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Summary: Objectives: To assess overall and malformation-specific trends in the prevalence and prenatal diagnosis of congenital anomalies in the Parisian population. Methods: The Paris Registry of Congenital Malformations is population-based and since 1981 has registered all cases with structural birth defects or chromosomal anomalies in the Parisian population. The total and livebirth prevalence and the proportion of cases with prenatal diagnosis were calculated for all anomalies and 20 malformations selected based on their higher frequency and their impact on health outcomes. Results: The overall prevalence was 3.30% (95% CI 3.27–3.33), and the livebirth prevalence 2.42% (95% CI 2.39–2.45). The proportion of cases diagnosed prenatally increased from 16.5% (95% CI 14.1–19.1) in 1983 to 70.7% (95% CI 68.3–73.1) in 2007. Terminations of pregnancy for fetal anomaly (TOPFA) increased from 8.8% (95% CI 7.0–10.8) in 1983 to 35.6% (95% CI 33.1–38.1) in 2007. These results varied substantially for the 20 congenital anomalies studied. Conclusion: We found an increase in the overall prevalence of all anomalies, especially for chromosomal abnormalities. The observed increase is at least to a large extent due to trends in delayed childbearing and an increase in both pre- and postnatal diagnosis of congenital anomalies in our population. [Copyright &y& Elsevier]

Summary: Objectives: To review clinical and epidemiologic data of orofacial clefts and to evaluate the efficacy and the impact of prenatal diagnosis. Material and methods: A population-based retrospective study was carried out on data from the Congenital Malformations of Alsace Registry (France) between 1995 and 2006. Results: A total of 321 orofacial clefts were recorded (overall prevalence, 2.1 per 1000), divided into cleft lip (CL) or cleft lip palate (CLP) (204 cases) and cleft palate (117 cases). The cleft lip and cleft lip palate CL±P sex-ratio was 1.87, whereas the CP sex-ratio was 1. CLs were more often unilateral than CLPs (79% versus 59%). CLs were unilateral in 79% of the cases (60/76), bilateral in 20% of the cases (15/76), and median in 1% (1/76); 55% of the unilateral CLs were right and 45% were left. CLPs were unilateral in 59% of the cases (76/128), bilateral in 39% of the cases (50/128), and median in 2% (2/128); 45% of the unilateral CLPs were right and 55% were left. The 117 CPs were divided into 50 clefts of the total palate (43%) and 67 clefts of the posterior palate (57%); 25 cases (21%) of Pierre Robin sequence were collected. Sixty-six percent of CL±P (134/204) were associated with other congenital anomalies, including chromosome abnormality in 31 cases and identified monogenic syndrome or association in 12 cases. The most frequent chromosome abnormalities were 16 cases of trisomy 13 and 7 cases of trisomy 18. No cases of 22q11.2 microdeletion or duplication were detected among CL±P. Monogenic syndromes were identified in 6% (12/204) of CL±P cases: Van der Woude syndrome (2 cases); CHARGE syndrome (2 cases); ectrodactyly, ectodermal dysplasia, and cleft/lip palate (EEC) syndrome (2 cases); branchiooculofacial (BOF) syndrome (1 case); Treacher-Collins syndrome (1 case); Nager syndrome (1 case); Goldenhar syndrome (1 case); holoprosencephaly spectrum (1 case); and Meckel syndrome (1 case). Forty-two percent of CPs (49/117) were associated with other congenital anomalies; chromosome abnormality was identified in 12 cases and monogenic syndrome was diagnosed in 14 cases. The most frequent chromosome abnormality was 22q11 microdeletion (5 cases). Monogenic syndromes were recognized in 12% of the CP cases (14/117): fragile X syndrome (2 cases), Meckel syndrome (2 cases), Orofaciodigital syndrome type I (OFD1) (1 case), Stickler syndrome (1 case), Larsen syndrome (1 case), Kniest syndrome (1 case), Cornelia de Lange syndrome (1 case), thanatophoric dysplasia (1 case), other unknown bone chondrodysplasia (1 case), Fryns syndrome (1 case), fetal akinesia sequence (1 case), and Silver-Russel syndrome (1 case). Fifty-two percent of CL cases (106/204) were prenatally diagnosed. An increasing tendency was observed between the 1995–2000 and 2001–2006 periods with a detection rate increasing from 47% to 56%. During the whole period, only 1 case of CP was prenatally diagnosed. Eighty-two percent of all cases (263/321) were livebirths; 8 stillbirths were reported (2%); 50 syndromic or associated cases (16%) led to medical abortion (no termination of pregnancy was performed for isolated cleft). Conclusion: Orofacial clefts are a frequent malformation with a total prevalence of 2.1 per 1000 total births. Sonbographic prenatal diagnosis of orofacial clefts remains difficult with a mean detection rate about 50% for CL±P and is extremely rare for CP. Associated malformations and genetic syndromes are frequent and require a systematic survey. This study also highlights the different pathogenic background of CL±P compared to CP, regarding the sex-ratio and the proportion and type of associated malformations. [Copyright &y& Elsevier]

