Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia: The diagnostic role of prenatal ultrasonography

Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is a rare congenital disease in which localized or widespread areas of skin are absent at birth. Alpha- fetoprotein (AFP) and skin biopsy have been used for prenatal diagnosis of this condition. A patient in whom normal levels of amniotic AFP at 16 weeks' gestation presumably excluded the disease and who was at risk for aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is described. However, 10 weeks later, ultrasonographic examination revealed hydramnios, a dilated stomach, a deformed external ear, and a contracted fisted hand. All signs were confirmed postnatally. The role of ultrasonography and the value of other diagnostic methods in this congenital disease are discussed.     

Prenatal diagnosis of laryngeal atresia

Prenatal diagnosis of congenital atresia of the larynx is difficult but is possible by the findings of increased lung echogenicity and size coexisting with fetal ascites in ultrasonography. Sonographic findings may not always be typical. We report on a case of congenital laryngeal atresia diagnosed prenatally by the findings of fetal hydrops and hyperechogenic lungs. Our case presented with oligohydramnios. We also review syndromes that demonstrate laryngeal anomalies. Copyright © 2003 John Wiley & Sons, Ltd.     

Amniotic fluid analysis in a fetus with laryngeal atresia

Complete laryngeal atresia is a rare congenital malformation that is known to cause hypertrophy of the fetal lung in utero. A fetus with laryngeal atresia was found to have markedly immature amniotic fluid lung maturity studies at term. Inappropriately low amniotic fluid lung maturity studies may be an important clue to the diagnosis of this condition.     

Fetal surgery for cardiac lesions

Intrauterine dilation of critical fetal aortic stenosis (AS) and pulmonary stenosis or atresia has the potential to change the natural course of these congenital heart defects preventing progression to a single ventricle circulation. This article reviews the world experience in fetal cardiac interventions. In carefully selected cases, fetal cardiac surgery can reverse end-stage heart failure and can provide biventricular outcome postnatally in about two thirds of the cases with successful interventions. Copyright © 2011 John Wiley & Sons, Ltd.     

Prenatal diagnosis of gall bladder anomalies—report of 17 cases

We describe here 17 cases of fetal gall bladder anomalies, detected as early as the 14th week of gestation, out of 10 016 fetal systemic examinations performed by us in the last 6 years (015 per cent). In seven cases, agenesis of the fetal gall bladder was detected. The diagnosis was confirmed by post-abortal examination in five cases and in two post-partum. In six other cases, a left-sided gall bladder and in one case, a ‘floating’ gall bladder were detected at 15 weeks' gestation. In two cases, a septated or bilobed gall bladder was visualized. None of these 15 cases was dyskaryotic, but in five cases, two with agenesis and three left-sided gall bladders were associated with other fetal malformations. In two other cases, the gall bladder appeared dysmorphic on sonographic examination and in both of them intrauterine growth retardation and other anomalies were detected. Trisomy 18 was diagnosed by amniocentesis in one of them. According to our experience, failure to visualize the fetal gall bladder by the 15th gestational week is diagnostic of its absence and should raise the differential diagnosis between gall bladder atresia, which has a good prognosis, and external biliary atresia, which has a poor prognosis. Further experience is needed to characterize the various gall bladder malformations and their prognosis.     

Prenatal obstruction of the ileum diagnosed by ultrasound

A case of low atresia of the ileum, diagnosed prenatally by real-time ultrasound scanning, is presented. The ultrasound examination showed progressive distension of intestinal loops, with strong peristaltic movements. The stomach was also distended, presenting as a large cystic area in the upper left abdomen. Real-time ultrasound technique is most advantageous in the diagnosis of fetal ileus. Prenatal diagnosis of fetal intestinal obstruction is of great importance, making early and safe treatment of the newborn possible.     

Syndromic encephalocele in a fetal case with a 1p35-pter deletion and a 14q32-qter duplication inherited from a maternal balanced translocation

Occipital encephalocele belongs to the family of neural tube defects, which occur in one among 2000 to 5000 live births. Syndromic encephaloceles include Meckel–Gruber syndrome and various chromosomal abnormalities. We report on a fetal case (13 WG) with bilateral cleft lip and palate, choanal atresia, occipital encephalocele, bilateral club feet, bilateral multicystic kidneys, enlarged bladder and urethral atresia. The fetal chromosome analysis showed a maternally inherited unbalanced translocation between the short arm of chromosome 1 and the long arm of chromosome 14, resulting in 1p35-pter deletion and 14q32-qter duplication (46,XY,der(1),t(1;14)(p35;q32)). Since the chromosomal breakpoints have not previously been implicated in syndromic encephalocele, this observation is of interest for the identification of other genes responsible for occipital encephalocele. Copyright © 2007 John Wiley & Sons, Ltd.     

