Patau and Edwards Syndromes in a University Hospital: beyond palliative care / Síndrome de Edwards e Patau em um hospital universitário: além do paliativo

ABSTRACT Objective: To describe the newborn population with Patau (T13) and Edwards Syndrome (T18) with congenital heart diseases that stayed in the Intensive Care Unit (ICU) of a quaternary care hospital complex, regarding surgical and non-surgical medical procedures, palliative care, and outcomes. Methods: Descriptive case series conducted from January/2014 to December/2018 through analysis of records of patients with positive karyotype for T13 or T18 who stayed in the ICU of a quaternary hospital. Descriptive statistics analysis was applied. Results: 33 records of eligible patients were identified: 27 with T18 (82%), and 6 T13 (18%); 64% female and 36% male. Eight were preterm infants with gestational age between 30-36 weeks (24%), and only 4 among the 33 infants had a birth weight >2500 g (12%). Four patients underwent heart surgery and one of them died. Intrahospital mortality was 83% for T13, and 59% for T18. The majority had other malformations and underwent other surgical procedures. Palliative care was offered to 54% of the patients. The median hospitalization time for T18 and T13 was 29 days (range: 2-304) and 25 days (13-58), respectively. Conclusions: Patients with T13 and T18 have high morbidity and mortality, and long hospital and ICU stays. Multicentric studies are needed to allow the analysis of important aspects for creating protocols that, seeking therapeutic proportionality, may bring better quality of life for patients and their families.

RESUMO Objetivo: Descrever a população de recém-nascidos com síndrome de Patau (T13) e Edwards (T18) portadores de cardiopatias congênitas, que permaneceram em Unidades de Terapia Intensiva (UTI) de um complexo hospitalar quaternário, com relação a conduta cirúrgica ou não, cuidados paliativos e seus desfechos. Métodos: Série de casos de pacientes internados entre janeiro de 2014 a dezembro de 2018, com análise dos prontuários de portadores de T13 ou T18 que permaneceram internados em UTI que recebem neonatos nesse hospital quaternário. Utilizou-se análise estatística descritiva. Resultados: Foram identificados 33 prontuários para análise — 27 T18 (81,8%) e seis T13 (18,2%); 64% do sexo feminino e 36% do sexo masculino. Oito foram prematuros, nascidos com 30 a 36 semanas (24,2%), e apenas quatro nasceram com mais de 2500 g (12,1%). Quatro pacientes foram submetidos a cirurgia cardíaca e um deles foi a óbito. A mortalidade intra-hospitalar foi de 83% para T13 e 59% para T18. A maioria apresentava outras malformações e foi submetida a outras cirurgias. Cuidados paliativos foram oferecidos a 54% dos pacientes. A mediana do tempo de hospitalização para T18 e T13 foi respectivamente de 29 dias (variação: 2-304) e 25 dias (13-58). Conclusões: Pacientes com T13 e T18 cursam com alta morbimortalidade e longa permanência hospitalar em UTI. São necessários estudos multicêntricos para melhor análise de aspectos importantes para a criação de protocolos que, buscando proporcionalidade terapêutica, tragam melhor qualidade de vida para os pacientes e suas famílias.

Enhancing understanding of SARS-CoV-2 infection among individuals with Down syndrome: An integrative review

ABSTRACT BACKGROUND: Down syndrome (DS) is a non-rare genetic condition that affects approximately 1 in every 800 live births worldwide. Further, it is associated with comorbidities, anatomical alterations of the respiratory tract, and immunological dysfunctions that make individuals more susceptible to respiratory infections. OBJECTIVE: To systematize the current scientific knowledge about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among individuals with DS. DESIGN AND SETTING: This integrative review was conducted at the Universidade Federal de São Carlos, São Paulo, Brazil. METHODS: This review was conducted in the following databases: the Virtual Health Library (Biblioteca Virtual em Saúde, BVS), PubMed, and Web of Science, using MeSH descriptors. The search included English or Portuguese studies published between January 1, 2020, and October 14, 2022. RESULTS: A total of 55 articles from 24 countries were selected, comprising 21 case-control or cohort studies, 23 case reports or series, and 11 narrative reviews or opinion studies. The articles were grouped into five categories: previous comorbidities, coronavirus disease 2019 (COVID-19) clinical features and evolution, cytokine storm and interleukins, living in institutions as a risk factor, and behavioral actions as a protective factor against SARS-CoV-2 infection. CONCLUSION: Individuals with DS are more susceptible to COVID-19 infection due to variables such as previous comorbidities, immunological factors, and their habitable environments. These aspects confer a higher risk of infection and an unfavorable clinical course. The precise pathways involved in the pathophysiology of COVID-19 in individuals with DS are not clear, thus requiring further studies. SYSTEMATIC REVIEW REGISTRATION: The Open Science Framework registered the research protocol (https://osf.io/jyb97/).

