Prenatal ultrasonographic diagnosis of congenital megalourethra

Congenital megalourethra is a rare genital anomaly characterized by dilatation of the penile urethra without evidence of distal obstruction. Reports of the prenatal diagnosis of this condition in the literature are limited. We present a case of congenital megalourethra with obstructive uropathy from the posterior urethra diagnosed prenatally at 18 weeks of gestation. ‘Prune-belly’-like features, colonic malrotation, and imperforate anus were also found on autopsy.     

Anatomic correlates of ultrasonographic prenatal diagnosis

In utero sonographic diagnoses from forty-five malformed infants were correlated with their autopsy findings. Fifty-two malformations were diagnosed prenatally in 42 of the patients but 90 additional malformations were not. Nine sonographically diagnosed abnormalities were not confirmed at autopsy. Factors compromising sonographic diagnosis included: limited examinations, small fetal size, timing of examination, oligohydramnios, fetal position, nature of the malformation and unfamiliarity of the ultrasonographer with specific malformation syndromes. In vitro ultrasonography is an invaluable tool of diagnosing congenital malformations but has limitations.     

Apert syndrome: what prenatal radiographic findings should prompt its consideration?

Apert syndrome was diagnosed in a newborn with typical facial and digital features whose only detected prenatal abnormality had been agenesis of the corpus callosum. This prompted a review of the central nervous system findings in all cases of Apert syndrome treated at the Craniofacial Center Boston Children's Hospital between 1978 and 2004. Two of 30 patients with Apert syndrome had prenatal identification of mild dilatation of the lateral cerebral ventricles and complete agenesis of the corpus callosum (ACC) documented with both ultrasound and MRI. Both had the common S252W mutation of FGFR2. Though cranial and orbital malformations typical of Apert were eventually seen in these fetuses in the third-trimester, even in retrospect, these were not detectable at mid second-trimester, ultrasound screening for congenital malformations. Hand malformations also went undetected in the second-trimester despite extensive imaging by experienced radiologists. We conclude that prenatal ultrasonographic identification of mild ventriculomegaly or ACC should stimulate a careful search for features of Apert syndrome and prompt follow-up imaging to look for bony abnormalities that have later onset. Prenatal molecular testing for Apert mutations should be considered in cases of mild ventriculomegaly and ACC. Copyright © 2006 John Wiley & Sons, Ltd.     

The prenatal diagnosis of the Walker-Warburg Syndrome

On the basis of physical features and autopsy findings, a child with congenital hydrocephalus, bilateral microphthalmia, myopathy, severe developmental retardation and multiple brain malformations was diagnosed to have the Walker-Warburg Syndrome (WWS). During a subsequent pregnancy in this family, a fetus at risk for this autosomal recessive condition was evaluated with serial ultrasound examinations. At 15 weeks of gestation an encephalo-cele was noted. Disproportionately slow growth of the head compared to the body was noted at 36 weeks. At birth, the diagnosis of WWS was confirmed in the child due to the presence of microcephaly, an encephalocele, a meningocele and bilateral microphthalmia. This is the first reported case of the early prenatal diagnosis of this recently categorized genetic condition, in which the major features are hydrocephalus, multiple central nervous system malformations, microphthalmia with ocular malformations, severe psychomotor retardation, congenital myopathy and a very limited life expectancy.     

Prenatal diagnosis of Fanconi anemia (Group C) subsequent to abnormal sonographic findings

Manifestations of Fanconi Anemia Complementation Group C (FA-C) include multiple major congenital malformations, hypoplastic radius, absent thumb, growth retardation, elfin-like facial features, microphthalmia, microcephaly, café-au-lait spots, early onset of hematologic disease and poor survival (Auerbach, 1997). We describe two cases in which second-trimester sonographic findings led to parental carrier testing for FA-C and subsequent prenatal diagnosis of affected fetuses. Copyright © 2005 John Wiley & Sons, Ltd.     

Nature and frequency of chromosomal abnormalities in pregnancies with abnormal ultrasound findings: An analysis of 117 cases with review of the literature

During a 7-year period, 117 fetal karyotypes were available from 131 genetic amniocenteses. These procedures were performed between 14 and 37 weeks' gestation for the following abnormal ultrasound findings: (1) intrauterine growth retardation (IUGR)—61 cases; (2) fetal malformation—71 cases; and (3) amniotic fluid volume (AFV) abnormality—60 cases. Chromosomal abnormalities were identified in 19 cases (16.2 per cent). Aneuploidy was 2.5 times as frequent in the presence of malformations than in their absence. No correlation was demonstrated between specific fetal malformations and specific chromosomal abnormalities. Aneuploidy was also twice as frequent in the presence of symmetrical IUGR than in its absence. No chromosomal abnormalities were found among eight cases of asymmetrical IUGR. Four cases of aneuploidy presented with isolated IUGR, three of these involving the X chromosome. The frequency of aneuploidy was the same with or without abnormalities of AFV (14.3 versus 16.4 per cent). No chromosomal abnormality was found associated with isolated AFV abnormalities.     

