Síndrome de Edwards: desde el diagnóstico prenatal hasta el neonatólogo

RESUMEN El síndrome de Edwards o síndrome de trisomía 18 es un trastorno cromosómico autosómico que se caracteriza por la presencia de un cromosoma 18 extra, con rasgos clínicos distintivos. Se presenta un caso con diagnóstico prenatal basados en la ecografía morfológica obstétrica que condujeron a la realización ecocardiografía fetal donde resalta la displasia de la válvula pulmonar con doble lesión y la comunicación interventricular. Posteriormente se realiza cordocentesis para realización del cariotipo y asesoramiento genético.

ABSTRACT Edwards' syndrome, or trisomy 18 syndrome, is an autosomal chromosomal disorder characterized by the presence of an extra chromosome 18, with distinctive clinical features. We present a case with a prenatal diagnosis based on obstetrical morphological ultrasound that led to the performance of a fetal echocardiography with findings of a pulmonary valve dysplasia with double injury and interventricular communication. Subsequently, cordocentesis is performed for karyotyping and genetic counseling.

Pregnancy outcomes among women with high and low risk in first and second trimester prenatal screening analysis / 预防医学

Objective To analyze adverse pregnancy outcomes among women with high risk and low risk during prenatal screening. Methods Clinical data of 180006 pregnancies in 5 prenatal screening center in Hangzhou were collected. We compared the adverse pregnancy outcomes of high and low risk pregnancies. Results Among 180006 pregnancies (age<35 years old), there were 10296 high-risk cases and 169710 low-risk cases, with 168654 cases followed. There were 9406 high-risk cases of Down's syndrome (DS) (5.23％), 273 high-risk cases of Edwards' syndrome (ES) (0.15％) and 617 high-risk cases of open neural tube defect (ONTD) (0.34％) . The detection rate of pregnancy outcome of premature birth, spontaneous abortion, termination of pregnancy, stillbirth in the high risk was 5.46％, 0.80％, 1.80％, 0.37％, respectively, and that rate in low risk results was 3.50％, 0.21％, 0.38％, 0.18％, respectively. Adverse pregnancy outcomes in high-risk group were significantly higher than that in low-risk group (all P<0.001) . The actual incidence rate of DS, ES or ONTD in high-risk group (4.56‰, 1.65‰, 0.97‰, respectively) were significantly higher than that in low-risk group (0.12‰, 0.04‰, 0.09‰, respectively, all P<0.001) . The detection rates of prenatal screening were 70.15％, 68.00％ and 38.46％, and false positive rates were 5.23％ , 0.14％ and 0.34％ . Conclusion High risk of serum prenatal screening analysis is associated with adverse pregnancy outcomes. The number of pregnancies experienced invasive prenatal diagnosis can be reduced by routine serum prenatal screening. That is an Effective method to reduce the birth defects.

Pancreatic hamartoma in a premature Trisomy 18 female

Pancreatic hamartomas are extremely rare tumors in adults and even more so in children. They are lesions characterized by acinar, islet and ductal components found in varying proportions and in a disorganized pattern. We report a case of a premature female with trisomy 18 diagnosed by amniocentesis. The newborn was delivered by cesarean section at thirty-three weeks of gestation and expired within one hour of birth. Postmortem examination exhibited numerous features associated with Trisomy 18 including lanugo on the torso and arms, micrognathia, microstomia, left low-set ear with small flat pinna, closed ear canal, clenched fists with overlapping fingers, rocker-bottom feet, narrow pelvis, large right diaphragmatic hernia and left pulmonary hypoplasia. Microscopic examination of the pancreas revealed an area, 1.2 cm in greatest dimension, with branching ducts and cysts lined by cuboidal epithelium intermingled within primitive mesenchymal proliferation and exocrine glands. The cysts measured up to 0.2 cm and were surrounded by a collarette of proliferating spindle cells as highlighted by Masson's trichrome stain. A diagnosis of pancreatic hamartoma was rendered. A total of thirty-four cases of pancreatic hamartomas have been reported in the literature including twenty-seven in adults, five in children and two in newborns. Our case may be the third pancreatic hamartoma reported in association with Trisomy 18. We recommend that careful examination of the pancreas be performed in individuals with Trisomy 18 to further characterize this lesion as one of the possible abnormal findings associated with this syndrome.