Summary: Inherited metabolic diseases are mostly due to enzyme deficiency in one of numerous metabolic pathways, leading to absence of a compound downstream from and the accumulation of a compound upstream from the deficient metabolite(s). Diseases of intoxication by proteins (aminoacidopathies, organic acidurias, urea cycle defects) and by sugars (galactosemia, fructosemia) usually do not give prenatal symptoms since mothers protect their fetuses from pathological metabolite accumulation. A well-known exception is hypoplasia of corpus callosum, as is sometimes observed in nonketotic hyperglycinemia and sulfite oxidase deficiency. Conversely, women with phenylketonuria “poison” their fetus if they are not treated (spontaneous abortions, intrauterine growth restriction [IUGR], cardiac malformations, and brain disease). Amino acid synthesis defects can lead to prenatal symptoms: microcephaly in serine deficiency (detectable by amino acid analysis in fetal cord blood), and brain malformations in glutamine synthetase deficiency. Impaired folate metabolism is involved in a large fraction of neurodevelopmental defects referred to as spina bifida, yet the underlying genetic component(s) are largely unknown. Energy metabolism diseases caused by defects in the synthesis or utilization of relevant metabolites lead to organ dysfunctions or malformations, but prenatal diagnosis is usually impossible unless genetic analysis can rely on a previously affected child in the family. A somewhat intermediate condition is defects of mitochondrial beta-oxidation of fatty acids, as they may sometimes be symptomatic prenatally (notably the HELLP syndrome or other presentations), and in this case, organic acid and acylcarnitine analysis in amniotic fluid can be informative in the absence of an index case. In contrast, complex molecule diseases commonly give prenatal symptoms that may permit the diagnosis even in the absence of index cases: hydrops fetalis and skeletal anomalies in lysosomal storage diseases, hydrops fetalis in congenital disorders of glycosylation (CDG) and transaldolase deficiency, brain malformations in O-glycosylation defects, brain malformations, kidney cysts and skeletal anomalies in peroxysomal diseases (Zellweger syndrome), syndactyly, genitalia malformations, and IUGR in Smith-Lemli-Opitz (SLO) syndrome. Although many metabolic disorders show biochemical abnormalities during fetal development that are informative for prenatal diagnosis, only a fraction of them are clinically/sonographically symptomatic before birth, thus allowing for prenatal diagnosis in the absence of an index case, i.e., serine deficiency, some fatty acid beta-oxidation defects, transaldolase deficiency, lysosomal diseases, CDG, Zellweger syndrome, and SLO syndrome. [Copyright &y& Elsevier]

Summary: Tumor predisposition in children is rare, accounting for approximately 10% of all cancers in childhood. Tumor predisposition involves very rare tumors such as pleuropulmonary blastoma, adrenocortical carcinoma, hepatoblastoma, rhabdoid tumors, optic pathway glioma, as well as rare tumors such as retinoblastoma, medulloblastoma, nephroblastoma, or more frequent tumors such as sarcomas, neuroblastoma, and leukemias. The identification of these predispositions is important for improved management for both the child and relatives. Prenatal and preimplantation genetic diagnosis are options that could be considered for young parents in a perspective of future pregnancies. This manuscript describes the main tumor predispositions in childhood. From each histological subtype, the different diagnosis directions are discussed in view of these main tumor predispositions. [ABSTRACT FROM AUTHOR]

Summary: We analyzed 16 cases of hypoplastic left heart syndrome (HLHS) submitted to the multidisciplinary center at Rennes Teaching Hospital from 2006 to 2010 for prenatal diagnosis. The information given to parents at the moment of choice is capital for them to make their own decision: in our team the real choice for parents stands between termination of pregnancy (TOP) and palliative care (PC). The Norwood procedure is rarely proposed to parents in France and it is performed in very few centers. Heart transplant is never proposed nor done at this age. The objectives of our study were to understand the reasons for the choice of PC, take stock of our experience of PC, and relate the benefits but also the disadvantages of PC. Over the 16 patients whose fetus had HLHS, 9 requested TOP, while 7 others wanted to live their pregnancy and meet their child at birth, therefore requesting neonatal PC. No family asked for the Norwood procedure. Four children died within the first days (D1, D2, D4, D9), 2 others died at 5 and 7 months, 1 child was operated on for coarctation of the aorta (unknown before birth) and is still alive 1.5 years later. Maternal motivations to continue the pregnancy were clearly described for 2 of the 7 cases: religious prohibition of TOP in 1 case, negative experiences of previous abortions in the second case. In another case, the parents hesitated between PC and Norwood surgery. For the other women, the reasons were less clearly expressed. In our series, HLHS is the first indication for PC from prenatal diagnosis (7/16 cases in the same period) while in the literature, heart diseases are the second cause of TOP after the neurological causes. The overrepresentation of this pathology in the families who opt for PC may be due to the unconscious image that both professionals and families have of HLHS: severity of an inevitably fatal disease, rapid postnatal death, and no suffering. Our study may change this view: a child was in fact carrying a curable defect which was discovered 12 days after birth, 2 children died at 5 and 7 months, and 5 of 6 children had major analgesics at the end of life. Nevertheless, the families were supported and followed by the PC network, except 1 who ruptured all contacts in a context of presumed intense suffering, but the other 6 do not regret their choice despite the difficulties. [Copyright &y& Elsevier]

