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.     

A rare case of isolated right atrial enlargement and TBX5 mutation associated with Holt–Oram syndrome

Holt–Oram syndrome or atriodigital dysplasia is commonly associated with cardiac malformations, most often with defects of the muscular septum. We describe the case of a fetus referred for fetal cardiology evaluation in the setting of right atrial enlargement without tricuspid valve abnormalities with small muscular VSDs, and without other significant cardiac lesions. On serial fetal echocardiograms, isolated right atrial enlargement was persistent as was relative fetal bradycardia without apparent AV block or other signs of abnormal conduction. Limb or other anatomic abnormalities were also not visualized on prenatal scans. A postnatal diagnosis of Holt–Oram Syndrome was made. In the setting of isolated right atrial enlargement, we suggest a comprehensive sonographic search for upper limb abnormalities as well as genetic evaluation.     

Familial orofaciodigital syndrome type I revealed by ultrasound prenatal diagnosis of porencephaly

Porencephaly is a rare central nervous system (CNS) abnormality that can be caused by an intraparenchymal destructive process or a developmental defect. Here we report on a prenatal ultrasound diagnosis of complex CNS abnormalities including agenesis of the corpus callosum, agenesis of the cerebellar vermis, bilateral hydrocephaly, and bilateral porencephaly in fetus at 33 weeks' gestation. The diagnosis of familial orofaciodigital syndrome type I (OFD I) was raised after fetal autopsy, clinical examination of the family, and the X-linked dominant inheritance pattern. This is the fourth report of porencephaly in association with OFD I. We discuss the difficulties in genetic counselling since OFD I shows variable expressivity of the phenotypic features. Furthermore, we emphasize the importance of a detailed ultrasound examination after a prenatal diagnosis of porencephaly. Copyright © 2001 John Wiley & Sons, Ltd.     

Trisomy 5 mosaicism detected prenatally with an affected liveborn

This paper reports a case of chromosomal mosaicism for trisomy 5 recovered from amniotic fluid cells and from skin fibroblasts of a liveborn dysmorphic male. Routine amniocentesis was performed at 16 weeks' gestation because of parental concern. Trisomy 5 cells were measured from 25 per cent of amniocytes from two culture vessels. No further invasive testing was performed until 32 weeks' gestation, at which time ultrasound examination showed fetus with intrauterine growth retardation. Fetal blood sampling was then performed, with only karyotypically normal cells recovered. At birth, the child was found to have multiple dysmorphic features and congenital anomalies, including an eventration of the diaphragm and ventricular septal defect, both of which required surgical correction. Chromosomal analysis of cord blood lymphocytes indicated 46,XY; however, 20 per cent of the cultured fibroblasts obtained from the chest skin at the incision site for diaphragmatic repair had a 47,XY,+5 karyotype. Trisomy 5 mosaicism may be another example of tissue-limited mosaicism. Fetal blood sampling can then be falsely reassuring. Furthermore, because some cell lines rarely appear in lymphocyte populations, cytogenetic analysis of multiple tissues warranted as part of the evaluation of individuals with developmental delay and dysmorphic features.     

Del(18p) syndrome with increased nuchal translucency in prenatal diagnosis

We report a de novo translocation between chromosome 15 and 18 resulting in monosomy 18p in prenatal diagnosis. The patient was referred for amniocentesis due to increased nuchal translucency (INT) (5 mm) at 13.6 weeks of gestation. Karyotype of the fetus revealed 45,XX,der(15;18)(q10;q10) in all metaphases. The targeted fetal ultrasound at 20 weeks of gestation did not show any special physical abnormalities other than 6.4 mm of nuchal fold thickness. Molecular cytogenetic findings using CGH and FISH confirmed the del(18p) with dicentromeres from both chromosome 15 and 18. The present study shows that the INT at first trimester was the only prenatal finding for the fetus with del(18p) syndrome and that molecular cytogenetic methods are useful for detecting chromosomal aberrations precisely. Copyright © 2004 John Wiley & Sons, Ltd.     