Sindrome de Edwards o Trisomia 18: reporte de un caso / Edwards syndrome or trisomy 18: a case report

RESUMEN Se presenta un caso de síndrome de Edwards, por sospecha ecográfica desde la semana 18 de gestación, con seguimiento ecográfico 2D, 3D y 4D, confirmado por cariotipo post natal. Óbito 48 hs post nacimiento.

ABSTRACT An Edwards’ case is presented, because of an ultrasound suspicion since the 18th gestation week, with an ultrasound follow-up using 2D, 3D and 4D, confirmed by post natal karyotype. Fetus died after 48 hours of its birth.

Aspectos clínicos da síndrome de Edwards / Clinical aspects of Edwards syndrome

Introdução: A síndrome de Edwards é polimalformativa decorrente da presença de um cromossomo extra no par 18 como trissomia. Tem mutação baseada em mais de 90% em trissomia livre e a minoria dos casos em mosaicismo e translocação. Métodos: Relato de série de 13 casos confirmados de trissomia 18 em hospital pediátrico terciário em cinco anos. Amostra com maior prevalência do sexo feminino, prematuros limítrofes, baixo peso, nascidos de parto cesáreo e sem diagnóstico pré-natal. Os estigmas genéticos mais registrados foram micrognatia, dedos de mãos superpostos, pés em taco de golfe, orelhas pontiagudas e sopro cardíaco. Todos os pacientes tinham cardiopatia congênita, com predomínio de comunicação interventricular e canal arterial patente. O cariótipo por banda G confirmou trissomia livre em todos os casos. A maioria foi internada em terapia intensiva neonatal e evoluiu para óbito até o terceiro mês de vida. As principais causas de óbitos foram insuficiência cardíaca, hipertensão pulmonar e pneumonia. Conclusão: Os pediatras ainda demonstram baixo grau de suspeição específica da doença e desconhecem o prognóstico reservado.

Feto Papiráceo en Gestación Gemelar y Síndrome de Edwards: A Propósito de un Caso / Vanishing Twin in Multiple Gestation and Edwards Syndrome: A Case Report

Se expone el caso clínico de una gestación gemelar bicorial biamniótica que dio lugar a la muerte fetal espontánea del segundo gemelo a las 16 semanas, por lo que curso desde el segundo trimestre con feto papiráceo. La causa de la muerte se atribuyó al diagnóstico de Síndrome de Edwards, cromosomopatía de muy mal pronóstico en la vida intrauterina y perinatal, con tasas de mortalidad intraútero de hasta el 80% de los casos. El segundo gemelo se obtuvo sin complicaciones estructurales y no se documentó repercusión en la madre; a pesar de que la bibliografía científica indica un mayor riesgo de morbimortalidad del gemelo vivo, la gestación y el parto cursaron sin complicaciones.

It was presented a case report of a dichorinic diamniotic twin pregnancy in which there was spontaneous fetal death of the second twin at 16 weeks, so on going since the second trimester with papyraceus fetus. The cause of death of the fetus was attributed to Edwards Syndrome, chromosomal disease with poor prognosis in intrauterine and perinatal life, intrauterine mortality rates of up to 80% of cases.The second twin was obtained without structural complications and no documented impact on the mother.Although described in the literature an increased risk of morbidity and mortality of the living twin, this case pregnancy and childbirth progressed without complications.