Trisomy 5:A Rare Isolated Finding in Pediatric B-lymphoblastic Leukemia

Background and Objectives: In acute leukemia, all diagnostic criteria and treatment protocols are based on cytogenetic and molecular geneticfindings. Despite recent advances in molecular biology, cytogenetic studies still play a pivotal role in the sub-classification of B-lymphoblastic leukemia (B-ALL). B-ALL is characterized by clonal cytogenetic abnormalities with numerical chromosomal aberrations being more common. An extra copy of chromosome 5 is common to see in cases with hyper diploidy. However, a gain of chromosome 5 as a sole anomaly is exceptionally rare in B-ALL. To date, trisomy 5 as a sole abnormality is reported in few cases only. We aimed to report the clinicopathologic profile of this rare finding to increase knowledge and highlight the disease course of these patients.Methods: We report a case of a 14-year boy presented with fever, lethargy and episodes of nasal bleeding for two weeks. He was admitted to the pediatric oncology unit at Indus hospital and health network, Karachi. Flowcytometry performed on peripheral blood using 8-color flowcytometry. Conventional karyotyping was performed by GTG banding. FISH panel was comprisedof dual color dual fusion probes for BCR::ABL1and ETV6::RUNX1whereas break apart probe for KMT2A (Metasystem, Germany).Digital image analysis for karyotyping and FISH was done on Leica Biosystems, Cytovision MB8.Results:Flowcytometry results were consistent with B-ALL. Cytogenetic analysis on his bone marrow aspirate revealed trisomy 5 as a sole abnormality with no evidence of any other clonal cytogenetic abnormality. FISH studies for BCR::ABL1, ETV6::RUNX1and KMT2Ashowed no evidence of gene rearrangements.Conclusion:Trisomy 5 is a very rare cytogenetic aberration. Only few cases reported in children. Inferior outcome is reported in both children and adults. The increasing number of reported cases raises the possibility of a distinct cytogenetic entity. Its prognostic and therapeutic implications are yet to be explored.

Cirugía plástica facial en niños con síndrome de Down / Facial Plastic Surgery in Children with Down Syndrome

Introducción: El síndrome de Down comprende diversos grados de retraso mental y un número de rasgos característicos en su facies. Debido a que estos pacientes presentan problemas en la vida social, laboral y educacional se han buscado soluciones que hagan de estos niños, individuos socialmente útiles. Este artículo muestra los resultados obtenidos en 22 pacientes con este síndrome que fueron tratados quirúrgicamente para corregir sus estigmas faciales. Objetivo: Demostrar los cambios funcionales y ventajas estéticas que se obtienen con la cirugía plástica facial en el paciente con síndrome de Down. Métodos: Se escogieron 22 pacientes con síndrome de Down de 3 a 14 años de edad en el período comprendido de 1986 a enero 2019. Se incluyeron los 15 primeros casos atendidos en el Hospital Pediátrico Docente William Soler en el Servicio de Cirugía Plástica y posteriormente en otros centros nacionales de salud. Los procederes quirúrgicos realizados para la corrección de los estigmas faciales fueron: glosectomía parcial, cantoplastia lateral, cantoplastia media y otoplastia. Resultados: Los cambios estéticos y funcionales fueron favorables, lo que mejoró la apariencia y eliminó los rasgos no atractivos. Se obtuvieron cambios positivos en el lenguaje y la respiración. La glosectomía y cantoplastia se realizó en el 100 por ciento de los casos. Conclusiones: Todos los pacientes operados atenuaron sus estigmas faciales, mientras que se reportaron beneficios respiratorios y mejoría en la esfera del lenguaje. El grado de satisfacción de los padres fue bueno(AU)

Introduction: Down syndrome comprises varying degrees of mental retardation and a number of characteristic facial features. Because these patients present problems in their social, occupational and educational life, solutions have been sought to make these children socially useful individuals. This work shows the results obtained in 22 patients with this syndrome who were surgically treated to correct their facial stigmata. Objective: To show the functional changes and aesthetic advantages obtained with facial plastic surgery in patients with Down syndrome. Methods: A number of 22 patients with Down syndrome aged 3 to 14 years were chosen, in the period from 1986 to January 2019. The first 15 cases attended in the plastic surgery service of Hospital Pediátrico Docente William Soler were included; later, others attended in other national health centers. The surgical procedures performed for the correction of facial stigmata were partial glossectomy, lateral canthoplasty, medial canthoplasty, and otoplasty. Results: Aesthetic and functional changes were favorable, improving appearance and eliminating unattractive features. Positive changes in speech and breathing were obtained. Glossectomy and otoplasty were performed in 100 percent of cases. Conclusions: All operated-on patients attenuated their facial stigmata, while respiratory benefits and speech improvement were reported. The degree of satisfaction of their parents was good(AU)

Prenatal Genetic Diagnosis and Origin Analysis of Rare Complete Translocation Trisomy 18 / 中山大学学报(医学科学版)

ObjectiveTo discuss the origin of rare abnormal karyotypes of fetuses with high risk of trisomy 18 revealed by non-invasive prenatal testing （NIPT） and its impact on fertility. MethodsThe cytogenetic and molecular genetic analyses were performed on the abnormal chromosomes of a prenatally diagnosed fetus with rare complete translocation trisomy 18. Using the keywords “translocation trisomy 18” or “trisomy 18 translocation” in both Chinese and English， we searched PubMed， CNKI， SinoMed， WanFang Data， CQ VIP and the Chinese Medicine database. The relevant case series were retrieved and critically appraised. ResultsG-banded karyotype analysis showed that the maternal karyotype was 46，XX，t（9；18）（q31.2；q23） and the fetal karyotype was 47， XN， t （9； 18） （q31.2；q23）mat， +18， which was a rare complete translocation type of trisomy 18. The SNP array revealed the fetus had increased copy number of chromosome 18 and two complete chromosome 18 inherited from the mother with balanced chromosomal translocation. Literature search found two children with complete translocation trisomy 18 reported abroad. Both of them had trisomy 18 phenotype and originated from the balanced translocation between parental chromosome 18 and other chromosomes. ConclusionNIPT gives an effective advance warning of trisomy 18. SNP array not only improves the detection rate of chromosomal abnormalities， but also helps identify the origin. The karyotype is still the gold standard for prenatal diagnosis.