Amniotic band disruption syndrome associated with elevated amniotic AFP and normal acetylcholinesterase gel test

Ultrasonography in an 18 week pregnancy selected for detailed scanning because of a single elevated maternal serum AFP result suggested the presence of anencephaly. Amniocentesis at 19 weeks yielded a clear AF with an elevated AFP result (5.4 MOM) and no evidence of an acetylcholinesterase band of neural origin on PAG electrophoresis. At termination, the fetus had cephalo-amniotic fusion and multiple abnormalities including bilateral cleft lip and palate and digital amputations characteristic of the amniotic band syndrome. The cranial defect was completely sealed by attachment of the amniotic surface of the placenta to the skull.     

Prenatal findings on ultrasound and X-ray in a case of overgrowth syndrome associated with increased nuchal translucency

A case of prenatal diagnosis of an overgrowth syndrome at 30 weeks of gestation is reported. The diagnosis was suggested on the basis of increased fetal growth from 16 weeks onwards, advanced bone age, and characteristic facial features such as hypertelorism, broad forehead and small chin. The fetus presented at 12 weeks with a markedly increased nuchal translucency thickness and generalized skin edema, but normal karyotype. Serial ultrasound scans revealed brain abnormalities including mild unilateral ventriculomegaly and a cyst in the cavum septi pellucidi. The pregnancy was terminated at the parents' request at 32 weeks of gestation and postmortem examination confirmed the prenatal findings. This case demonstrates the possibility of prenatal diagnosis of early overgrowth syndromes and highlights the dilemma arising from the prenatal diagnosis of a non-lethal condition associated with an uncertain prognosis and poorly documented in utero. Copyright © 2001 John Wiley & Sons, Ltd.     

Maternally inherited autosomal dominant PLAG-1 related Silver Russell syndrome in a fetus with intra-uterine growth restriction

We report a case of maternally inherited autosomal dominant PLAG-1 related Silver Russell syndrome (SRS) in a fetus with IUGR and a mother who had growth and feeding problems in early life, dextrocardia and an atrio-ventricular septal defect. Amniocentesis was performed due to marked intra-uterine growth restriction (IUGR). The array was normal. Whole exome sequencing (WES) revealed a maternally inherited heterozygous likely pathogenic variant in PLAG1 (NM_002655.3): c.402delT p.(Gly135Aspfs*94). This variant has not been reported previously. PLAG1 pathogenic variants are associated with autosomal dominant Silver Russell syndrome, which fits with the clinical phenotypes of both fetus and mother. PLAG1 variants have previously been reported post-natally in Silver Russell syndrome, but the phenotype tends to be milder than in 11p15.5 methylation-related cases with fewer physical features. Although cardiac anomalies are uncommon in SRS, they have been previously reported. To our knowledge, dextrocardia has not been previously associated with SRS and there were no other potential causative genetic variants found. This report aims to highlight this rare type of SRS as a cause of IUGR.     

Prenatal echocardiographic diagnosis of right atrial isomerism

A prenatal diagnosis of right atrial isomerism is often inferred through the recognition of a constellation of cardiac anomalies on the four-chamber view or by the detection of visceral heterotaxy and asplenia. However, the actual occurrence of discordance between the arrangement of the atria and thoracic and abdominal organs makes the identification of the morphology of both atrial appendages the only reliable way to make a final diagnosis of atrial isomerism. Three cases of right atrial isomerism with visceral heterotaxy and a complex cardiac defect, diagnosed in utero by cross-sectional and colour flow Doppler echocardiography, are reported. In all the patients, the right atrial isomerism was associated with an atrioventricular septal defect, a single aortic outlet from the right ventricle, and total anomalous venous return. The diagnosis of right atrial isomerism, always confirmed by neonatal re-evaluation and/or by post-mortem examination, was made through identifying two pyramidal atrial appendages in an echocardiographic transverse plane at the level of the atria and of the origin of the great arteries. This report demonstrates that a final intrauterine diagnosis of atrial isomerism is possible, whatever the visceral situs is.     

Early prenatal diagnosis of short rib-polydactyly (SRP) syndrome type I (Majewski) by ultrasound in a case at risk

Short rib-polydactyly (SRP) syndrome Type I was diagnosed accurately in an at-risk fetus at 16 weeks of gestation by real-time sonography. The most important findings were a narrow thorax, significant shortening of the long bones, particularly the tibiae, and–by directed search–the polydactyly.     