Doble aneuploidía (trisomía X, trisomía 18) en una recién nacida con fenotipo de trisomía 18 / Double aneuploidy (trisomy x, trisomy 18) in a newborn with trisomy 18 phenotype

Se presenta el caso de una recién nacida con una doble trisomía, con complemento cromosómico 48,XXX,+18, con fenotipo de síndrome de Edwards (trisomía 18). Las características clínicas fueron restricción del crecimiento intrauterino, facies dismórfca, mano con sobreposición de dedos, comunicación interventricular, estenosis pulmonar y pie equinovaro izquierdo. Se realiza una revisión de la bibliografía y discusión de los casos previamente comunicados.

We report the case of a newborn girl with a double trisomy, with a chromosome complement 48,XXX,+18, with Edwards syndrome phenotype (trisomy 18). The clinical feature included intrauterine growth retardation, dysmorphic facies, hand with overlapping fngers, ventricular septal defect, pulmonary stenosis and left clubfoot. A review of the literature and discussion of previously reported cases is made.

Síndrome de Edwards asociado a inmunodeficiencia combinada / Edwards' syndrome associated to combined immunodeficiency

El síndrome de Edwards es originado por un desbalance cromosómico representado por una trisomía 18. Alrededor de 95 por ciento de los pacientes corresponden a trisomía completa, donde están presentes múltiples malformaciones en órganos y sistemas. El 5 por ciento restante pertenece a trisomía parcial o mosaicismo, con un fenotipo incompleto por la ausencia de algunas anomalías típicas del síndrome. La inmunodeficiencia es una manifestación poco frecuente del síndrome Edwards. Se presenta el caso de una paciente de 9 meses de edad con trisomía 18 parcial e infecciones severas recurrentes desde la etapa neonatal, asociadas a anemia, linfopenia, trombocitopenia y neutrofilia. La ecografía mostró una hipoplasia del timo. Se encontraron cifras disminuidas de linfocitos TCD4+, CD8+ y de células asesinas naturales. La cuantificación de linfocitos B fue normal. Se hallaron concentraciones normales de inmunoglobulinas séricas IgM e IgG y disminuidas de IgA. Se encontró una disminución de la actividad hemolítica total de la vía clásica del complemento. No se encontraron alteraciones en la función opsonofagocítica. Se diagnosticó una inmunodeficiencia combinada asociada, hecho que demostró la heterogeneidad de la expresión clínica del síndrome Edwards y la relación entre el defecto cromosómico y la formación del sistema inmune en el período intrauterino

Edwards' syndrome is caused by a chromosomal imbalance represented by trisomy 18. Complete trisomy accounts for 95 percent of patients who present multiple malformations in organs and systems. The remaining 5 percent presents partial trisomy or mosaicism, with incomplete phenotype due to lack of some typical anomalies of this syndrome. Immunodeficiency is a rare manifestation of Edwards' syndrome. The case of a 9-months old female patient with partial trisomy 18 and recurrent severe infections since the neonatal phase, all associated to anemia, lymphopenia, thrombocytopenia and neutrophilia, was presented in this paper. The echographic test indicated tymus hypoplasia. There were reduced numbers of TCD4+, CD8+ lymphocytes and of natural killer cells. The lymphocyte B count was normal. Normal concentrations of serum IgM and IgG immunoglobulins as well as decreased concentrations of IgA were found. The total hemolytic activity of the classical complement pathway declined. No alteration was found in the opsonocytophagic function. The diagnosis was associated combined immunodeficiency, which proved the heterogeneity of the clinical expression of Edwards' syndrome and the relationship between the chromosomal defect and the formation of immune system in the intrauterine period

Anestesia caudal combinada à anestesia geral para cirurgia abdominal em paciente com Síndrome de Edwards: relato de caso / Combined caudal-general anesthesia for an abdominal procedure in a patient with Edwards?s syndrome: case report