Summary: The value of prenatal diagnosis of major congenital heart diseases (CHDs) has already been proved. In this study, we observed the evolution of the detection rate of CHDs and the quality of the diagnoses over a 15-year period in the Indre-et-Loire department of France. Method: Retrospective analysis of the quantitative and qualitative data of prenatal diagnosis between 2000 and 2005 (period 3) and comparison with studies conducted from 1991 to 1994 (period 1) and from 1995 to 1999 (period 2). The CHDs considered to be detectable are the major CHDs with neonatal symptoms. In order to analyze the quality of prenatal diagnosis, each diagnosis was classified as correct, false, or incomplete during period 3. Results: Period 3: 65.7% detectable CHDs were screened. Using period 1 criteria for prenatal diagnosis, the percentage of CHDs detected for periods 1, 2, and 3 was 43.2, 66.7, and 78%, respectively. Between periods 2 and 3, the detection rate increased from 52 to 74% for CHDs diagnosed with the visualization of the outflow tract. It increased from 63 to 71% for CHDs diagnosed with a four-chamber view. During period 3, diagnoses made by a pediatric cardiologist were correct and complete in 80% of cases. It was less than 25% otherwise. Conclusion: The improvement of prenatal diagnosis over time results from technological progress, the greater experience of ultrasonographers, and the systematic visualization of the outflow tract in addition to the four-chamber view. Despite the improvement in prenatal diagnosis, one-third of major CHDs were not screened before birth. Pediatricians still need to diagnose CHDs after birth. [ABSTRACT FROM AUTHOR]

Summary: Netherton syndrome is a rare autosomal recessive disorder characterized by the triad of ichthyosiform erythrodermia, typical hair dysplasia, and severe atopic features. The broad range of variable expression of this disease is well described and 20% of complications occur during the neonatal period such as hypernatremic dehydration, electrolyte imbalances, recurrent or severe infections, and failure to thrive. Mutation of the SPINK5 gene has been identified as disease-causing in Netherton syndrome, but the pathophysiology still remains unclear. Almost all SPINK5 mutations result in the absence of the serine-protease inhibitor LEKTI protein in both keratinocytes and lymphocytes. In this study, we report on a severe form of Netherton syndrome observed in three patients within a large inbred Rom family. All of them died in the first months of life despite early treatment. They were found to be homozygous for the c.1431-12G>A SPINK5 gene mutation, which has not been associated with a lethal form of the disease thus far. This family illustrates the extreme phenotype of Netherton disease of neonatal onset. Molecular diagnosis allowed further genetic counseling and prenatal testing during other pregnancies. [Copyright &y& Elsevier]

Abstract: Cystic fibrosis (CF) is a frequently fatal autosomal recessive inherited disease affecting around one in 3000 newborns in France, the carrier frequency varying from one in 20 to one in 40 subjects depending on the geographical area. The disease is caused by a chloride channel defect that is attributable to mutations in the gene that encodes the CF transmembrane conductance regulator (CFTR). Approximately, 1200 different mutations have been discovered. Among them, the F508del mutation accounts for 70% of mutated alleles worldwide. Prenatal diagnosis (PND) of inherited monogenic disorders such as CF currently relies on invasive procedures-amniocentesis, chorionic villus sampling (CVS) – which carry a significant risk of miscarriage (from 0.5 to 3%). Several methods have been proposed to enrich circulating fetal cells (CFCs) from blood and use them in PND. However, up to now, no assay has been shown to be reliable enough for routine application in place of the invasive protocols. When combined with laser microdissection, isolation by size of epithelial tumor/trophoblastic cells (ISET) allows mutation analysis of DNA from single cells demonstrated to be fetal (circulating fetal trophoblastic cells [CFTC]) by short tandem repeat (STR) genotyping and uncontaminated with maternal DNA. Application of this protocol to 12 couples at risk of having a child affected by CF has shown, in a blind study, that the new method affords a reliable and safe PND of affected fetus, healthy carrier or normal non carrier fetus. A following prospective blind study has then been performed on 32 couples at risk of having an affected child. For each mother, five or 10 CFTCs have been analyzed with an individual genetic diagnosis performed per CFTC. Results have been obtained in 240 CFTC showing that seven mothers were carrying an affected foetus, with 100% sensitivity and 100% specificity. These results open the way to a multicenter clinical validation trial and to the potential future application of the ISET non invasive approach as a reliable alternative to the invasive PND procedures. [Copyright &y& Elsevier]