The early prenatal sonographic diagnosis of renal agenesis: Techniques and possible pitfalls

Out of 13 252 cases in which fetal bilateral echogenic kidneys were detected by transvaginal sonography between 12 and 18 weeks' gestation, there were nine fetuses where oval hypoechogenic masses were detected in the renal bed. In five fetuses where hypoechogenic masses in the renal bed were sonographically visualized, postabortal examination was compatible with renal agenesis and the hypoechogenic masses proved to be enlarged adrenals. In three additional cases, unilateral renal agenesis was accompanied by unilateral enlarged adrenals, radiologically confirmed postnatally. In one case, a false-positive sonographic diagnosis of Potter syndrome was made because of bilateral hypoechogenic masses in the renal bed. Postabortal examination detected hypoplastic kidneys, but of normal histology, in a dyskaryotic fetus with trisomy 22. In four cases of renal agenesis, the amniotic fluid was of normal volume until the 17th week. In two of the five cases of Potter syndrome, a cystic structure, compatible with the urinary bladder, was detected in the pelvis at 14 weeks. The diagnostic criteria for renal agenesis in the early fetus differ from those used in the second half of gestation.     

Early sonographic diagnosis of body stalk anomaly

Ultrasonographic features of a fetus at 18 weeks of gestation suggesting a body stalk anomaly are presented. These included a large abdominal anterior wall defect in apparent continuity with the placenta, severe kyphoscoliosis of the lower spine, the absence of one kidney, and a very short umbilical cord with only one umbilical artery. The amniotic fluid was reduced and the fetus was almost immobile at short-interval ultrasound examinations. The pregnancy was terminated and autopsy of the fetus showed abnormalities compatible with maldevelopment of both cephalic and caudal embryonic folds.     

First-trimester prenatal diagnosis of osteogenesis imperfecta type II by DNA analysis and sonography

Osteogenesis imperfecta type II was diagnosed prenatally by analysis of DNA obtained from chorionic villus sampling (CVS) performed at 12 weeks of gestation in a woman who previously had had an affected child. The father had been shown to be mosaic for a mutation in the gene (COL1A2) which encodes the α2(I) chain of type I collagen. An affected fetus was predicted by detection of the mutation in amplified chorionic villus genomic DNA. Ultrasound examination at 13 weeks 4 days demonstrated femoral deformity and virtual absence of calvarial mineralization. In pregnancies at risk for osteogenesis imperfecta type II, sonographic evidence of skeletal abnormalities may be evident by 13 weeks' gestation.     

First-trimester biochemical screening for fetal chromosome abnormalities and neural tube defects

Alpha-fetoprotein (AFP), unconjugated oestriol (UE3), intact human chorionic gonado-trophin (intHCG), and the free β subunit of chorionic gonadotrophin (FβHCG) were investigated in a series of 21 chromosomally abnormal and 14 open neural tube defect pregnancies ascertained from a series of 14 000 prospectively collected maternal serum samples at 6–14 weeks' gestation. In 16 cases of Down's syndrome, significant reductions were found for AFP (0.65 multiples of the normal median) and UE3 (0.67 MOM). IntHCG levels were unaltered (0.97 MOM) but a significant increase was found for FβHCG (1.96 MOM). Significant correlations were found for AFP and UE3 in the controls and for int HCG and FβHCG in both the control and the Down's syndrome pregnancies. In a group of five trisomy 18 pregnancies, median MOMs were for AFP 0. 71 , for UE3 0. 34 , for intHCG 0. 27 , and for FβHCG 0.15. None of 13 pregnancies with open neural tube defects at 8-13 weeks gestation had elevated maternal serum AFP levels, whereas matched second-trimester samples from the same pregnancies at 16-18 weeks gestation all had significantly elevated AFP levels. Thus, biochemical screening for chromosome abnormalities may be practicable in the first trimester using free β human chorionic gonadotrophin in combination with AFP and maternal age. However, a separate screening protocol using AFP at 15-18 weeks gestation would still be required for effective detection of neural tube defects.     

