Pierre Dechelotte

Severe Prenatal Renal Anomalies Associated with Mutations in HNF1B or PAX2 Genes

BACKGROUND AND OBJECTIVES Congenital anomalies of the kidney and urinary tract (CAKUT) are a frequent cause of renal failure in children, and their detection in utero is now common with fetal screening ultrasonography. The clinical course of CAKUT detected before birth is very heterogeneous and depends on the level of nephron reduction. The most severe forms cause life-threatening renal failure, leading to perinatal death or the need for very early renal replacement therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study reports the screening of two genes (HNF1B and PAX2) involved in monogenic syndromic CAKUT in a cohort of 103 fetuses from 91 families with very severe CAKUT that appeared isolated by fetal ultrasound examination and led to termination of pregnancy. RESULTS This study identified a disease-causing mutation in HNF1B in 12 cases from 11 families and a mutation in PAX2 in 4 unrelated cases. Various renal phenotypes were observed, but no case of bilateral agenesis was associated with HNF1B or PAX2 mutations. Autopsy identified extrarenal abnormalities not detected by ultrasonography in eight cases but confirmed the absence of extrarenal defects in eight other cases. A positive family history of renal disease was not significantly more frequent in cases with an identified mutation. Moreover, in cases with an inherited mutation, there was a great phenotypic variability regarding the severity of the renal disease within a single family. CONCLUSIONS Our results suggest that mutations in genes involved in syndromic CAKUT with Mendelian inheritance are not rare in fetal cases with severe CAKUT appearing isolated at prenatal ultrasound, a finding of clinical importance because of genetic counseling.

Pseudo-Meconium Ileus Due to Cytomegalovirus Infection: A Report of Three Cases

We observed three cases of antenatal ileus associated with cytomegalovirus (CMV) infection of the fetus and placenta. Two were detected antenatally because of increased echogenicity of the lower abdomen. In the first fetus, the ileus was associated with abnormalities of amniotic fluid enzymes but it was transient and not present at autopsy and the CMV infection was mild, without inflammatory infiltration or necrosis. In the two others, the ileus persisted and CMV-associated lesions were severe. In all three cases the virus was demonstrable in ganglion cells or within myenteric and submucosal plexuses all along the small and large intestine; ileus was imputed to CMV, which caused a paralytic ileus, and in one fetus meconium ileus was also present. A transient episode of ileus does not indicate that the fetus is free of disease and a wide range of causes must be considered, including CMV infection as well as the more usual causes such as cystic fibrosis (CF) and Hirschsprungs disease.

Hyperechoic congenital lung lesions in a non-selected population: from prenatal detection till perinatal management.

To present longitudinal observations of hyperechoic lung lesions (HLL) in a non‐selected population from the time of prenatal diagnosis by ultrasound (US) until postnatal surgery.

Meconium Ileus and Intestinal Atresia in Fetuses and Neonates

A collaborative study was performed to determine the different types and mechanisms of intestinal abnormalities during gestation. Cases had to fulfill one or more of the following three criteria: (1) meconium ileus, (2) intestinal stenosis or atresia, and (3) meconium peritonitis. Esophageal atresia, anorectal atresia, and abdominal wall defects were excluded. One hundred two cases were reviewed from the autopsies of 42 induced abortions, 22 stillborns, and the surgical findings in 38 neonates. Meconium ileus was detected mainly during the second trimester (28/38), and was associated with cystic fibrosis (15), fetal blood deglutition (4), infection (6), or multiple-abnormalities (10), in which three chromosomal aberrations were found. Intestinal stenosis or atresia was more commonly detected during the third trimester of gestation (46/56). Sixteen of the 30 duodenal malformations were associated with trisomy 21, whereas in the 26 small intestinal atresias, signs of distress or ischemia were most frequently detected. Only 8 of 25 meconium peritonitis cases were isolated. A total of 20 cystic fibrosis cases could be proved. In this series, functional abnormalities were observed predominantly in the second trimester and associated mainly with cystic fibrosis or amniotic fluid abnormalities. Anatomic lesions were commonly detected later on and associated with ischemic conditions, chromosomal aberrations, and even cystic fibrosis.

Fetal midgut volvulus as a sign for cystic fibrosis.