Holoprosencephaly in Patau Syndrome / Holoprosencefalia na Síndrome de Patau

ABSTRACT Objective: To evaluate radiological (gestational and perinatal) and neonatal signs of patients with Patau syndrome and semilobar holoprosencephaly, as well as to report the association of both pathologies. Case description: This case report is about a female infant, born at term with trisomy of the chromosome 13 and semilobar holoprosencephaly, with thalamic fusion and a single cerebral ventricle, in addition to several other changes that worsened the patient's prognosis. Comments: Chromosome 13 trisomy is a genetic alteration that leads to the symptoms that determines Patau syndrome. In this syndrome, cardiovascular, urogenital, central nervous system, facial structure and intellectual impairment are common, in addition to problems in limb formation, such as decreased humerus and femur length, polydactyly, hypotelorism and low ear implantation. It is estimated, however, that holoprosencephaly is present in only 24 to 45% of the patients with trisomy 13.

RESUMO Objetivo: Avaliar sinais radiológicos (gestacionais e perinatais) e neonatais de paciente com síndrome de Patau e holoprosencefalia semilobar, assim como relatar a associação de ambas as patologias. Descrição do caso: Trata-se de um relato de recém-nascido do sexo feminino a termo, que apresentou trissomia do cromossomo 13 e holoprosencefalia semilobar, com fusão talâmica e ventrículo cerebral único, além de várias outras alterações que pioraram o prognóstico da paciente. Comentários: A trissomia do cromossomo 13 é um defeito genético que caracteriza um conjunto de sintomas que compõem a Síndrome de Patau. Nesta síndrome, é comum o acometimento cardiovascular, urogenital, do sistema nervoso central, da estrutura facial e da capacidade intelectual, além de falhas na formação dos membros, como diminuição no comprimento do úmero, fêmur, polidactilia, hipotelorismo e baixa implantação das orelhas. Estima-se, no entanto, que a holoprosencefalia apresente-se nesse grupo de malformações congênitas apenas em 24 a 45% dos casos.

Non-invasive prenatal testing for the diagnosis of congenital abnormalities: Insights from a large multicenter study in southern China

Although non-invasive prenatal testing (NIPT) is widely used to detect fetal abnormalities, the results of NIPT vary by population, and data for the screening efficiency of NIPT positive predictive value (PPV) from different populations is limited. Herein, we retrospectively analyzed the NIPT results in a large multicenter study involving 52,855 pregnant women. Depending on gestational age, amniotic fluid or umbilical cord blood was extracted for karyotype and/or chromosome microarray analysis (CMA) in NIPT-positive patients, and the PPV and follow-up data were evaluated to determine its clinical value. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 chromosomal abnormalities, with a PPV of 45.1%. PPV for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosomal aneuploidies (SCAs), and copy number variations (CNVs) were 78.9, 35.3, 22.2, 36.9, and 32.9%, respectively. The PPVs for T21, T18, and T13 increased with age, whereas the PPVs for SCAs and CNVs had little correlation with age. The PPV was significantly higher in patients with advanced age and abnormal ultrasound. The NIPT results are affected by population characteristics. NIPT had a high PPV for T21 and a low PPV for T13 and T18, and screening for SCAs and CNVs showed clinical significance in southern China.

Conducta médica frente al diagnóstico prenatal de trisomía 18: ¿se aproxima un cambio de paradigma?

El objetivo del trabajo es analizar dos conductas médicas opuestas en la vida prenatal de los niños con trisomía 18: el aborto y los cuidados paliativos perinatales. Se realizó una búsqueda bibliográfica en PubMed a partir de los términos "trisomy 18", "abortion" y "palliative care". Actualmente, están cambiando las conductas médicas dirigidas a los niños nacidos con trisomía 18, debido a que ya no se la considera una enfermedad incompatible con la vida. Este cambio de paradigma en la conducta médica posnatal debería reflejarse en la conducta prenatal, para ofrecer a los padres alternativas distintas al aborto. Los cuidados paliativos fetales y perinatales constituyen una respuesta ética válida para el tratamiento de niños con trisomía 18.

This article intends to analyze two opposing medical behaviors in the prenatal life of children with trisomy 18: abortion and perinatal palliative care. A literature search was carried out in PubMed using the terms "trisomy 18," "abortion," and "palliative care." Medical behaviors toward children born with trisomy 18 are changing because it is no longer considered a disease incompatible with life. This paradigm shift in postnatal medical conduct should be reflected in prenatal behavior to offer parents alternatives to abortion. Fetal and perinatal palliative care is a valid ethical response for treating children with trisomy 18.

O objetivo deste trabalho é analisar duas condutas médicas opostas na vida pré-natal das crianças com trissomia 18: o aborto e os cuidados paliativos perinatais. Foi realizada uma busca bibliográfica no PubMed a partir dos termos "trisomy 18", "abortion" e "palliative care". Atualmente, as condutas médicas para com as crianças nascidas com trissomia 18 estão mudando devido a não ser considerada mais como uma doença incompatível com a vida. Essa mudança de paradigma na conduta médica pós-natal deveria ser refletida na conduta pré-natal, para oferecer aos pais alternativas diferentes do aborto. Os cuidados paliativos fetais e perinatais constituem uma resposta ética válida para tratar crianças com trissomia 18.