The value of sonographic diagnosis of fetal malformations: Different results between indication-based and screening-based investigations

The advantages of a routine screening or indication-based ultrasound investigation during pregnancy are still under debate. This is the first study where both methods are compared in two different time periods. More malformations were diagnosed before the 24th week of gestation by means of screening-based than indication-based investigation (18 per cent vs. 5 per cent, P<0·005), and before 28 weeks in 26 per cent compared with 15 per cent respectively (P<0·01). Twenty-six per cent of all malformations were detected by means of screening-based investigations as opposed to 15 per cent by means of indication-based scans. Primary fetal malformations were also diagnosed much earlier (25 weeks vs. 30 weeks). Except for the fetal head, the detection rate of malformations was higher in nearly all other body regions of the fetus in the screening-based investigation. The most important advantage of a screening-based ultrasound investigation during pregnancy is to detect the malformations early enough in pregnancy for possible intrauterine treatment or to offer safe termination of pregnancy for the woman, at least for those anomalies that are lethal or significantly handicapping.     

Prenatal molecular diagnosis in RASA1-related disease

RASA1-related disease is a rare autosomal dominant disease characterized by capillary malformations, arteriovenous malformations (AVMs), and/or arteriovenous fistulas (AFVs). Penetrance is nearly complete and vascular malformations may cause serious complications such as organ injury due to oxygenation disorder, brain abscess, hemorrhage, and stroke. Early diagnosis is useful in order to discuss optimal management, including AVMs/AVFs embolization or surgical procedures, and try to prevent some of the complications. In this context, molecular testing of RASA1 gene mutation in relatives may help to better manage the family. All arteriovenous malformations are however not accessible to such procedures. In addition, these therapeutic procedures may result in potential side effects and complications. A couple was referred to our genetics unit and asked us for prenatal genetic testing about a RASA1 mutation. Here, we discuss about arguments that led our team to accept prenatal testing. To the best of our knowledge, no molecular prenatal diagnosis was reported until now in RASA1-related diseases. This first report of prenatal diagnosis in RASA1-related diseases may also offer perspectives for a more general discussion in the field of inherited arteriovenous malformations.     

Neural tube defects in the sample of genetic counselling

Objective This study was conducted to evaluate the major demographic details, diagnostical and clinical features, as well as the risk of recurrence of cases with the major types of neural tube defects (NTD). We also examined the efficiency of ultrasonography based on autopsy examinations during 26 years. Methods The investigations were made into the sample of 743 NTD diagnosed between 1 January 1976 and 31 December 2002. A computerized database was used to sum up the available information about the individual cases; in addition to surveying the couples' major demographic details, we also had the opportunity to collect detailed information about the history, diagnostics (ultrasound) and outcome of the pregnancies as well as the results of the autopsies during the investigation. Results In the 743 cases of NTD, maternal and paternal median ages turned out to be 23.7 years (±5.22 years) and 28.7 years (±5.81 years), respectively. The male:female ratio was 0.78. Comparable samples of anencephaly and spina bifida allowed for the conclusion that a positive genetic history was equally often found while a positive obstetrical history was almost twice as common in anencephaly. The sensitivity of the maternal serum-alpha fetoprotein (AFP) screening test is the highest in anencephaly and lowest in encephalocele. While the majority of cases of anencephaly were diagnosed before the 24th gestational week, examples of diagnosing spina bifida and encephalocele at a later time could also be found. Among the associated malformations other than those of the central nervous system special mentioning should be made of fetal pyelectasia, cleft palate as well as diaphragmatic herniation. No pathological karyotypes were found in association with encephalocele or spina bifida, but anencephaly was accompanied with trisomy 21 and trisomy 18 in one case each. Anencephaly was found to have the highest risk of recurrence in both nervous system malformations and malformations other than those of the nervous system. Sonography proved to be the most reliable method in cases of enecephalocele. Conclusion The respective median values of maternal and paternal age show that aetas has no role in the occurrence of NTDs. NTDs are more common among girls. Positive genetic, obstetrical and medical findings are of great importance in the incidence of NTDs. Although reliable to only a limited extent, maternal serum-AFP tests are considered to be useful and necessary in screening NTDs, while sonography is the gold standard method in recognizing these frequent malformations. The knowledge of the eventual associated malformations is mainly important in certain cases of spina bifida, which may also yield a good post-natal prognosis. Our data obtained from the sample of 26 years also confirm that the periconceptional administration of folic acid reduces the incidence and risk of recurrence of NTDs. Copyright © 2007 John Wiley & Sons, Ltd.     