Abstract: Cleft lips and palates (CLPs) are the most common human facial malformations. Depending on the ethnic and/or geographical origin of the studied populations, they can affect up to 1/500 newborns. The treatment of these patients is multidisciplinary because these malformations have not only aesthetic consequences but also functional consequences as the phonation, hearing, deglutition, mastication and ventilation are altered. These consequences can also be psychological since the building of the body image, the way others perceive it, is likely to be seriously altered. In Europe there are over 210 reference hospitals for children affected by CLP. Besides, about 190 different protocols were identified. So far no generic protocol was recognized by the medical community as a whole. This discrepancy can be explained by the fact that the aesthetic and functional result of a protocol cannot be accurately assessed before adulthood when the child''s growth is complete. Patients presenting with CLP don’t usually seem to present with any serious psychological or psychiatric pathology. Yet a close review of the related literature shows that disorders are actually described: behavioural troubles, anxiety, depression and esthetical dissatisfaction with one''s face in children as well as in adults. The difficulty in interpreting these disorders lies in the various factors that are likely to impact this condition (family setting, importance and type of the cleft, surgery protocol, growth, social environment…). A multidisciplinary examination of the face and a careful consideration of concerned families show the importance of the psychological context and the risks of a disharmonious structuring of the parents-child relationships on the child''s development. The identification of the difficulties faced by these families, depending on the child''s age, can be easily identified. Of course they can be identified at birth when the family first sees the child and later on at each stage of the child''s life cycle (when starting at kindergarten where the child socialises for the very first time, at the start of the first year in primary school where pupils learn how to read and then at the start of secondary school which is yet another crucial step for the child due to the adolescence period). It is also obvious that an adult affected by CLP has a particularly heavy medical history as the patient had to go through various treatments and surgical interventions during his childhood and adolescence, which is even sometimes maintained at adulthood. Repeated appointments with the different specialists involved in their treatment punctuate their life as well as their parents’. This medico-surgical setting for facial malformations i.e. the features of the patient''s face which are largely involved in their interpersonal relationships and the expression of emotions can have serious consequences. Most children presenting with CLPs and living in France benefit from regular follow-up schemes carried out in competent reference centres by a multidisciplinary team whose members represent each of the fields of expertise involved in the correction of this malformation: infantile and maxillofacial surgery, otorhinolaryngology (or ENT), orthophony and dentofacial orthopedics. Only the two French reference centres benefit from the permanent presence of a psychologist. This raises the question whether every care centre should take into care these children and their parents’ mental health by offering psychological support during the course of the therapeutic follow-up scheme for these children, and this from an early age on as is recommended by the American Cleft Palate Craniofacial Association. [Copyright &y& Elsevier]

Abstract: Microarray-based comparative genomic hybridization (aCGH) is becoming an efficient clinical diagnostic tool enabling genome-wide screening of segmental copy number variations (CNVs). Regarding its ability to detect segmental genomic CNVs in individuals with mental retardation, autism and multiple congenital anomalies, aCGH is gradually replacing cytogenetic methods. Using this tool as a prenatal test for foetal genomic imbalance offers the promise of detecting pathogenic gain or loss of genomic material more quickly and much more frequently than current methods. However, there is a concern about CNVs of uncertain significance (for example, predisposition to adult occurring disease with incomplete penetrance) which might lead to termination of normal pregnancies. We report in this article recent data using aCGH in foetuses from spontaneous or medically terminated pregnancies associated with multiple malformations. aCGH should be considered as a diagnostic tool to improve genetic counselling in fetopathology. We also report recent data on aCGH as a prenatal test. Larger studies with targeted arrays are mandatory to determine whether the improved overall detection rates of clinically chromosomal abnormalities will justify offering aCGH in a prenatal diagnosis setting. [Copyright &y& Elsevier]

Summary: Triploidy is one of the most common chromosomal aberrations in spontaneous abortions characterized by a 69-chromosome karyotype. This chromosome abnormality is rare in live-born children. Prevalence is lower than 1/50,000. We report on two premature newborns, male and female, born at 35 and 37 weeks of gestation, who presented with severe intrauterine growth retardation, facial dysmorphy, myelomeningocele, and syndactyly. They died during the first hours of life due to respiratory distress syndrome. Analysis of the karyotype showed a homogeneous triploidy on all mitoses: 69 XXY and 69 XXX. The parental origin of the triploidy can have specific effects in the fetal phenotype and the development of the placenta. [Copyright &y& Elsevier]

Summary: Introduction: Monochorial twin pregnancies are characterised by the presence of vascular connections between the twins. These connections can be the cause of pathologies such as the twin-twin transfusion syndrome or the TRAP syndrome, which is defined as the association of a headless, acardiac twin with a healthy twin. Case report: The case of an acardiac, headless twin diagnosed during pregnancy at 24 weeks of amenorrhea is described. Discussion: An acardiac headless twin is a rare phenomenon. Yet early diagnosis is crucial during pregnancy to provide adequate monitoring. It is associated with a high death rate in the healthy twin caused by anaemia and heart failure. Therapeutic resources involve interruption of vascular anostomoses between the twins in order to perform a selective feticide. Conclusion: Treatment of acardiac headless twin pregnancy ranges from obstetric abstentionism to interventionism, which depends on the prognosis for the healthy twin, dominated by the risk of preterm birth and heart failure. [Copyright &y& Elsevier]

Summary: The purpose of this study was to investigate the changes between 2000 and 2006 in pregnancy outcome when a diagnosis of either isolated or associated fetal corpus callosum agenesis (CCA) was made, given that beginning in 2003, the information provided to couples facing this problem related a good prognosis in nearly 80 % of cases of isolated CCA and a poor prognosis in 20 % of cases. We retrospectively analyzed all pregnancies with a fetal diagnosis of CCA between 2000 and 2006 (n =155) and compared two periods: the first group from 2000 to June 2003, the second from July 2003 to 2006. For each group, we analyzed the type of CCA during pregnancy – either isolated or associated – and the outcome of pregnancy. We compared the rate of pregnancy termination before and after 2003 and analyzed the accuracy of the prenatal CCA diagnosis. Of the 155 patients studied, 62 terminated the pregnancy. The overall rate of termination decreased from 31/70 to 31/85. When CCA was said to be isolated prenatally, the rate of pregnancy termination fell from 13/35 to 9/44 (−17 %) (p <0.05). Nine diagnoses of CCA were corrected after birth or by postmortem examination. Improvement of prenatal diagnosis requires better quality of prenatal screening, with a more systematic study of dysmorphic features, a study of correlations between the type of CCA and the neurological prognosis, and more genetic studies. [Copyright &y& Elsevier]