Diagnóstico prenatal de enfermedad de canal atrio-ventricular, análisis epidemiológico y experiencia CERPO entre 2003 y 2021 / Prenatal diagnosis of atrio-ventricular canal disease, epidemiological analysis and CERPO experience between 2003 and 2021

Antecedentes: En Chile, la mitad de los casos de mortalidad perinatal son atribuibles a anomalías congénitas, y un tercio de estas corresponde a cardiopatías congénitas. Aproximadamente un 35% de estos últimos requerirán cirugía antes del año de vida, por lo que la pesquisa prenatal impacta profundamente en el pronóstico. Objetivo: Dar a conocer los resultados perinatales de pacientes con diagnóstico prenatal de canal atrio-ventricular controlados en el Centro de Referencia Perinatal Oriente (CERPO) entre los años 2003 y 2021, su asociación a otras anomalías, características demográficas y pronóstico a un año. Métodos: En este estudio se puede apreciar que tanto el pronóstico como el plan terapéutico posnatal dependerán de la presencia de otras alteraciones morfológicas y del estudio genético. De los factores estudiados, se puede concluir que tanto la presencia de anomalías cardiacas asociadas, como el grado de insuficiencia valvular y el tipo de canal no son predictores de la sobrevida perinatal. Conclusiones: Finalmente, en relación con la sobrevida posnatal, en este estudio, la sobrevida a un año de los recién nacidos vivos fue de un 52%, pero al desglosarlo en los niños con cariotipo euploide y trisomía 21, estos valores se tornan muy distintos, 44 y 81% respectivamente.

Background: In Chile, half of the perinatal mortality cases are attributable to congenital anomalies, and one third of these correspond to congenital heart disease. Approximately 35% of the later will require surgery before one year of life, so prenatal screening has a profound impact on the prognosis. Objective: To present the perinatal results of patients with a prenatal diagnosis of atrio-ventricular canal controlled at Centro de Referencia Perinatal Oriente CERPO) between 2003 and 2021, its association with other anomalies, demographic characteristics, and 1-year prognosis. Methods: In this study it can be seen that both the prognosis and the postnatal therapeutic plan will depend on the presence of other morphological alterations and the genetic study. From the factors studied, it can be concluded that the presence of associated cardiac anomalies, the degree of valvular insufficiency, and the type of canal are not predictors of perinatal survival. Conclusions: Finally, in relation to postnatal survival, in this study, the 1-year survival of live newborns was 52%, but when broken down into children with euploid karyotype and trisomy 21, these values become very different, 44 and 81% respectively.

Características ecográficas y anomalías congénitas en fetos con síndrome de Down / Ultrasound features and congenital anomalies in fetuses with Down syndrome

Resumen Objetivo: Describir y analizar los hallazgos ecográficos en 97 fetos portadores de síndrome de Down (SD) confirmado. Método: Se incluyeron todas las gestantes con diagnóstico prenatal de SD de nuestro centro, realizado por cariograma o reacción en cadena de la polimerasa cuantitativa fluorescente para aneuploidía. Se analizaron los informes genéticos y ecográficos, y se realizó un seguimiento posnatal. Resultados: De los 97 casos de SD, el 73% de los diagnósticos fueron entre las 11 y 14 semanas. El promedio de edad de las madres fue de 35,7 años. El 83% de los fetos con SD, evaluados a las 11-14 semanas, tuvieron una translucencia nucal ≥ 3,5 mm. Del total de los casos analizados, el 33% fueron portadores de una cardiopatía congénita, correspondiendo el 58% de estas a defectos mayores, principalmente anomalías del tabique auriculoventricular. Un 7,6% de los casos terminaron como mortinato, principalmente durante el tercer trimestre. Conclusiones: El ultrasonido es una herramienta muy sensible para la sospecha prenatal de SD y la detección de sus anomalías asociadas. Consideramos que la información aportada será útil para programar estrategias de pesquisa, organizar el control perinatal y precisar el consejo a los padres de fetos portadores de esta condición.

Abstract Objective: To describe and analyze the ultrasound findings in 97 fetuses with confirmed Down syndrome (DS). Method: All pregnant women with prenatal diagnosis of DS in our center, performed by karyotype or quantitative fluorescent polymerase chain reaction for aneuploidy, were included. Genetic and ultrasound reports were analyzed, as well as postnatal follow-up. Results: Of the 97 cases of DS, 73% of the diagnoses were between 11-14 weeks. The average age of the mothers was 35.7 years. 83% of our fetuses with DS, evaluated between 11-14 weeks, had a nuchal translucency ≥ 3.5 mm. Of the total of the fetuses analyzed, 33% were carriers of congenital heart disease, 58% of these correspond to a major defect, mainly anomalies of the atrioventricular septum. 7.6% of cases ended as stillbirth, mainly during the third trimester. Conclusions: Ultrasound is a very sensitive tool for prenatal suspicion of DS and the detection of its associated abnormalities. We believe that the information provided will be useful to program screening strategies, organize perinatal control and to counselling parents of fetuses carrying this condition.

