Prenatal Diagnosis of Bilateral Ectrodactyly and Radial Agenesis Associated with Trisomy 10 Mosaicism

Ectrodactyly or split hand and foot malformations (SHFMs) are rare malformations of the limbs, characterized by median cles of the hands and feet, syndactyly, and aplasia and/or hypoplasia of the phalanges. ey represent a clinically and genetically heterogeneous disorder, with both sporadic and familial cases. Most of the genomic rearrangements identi�ed to date in some forms of SHFM are autosomal dominant traits, involving various chromosome regions. Bilateral radial ray defects comprise also a large heterogenous group of disorders, including trisomy 18, Fanconi anemia, and thrombocytopenia-absent-radius syndrome, not commonly associated with ectrodactyly. e present paper describes a case of ectrodactyly associated with bilateral radial ray defects, diagnosed in the �rst trimester of pregnancy, in a fetus affected by trisomy 10. Only four cases of sporadic and isolated ectrodactyly, diagnosed by ultrasonography between 14 and 22 weeks' gestation, have been reported. To our knowledge, the present case is the �rst report of mosaic trisomy 10 associated with SHFM and radial aplasia. Trisomy 10 is a rare lethal chromosomal abnormality, most frequently found in abortion products. Only six liveborn mosaic trisomy 10 infants, with severe malformations, dead in early infancy, have been reported. A severe clinical syndrome can be de�ned, comprising ear abnormalities, cle lip/palate, malformations of eyes, heart, and kidneys, and deformity of hands and feet and most oen associated with death neonatally or in early infancy

Phenotypic spectrum of fetal Smith-Lemli-Opitz syndrome.

International audienceThe Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation syndrome caused by dehydrocholesterol reductase deficiency. The diagnosis is confirmed by high 7- and secondarily 8-dehydrocholesterol levels in plasma and tissues and/or by detection of biallelic mutations in the DHCR7 gene. The phenotypic spectrum of SLOS is broad, ranging from a mild phenotype combining subtle physical anomalies with behavioral and learning problems, to a perinatally lethal multiple malformations syndrome. The fetal phenotype of SLOS has been poorly described in the literature. We report a series of 10 fetuses with molecularly proven SLOS. Even in young fetuses, the facial dysmorphism appears characteristic. Genital abnormalities are rare in 46,XX subjects. Gonadal differentiation appears histologically normal and in agreement with the chromosomal sex, contrary to what has been previously stated. We observed some previously unreported anomalies: ulnar hypoplasia, vertebral segmentation anomalies, congenital pulmonary adenomatoid malformation, fused lungs, gastroschisis, holomyelia and hypothalamic hamartoma. This latter malformation proves that SLOS phenotypically overlaps with Pallister-Hall syndrome which remains clinically a major differential diagnosis of SLOS

Prise en charge anténatale et néonatale des enfants porteurs de transposition des gros vaisseaux (valeur prédictive de l'échocardiographie fœtale)

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Apports de la modélisation ontologique au partage des connaissances en médecine périnatale