M. Durand1, K. Coste2,3, A. Martin1, T. Scheye2, I. Creveaux4,3, P. Vanlieferinghen2, H. Laurichesse-Delmas1,3, P. J. Dechelotte5,3, A. Labbe2,3, B. Jacquetin1, D. Lemery1,3 and D. Gallot1,3* 1Maternal Fetal Medicine Unit, CHU Clermont-Ferrand, France 2Department of Pediatrics, CHU Clermont-Ferrand, France 3GReD CNRS UMR6247, Clermont Université, France 4Laboratory of Molecular Biology, CHU Clermont-Ferrand, France 5Laboratory of Pathology, CHU Clermont-Ferrand, France

Prenatal diagnosis of lobar bronchial atresia

We report three cases of fetal lobar bronchial atresia referred to our Fetal Medicine Center during the mid‐trimester of pregnancy over the last 15 years. Lobar bronchial atresia can mimic a main stem bronchial atresia on mid‐trimester ultrasound examination as it induces extensive lobar enlargement, major mediastinal shift and eversion of the diaphragm. It was associated with severe pulmonary hypoplasia in all three cases, even though polyhydramnios and ascites were absent in two. Termination of pregnancy was performed at parental request after extensive counseling in each of the cases and necropsy confirmed one or two enlarged lung lobes leading to major compression of the remaining lobe(s) of the ipsilateral lung, the contralateral lung and the heart. No other anomalies were observed and the karyotype was normal in all cases. Copyright

Renal tubular dysgenesis-like lesions and hypocalvaria. Report of two cases involving indomethacin.

We describe a case of twins with twin-to-twin transfusion syndrome (TTS) who were found to have renal tubular dysgenesis (TRD)-like lesions and hypocalvaria attributed to indomethacin treatment of the mother for acute polyhydramnios. History of pregnancy, postnatal clinical course, pathological findings of the kidneys, and the skulls are presented and discussed. These findings include incompletely differentiated proximal tubules in the kidneys and hypoplastic calvaria in both twins. The renal tubular lesions were more marked in the donor than in the transfused twin, probably due to the greater degree of ischemia in that twin. This seems to be in favor of a vascular etiology of the renal defects. However, the fact that similar renal lesions and hypocalvaria were also present in the transfused twin seems to indicate that indomethacin played a role in their onset. This so-called kidney-skull connection has never been reported in conjunction with indomethacin therapy.

Recurrent congenital pulmonary lymphangiectasia

using real-time three-dimensional echocardiography and a novel ‘sweep volume’ acquisition technique. Ultrasound Obstet Gynecol 2005; 25: 435–443. 10. Goncalves LF, Espinoza J, Kusanovic JP, Lee W, Nien JK, Santolaya-Forgas J, Mari G, Treadwell MC, Romero R. Applications of 2-dimensional matrix array for 3and 4-dimensional examination of the fetus: a pictorial essay. J Ultrasound Med 2006; 25: 745–755.

Fraser syndrome: Features suggestive of prenatal diagnosis in a review of 38 cases.

Fraser syndrome (FS) is a rare malformation recessive disorder. Major criteria are cryptophtalmos, syndactyly, respiratory, genital and urinary tract anomalies. Few prenatal presentations have been reported.

P009: Corpus callosum or not corpus callosum? Lobar holoprosencephaly associated with a mimicking corpus callosum: value of “the anterior cerebral artery crawling under the skull”

underwent detailed anatomy scan, multiplanar magnetic resonance examination, fetal echocardiography and karyotyping. Results: Among a total number of 29 cases of US isolated borderline ventriculomegaly at the first presentation, we identified three cases in which a further US examination disclosed an enlargement of subarachnoid spaces. The mean gestational age at the time of diagnosis was 26 weeks (range 21–32 weeks). All cases showed mild ventricular dilatation at the level of the atrium (12 mm in two cases and 11 mm in the third case), with bilateral enlargement of the subarachnoid spaces, predominantly in the parieto-occipital areas. MRI did not show abnormal signal within brain parenchyma or loss of normal layering of the developing brain. All cases demonstrated benign external hydrocephalus postnatally. No karyotypic and/or cardiac abnormalities were present. Conclusion: Fetal borderline ventricular dilatation and prominent subarachnoid spaces in posterior distribution can be considered an early stage of benign external hydrocephalus that is well depicted by prenatal MRI.