Caracterización de los recién nacidos con síndrome de down según condiciones de salud, demográficas y sociales en Medellín del periodo 2015 a 2019 / Characterization of newborns with Down Syndrome according to health, demographic and social conditions in Medellín from the period 2015 to 2019

Resumen La adaptación de una atención especializada para recién nacidos con Síndrome de Down (SD) requiere el reconocimiento de sus características a nivel local. Objetivo: caracterizar los recién nacidos diagnosticados con SD y sus madres en unidades de atención materno infantil de la ciudad de Medellín. Adicionalmente, se exploraron factores asociados al diagnóstico oportuno antenatal. Método: estudio observacional descriptivo de tipo transversal con intención analítica basado en registros médicos de recién nacidos diagnosticados con SD en siete instituciones de Medellín, Antioquia entre enero de 2015 y diciembre de 2019 teniendo en cuenta variables tanto maternas como neonatales. Se realizó un análisis univariado mediante frecuencias absolutas y relativas, luego se realizó un análisis bivariado teniendo en cuenta los desenlaces neonatales según el acceso al control prenatal y el momento en el cual se realizó el diagnóstico (prenatal o neonatal) y finalmente se realizó un análisis multivariado para diagnóstico neonatal tardío. Resultados: el 50,2% de las madres al momento del parto tenía 35 años o menos, de estas el 59,9% pertenecía al régimen contributivo y el 83,4% realizó 4 controles prenatales (CPN) o más, a pesar de esto, se encontró que sólo el 33,7% tenían diagnóstico prenatal de SD. La mayoría (91,4%) de los neonatos tuvo diagnóstico de cardiopatía congénita y la estancia hospitalaria prolongada estuvo en relación a morbilidad relacionadas. Conclusión: el SD es una de las cromosomopatías más común en nuestro medio, la cual se puede diagnósticar de forma temprana. Sin embargo en nuestro estudio se pudo evidenciar que pese a la alta cobertura de CPN la frecuencia del diagnóstico antenatal es menor, lo cual requiere que estos controles sean realizados por personal médico entrenado en pacientes con este tipo de patología. Esto finalmente se va a ver reflejado en una mejor aceptación por parte de la familia hacia la llegada de un hijo con esta condición y por supuesto, mejor acceso a servicios de salud especializados.

Abstract The adaptation of specialized care for newborns with Down syndrome (DS) requires recognition of its characteristics at the local level. Goal: to characterize newborns diagnosed with DS and their mothers in maternal and child care units in the city of Medellín. Also, explore the factors associated with timely prenatal diagnosis. Methods: observational, cross-sectional study, based on medical records of newborns diagnosed with DS in seven institutions in Medellín, Antioquia between January 2015 and December 2019, taking into account both maternal and neonatal variables. Initially, a univariate analysis was performed using absolute and relative frequencies, then a bivariate analysis was performed taking into account neonatal outcomes according to access to prenatal care and the time at which the diagnosis was made (prenatal or neonatal), and finally a multivariate analysis for late neonatal diagnosis. Results: 50.2% of the mothers at the time of delivery were 35 years old or younger, of these 59.9% belonged to the contributory regime and 83.4% had 4 prenatal check-ups or more, despite this, it was found that only 33.7% had a prenatal diagnosis of DS. The majority (91.4%) of the neonates had a diagnosis of congenital heart disease and the prolonged hospital stay was related to related morbidity. Conclusion: DS is one of the most common chromosomal abnormalities in our environment, which can be diagnosed early. However, in our study it was possible to show that despite the high coverage of prenatal controls, the frequency of antenatal diagnosis is lower, which requires that these controls be carried out by medical personnel trained in patients with this type of pathology. This will finally be reflected in a better acceptance by the family towards the arrival of a child with this condition and, of course, better access to specialized health services.

Genetic testing and analysis of 2 cases of trisomy 11 mosaicism / 南方医科大学学报

Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management.

Genetic analysis and prenatal diagnosis of intellectual disability caused by Xq25 microduplication in a pedigree / 中华围产医学杂志

Objective:To analyze the clinical and genetic characteristics of a 27-year-old male patient with intellectual disability and his pedigree to provide a reference for genetic counseling and prenatal diagnosis.Methods:G-banding and array comparative genomic hybridization (aCGH) were performed to analyze the karyotypes and genomic copy number variations of the proband (Ⅲ-1) and his family members. Based on the results, prenatal diagnosis was performed for one pregnant woman (Ⅲ-2) in the pedigree who is the sister of the proband.Results:All karyotyping were normal in the family members, while aCGH results showed a 1 533 kb microduplication in the Xq25 region of the proband, his mother (Ⅱ-3), his uncle (Ⅱ-2), and his sister (Ⅲ-2), which was confirmed to be pathogenic. The proband and his uncle presented with intellectual disability, bradylalia, and facial dysmorphism. In contrast, his mother and sister showed normal phenotypes. His sister's fetal karyotype and aCGH results were normal, and the pregnancy continued. A male baby (Ⅳ-1) was delivered vaginally at term and showed no physical or intellectual abnormalities during a 46-month follow-up.Conclusions:Xq25 microduplication might be the cause of intellectual disability in the proband. STAG2 is probably the essential gene in Xq25 region.

Chronic lymphocytic leukemia with t(14;18)(q32;q21): report of 3 cases and review of literature / 白血病·淋巴瘤

Objective:To improve the understanding of chronic lymphoblastic leukemia (CLL) with t(14;18)(q32;q21).Methods:The clinical data of 3 cases diagnosed as CLL with t(14;18)(q32;q21) in the Tianjin KingMed Medical Laboratory from January 2020 to January 2021 were retrospectively analyzed. The clinicopathological data, morphological examination, immunophenotype, cytogenetics and somatic mutation of immunoglobulin heavy chain variable region genes of patients were comprehensively analyzed, and the literature was reviewed.Results:All the 3 patients showed lymphatic proliferative diseases, and their morphological characteristics and immunophenotype were typical characteristics of CLL.Conclusions:The diagnosis of CLL is mainly based on the typical morphology and immunophenotype of tumor cells. The presence of t(14;18) should not be used to exclude the diagnosis of CLL.