Summary: Routine prenatal ultrasound screening for the detection of possible cardiopathy has existed in Upper Normandy since 1987, including the continuous training of obstetric ultrasonographers. We evaluated the profitability and the expected benefit of prenatal detection in a nonselected population in this region. Methods: A retrospective study was undertaken from October 2003 to September 2007 in the cardiopediatric units of Upper Normandy. All fetuses and infants with a diagnosed major cardiac defect were classified into 3 groups: no possibility of anatomic surgical repair (group 1), risk of early decompensation (group 2), and anatomic surgical repair possible but without early decompensation (group 3). Prenatal and postnatal mortality and morbidity were reported. Results: One hundred and sixty-five major congenital heart defects were detected prenatally and 68 postnatally. The prenatal detection rate was 71% (93, 53, and 77% for groups 1, 2, and 3, respectively; p <0.0001). The rate of pregnancy termination was 92, 17, and 45%, respectively. The mortality rate tended to be higher in the undiagnosed group of urgent neonatal heart cases (10.6% vs 4.4%). The prenatal prevalence of abnormal karyotype was 21% and was 11.5% for congenital malformation syndrome. Conclusion: Prenatal detection of major cardiac defects has continued to attain high success in Upper Normandy. However, 50% of urgent neonatal heart cases often remain undiagnosed, and therefore the neonatologist must treat this patient population with particular care. Prenatal diagnosis can reduce preoperative mortality and morbidity of cardiopathy with a risk of early decompensation with specific neonatal intensive care. [Copyright &y& Elsevier]

Summary: Aim of the study: To evaluate the impact of prenatal diagnosis on the epidemiology and outcome of children with posterior urethral valves (PUV), considering that today termination of pregnancy may be proposed in the most severe cases. Patients and methods: Forty-three cases of patients with PUV were diagnosed between 1998 and 2007 in the Languedoc-Roussillon region. In this study, we detailed the prenatal data and postnatal outcome of those patients with a mean follow-up period of 7.6 years. Results: Medical interruption of pregnancy was performed in 15 severe cases. One death in utero was also observed. Twenty-seven patients were managed postnatally and one child died during the neonatal period because of lung hypoplasia. For the 26 remaining patients at the end of the follow-up period, 5 had mild renal insufficiency with a creatinine clearance calculated with the Schwartz formula of less than 80ml/min/1.73m2. One reached end-stage renal failure at the age of 7 years. Proteinuria and hypertension were rare. Discussion and conclusion: Today, because of the increase in medical termination of pregnancy in the most severe cases, most of the children born alive with PUV experienced a better renal prognosis when compared with previous data. Prenatal diagnosis and therapeutic progress significantly modified the epidemiology and outcome of this disease. Nevertheless, the best predictor of renal outcome remains renal function at 1 year of age. [Copyright &y& Elsevier]

Summary: Early diagnosis of congenital toxoplasmosis (CT) is necessary to prevent serious complications. The CT is diagnosed by the identification of the parasite in amniotic fluid during pregnancy or at birth by detection of antibodies synthesized by the fetus. The aim of this study was to determine the clinical and biological particularities of CT in a cohort of 11 cases observed in Tunisia and to evaluate the performance of the prenatal and neonatal diagnostic techniques that were used. In all patients, the presumed date of maternal contamination was determined based on the mother''s serological data. Neonatal serological screening included assays for immunoglobulins (Ig) G and IgM by enzyme-linked-immuno-sorbent assay (ELISA), IgM by immuno-sorbent-agglutination-assay (ISAGA), and comparison of the mother–baby immunological profile by western blot IgG and IgM. Seven out of the 11 cases had been diagnosed prenatally; only 3 (43%) had a positive polymerase chain reaction (PCR) test. Ten newborns out of 11 had serological criteria of fetal infection; western blot results were positive in all of them, ISAGA was positive in 2 and ELISA in none. The newborn who had a negative serology had been treated in utero. The date of positivity of the western blot test varied: 6 cases at birth, 2 at 12 days of life and 2 at 1month of life. The 2 patients who had positive ISAGA results had been contaminated during the 3rd trimester of gestation. [Copyright &y& Elsevier]

Summary: Aim: We evaluated the utility of systematic neonatal radiological explorations in 20 instances of isolated cleft lip and palate in 20 cases. Methods: This study included 13 infants with prenatal ultrasound diagnosis. The type of cleft and possible associated anomalies were noted. A systematic chromosomal test was done. In 7 cases, the cleft lip was noted at birth. Postnatal outcome was obtained and a clinical examination and radiological explorations were carried out. Results: For the cases with prenatal diagnosis, the chromosomal test was normal in 11 cases and we noted associated anomalies in three cases. For the cases with neonatal diagnosis, the chromosomal test was normal in 6 cases and 1 infant had associated anomalies. Conclusions: The biological and radiological explorations can be numerous. In our study, the systematic neonatal radiological explorations did not find more elements compared with neonatal clinical examinations. The high risk of having a chromosomal anomaly in children with cleft lip requires systematic prenatal chromosomal exploration. [Copyright &y& Elsevier]