Prenatal diagnosis in three cases of iniencephaly with unusual postmortem findings

Iniencephaly is a rare and lethal congenital malformation of the neural tube characterized by occipital bone defect, cervical dysraphism, fixed retroflexion of the fetal head and severe lordosis of the cervicothoracic spine. The etiology is unknown. Prenatally diagnosed cases of iniencephaly are rare because careful and early ultrasonographic evaluation is necessary. We present three cases of iniencephaly prenatally diagnosed by sonography at 20–22 weeks' gestation in which therapeutic abortion was induced. The sonographic findings were compatible with the postmortem findings. The present cases of iniencephaly were found to carry unusual associated malformations such as two lobes in the right lung and chorangiosis of the placenta. Only hypoplastic lungs have been reported by previous authors. We also studied the 677C→T mutation on the methylenetetrahydrofolate reductase gene in the parents in one of the present cases. The mother was found to be heterozygous for the 677CT polymorphism. Copyright © 2001 John Wiley & Sons, Ltd.     

Potter's syndrome in the second trimester—prenatal screening and pathological findings in 60 cases of oligohydramnios sequence

Fifty-two second-trimester and eight third-trimester (>28/40) autopsies with clinical or pathological evidence of oligohydramnios sequence (“Potter's syndrome”) were reviewed. Twenty-eight cases had renal anomalies (71 per cent in terminations following prenatal ultrasound), 27 had no renal malformation (35 per cent with chorioamnionitis), and five had external assessments only. In 15 cases, the renal lesion was part of a multiple malformation syndrome. Seven cases had a lesion which either recurred in a sibling in the same family or was a recognized autosomal recessive syndrome. Three cases had an abnormal karyotype, two of which had renal anomalies. Maternal serum alpha-fetoprotein (AFP) did not discriminate between cases with renal malformations and those without. Pulmonary hypoplasia was commoner in third-trimester than in second-trimester cases. External appearance and absent umbilical artery were not reliable predictors of underlying internal anomalies. These findings reflect the shift from postnatal to prenatal diagnosis in modern practice. In this series, mainly second-trimester cases, 50 per cent of cases had no malformations, in a condition which is traditionally associated with renal disease. The high incidence of chorioamnionitis suggests that the mechanism of oligohydramnios is occult amniotic fluid leakage. Prenatal diagnosis of oligohydramnios in the second trimester is dependent on ultrasound scanning and a full post-mortem examination is necessary to identify any underlying fetal cause.     

A case report of prenatally diagnosed ophthalmo-acromelic syndrome type Waardenburg

Ophthalmo-acromelic syndrome type Waardenburg is an extremely rare autosomal recessive syndrome comprising eye malformations ranging from true anophthalmia to mild microphthalmia with acromelic malformations. We report a case of ophthalmo-acromelic syndrome type Waardenburg diagnosed prenatally. Copyright © 2002 John Wiley & Sons, Ltd.     

Antenatal thrombocytopenia in three patients with TAR (thrombocytopenia with absent radii) syndrome

Three fetuses with TAR (thrombocytopenia with absent radii) or TAR variant syndrome were found to be thrombocytopenic during the third trimester of the pregnancy. These findings indicate that fetal blood sampling, besides ultrasonography, skeletal radiographs, or even fetoscopy, may indeed contribute to the prenatal diagnosis of TAR syndrome, and thus may help in differentiating TAR syndrome from other syndromes with malformations of the upper limbs.     

Prenatal diagnosis of complete trisomy 19q

This communication presents the first case of complete trisomy 19q, prenatally detected by ultrasound investigation. Real-time high-resolution ultrasound examination was performed at 19 weeks of gestation. After termination of the pregnancy, autopsy investigation was done. GTG-banding, fluorescence in situ hybridization m-(FISH) analysis, and FISH analysis with a 19q subtelomeric specific probe were used for identification of the fetal karyotype. Sonographic examination revealed an enlarged cisterna magna, cerebellar hypoplasia and aplasia of the inferior part of the vermis, combined and bilateral kidney malformations, significant nuchal fold, absence of fetal nasal bones, and intracardial calcifications. Autopsy confirmed ultrasound findings, but also revealed situs viscerum inversus of the lungs. Fetal karyotype was defined as: 46,XY,der(21)t(19;21)(q11;p13)mat. Our ultrasound and autopsy findings will certainly contribute to better knowledge of phenotype characterization of this rare chromosomal disorder. Copyright © 2007 John Wiley & Sons, Ltd.     