Falsos positivos del cribado de trisomía 21 y 18 del primer trimestre y complicaciones obstétricas / Adverse outcomes in pregnancies with false positive trisomy 21 and 18 screening results

OBJETIVO: Analizar si los casos positivos de cribado combinado de trisomía 21 (t21) o trisomía 18 (t18) en ausencia de aneuploidía (falsos positivos- FP) se relacionan con complicaciones de la gestación, ajustando por factores demográficos y clínicos de riesgo. MATERIAL Y MÉTODOS: Estudio retrospectivo de casos y controles anidado en una cohorte de pacientes que acudieron para cribado del primer trimestre. Los casos fueron las pacientes con FP de riesgo combinado de t21 superior a 1/270 o riesgo de t18 superior a 1/100. Se consideraron complicaciones de la gestación: óbito fetal, parto prematuro menor de 34 semanas o prematuro menor de 37 semanas, preeclampsia, retrasos de crecimiento, pequeño para la edad gestacional (CIR, PEG) y diabetes gestacional (DG). Se ajustó por obesidad, edad, paridad, tabaquismo, y técnicas de reproducción asistida. RESULTADO: Se obtuvieron 204 casos de FP, 149 FP para trisomía 21, 41 para trisomía 18, y 14 FP para ambos riesgos. Se encontró asociación estadísticamente significativa de FP t21 con óbito fetal (OR=3,5; ic95% 1,4-8,7; p=0,01), parto prematuro menor de 37 semanas (OR=2,2; IC95% 1,4-3,4; p=0,001), preeclampsia (OR =2,6; IC95% 1,17-6,1; p=0,02), PEG (OR =2,2; IC95% 1,2-4,1; p=0,02), CIR (OR=2,8; IC95% 1,6-5,1; p=0,001), y DG (OR=2,1; IC95% 1,2-3,7; p=0,01). Los FP t18 se asociaron con óbito (OR=8,9; IC95% 2,9-27; p=0,002). CONCLUSIÓN: Los FP del cribado del primer trimestre, para trisomía 21 y trisomía 18, se asocian con resultados obstétricos adversos.

We have studied whether positive cases of combined trisomy 21 (t21) or 18 (t18) screening in the absence of aneuploidy (false positives -FP-) are related to pregnancy complications adjusting for demographic and clinical risk factors. METHODS: Retrospective case-control study nested in a cohort of patients who came for first trimester aneuploidy screening. The cases were patients with FP combined risk of t21 (greater than 1/270) or t18 risk (greater than 1/100). The control group was a sample of patients with low-risk screening. We considered pregnancy complications: stillbirth, premature delivery before 34 and 37 weeks, preeclampsia, growth retardation, small for gestational age (FGR, SGA), and gestational diabetes (GD). Or were adjusted for obesity, age, parity, smoking, and assisted reproduction techniques. RESULTS: 204 cases of FP were obtained, 149 FP for trisomy 21, 41 for trisomy 18, and 14 FP for both risks. A statistically significant association between t21 FP was found with stillbirth (OR = 3.5; 95% CI 1.4-8.7; p = 0.01), preterm delivery less than 37 weeks (OR = 2.2; 95% CI 1.4-3.4; p = 0.001), preeclampsia (OR = 2.6; 95% CI 1.17-6.1; p = 0.02), SGA (OR = 2.2; 95% CI 1, 2-4.1; p = 0.02), FGR (OR = 2.8; 95% CI 1.6-5.1; p = 0.001), and GD (OR = 2.1; 95% CI 1.2 −3.7; p = 0.01). FP t18s were associated with fetal loss (OR= 8.9 (95% CI 2.9-27) p = 0.002. CONCLUSION: FP from first trimester screening for t21 and t18 are associated with adverse obstetric outcomes.

Síndrome de Down e patologias associadas: uma revisão narrativa da literatura / Down syndrome and associated pathologies: a narrative review of the literature / Síndrome de Down y patologías asociadas: una revisión narrativa de la literatura

Objetivo: identificar por meio de uma revisão narrativa de literatura as patologias mais recorrentes em indivíduos com Síndrome de Down. Método: trata-se de uma revisão narrativa. Realizou-se um levantamento da literatura no Portal Pubmed e nas bases de dados de publicações científicas indexadas: Scientific Eletronic Library Online (Scielo), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Base de Dados de Enfermagem (BDENF) e Cumulative Index to Nursing and Allied Health Literature (CINAHL) e Portal PubMed, usando os descritores "Down's syndrome", "Pathologies", "Trisomy 21", "Intellectual Disability", "Clinical manifestations". Resultados: foram encontrados 696 artigos, dos quais 24 foram analisados na íntegra, destes, foram selecionados 9 artigos que compuseram a amostra desta revisão. A maioria dos estudos selecionados mensurou as características fenotípicas peculiares nos indivíduos com essa anomalia, a saber: olhos oblíquos, orelhas baixas, braquidactilia, hipotonia, baixa estatura, braquicefalia, fissuras oblíquas na pálpebra, epicanto, manchas de Brushfield na íris, dentre outras. Conclusão: torna-se necessária uma atenção e acompanhamento regular dos profissionais de saúde acerca das patologias malignas, doenças autoimunes e inflamatórias que acometem as pessoas com SD.

