-de Lange syndrome

We describe two independent cases of Brachmann-de Lange syndrome (BDLS) in which second trimester fetal sonographic studies showed the presence of a diaphragmatic hernia and upper limb anomalies. In both cases the karyotypes were normal. Intrauterine growth restriction (IUGR) developed in the third trimester. Postnatal and postmortem physical examinations demonstrated typical physical findings associated with BDLS. The prenatal diagnosis of diaphragmatic hernia with associated anomalies should prompt consideration of an underlying genetic etiology. Copyright © 2002 John Wiley & Sons, Ltd.     

Tetrasomy 12p (Pallister-Killian syndrome): Ultrasound indicators and confirmation by interphase fish

Tetrasomy 12p (Pallister-Killian syndrome) is a mosaic aneuploidy syndrome in which the isochromosome is present in amniocytes with a much greater percentage than fetal lymphocytes. Two new cases identified by prenatal diagnosis are reported. Indications for prenatal diagnosis were advanced maternal age and fetal anomalies. The most consistent reported prenatal ultrasound findings for tetrasomy 12p include polyhydramnios with short femurs and a diaphragmatic hernia. Recognition of congenital malformation patterns prenatally may allow appropriate selection of tissue for chromosome analysis. Molecular cytogenetic analysis using fluorescence in situ hybridization was used retrospectively to confirm the presence of the isochromosome 12p in various formalin-fixed fetal tissues. The levels of mosaicism detected in fetal and placental tissues were lower than those detected prenatally.     

Pericardial teratoma complicated by hydrops: successful fetal therapy by thoracoamniotic shunting

Pericardial teratoma is a potentially curable lesion that may become life threatening when it induces mediastinal compression and fetal hydrops. So far, cases with fetal hydrops have been managed by elective delivery or pericardial needle decompression. We report a case in which pericardial teratoma resulted in fetal hydrops. Following transpleural needling of the fetal pericardium at 29 weeks and 6 days, pericardial effusion decreased but hydrops persisted, while major unilateral pleural effusion appeared. A thoracoamniotic shunt was placed at 30 weeks and 5 days. Hydrops resolved, although incompletely. The baby was delivered at 32 weeks and was operated upon on day 3. This observation suggests that fetal hydrops associated with pericardial teratoma may improve following thoracoamniotic shunting. Fetal therapy may limit the risks of respiratory distress arising from the combined effect of airways compression and lung immaturity. Copyright © 2003 John Wiley & Sons, Ltd.     

Prenatal diagnosis of Opitz (BBB) syndrome in the second trimester by ultrasound detection of hypospadias and hypertelorism

Prenatal diagnosis in a kindred with the Opitz (BBB) syndrome is presented. The inheritance is consistent with either autosomal dominant inheritance with sex limited expression or X-linked inheritance. The abnormalities in the kindred consist of hypertelorism, hypospadias, ambiguous genitalia, urocolic fistula, imperforate anus, mental retardation, diaphragmatic hernia, and malrotation with volvulus. A male fetus at 19 weeks was found by ultrasound to have hypertelorism and hypospadias with a small phallus consistent with the syndrome. The diagnosis was confirmed by pathologic examination after pregnancy termination. This is the first report of prenatal diagnosis of Opitz syndrome by ultrasonographic demonstration of hypertelorism and hypospadias in the second trimester.     

Twin-twin transfusion syndrome recipient with arterial calcification and heterozygous variant in ABCC6: Evidence of a gene-environment interaction?

We report a case of a twin-twin transfusion syndrome (TTTS) recipient who, after successful fetoscopic surgery, developed a large pericardial effusion and calcifications of the aorta and main pulmonary artery. The donor fetus never had cardiac strain and never developed cardiac calcifications. A heterozygous likely pathogenic variant in ABCC6 (c.2018T > C, p.Leu673Pro) was identified in the recipient twin. While TTTS recipient twins are at risk of arterial calcifications and right heart failure secondary to the disease, calcifications of the great vessels are also observed in generalized arterial calcification of infancy, a Mendelian genetic disorder with associated biallelic pathogenic variations in ABCC6 or ENPP1, which can result in significant pediatric morbidity or mortality. The recipient twin in this case had some degree of cardiac strain prior to TTTS surgery; however, the progressive calcification of the aorta and pulmonary trunk occurred weeks after TTTS resolution. This case raises the possibility of a gene-environment interaction and emphasizes the need for genetic evaluation in the setting of TTTS and calcifications.     