Les nouvelles technologies de l information et des communications ouvrent de nouvelles possibilités de partage des connaissances entre personnes et entre machines. Les ontologies sont des artefacts informatiques permettant de représenter la sémantique des données et, par cette représentation, de les faire inter-opérer. Ce travail explore les apports des ontologies comme supports au partage des connaissances médicales en périnatalité (dans les domaines des maladies rares, du diagnostic prénatal et de la dysmorphologie fœtale). Le détail de la construction d une ontologie des maladies rares en collaboration avec Orphanet est présenté. Cette ressource est évaluée par des mises en situation concrètes, avec des résultats positifs, dans différents contextes comme l édition des connaissances, le contrôle de leur cohérence et la génération de classifications de maladies rares. L ontologie produite dans ce travail constitue la première ressource de ce type pour le domaine des maladies rares. Sa structure actuelle et sa compliance aux standards du W3C (OWL, RDF, SKOS) permettent d envisager son exploitation sur le Web de données (Linked Open Data). Des évolutions de l'ontologie sont envisagées pour le domaine de la dysmorphologie fœtale (projet Accordys) et pour le suivi de patients atteints de maladies rares (projets BNDMR/RaDiCo).The Information Communication Technologies offer new opportunities for knowledge sharing among individuals and between machines. Ontologies are computer artifacts to represent the semantics of data, leading to semantic interoperability. This thesis explores the contributions of ontologies as support for perinatal Medicine knowledge sharing (in the field of rare diseases, prenatal diagnosis and fetal dysmorphology). The design of a rare diseases ontology (in collaboration with Orphanet) is detailled. This resource is evaluated in real situations and showed positive results for knowledge base curation, consistency and quality control procedures and automated rare diseases classifications generation. The ontology produced in this work is the first one of its kind in the field of rare diseases. Its current structure and its compliance with the W3C standards (OWL, RDF, SKOS) allows its use over the Web of Data (Linked Open Data). Evolutions of the model will follow for the representation of fetal dysmorphology (Accordys project) and for the representation of patients cohorts (BNDMR/RaDiCo projects).PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Choix méthodologiques pour la construction d'une ontologie de domaine en médecine prénatale

National audienceNous décrivons une méthode de construction d'ontologie d'interface en médecine prénatale avec une double approche d'expert du domaine et d'ingénieur de connaissance ; notre stratégie est à la fois bottom-up à partir de l'analyse des documents du domaine (Syntex-Upéry, ArchOntE), et top-down par réutilisation de ressources terminologiques et ontologiques existantes (ontoMénélas, FMA, Orphanet, CCAM, CIM-10)

Anomalies cardiaques fœtales : diagnostic prénatal et prise en charge périnatale

International audienceL'incidence des cardiopathies congénitales est voisine de 1 % des naissances d'enfants vivants, dont environ 30 à 40 % sont des formes sévères. Elles sont responsables à elles seules de la moitié de la mortalité infantile par malformations. Les cardiopathies malformatives sont accessibles au diagnostic prénatal par échographie. Le diagnostic prénatal des cardiopathies congénitales permet d'éliminer des malformations associées, de discuter d'une vérification du caryotype fœtal, la recherche d'anomalie génétique via l'utilisation de puce à acide désoxyribonucléique (ADN) et, après un examen d'expertise de l'anatomie cardiaque, de préciser le pronostic et les possibilités de prise en charge postnatale. Environ 80 % des cardiopathies congénitales sont dépistés en prénatal dans le groupe à bas risque au cours des examens de dépistage des malformations à 22 ou 32 semaines d'aménorrhée (SA). La réalisation systématique des trois coupes de référence rend possible le diagnostic de la majorité des cardiopathies malformatives. Pour le groupe à risque accru pour les malformations cardiaques - antécédent familial de cardiopathie congénitale, exposition à des toxiques embryonnaires, pathologie maternelle, augmentation de la clarté nucale supérieure à 3,5 mm au 1er trimestre -, il est possible d'effectuer une première vérification de l'anatomie du cœur fœtal vers 13 à 14 SA. Dans le cas des cardiopathies isolées, le diagnostic prénatal permet une organisation de la naissance dans une structure adaptée permettant, en fonction du type de la cardiopathie, une prise en charge optimale de l'enfant après la naissance

Prenatal Diagnosis of Bilateral Ectrodactyly and Radial Agenesis Associated with Trisomy 10 Mosaicism