Summary: Objective: When a baby is born deformed, his birth breaks up plans his family has made for his life as well as for the family itself. So, our objective was to describe the experience undergone by the mothers who gave birth to babies with serious deformities. Method: A prospective and descriptive study was carried out during 12 months about 35 mothers whose babies were born seriously deformed. The data were collected from newborn''s medical file and from a well-conducted interview with volunteered mothers. Results: The incidence of the major deformities was 1.4% and the antenatal diagnosis was carried out on only 6 cases. The announcement of deformities in the 30 cases discovered at birth by the clinical staff brought about a shock among mothers. In fact, 28 mothers were disappointed, while 23 experienced fear and 10 others felt guilty. Six mothers thought in terms of aborting, followed by 25 mothers who without any psychological aid felt lonely. Furthermore, 30 mothers suffered from a lack of communication with nurses and with medical staff concerning deformities. The anxiety of mothers was linked, respectively to fear of their husband (33 cases), to the social environment (35 cases) and to the health care (10 cases). Conclusion: Mothers facing congenital deformity experienced painful and violent emotional distress. Therefore, the emphasis must be put on the improvement of the neonatal diagnosis and of relationship between physicians and parents in order to achieve a close support toward mothers. [Copyright &y& Elsevier]

Abstract: Mucopolysaccharidosis type I (MPS I) is a lysosomal disease due to mutations in the gene encoding α-l-iduronidase (IDUA) leading to variable clinical phenotypes with progressive severe organomegaly, bone and neurological involvement in the most severe forms. The aim of our study was to propose in Tunisia a strategy of molecular and prenatal diagnosis of the MPS I. Population and methods: Our study was carried out on 8 MPS I patients recruited from different Tunisian regions and issued from 5 unrelated families. All the patients were offspring of consanguineous marriages. Results: The clinical and biological study led to diagnose 5 Hurler patients and 3 Hurler–Scheie patients. Three IDUA mutations were identified by molecular analysis within 6 different families: a novel mutation p.F602X and 2 already described mutations p.P533R and p.R628X. Discussion: MPS I is a heterogeneous disease characterized by variability of the phenotypes. The missense mutation p.P533R associated with the intermediate phenotype was the most frequent in the Tunisian but also in the Moroccan population. In Tunisia, the incidence of p.P533R mutation seems to be associated with the high frequency of consanguineous marriages. Conclusion: The identification of known MPS I mutations (p.P533R and p.R628X) and of the novel mutation p.F602X permits reliable genetic counselling of at-risk relatives and molecular prenatal diagnosis. [Copyright &y& Elsevier]

Abstract: The aim of this review is to focus on the nosological classification of neonatal « convulsions », to precise the underlying aetiologies and the prognosis, and to propose diagnostic and therapeutical approach. Seizures may be epileptic or not, they may be occasional, part of an epilepsy syndrome or associated to a metabolic disease. Electroencephalography plays a central role; it enables to confirm the epileptic nature of the ictal events, it allows to evaluate the prognosis and to guide the treatment decision, and sometimes may help in the etiological diagnosis. Work up should include cerebral imaging (MRI) completed by other exams according to the diagnostic hypothesis. It is essential to go as far as possible in the etiological work-up not to attribute convulsions to an occasional event as HIE in which criteria remain very strict, when convulsions could be due to genetic origin or to maternal pathology. Treatment decision should comprise different ways: treatment of the underlying cause, of the eventual associated pathologies, maintenance of vital functions and antiepileptic treatment. Phenobarbitone remains the first line drug in occasional seizures, and second line drugs for which further studies are needed both for immediate and long-term secondary effects. Besides occasional seizures epilepsy syndromes and metabolic diseases remain exceptional. Nevertheless recognition of these conditions allows to establish the prognosis and to start immediately with an appropriate and specific medication depending on the epilepsy syndrome and can contribute to a prenatal diagnosis. It is important to recognize the inborn errors of metabolism because emergency appropriate treatment is required. Prognosis which is generally bad is essentially related to the underlying aetiology and probably to the duration of the active period of seizures. [Copyright &y& Elsevier]

Abstract: Renal tubular dysgenesis (RTD) is a rare and severe nephropathy characterized by persistent fetal anuria leading to oligohydramnios with the Potter sequence, and perinatal death. The diagnosis is based on the histological finding of absence or paucity of proximal tubules. A consanguineous family is described in which 2 siblings, born after pregnancies complicated by oligohydramnios were affected with RTD. Patients were small for gestational age at birth. The first patient died after a few hours, the second after a few days of life, with persistent anuria unresponsive to treatment. Histologically, there was marked reduction in the number of proximal tubule sections and no renin was detected by immunohistochemistry. An homozygous mutation of the gene encoding renin was identified in both patients. This study underlines the interest of the histological examination of the kidney for the diagnostic of RTD in anuric fetuses and newborns, and the possibility of mutation analysis of RAS genes for genetic counselling and early prenatal diagnosis. [Copyright &y& Elsevier]