Introdução: a síndrome de Edwards, ou trissomia do 18, é uma anomalia cromossômica rara e frequentemente fatal. Os pacientes que sobrevivem têm múltiplas malformações, que resultam em risco anestésico aumentado, mesmo em cirurgias de menor porte. Objetivo: discutir o uso da anestesia caudal, em associação com anestesia geral, como técnica anestésica e analgésica para cirurgia abdominal em criança portadora de síndrome de Edwards. Relato do caso: criança de 75 dias de idade, 2,9 kg, com diagnóstico de síndrome de Edwards e cardiopatia congênita, foi submetida à correção de refluxo gastroesofágico sob anestesia geral combinada ao bloqueio peridural caudal com bupivacaína 0,125%, morfina e clonidina. A anestesia geral foi mantida com sevoflurano, sem a necessidade do uso endovenoso de opioides. O paciente manteve estabilidade durante todo o procedimento cirúrgico. No final da cirurgia, o anestésico inalatório foi suspenso e a paciente foi extubada na sala de ciurgia após 17 minutos. O pós-operatório foi realizado em centro de terapia intensiva, sem intercorrências e sem a necessidade do uso suplementar de analgésicos. Conclusão: a anestesia geral inalatória combinada com o bloqueio caudal mostrou-se técnica anestésica segura e satisfatória em crianças com síndrome de Edwards.

Introduction: Edwards syndrome or trisomy 18 is a rare and often fatal chromosome abnormality. Patients who survive are dysmorphic with multiple malformations leading to an increase anesthetic risk even during small surgery. Objective: to discuss the use of caudal anesthesia combined with general anesthesia as an anesthetic and analgesic technique for abdominal surgery in a child with Edwards?s syndrome. Case report: a girl with 75-day-old, 2.9 kg, with Edward?s syndrome and congenital heart disease who underwent surgical correction of gastroesophageal reflux with combined caudal-general anaesthesia using 0.125% bupivacaine, morphine and clonidine. General anesthesia was maintained with sevoflurane and no opioid was used. Throughout the procedure, no major changes in the monitored parameters were recorded. At the completion of the procedure, the inhalational agent was discontinued and the patient was extubated in the operating room after 17 min. The postoperative period at the intensive care unit was uneventful and no postoperative analgesics were necessary. Conclusion: inhalatory general anesthesia associated with caudal anesthesia seems to be a good and safe technique in children with Edwards?s syndrome.

Partial trisomy of chromosome 18q11.2-q12: A case report / 소아과

Edwards syndrome, also called trisomy 18, is one of the most common autosomal anomalies. The survival rate of patients with Edwards syndrome is very low and its characteristic findings include cardiac malformations, mental retardation, growth retardation, specific craniofacial anomalies, clenched hands, rocker-bottom feet, and omphalocele. Compared with the classic Edwards syndrome, the symptom of partial duplication of chromosome 18 is relatively mild with a good prognosis. We report the case of a baby with partial duplication 18q11.2-q12. The characteristic phenotype features of Edwards syndrome were observed in the patient. However, the symptom was milder than the typical Edwards syndrome. At present, we can expect better prognosis for this patient.

A case of heterotopic pregnancy: 16 weeks of intrauterine pregnancy with fetal Edwards syndrome and tubal pregnancy, following IVF-ET / 대한산부인과학회지

Heterotopic pregnancy is defined as coexistence of intrauterine and ectopic pregnancy. The reported incidence of heterotopic pregnancy, which is normally rare, is particularly high (1%) after IVF treatment. It is important to have a high index of suspicion for the occurrence of heterotopic pregnancies because only 40% to 84% of cases can be diagnosed with transvaginal ultrasound at the initial presentation. Edwards syndrome occurs in 8,000 newborns and the incidence is much higher in elderly gravidas. We report a case of heterotopic pregnancy following IVF-ET resulting in 16 weeks of intrauterine pregnancy with fetal Edwards syndrome, and tubal pregnancy with a brief review of literature.