Cornelia de Lange Syndrome in association with a balanced reciprocal translocation involving chromosomes 3 and 5

We present a case report on a fetus with multiple malformations, diagnosed by ultrasound at 20 weeks' gestation. From the combination of intrauterine growth retardation and limb abnormalities that were observed, the most likely diagnosis was considered to be Cornelia de Lange Syndrome (CdLS). Following counselling, the mother opted to terminate the pregnancy. Chromosome analysis of cultured amniotic fluid cells showed a karyotype of 46,XX,t(3;5)(q21;p13). Postmortem examination of the baby confirmed the presence of features consistent with a diagnosis of CdLS. This case provides a report of a definitive diagnosis of Cornelia de Lange Syndrome, suspected on the basis of ultrasound imaging and confirmed by amniocentesis findings. Copyright © 2005 John Wiley & Sons, Ltd.     

Unusual case of a fetus with congenital cystic adenomatoid malformation of the lung associated with trisomy 13

Congenital cystic adenomatoid malformation of the lung can be detected with antenatal ultrasound as hyperechogenic areas in the fetal chest. Associated extrapulmonary malformations as well as chromosomal aberrations are described as very rare. We present a case report of a fetus in the 23rd week of gestation who showed in the course of a routine ultrasound screening a large number of malformations: holoprosencephaly, arrhinencephaly, cleft palate, CCAM type III of the right inferior pulmonary lobe, ventricular septal defect and bilateral clubfeet. Chromosome analysis confirmed the suspicion of trisomy 13. The present case shows how important it is—even with malformations that are rarely accompanied by associated anomalies and which have a very good prognosis—to carry out a directed diagnosis including a fetal karyotyping. Copyright © 2003 John Wiley & Sons, Ltd.     

Monosomy 8q: Prenatal diagnosis and autopsy findings

The autopsy findings of a fetus with deletion of the long arm of chromosome 8 are described. Many of the features are similar to those of the tricho-rhino-phalangeal syndromes, types I and II, which are associated with deletions on chromosome 8q24. Other findings in this case, such as total absence of the corpus callosum and intestinal malrotation, have not been described in these syndromes. Genes involved in the development of the latter malformations may reside in adjacent regions on the long arm of chromosome 8. An elevated serum level of beta human chorionic gonadotropin (βhCG) was found during pregnancy. This aberration should be included with other chromosomal disorders which may be detected by this test.     

Disorders of prosencephalic development

Abnormal ventral induction may result in disorders of formation, cleavage, and midline development of prosencephalic structures. Holoprosencephaly is a developmental field defect of impaired cleavage of prosencephalon. The most widely accepted classification of holoprosencephaly recognizes three major varieties: the alobar, semilobar and lobar types, according to the severity of the malformation. The brain malformations, characterized by the fusion of the cerebral hemisphere along the midline are commonly associated with facial anomalies. Corpus callosum agenesis and septo-optic dysplasia are disorders of prosencephalic midline development, and usually have less severe presentations but still, affected subjects may suffer from neurodevelopmental retardation, and/or endocrinologic and visual disorders. In this article we report an up-to-date of pathogenesis, prenatal sonographic findings, differential diagnosis and prognosis of the aforementioned anomalies. Copyright © 2009 John Wiley & Sons, Ltd.     

Prenatal sonographic diagnosis of Malpuech syndrome

Malpuech syndrome (MS) is a rare autosomal recessive syndrome featuring pre- and post-natal growth deficiency, mental retardation, facial dysmorphism, cleft lip and palate (typically midline or bilateral), caudal appendage, renal malformations and male genital abnormalities. A prenatal diagnosis of MS was made in this fetus based on the family history and a combination of conventional and 3D prenatal ultrasound findings. The family were consanguineous with an affected first child. Prenatal ultrasound in the second pregnancy demonstrated bilateral cleft lip and palate in association with intrauterine growth retardation on serial prenatal ultrasound scans. Dysmorphic facial features and a small penis consistent with the diagnosis were confirmed on 3D scanning. Post-natal examination of the neonate confirmed the diagnosis of MS. To the best of our knowledge, this is the first prenatal diagnosis of this syndrome. Copyright © 2006 John Wiley & Sons, Ltd.     

The significance of fetal ventriculomegaly: etiology,short- and long-term outcomes

Fetal cerebral ventriculomegaly (VM) is diagnosed when the width of one or both ventricles, measured at the level of the glomus of the choroid plexus (atrium), is ≥ 10 mm. VM can result from different processes: abnormal turnover of the cerebrospinal fluid (CSF), neuronal migration disorders, and destructive processes. In a high percentage of cases, it is associated with structural malformations of the central nervous system (CNS), but also of other organs and systems. The rate of associated malformations is higher (≥60%) in severe VM (>15 mm) and lower (10–50%) in cases of borderline VM (10–15 mm). When malformations are not present, aneuploidies are found in 3–15% of borderline VM; the percentage is lower in severe VM. The neurodevelopmental outcome of isolated VM is normal in > 90% of cases if the measurement of ventricular width is between 10 and 12 mm; it is less favorable when the measurement is > 12 mm. Copyright © 2009 John Wiley & Sons, Ltd.