Objective: to identify through a narrative literature review the most recurrent pathologies in individuals with Down syndrome. Method: this is a narrative review. A survey of literature was conducted on the Pubmed Portal and in the databases of indexed scientific publications: Scientific Electronic Library Online (Scielo), Latin American and Caribbean Literature on Health Sciences (LILACS), Nursing Database (BDENF) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PubMed Portal, using the descriptors "Down's syndrome", "Pathologies", "Trisomy 21", "Intellectual Disability" , "Clinical manifestations". Results: 696 articles were found, of which 24 were fully analyzed, of which 9 articles were selected that comprised the sample of this review. Most of the selected studies measured the peculiar phenotypic characteristics in individuals with this anomaly, namely: oblique eyes, low ears, brachydactyly, hypotonia, short stature, brachycephaly, oblique clefts in the eyelid, epicant, Brushfield spots on the iris, among others. Conclusion: it is necessary to have regular attention and follow-up of health professionals about malignant pathologies, autoimmune and inflammatory diseases that affect people with DS.

Objetivo: identificar a través de una literatura narrativa revisar las patologías más recurrentes en individuos con síndrome de Down. Método: esta es una revisión narrativa. Una encuesta de literatura se realizó en el Portal Pubmed y en las bases de datos de publicaciones científicas indexadas: Biblioteca Electrónica Científica en Línea (Scielo), Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), Base de Datos de Enfermería (BDENF) e Índice Acumulativo de Literatura de Enfermería y Salud Aliada (CINAHL) y PubMed Portal, utilizando los descriptores "Síndrome de Down", "Patologías", "Trisomy 21", "Discapacidad Intelectual" , "Manifestaciones clínicas". Resultados: se encontraron 696 artículos, de los cuales 24 fueron analizados en su totalidad, de los cuales se seleccionaron 9 artículos que comprendían la muestra de este examen. La mayoría de los estudios seleccionados midieron las peculiares características fenotípicas en individuos con esta anomalía, a saber: ojos oblicuos, orejas bajas, braquidactilia, hipotonía, estatura baja, braquicefalia, hendiduras oblicuas en el párpado, epicante, manchas de Brushfield en el iris, entre otros. Conclusión: es necesario tener atención regular y seguimiento de los profesionales de la salud sobre patologías malignas, enfermedades autoinmunes e inflamatorias que afectan a las personas con DS.

Cytogenetic and molecular genetic analysis of three fetuses at high risk of trisomy-16 detected by cell-free fetal DNA testing / 中华围产医学杂志

Objective:To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA (cffDNA) testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods:This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020. Results of the conventional G-banding karyotype analysis of amniotic fluid, single nucleotide polymorphism array (SNP-array) and low-coverage massively parallel copy number variation sequencing (CNV-seq) of placenta/fetal skin samples were analyzed.Results:(1) cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57, 24.88 and 17.87, respectively. (2) Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2, while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1, and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2. Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97] and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation. (3) Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3. All three pregnancies were terminated. CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16, with the copy numbers of chromosome 16 of 2.56/2.70, 2.73/2.82, 2.80/2.81, respectively. However, no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues. Conclusions:cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21. For high-risk cases of trisomy-16 indicated by cffDNA testing, SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.

Prenatal ultrasound analysis of 200 fetuses with trisomy 21 syndrome / 中国医师杂志

Objective:To analyze the prenatal ultrasound manifestation of trisomy 21 syndrome and investigate the clinical significance of prenatal ultrasound in screening 21-trisomy syndrome.Methods:A retrospective analysis of prenatal ultrasound results of 200 fetuses diagnosed with 21-trisomy syndrome by karyotype from May 2017 to August 2018 in Hunan Provincial Maternal and Child Health Care Hospital. Ultrasound abnormalities were divided into isolated soft markers, simple structural abnormalities, complex ultrasound markers. The relationship between these markers and trisomy 21 was analysed.Results:200 fetuses with trisomy 21 syndrome diagnosed by karyotype, in which 39 cases (19.5%, 39/200) abnormalities were detected by ultrasound, including soft indexes and structural abnormalities/other abnormalities. The rates of isolated soft indexes, simple structural abnormalities/ other abnormalities and complex ultrasound markers were 15.5%(31/200), 2.0%(4/200), 2.0%(4/200), respectively. The most common of soft markers in the first trimester was thickened nuchal translucency (4/18), thickened nuchal fold (13.19%, 24/182) in the second trimester, followed by nasal bone dysplasia, tricuspid regurgitation and polyhydramnios (1.65%, 3/182). The most common structural malformations in the second trimester was cardiovascular malformation (3.30%, 6/182).Conclusions:Prenatal ultrasound has a role to play in the screening of 21-trisomy syndrome, but exerts certain limitations. It is necessary to strengthen the understanding of the ultrasonographic features of trisomy 21 and improve the detection rate of abnormal indicators. Meanwhile, it should be combined with serological screening, non-invasive prenatal testing technology to increase the detection rate of trisomy 21.