Ectrodactyly or split hand and foot malformations (SHFMs) are rare malformations of the limbs, characterized by median clefts of the hands and feet, syndactyly, and aplasia and/or hypoplasia of the phalanges. They represent a clinically and genetically heterogeneous disorder, with both sporadic and familial cases. Most of the genomic rearrangements identified to date in some forms of SHFM are autosomal dominant traits, involving various chromosome regions. Bilateral radial ray defects comprise also a large heterogenous group of disorders, including trisomy 18, Fanconi anemia, and thrombocytopenia-absent-radius syndrome, not commonly associated with ectrodactyly. The present paper describes a case of ectrodactyly associated with bilateral radial ray defects, diagnosed in the first trimester of pregnancy, in a fetus affected by trisomy 10. Only four cases of sporadic and isolated ectrodactyly, diagnosed by ultrasonography between 14 and 22 weeks’ gestation, have been reported. To our knowledge, the present case is the first report of mosaic trisomy 10 associated with SHFM and radial aplasia. Trisomy 10 is a rare lethal chromosomal abnormality, most frequently found in abortion products. Only six liveborn mosaic trisomy 10 infants, with severe malformations, dead in early infancy, have been reported. A severe clinical syndrome can be defined, comprising ear abnormalities, cleft lip/palate, malformations of eyes, heart, and kidneys, and deformity of hands and feet and most often associated with death neonatally or in early infancy

Patterns of Detection of Fetal Posterior Fossa Anomalies: Analysis of 81 Cases in the Second Half of Gestation

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To establish which characteristics of fetal ultrasound screening lead to the diagnosis of posterior fossa (PF) anomalies. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A total of 81 fetuses with PF anomalies diagnosed after dedicated neuroimaging between July 1, 2007, and January 1, 2013, were included. The ultrasound characteristics of the fetal cerebellum categorized according to an anatomical approach to the PF, associated fetal anomalies, gestational age at diagnosis, and the potential benefits from systematic measurement of the transverse cerebellar diameter (TCD) were analyzed. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Fifty fetuses (61.7%) presented with a PF malformation responsible for an increased “fluid-filled” space of the PF, 24 fetuses (29.6%) had a malformation associated with a decreased cerebellar biometry, 23 fetuses (28.4%) had an abnormal cerebellar anatomy and/or echogenicity, and 2 fetuses (2.4%) showed an isolated malformation of the brainstem. Forty-seven cases (58%) showed additional cerebral or extracerebral anomalies, which led to the diagnosis of PF anomaly in 55.3% of the cases. Isolated PF anomalies were associated with an increased “fluid-filled” space of the PF in 91.2% of the cases. Twenty-eight fetuses had a TCD measurement considered as pathological. &lt;b&gt;&lt;i&gt;Discussion:&lt;/i&gt;&lt;/b&gt; Examination of the transcerebellar plane during 2nd- and 3rd-trimester ultrasound screening combined with systematic measurement of the TCD would allow improving the detection of PF anomalies.</jats:p

Prognosis of Fetal Parenchymal Cerebral Lesions without Ventriculomegaly in Congenital Toxoplasmosis Infection

Objective: To evaluate the neurodevelopmental and ocular outcome of a continuous retrospective series of fetal toxoplasmosis infections for which prenatal ultrasound (US) follow-up revealed abnormal cerebral findings without associated ventriculomegaly. Materials and methods: We retrospectively reviewed all cases of proven fetal Toxoplasma gondii infection with fetal cerebral anomalies at US examination without significant ventriculomegaly (≥10 mm) evaluated in our center over a 5-year period. US and magnetic resonance imaging findings were collected. The neurodevelopmental and ocular outcomes of the cases were studied. Results: Nine fetuses were included. Hyperechogenic foci of the cerebral parenchyma were isolated in five cases. Among those, four children had normal neurological development. Amblyopia was detected in on case. Hyperechogenic foci were associated with other anomalies of cerebral parenchyma in three cases among which two children had normal neurological development. Termination of pregnancy was performed in three cases: one case within the context of severe maternal schizophrenia with isolated hyperechogenic foci, one case where hyperechogenic foci were associated with extensive lesions of the white matter, and one case for severe fetal hydrops. Conclusion: The neurological prognosis of cerebral hyperechogenic lesions without ventriculomegaly in fetal toxoplasmosis infection may be favorable. The risk of ocular damage however remains high and unpredictable in the prenatal period