Abstract: We report on a neonatal patient case with a cerebral vascular dilation consistent with a vein of Galen malformation diagnosed on an antenatal doppler ultrasound examination. Antenatal diagnosis was confirmed by fetal MRI scan. After delivery, cerebral MRI scan found the same dilatation and showed no cerebral parenchymal damage. The infant''s condition was stable and particularly there was no congestive cardiac failure. Before discharge at ten days of age, clinical examination and particularly cardiac examination was normal. At 14 days of age, symptoms in relation to a congestive cardiac failure appeared. Echocardiography showed a high output cardiac failure with no cardiac malformation. Infectious laboratory tests were normal. Evolution was initially favourable after digitalo-diuretic treatment. Unfortunately, death occurred at 36 days of age due to intractable cardiac failure. This case highlights that, unusually, heart failure can occur long after the first days of life in cases of Galen vein aneurysmal malformation. The optimal time for vascular embolization in neonatal cases of Galen vein aneurysmal malformation is discussed. [Copyright &y& Elsevier]

Abstract: Leigh syndrome is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Mutations in SURF1 gene have been identified in patients with cytochrome c oxidase deficiency. We report a homozygous splice site deletion [516-2_516-1delAG] in a young girl presenting with cytochrome c oxidase-deficient Leigh syndrome. Identification of molecular defect is indispensable for genetic counselling and prenatal diagnosis. [Copyright &y& Elsevier]

Abstract: We report the fifth case of neonatal form of type C2 (NP-C2) Niemann-Pick disease with early and fatal respiratory distress. Eleven families presenting such cases are known to date in the world. Since December 2000, isolation of the underlying gene HE1/NPC2 and its mutations has allowed major advances in diagnosis. Case report. – Elisa was born in May 2000. NP-C2 disease was associated with severe respiratory distress leading to death at the age of four months. On the next pregnancy in September 2000, prenatal diagnosis was performed by means of biological tests that required four weeks response time. In December 2000, isolation of the HE1/NPC2 gene located to 14q24.3 and of some of its mutations allowed to characterize the patient as being homozygote for the nonsense mutation E20X. On the the two next pregnancies, prenatal diagnosis was performed at 12 SA, in 48 hours, by the means of mutation analysis. The last fetus was heterozygote for the mutation E20X, allowing the birth at term of a healthy male newborn baby. Conclusion. – Niemann-Pick type C disease is a rare lysosomal lipid storage disease with severe prognosis. It is characterized by abnormalities of intracellular transport of endocytosed cholesterol. Diagnosis relies on biological tests that require cultured cells. Genetic heterogeneity defines two different genetic complementation groups C1 and C2. Severe and early respiratory distress is more likely to be associated with the rare type C2. Since December 2000, after identification of the disease-causing mutations in the proband, mutation analysis of gene HE1/NPC2 on direct chorionic villus samples allows early and fast (48 hours) prenatal diagnosis. [Copyright &y& Elsevier]

Fetal ultrasounds examinations allow identification of brain malformations; announce of diagnosis and information about prognosis may be difficult when malformation is rare and prognosis uncertain.Objectives. – In this study we tried to analyze how fetal imaging for prenatal screening was organized and how couples were managed and supported.Methods. – We focused on the procedures used to inform couples: content, method of delivery and consequences. A referent physician in each large multidisciplinary center for prenatal diagnosis in Paris area was questioned by semi-directed interview.Results. – Our study showed that it is difficult to standardize the way in which information is supplied before and after fetal ultrasounds examination; uncertainty about prognosis led more often to abortion.Conclusion. – Thus, couples should have clear and complete information provided by a multidisciplinary team including specialists particularly concerned by the malformation (neuropediatrician and/or neurosurgeon)—moreover when prognosis is uncertain, in order to support them, and to accompany their decision concerning pregnancy. [Copyright &y& Elsevier]

Purpose. – The aim of this study was to evaluate the change in ureteropelvic junction management, from surgical correction to observation of the hydronephrosis. We checked wether or not it was deleterious for kidney.Materials and methods. – We retrospectively reviewed 96 charts between 1988 and 1998. Initial ultrasonography, and voiding cystourethrogram were available for all cases. Intravenous urography and diuretic renography were studied when available. Minimal follow-up of patients was one year. Patients were divided into three groups: surgery right away, surgery after observation, and observation only.Results. – Later was the diagnosis, more significant were the hydronephrosis and impairment of renal function (p < 0.01). In group operated on right away (69 cases), drainage improved, hydronephrosis decreased, but renal function did not improve significantly (p = 0.37). Sixteen patients were operated on after observation without deleterious effect for kidney. Eleven patients were only observed: hydronephrosis progressively decreased. Initial radiological results were not different between the last two groups (p > 0.05), and were not predictive of their course.Conclusion. – Initial non operative management of hydronephrosis was not dangerous for renal function. It is advisable to detect at the earliest all signs of obstruction, because surgery improves renal drainage but not renal function. [Copyright &y& Elsevier]