Fetal bradycardia in the first trimester: an unusual presentation of atrial extrasystoles

We report a fetus with fetal bradycardia at 13 weeks of gestation secondary to atrial extrasystoles. The fetus subsequently developed paroxysmal supraventricular tachycardia and hydrops fetalis. The cardiac arrhythmia recovered spontaneously without any medical intervention. This case illustrates that atrial ectopic beats can present in the first trimester with fetal bradycardia. Rapidly evolving hydrops fetalis secondary to supraventricular tachycardia can develop, warranting close monitoring with weekly heart rate assessment. Fetal bradycardia secondary to atrial extrasystole should be differentiated from first trimester sinus bradycardia and those associated with major structural cardiac abnormality, which have a high fetal loss rate. Copyright © 2002 John Wiley & Sons, Ltd.     

Limb reduction and chorion villus sampling

Upper limb reduction was diagnosed by ultrasound scan at 17 weeks after chorion villus sampling at 9 weeks' gestation. Pregnancy was terminated and necropsy confirmed limb reduction in an otherwise normal fetus. The relationship of limb reduction to amniotic band syndrome is discussed.     

Prenatal diagnosis of septal agenesis with normal pituitary function

Septal agenesis is a rare brain malformation that is characterized by partial or complete absence of the septum pellucidum, either isolated or associated with other brain anomalies. We report a case presenting with septal agenesis and normal optic chiasm and pituitary function in a fetus at 19 weeks of gestation. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis of a fetus with androgen insensitivity syndrome (AIS)

Objective The aim of this study is to describe a fetus with androgen insensitivity syndrome diagnosed at mid-second trimester. Case and Methods Nuchal translucency was measured thick and double test was found higher. The patient referred to our center at 16^th weeks of gestation. Fetal ultrasound examination and amniocentesis was performed. Results The nuchal translucency (NT) of fetus in present pregnancy was measured approximately 10 mm at 13 weeks and Down syndrome risk was calculated 1 in 10 by double test. On ultrasound examination; thick nuchal fold (NF) and short fetal limbs were found, and the fetus was seen a female and amniocentesis was performed. Three weeks later the fetal karyotype was reported normal as 46,XY. Thereupon the fetus reexamined for 2D and 4D ultrasound, and confirmed previous findings. The fetus was terminated at 19^th weeks and seen a female phenotype. The fetal gonads removed in abdomen and testicles confirmed histopatologically. Conclusion In generally, diagnosis of AIS is most made postnatally. This is the second case in English literature, which diagnosed mid-second trimester. In this situation, the fetus with thick NT/NF and short limbs may be AIS, therefore appearance of fetal sex on ultrasound should be compared with genetic sex Copyright © 2007 John Wiley & Sons, Ltd.     

Prenatal ultrasound diagnosis of congenital heart disease associated with intrauterine growth retardation. A report of 2 cases

Two fetuses with extreme growth retardation (IUGR) of 31 and 34 weeks gestation were studied using a combination of two dimensional echocardiography (2DE), pulse wave Doppler (PWD) and differential measurement of the instantaneous vessel diameter techniques. The first fetus was diagnosed as having univentricular heart or possible double outlet right ventricle (DORV). Descending aorta blood flow was reduced as was indexing for weight. The second fetus was diagnosed as having univentricular heart with periodic bigeminal and trigeminal rhythm. Descending aorta blood flow was measured on two occasions and was reduced both times. Indexing for weight was within normal limits the first time and showed gross reduction on the second occasion prior to fetal demise. Fetal death occurred in both cases at 34 weeks gestation. Cardiovascular evaluation in fetuses with IUGR is useful as the detection of severe congenital cardiac abnormalities may substantially alter the management of these pregnancies, in particular caesarean section may be avoided when the prognosis for the fetus is considered hopeless.     

Prenatal transvaginal diagnosis of the ectrodactyly,ectodermal dysplasia,cleft palate (EEC) syndrome

Transvaginal ultrasonography performed at 14 weeks' gestation demonstrated a bilateral cleft lip and lobster-claw deformities of the hands and feet, in keeping with the diagnosis of EEC syndrome (ectrodactyly or lobster-claw deformity, ectodermal dysplasia, and cleft lip and palate). The fetus was aborted and the diagnosis of EEC syndrome was confirmed.