RESUMO
OBJECTIVE: Belgian genetic centers established a database containing data on all chromosomal microarrays performed in a prenatal context. A study was initiated to evaluate postnatal development in children diagnosed prenatally with a non-benign copy number variant (CNV). METHODS: All children diagnosed with a prenatally detected non-benign CNV in a Belgian genetic center between May 2013 and February 2015 were included in the patient population. The control population consisted of children who had undergone an invasive procedure during pregnancy, with no or only benign CNVs. Child development was evaluated at 36 months using three (3) questionnaires: Ages and Stages Questionnaire Third edition, Ages and Stages Questionnaire Social-Emotional Second Edition and a general questionnaire. RESULTS: A significant difference in communication and personal-social development was detected between children with a reported susceptibility CNV and both children with an unreported susceptibility CNV and the control population. The outcome of children with a particular CNV is discussed in a case-by-case manner. CONCLUSION: Our postnatal follow-up project of children with a prenatally detected non-benign CNV is the first nationwide project of its kind. A higher number of cases for each CNV category is however needed to confirm our findings.
Assuntos
Variações do Número de Cópias de DNA , Resultado da Gravidez/epidemiologia , Diagnóstico Pré-Natal/estatística & dados numéricos , Bélgica/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Aberrações Cromossômicas/estatística & dados numéricos , Estudos de Coortes , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/genética , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Análise em Microsséries/métodos , Gravidez , Diagnóstico Pré-Natal/métodosRESUMO
Detection of genetic aberrations in prenatal samples, obtained through amniocentesis or chorion villus biopsy, is increasingly performed using chromosomal microarray (CMA), a technique that can uncover both aneuploidies and copy number variants throughout the genome. Despite the obvious benefits of CMA, the decision on implementing the technology is complicated by ethical issues concerning variant interpretation and reporting. In Belgium, uniform guidelines were composed and a shared database for prenatal CMA findings was established. This Belgian approach sparks discussion: it is evidence-based, prevents inconsistencies and avoids parental anxiety, but can be considered paternalistic. Here, we reflect on the cultural and moral bases of the Belgian reporting system of prenatally detected variants.
Assuntos
Transtornos Cromossômicos/diagnóstico , Cromossomos , Variações do Número de Cópias de DNA , Revelação/ética , Ética Médica , Pais , Diagnóstico Pré-Natal/ética , Aneuploidia , Ansiedade , Bélgica , Cultura , Análise Citogenética/métodos , Bases de Dados de Ácidos Nucleicos , Feminino , Feto , Aconselhamento Genético/ética , Aconselhamento Genético/psicologia , Humanos , Análise em Microsséries , Pais/psicologia , Paternalismo , Fenótipo , Gravidez , Diagnóstico Pré-Natal/psicologia , Relatório de Pesquisa , Valores Sociais , Manejo de EspécimesRESUMO
OBJECTIVE: With the replacement of karyotyping by chromosomal microarray (CMA) in invasive prenatal diagnosis, new challenges have arisen. By building a national database, we standardize the classification and reporting of prenatally detected copy number variants (CNVs) across Belgian genetic centers. This database, which will link genetic and ultrasound findings with postnatal development, forms a unique resource to investigate the pathogenicity of variants of uncertain significance and to refine the phenotypic spectrum of pathogenic and susceptibility CNVs. METHODS: The Belgian MicroArray Prenatal (BEMAPRE) consortium is a collaboration of all genetic centers in Belgium. We collected data from all invasive prenatal procedures performed between May 2013 and July 2016. RESULTS: In this three-year period, 13 266 prenatal CMAs were performed. By national agreement, a limited number of susceptibility CNVs and no variants of uncertain significance were reported. Added values for using CMA versus conventional karyotyping were 1.8% in the general invasive population and 2.7% in cases with an ultrasound anomaly. Of the reported CNVs, 31.5% would have remained undetected with non-invasive prenatal test as the first-tier test. CONCLUSION: The establishment of a national database for prenatal CNV data allows for a uniform reporting policy and the investigation of the prenatal and postnatal genotype-phenotype correlation.