Amniotic Chromosomal Analysis in Pregnant Women Identified by Triple-Marker Testing as Screen Positive / 대한진단검사의학회지

BACKGROUND: Maternal serum triple marker screening (alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol) can detect 60-70% of Down syndrome and 60% of Edwards syndrome. Previous studies have reported that positive serum screening is related to other fetal chromosomal abnormalities, pregnancy complications, and adverse outcomes. We determined the incidence and karyotype of chromosomal abnormalities in screen positive women and evaluated a relationship between chromosomal and ultrasonographic abnormalities. METHODS: Of the 49,806 pregnant women between 15 and 23 weeks' gestational age who received prenatal serum screening with a cut-off value (a risk of 1:270 for Down and 1:100 for Edwards syndrome), 2,116 (4.2%) and 196 (0.4%) were screen positive for Down syndrome and for Edwards syndrome, respectively. Chromosomal analysis in amniotic fluid was performed for 1,893 (89.5%) of the Down positive and 140 (71.4%) of the Edwards positive pregnant women. Ultrasonographic examination was performed to detect fetal abnormalities. RESULTS: Eighty-three cases of chromosomal abnormalities including 40 trisomy 21 (2.1%) and 43 other chromosomal abnormalities (2.3%) were identified in the Down screen positive. Other chromosomal abnormalities included 9 numerical and 34 structural abnormalities. Ten cases of chromosomal abnormalities (9 trisomy 18 and 1 trisomy 9) were detected in the Edwards screen positive. Ultrasonographic abnormalities were found more frequently in the women who had chromosomal aberrations. CONCLUSIONS: These data suggest that 4.4% of the Down screen and 7.1% of the Edwards screen positive pregnancy have fetal chromosomal abnormalities. Positive Down screening results reflect a relatively high probability of other abnormalities except trisomy 21. Edwards screen positive group show a low frequency of other chromosomal abnormalities except trisomy 18. A simultaneous use of maternal serum screening and ultrasonograms could be useful for the diagnosis of fetal abnormalities.

An Evaluation of Prenatal Triple Marker Screening / 대한진단검사의학회지

BACKGROUND: Maternal serum triple marker screening has become standard in prenatal care to help identify women at risk for neural tube defects (NTDs), trisomy 21 (Down syndrome) and trisomy 18 (Edwards' syndrome). This study was undertaken to evaluate the results of maternal serum triplemarker screening performed in pregnant women visiting Chung-Ang University Hospital and to assess the effectiveness of prenatal triple-marker screening. METHODS: Alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) were measured by radioimmunoassay (Amerlex-M 2nd Trimester Kit, Ortho Clinical Diagnostics, Amersham, Aylesbury, UK) in 506 pregnant women visiting Chung-Ang University Hospital. Women at risk for NTDs, trisomy 21 and trisomy 18 were identified using the computer program (HIT Program). Amniocentesis with chromosome analysis was performed in women who had positive screening results. RESULTS: Positive screening results were found in 41 (8.1%) women among 506 pregnant women who had undergone prenatal triple-marker screening between 14 and 22 weeks of gestation. Of these 41 women, 39 (7.7%) had a positive screening results for Down syndrome and 2 (0.4%) for NTDs. Thirty-two women with positive screening results for Down syndrome chose amniocentesis for chromosomal analysis, of which the results showed normal in 28 (87.5%), inv(9) in 3 (9.4%) and 48, XXY, +18 in 1 (3.1%). Although all but one of the fetuses with normal karyotypes and inv(9) were born with normal phenotypes, one pregnancy with 48, XXY, +18 was terminated due to fetal death in-utero. One of 2 pregnancies affected with NTDs was correctly identified, showing meningocele, abdominal wall defect and scoliosis. CONCLUSIONS: Our data confirm chromosome abnormalities or congenital anomalies in about 5% of the pregnancies with positive triple-marker screening results, suggesting an effective prenatal screening test. It has been found that the presence of inv(9) in fetuses might be accompanied by false-positive results for Down syndrome.