First-trimester fetal heart block and increased nuchal translucency: an indication for early fetal echocardiography

Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-trimester fetal bradycardia may result from heart block associated with complex congenital heart disease. We report two cases detected in the first trimester of pregnancy, in which both fetuses showed an increased nuchal translucency and bradycardia. Fetal karyotype was normal in both fetuses. First-trimester fetal echocardiography was performed and, in both cases, complex congenital heart disease was diagnosed. We discuss the added role of fetal heart rate in first-trimester ultrasound screening, in fetuses with increased nuchal translucency and normal karyotype. We stress, as well, the importance of echocardiography performed in the first trimester as a potential tool for early diagnosis in selected cases. Copyright © 2005 John Wiley & Sons, Ltd.     

Increased nuchal translucency as a prenatal manifestation of congenital adrenal hyperplasia

We present two cases of pregnant women with a previous history of congenital adrenal hyperplasia. In both cases the only abnormal feature in the initial pregnancy had been increased nuchal translucency at 10–14 weeks of gestation. The fetal karyotype was normal and a diagnosis of congenital adrenal hyperplasia was made after delivery. In their current pregnancies, both fetuses also had increased nuchal translucency and normal fetal karyotype. Diagnosis of 21-hydroxylase deficiency was made prenatally by DNA analysis. These findings in four affected fetuses suggest that congenital adrenal hyperplasia should be added to the list of genetic anomalies associated with an increase in nuchal translucency. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of congenital mesoblastic nephroma in mid-second trimester by sonography and magnetic resonance imaging

Although congenital mesoblastic nephroma (CMN) is a rare benign congenital renal tumor, it is the most common solid renal tumor in the newborn period. The most common presentation of congenital mesoblastic nephroma is polyhydramnios, and only one case with prenatal fetal hydrops has been previously reported. Prenatal diagnosis of CMN has previously been made on the basis of the findings of sonography in the third trimester, and magnetic resonance imaging (MRI)–based diagnosis has been reported recently. Here we report a case of prenatally diagnosed classical type CMN diagnosed at 22 + 3 weeks of gestation based on the findings of sonography and magnetic resonance imaging. The characteristic imaging findings in this case were fetal hydrops and polyhydramnios. To our knowledge, this is the youngest reported gestational age for prenatal diagnosis of CMN and it is the second case of CMN associated with fetal hydrops detected prenatally. Copyright © 2003 John Wiley & Sons, Ltd.     

Fetal skin biopsy in prenatal diagnosis of some genodermatoses

Various methods of obtaining fetal skin for prenatal diagnosis of certain autosomal-recessive congenital genodermatoses have been assessed. An attempt was made to obtain fetal skin by fetoscopy in 15 patients prior to pregnancy termination for a variety of medical reasons at 18–26 weeks. Specimens were obtained only in five cases (8 successful attempts out of 48). In twelve cases, of which five had a history of a child with junctional (Herlitz type) or dystrophic (Hallopeau-Siemens type) epidermolysis bullosa or non-bullous congenital ichthyosiform erythroderma at 16–25 weeks of pregnancy, fetal skin was obtained without fetoscopy under direct ultrasonic control. Specimens were obtained in all cases (33 successful attempts out of 39). In three cases, fetal pathology was diagnosed by the method of semi-thin and ultra-thin skin sections, and the respective pregnancies were terminated.     

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Objective

The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging.

Methods

In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7).

Results

A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases.

Conclusions

These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making.     

The clinical impact of the first-trimester nuchal translucency between the 95th–99th percentiles

Objectives

To evaluate the clinical significance of nuchal translucency (NT) between the 95th–99th percentile in terms of typical and atypical chromosomal abnormalities (ACAs), associated fetal congenital defects and postnatal outcome.

Methods

A retrospective cohort study of fetuses with NT between the 95th–99th percentile. Data regarding the rate of associated fetal defects, genetic abnormalities and postnatal outcome were collected.

Results

A total of 306 cases of fetuses with an NT between the 95th–99th percentiles were included. The overall rate of genetic abnormalities was 12.1% (37/306). Chromosomal abnormalities were found in 10.1% (31/306) of cases and 2% were ACA (6/306). Within this group, two were pathogenic Copy Number Variants (CNVs) and four were single gene disorders. The overall rate of fetal congenital defects was 13.7% (42/306). All ACAs were found in fetuses with congenital defects. Postnatally, a new diagnosis of a single gene disorder was made in 0.85% of cases (2/236).