Non-immunological hydrops fetalis and intrapericardial teratoma: Case report and review

A large intrapericardial teratoma was found at necropsy in a 38−week stillborn fetus, in which prenatal diagnosis of hydrops fetalis and an ehogenic cardiac mass had been made. Clinical and pathological data are reported. In utero intrapericardial teratomata lead to different outcomes depending on whether fetal hydrops is associated. When generalized fetal hydrops is not present, the outcome is good, even in cases with large pericardial effusions. When generalized fetal hydrops occurs, it often results in a poor outcome. In our literature review, we have found eight perinatal deaths in nine similar cases reported.     

Prenatal diagnosis of congenital diaphragmatic hernia: A retrospective analysis of 28 cases

In a retrospective analysis of 28 cases of fetal diaphragmatic hernia, overall mortality was 86 per cent, but fell to 70 per cent when multiple anomalies were excluded. Congenital heart disease constituted the majority of associated anomalies. The incidence of an abnormal karyotype was 10·5 per cent, but rose to 20 per cent when only fetuses with multiple anomalies were included. Polyhydramnios, which occurred in 75 per cent, was a poor predictor of fetal outcome. The same applied to the intrathoracic position of the fetal stomach. In all four survivors, diaphragmatic hernia was diagnosed beyond 32 weeks of gestation.     

Early prenatal sonographic appearance of rare thoraco-abdominal eventration

Fetal ventral wall malformations may be diagnosed prenatally with ultrasound. These include omphalocele, gastroschisis, or even thoracic defects with or without ectopia cordis. It is important whenever such a defect is found to carefully define the full extent of the lesion prior to parental counselling. Described and illustrated here is the prenatal diagnosis with real-time ultrasound at 17 weeks gestation of a rare thoraco-abdominal ventral wall defect including omphalocele, bifid sternum, diaphragmatic aplasia, and pericardial aplasia with incomplete ectopia cordis. The technique is described and the importance of the complete, accurate delineation of anatomic malformations is emphasized.     

Ultrasonography in pregnancy and fetal abnormalities: Screening or diagnostic test? IPIMC 1986–1990 register data

The aim of the present study was to assess the sensitivity of ultrasound diagnosis used as a screening test in detecting major congenital anomalies in the prenatal period in a large nation-based multicentre setting. Data from the IPIMC register were collected in the period 1986–1990. One hundred and thirty-five hospitals, located in 17 out of the 20 regions in Italy, participated in the register. Study cases were 3479 infants with major congenital anomalies diagnosed at birth or in the first week of life. Subjects with chromosomal anomalies or multiple defects were excluded. The sensitivity of ultrasound prenatal diagnosis was 49.5 per cent for central nervous system anomalies, 3.8 per cent for congenital heart diseases, 17.1 per cent for gastrointestinal tract defects, 46.6 per cent for abdominal wall defects, 74.8 per cent for urinary tract anomalies, and 22.9 per cent for skeletal abnormalities. The detection rate for diaphragmatic hernia was 24.2 per cent. Overall, only 18 per cent of the defects diagnosed in utero were detected before 24 weeks' gestation. The sensitivity of prenatal diagnosis was 30.1 and 19.0 per cent in the northern, central, and southern regions, respectively. In light of its low sensitivity, ultrasonography as a screening test in the general population should be abandoned, although some improvement in its performance should be expected following adequate training of the ultrasound staff and the use of good technical equipment.     