Assuntos
Aberrações Cromossômicas , Anormalidades Congênitas/genética , Variações do Número de Cópias de DNA/genética , Haploinsuficiência/genética , Análise em Microsséries/métodos , Adulto , Artrogripose/diagnóstico , Artrogripose/genética , Bélgica , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Hibridização Genômica Comparativa , Anormalidades Congênitas/diagnóstico , Bases de Dados Genéticas , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Feminino , Predisposição Genética para Doença , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Neuropatia Hereditária Motora e Sensorial/genética , Humanos , Ictiose Ligada ao Cromossomo X/diagnóstico , Ictiose Ligada ao Cromossomo X/genética , Cariotipagem , Gravidez , Diagnóstico Pré-NatalRESUMO
In selected cases, homozygosity mapping followed by direct sequencing of one or a few carefully selected candidate genes in a prenatal setting can be beneficial to obtain diagnosis in consanguineous families.
RESUMO
We report on the obstetric outcome of a woman aged 27â years with Hermansky-Pudlak syndrome (HPS). She underwent a caesarean section after failed induction of labour. Platelet transfusion was administered in a set schedule for 36â hours, starting 2â hours before delivery. The child had good Apgar scores and there were no significant problems of prolonged bleeding during the procedure. 72â hours postpartum, a haematoma developed at the site of the wound, subsequently complicated by a secondary infection for which she received antibiotics. Wound care was provided in an outpatient setting during 2â weeks, in which the infection stabilised and responded to the treatment. Mother and child could leave the hospital after 6â days.
Assuntos
Índice de Apgar , Cesárea , Gerenciamento Clínico , Síndrome de Hermanski-Pudlak/complicações , Transfusão de Plaquetas , Complicações na Gravidez/terapia , Cicatrização , Adulto , Antibacterianos/uso terapêutico , Feminino , Hematoma , Síndrome de Hermanski-Pudlak/terapia , Humanos , Recém-Nascido , Infecções/complicações , Infecções/tratamento farmacológico , Trabalho de Parto Induzido , Período Pós-Parto , Gravidez , Complicações Hematológicas na Gravidez/prevenção & controleRESUMO
Ticagrelor was daily administered throughout pregnancy to a 37-year-old pregnant woman until 36 weeks of gestation. The patient, with Behçet disease, suffered from a non-ST elevation myocardial infarction 4 months before conception, possibly related to hypertension and tobacco abuse. Pregnancy and postpartum periods were uneventful. She delivered a healthy but small-for-gestational-age term neonate.
Assuntos
Adenosina/análogos & derivados , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações na Gravidez/prevenção & controle , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Prevenção Secundária , Tromboembolia/prevenção & controle , Adenosina/uso terapêutico , Adulto , Aspirina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Gravidez , TicagrelorRESUMO
Disorders of sexual development are conditions where sexual phenotype and genotype are discordant. Genetic sex is determined at conception as the ovum is fertilised by a spermatozoon that contains either an X or Y chromosome. A complex pathway determined by genes and hormones leads to gonadal differentiation into testis or ovary and promotes the development of internal and external genitalia. We present a case of an 18-year-old woman who presented with primary amenorrhoea. She was a virgin, and apart from hirsutism and overweight, had no complaints. Her family history was insignificant. The patient was tall and had underdeveloped breasts. Her blood results showed hypergonadotropic hypogonadism. A 46, XY genotype was detected with karyotype analysis. Ultrasound and MRI demonstrated the presence of a uterus, but no overt gonads. Laparoscopy was performed, with bilateral removal of streak ovaries.
Assuntos
Amenorreia/etiologia , Disgenesia Gonadal 46 XY/complicações , Adolescente , Amenorreia/diagnóstico , Diagnóstico Diferencial , Feminino , Disgenesia Gonadal 46 XY/diagnóstico , Humanos , Cariotipagem , Imageamento por Ressonância MagnéticaRESUMO
We report a case of bilateral fetal hydrothorax presenting at 20â weeks of pregnancy, spontaneously resolving at 22â weeks and severely relapsing at 28â weeks in a fetus with normal karyotype. The cause was a high-output heart failure caused by vein of Galen malformation.