Cardiac hamartomas are frequently the earliest revelation of Bourneville''s tuberous sclerosis. They sometimes allow to consider the diagnosis during the antenatal period, and to plan therefore genetic and CNS investigations. After the neonatal period, the evolution of hamartomas is frequently favourable, characterised with at least partial involution.Observation – Antenatal equivocal cardiac echographic images did not allow the diagnosis in a fetus whose father had Bourneville''s disease. Other antenatal investigations (genetics, central nervous system MRI) were not helpful. The diagnosis was carried out at birth as cardiac ultrasound reliably showed two cardiac hamartomas.Conclusion – Even when suspected, the antenatal diagnosis of Bourneville''s disease is difficult. The presence of cardiac hamartomas at birth is a reliable mean to make the diagnosis. [Copyright &y& Elsevier]

One of the major progress in fetal medicine in recent years is the increased sensitivity of sonographic screening for foetal malformations, due to technical improvement but also to a better training of professionals. Screening for chromosomal abnormalities is no longer based on maternal age alone. Second trimester maternal serum screening (MSS) is increasingly used : thus in 1997, 376 798 MSS tests were performed in France, yielding to the prenatal diagnosis of 391 cases of Down’s syndrome. First trimester sonographic nuchal translucency measurement (NTM) is an effective screening method when performed under stringent conditions. Quality control however, is more difficult to implement on a large scale for NTM than for MSS. Performing screening tests sequentially carries a danger of generating an unnecessarily high number of amniocentesis, which may be obviated by a rational calculation of an individual’s risk to carry an aneuploid baby. First trimester MSS is expected to become standard practice in the next years, probably in combination with NTM. Cytogenetics underwent substantial innovations recently, due to the ever-increasing use of molecular cytogenetics. FISH techniques allow : 1) precise analysis of unexpected structural chromosomal abnormalities diagnosed by routine amniocentesis, 2) rapid screening of the most common aneuploidies by amniocentesis when a fetal structural anomaly is detected by 3rd trimester ultrasound, 3) diagnosis of micro-deletions suspected by fetal ultrasound or post-mortem. Prenatal diagnosis by maternal blood sampling and fetal cells or DNA analysis is now part of routine clinical practice in selected cases, such as fetal sexing in families affected by an X linked disease. Thus one can select those pregnancies eligible to invasive prenatal diagnosis. Pre implantation diagnosis, which has not been legal in France until 1999 is now increasingly used as an alternative to first trimester diagnosis. As for fetal therapy, a major recent breakthrough is the prenatal management of twin to twin transfusion syndrome by either amnioreduction or laser coagulation of inter-twin vascular shunts. In addition, new pathophysiologic concepts involving the renin angiotesin system could lead to further therapeutic innovations. A European randomised trial is now being completed to establish the respective indications of drainage and Laser. All this underscores that fetal medicine is no longer solely a succession of dramatic technical breakthroughs, but is entered an era of large-scale diffusion that requires evidence based evaluation. [Copyright &y& Elsevier]

Abstract: Antenatal ultrasounds allow the detection of renal tumors, especially renal mesoblastic nephromas, but only the pathological analysis of the surgical specimen can confirm this diagnosis postnatally. Observation. – We report the prenatal discovery of a mesoblastic nephroma because of premature labour. Postnatal early surgery was decided because of possible complications in this premature infant. Histology revealed mesoblastic nephroma. Comments. – We point out the diagnostic elements of congenital mesoblastic nephroma, especially in what is related to arterial hypertension and hypercalcemia, histology and cytogenetics. [Copyright &y& Elsevier]

Agenesia of corpus callosum belongs to a group of cerebral malformations whose prognosis is uncertain. In such cases, assessment of prognosis may benefit from eventual associated fetal, obstetrical or familial features. We report a patient with an isolated corpus callosum agenesia that led to the discovery of a similar malformation in her father. This observation demonstrates that some forms of isolated and familial corpus callosum agenesia could have a favorable outcome. However, the difficulty of the assessment of prognosis in isolated corpus callosum agenesia is emphasized and the question of parental RMI exploration in such a peculiar context is raised. [Copyright &y& Elsevier]

Case report. – A case of intrauterine intussusception causing ileal atresia is reported. The neonate presented at the age of one day with bilious vomiting, failure to pass meconium and progressive abdominal distension. A clinical diagnosis of intestinal obstruction was made, and was confirmed by plain abdominal radiographs. At laparotomy, atresia of the terminal ileum was found. The lumen of the resected distal segment contained an intussusceptum. The blind ends were resected and an anastomosis was performed. Recovery was uneventful.Comments. – Intrauterine bowel intussusception is a rare clinical entity. When intussusception occurs in the foetus and the time elapsed is enough to allow for gangrene and resorption of the intussuscepted portions of the bowel, intestinal atresia may result.Conclusions. – The careful examination of the distal blind end of the ileum aids to obtain a correct classification and etiologic diagnosis of the atresia. [Copyright &y& Elsevier]

Summary: Syphilis is a re-emerging infectious disease in Western Europe. Congenital syphilis is a potentially serious pathology affecting newborns of infected mothers. This disease is easily curable by a simple antibiotic treatment. Because of systematic antenatal screening it should no longer exist in industrialized countries. Nevertheless, we report a case of a six-week-old infant with a delayed diagnosis of congenital syphilis. Physicians, especially gynaecologists, obstetricians and paediatricians, have to be vigilant in order to allow for early diagnosis and appropriate treatment of congenital syphilis. [Copyright &y& Elsevier]