Congenital malformations subsequent to chorionic villus sampling: Outcome analysis of 1048 consecutive procedures

We wished to identify the types and frequencies of malformations among continuing pregnancies exposed to chorionic villus sampling (CVS) and to determine whether selected procedure-related variables differ between the normal and anomalous cohorts. CVS was performed in 1048 patients between May 1988 and January 1992. Prospective assessment of perinatal outcome was ascertained by (1) physician—patient phone contact within 1 week of sampling, (2) ultrasound evaluation of the fetal anatomy at mid-gestation, (3) a detailed post-partum questionnaire completed by the referring obstetrician, and (4) a telephone interview with each patient after the expected date of confinement. Twenty-seven major malformations were documented among 938 pregnancies (live born, n=934; electively terminated, n=4), and included cardiac malformations (5), hypospadias (5), craniosynostosis (2), pyloric stenosis (2), inguinal hernia (2), polydactyly (2), syndactyly, distal extremely hemimelia, anencephaly, hydrocephalus, cleft lip and palate, omphalocele, diaphragmatic hernia, thanatophoric dysplasia, and unilateral cataract. Normal and anomalous cohorts were similar with respect to sampling method (transabdominal/transcervical ratio), mean gestational age at CVS, single-pass success rate, and mean total sample weight. No relationship between any procedure-related variable and the risk of malformation was observed.     

Pallister Killian-mosaic tetrasomy 12 p syndrome. Another prenatally diagnosed case

A new case of mosaic tetrasomy 12 p (46, XY/47, XY, + i 12 p), diagnosed during pregnancy from ultrasonographic signs, is reported. We emphasize the peculiar position of the diaphragmatic hernia in this syndrome. Its presence or absence determines the vital prognosis and the age of diagnosis. The knowledge of its possible association with tetrasomy 12 p can contribute considerably to the neonatal diagnosis by directing the work of the cytogeneticist to tissue cultures which enable him to detect the presence of the tetrasomy.     

Prenatal diagnosis of tetrasomy 12p by in situ hybridization: Varying levels of mosaicism in different fetal tissues

Prenatal diagnosis of tetrasomy 12p is complicated by the discrimination of the 12p isochromosome from the duplication 21q as well as the level of mosaicism demonstrated in the particular tissue sampled. In this disease, a high percentage of chromosomally abnormal cells are generally found in fibroblastic cells, but lymphocyte karyotypes from the same individual may be normal. We report on the pregnancy of a 37-year-old female who presented to our centre at 16 weeks' gestation for genetic amniocentesis. Sonography of the fetus revealed dextrocardia and diaphragmatic hernia. Chromosome analysis of amniocytes demonstrated mosaicism of a 47,XY,+i(12p) line in 80 per cent of cells and a normal male line (20 per cent), consistent with the Pallister-Killian syndrome. Following termination, a 220 g male fetus of 18 weeks was examined. A flattened nose and low-set ears were noted. In situ hybridization with a chromosome 12 centromeric probe in lymphocytes and skin cells unequivocally confirmed the karyotype and showed the presence of a single centromere in the abnormal chromosome, suggesting a true isochromosome. Chromosome analysis of various fetal tissues was performed and the following percentages of abnormal cells were found: skin 100 per cent, chorion 50 per cent, placenta 30 per cent, and blood 80 per cent. The high frequency of tetrasomic cells in fetal blood at this early gestational age is noteworthy, since most reports of this syndrome show a very low percentage of abnormal cells postnatally.     

The making of fetal surgery

Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials. Copyright © 2010 John Wiley & Sons, Ltd.     

Prenatal diagnosis of complete sole trisomy 1q

The prenatal diagnosis of a complete trisomy of the long arm of chromosome 1 is reported. Major ultrasound findings included: nuchal thickening, bi-temporal narrowing, a single choroid plexus cyst, andmild ventriculomegaly. There was a mass in the chest and abdomen, pleural effusion, ascites and a hyperechoic bowel. Skin edema was present. The fetus died at 26 weeks' gestation. A literature review is presented of 17 de novo and two inherited cases with only trisomy 1q. Of note is the fact that 3/5 prenatally detected 1q trisomies have teratomas. A review of the literature reveals a dismal outcome fortrisomy 1q cases if the duplication involves bands 1q25→q32. Copyright © 2001 John Wiley & Sons, Ltd.