Anomalías congénitas y comorbilidad en neonatos con Síndrome de Down / Congenital anomalies and comorbidities in neonates with Down Syndrome

INTRODUCCIÓN: El Síndrome de Down se presenta en 2,5 de 1.000 recién nacidos vivos chilenos. Presentan más anomalías congénitas y comorbilidades que la población general, aumentando su tasa de hospitalización. OBJETIVO: Describir las anomalías congénitas y comorbilidades de neonatos con Síndrome de Down nacidos y/u hospitalizados en la década 2008-2018. PACIENTES Y MÉTODO: Retrospectiva mente se revisaron registros de los pacientes nacidos y/u hospitalizados dentro de sus 28 días de vida entre el 1 de enero de 2008 y el 31 de diciembre de 2018. Para cada paciente se consignó: edad materna, antecedentes familiares de Síndrome de Down, antecedentes pre y perinatales y resultado de estudio genético. Se consignó la edad al ingreso, el motivo principal de ingreso, comorbilidades, días de hospitalización y fallecimiento. Se excluyeron dos pacientes con más del 50% de ficha in completa. Se exploraron asociaciones entre morbilidades, anomalías y fallecimiento. RESULTADOS: 140 de 79.506 (0,2%) recién nacidos vivos fueron diagnosticados con Síndrome de Down en el período neonatal. 24,7% fueron prematuros y 26,4% tuvieron bajo peso para su edad gestacional. Los porcentajes de morbilidad y hospitalización fueron 83,6% y 90%. La principal causa de ingreso fue la poliglobulia, y la más frecuente hiperbilirrubinemia. Fallecieron 4 pacientes (2,9%) y 70,7% presentó alguna una anomalía congénita, principalmente cardíaca. La mediana de edad materna fue de 36 años y 57,1% tenía 35 años o más. CONCLUSIONES: Esta investigación aporta información relevante para optimizar el manejo perinatal y el seguimiento de los pacientes con Síndrome de Down.

INTRODUCTION: In Chile, Down syndrome has a prevalence of 2.5 in 1,000 live births. These patients present more congenital anomalies and comorbidities than the general population, increasing their hospitaliza tion rate. OBJECTIVE: To describe congenital anomalies and comorbidities of neonates with Down syndrome born and/or hospitalized between 2008 and 2018. PATIENTS AND METHOD: We conducted a retrospective review of patient's medical records born and/or hospitalized during their first 28 days of life between January 1st, 2008, and December 31st, 2018. For each patient, we recorded maternal age, familiar cases of Down Syndrome, pre and perinatal history, genetic study result, as well as age at admission, reason for hospitalization, comorbidities, length of stay, and death. Two patients that had more than 50% of incomplete medical records were excluded. We studied the associations between comorbidities, congenital anomalies, and death. RESULTS: 140 in 79,506 newborns (0.2%) were diagnosed at our center with Down Syndrome in their neonatal period. 24.7% were born preterm and 26.4% had low birth weight for gestational age. Morbidities and hospitalizations were present in 83.6% and 90%, of the study population, respectively. The main reason for hospitalization was polycythemia and the most frequent was hyperbilirubinemia. Four patients died (2.9%) and 70.7% presented at least one congenital anomaly, mainly heart disease. Median maternal age was 36 years and 57.1% of mothers were aged 35 or older. CONCLUSIONS: This cohort of patients with Down Syndrome provides important information for the optimization of their perinatal management and follow-up.

Prevalencia y perfil de cardiopatías congénitas en pacientes con Síndrome de Down. Hospital de Especialidades Pediátricas Omar Torrijos Herrera. 2011-2018 / Prevalence and profile of congenital heart disease in patients with Down syndrome. Omar Torrijos Herrera Pediatric Specialties Hospital. 2011-2018

Introducción: En los pacientes con Síndrome de Down, las cardiopatías congénitas alcanzan una prevalencia entre el 40 y 50%. Materiales y Métodos: El presente es un estudio descriptivo, retrospectivo, de corte transversal en el que se determinará la frecuencia de cardiopatías congénitas en la población con síndrome de Down síndrome de Down atendida en el Hospital de Especialidades Pediátricas "Omar Torrijos Herrera" entre los años 2011 y 2018, así como las cardiopatías congénitas más frecuentes encontradas. Resultados: 53 pacientes ingresaron en el estudio. Se encontró síndrome de Down asociado a cardiopatías congénitas en un 54.7% de los casos. De estos las cardiopatías más frecuentes encontradas fueron comunicación interventricular (CIV) con un 31.03%, ductus arterioso persistente (DAP) en un 20.69% y canal auriculoventricular (canal AV) en un 13.79% de los casos. Conclusiones: La prevalencia de cardiopatías congénitas en esto pacientes es similar a lo encontrado en la literatura. La cardiopatía más frecuente fue la comunicación interventricular. La prevalencia de hipertensión pulmonar y la mortalidad fueron menores que lo reportado en la literatura.

Introduction: Among patients with Down's syndrome, there is a prevalence of congenital heart disease of 40-50%. Materials y Methods: The present is a descriptive, retrospective, transversal study in which will be evaluated the frequency of congenital heart disease in children with Down's Syndrome attended in Omar Torrijos Herrera Pediatric Specialties Hospital between 2011 and 2018, and which congenital heart diseases are the most common in these population. Results: 53 patients were included in the study. It was found congenital heart disease in 54.7% of the cases. From these, 31.03% were ventricular septal defect (VSD), 20.69% were persistence of ductus arteriosus (PDA) and 13.79% auricular-ventricular septal defects (AVSD). Conclusions: The prevalence of congenital heart disease is similar to what is reported in literature. The congenital heart disease most frequent was ventricular septal defect. The prevalence of pulmonary hypertension and the mortality was lower than the reported in literature.