Conclusions

The presence of an NT between the 95th–99th percentiles carries a 10-fold increased risk of fetal defects, representing an indication for referral for a detailed fetal anatomy evaluation. The risk of ACA is mainly related to the presence of fetal defects, irrespective of the combined test risk.     

Prenatal diagnosis of extrahepatic biliary duct atresia

A rare case of extrahepatic biliary atresia was diagnosed by a combination of prenatal ultrasound and measurements of fetal digestive enzymes in amniotic fluid. Ultrasound at 15 and 18 weeks' gestation failed to detect the gall bladder, and amniotic fluid digestive enzyme values were below the fifth percentile. The patient decided to terminate the pregnancy. Post-abortal pathological examination confirmed the diagnosis. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of chromosomal abnormalities from chorionic biopsy samples: Improved success rate using a modified direct method

Several methods for fetal chromosome analysis using chorionic biopsy samples were compared. A modified direct method for culturing villi was considered to be the method of choice and details are presented of 186 pregnancies tested prenatally. The success rate in obtaining a fetal karyotype with the direct method was 93 per cent. The fetal loss rate in the prenatal series was 4.3 per cent and congenital abnormalities in the babies already born did not differ from the expected incidence.     

Prenatal diagnosis of congenital nephrosis by in utero kidney biopsy

The diagnosis of congenital nephrosis is difficult during the antepartum period. The combination of an elevated amniotic fluid alpha-fetoprotein, a negative acetylcholinesterase, and a negative ultrasound examination is highly indicative of congenital nephrosis; however, these findings can also be associated with a normal gestation. This is the first report of pathologic confirmation of congenital nephrosis from an in utero fetal kidney biopsy. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal hydrops caused by a novel pathogenic MECOM variant

We report a fetus with hydrops, congenital heart disease and bilateral radioulnar synostosis caused by a novel pathogenic MECOM variant. The female fetus was referred for post-mortem examination after fetal hydrops and intrauterine death was diagnosed at 20 weeks gestation. Post-mortem examination confirmed fetal hydrops, pallor, truncus arteriosus and bilateral radioulnar synostosis. Trio whole genome sequencing analysis detected a novel de novo heterozygous pathogenic loss-of-function variant in MECOM (NM_004991), associated with a diagnosis of Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia 2 (RUSAT-2). RUSAT-2 is a variable condition associated postnatally with bone marrow failure, radioulnar synostosis and congenital anomalies. RUSAT-2 is not currently associated with a prenatal phenotype or fetal demise, and was not present on diagnostic NHS prenatal gene panels at time of diagnosis. This case highlights the diagnostic value of detailed phenotyping with post-mortem examination, and of using a broad sequencing approach.     

Fetal therapies for cytomegalovirus: What we tell prospective parents

Congenital CMV is the most common congenital infection in the developed world. Infection results in congenital disease ranging from asymptomatic infection to severe neurodevelopmental impairment, and occasionally fetal or neonatal death. Fetal infection can occur through maternal-fetal transmission during primary maternal infection or maternal reactivation or re-infection. Awareness among maternal health care providers and parents is low. The prevention of maternal CMV infection currently relies on hygiene measures, with no effective CMV vaccine or prophylactic therapies. No licensed treatment options are available to prevent maternal-fetal transmission or fetal disease. Hyperimmunoglobulin and valaciclovir have been investigated for prevention of maternal-fetal transmission or fetal treatment, with some evidence supporting consideration of maternal administration of hyperimmunoglobulin or valaciclovir therapy in certain circumstances. This article outlines the clinical evidence regarding proven preventative behavioral measures and experimental hyperimmunoglobulin and valaciclovir therapies, that is structured around common questions asked by pregnant women about CMV infection. It is aimed to help maternity health care providers counsel prospective parents about congenital CMV disease and the preventative and therapeutic strategies currently available.     

Misdiagnosis of omphalocele associated with Edwards syndrome and congenital heart disease

We present a case in which an apparent omphalocele, diagnosed at 30 weeks gestation ultrasound, led to identification of fetal trisomy 18 and congenital heart disease. At delivery, the fetus had the features of trisomy 18 and congenital heart disease but the omphalocele was absent. We suggest that the appearances seen are easily confused with a small omphalocele and could potentially result in unnecessary further investigations being performed.