Avaliação das habilidades funcionais de crianças e adolescentes com trissomia 21 (T21) e a relação com suas variáveis socioambientais e de saúde / Assessment of the functional abilities of children and adolescents with trisomy 21 (T21) and the relationship with their socio-environmental and health variables, 2021

Introdução. A síndrome de Down (SD), também denominada trissomia 21 (T21), é a cromossomopatia mais frequentemente associada à deficiência intelectual. A informação sobre as potencialidades e dificuldades funcionais das crianças com T21 pode auxiliar pais, terapeutas, gestores da saúde e educadores, favorecendo serviços de apoio à saúde e educação dessa população. Objetivo. Avaliar as habilidades funcionais e a assistência prestada pelos pais de crianças e adolescentes com T21 em idade escolar e explorar a eventual influência de algumas características socioambientais. Método. Estudo observacional, analítico, transversal com amostra de conveniência composta por 44 crianças em idade escolar e adolescentes, parte de um estudo anterior, cujos dados foram coletados através da aplicação do Inventário de Avaliação Pediátrica de Incapacidades (PEDI) e respondidos pelos pais de crianças e adolescentes com T21 que aceitaram participar do estudo, após terem assinado o termo de consentimento livre e esclarecido. Resultados. 45,5% eram crianças e adolescente com idade entre 7 anos e 7 meses a 12 anos e 54,5% entre 12 anos e 1 mês a 19 anos e 6 meses, predominando o sexo masculino (63,5%). 36,6% tiveram diagnóstico de cardiopatia congênita, 93,0% frequentavam escolas. Dos cuidadores 47,6% tinham apenas o primeiro grau incompleto. Quanto ao acompanhamento terapêutico algumas crianças e adolescentes ainda recebiam cuidados: por fisioterapeutas (9,1%), por fonoaudiólogos (31,8%) e por terapeutas ocupacionais (13,6%). Observou-se diferença estatisticamente significante (p<0,005) no domínio função social e o grau de assistência prestado pelo cuidador no mesmo. As demais relações entre o grau de desempenho da criança e o grau de atenção que o cuidador presta nos demais domínios não evidenciaram diferenças estatisticamente significantes. Quanto às outras variáveis apenas idade e frequência à escola da criança e do adolescente, bem como, receber assistência de Fisioterapia e Fonoaudiologia mostraram discrepâncias entre desempenho e o grau de cuidado prestado, de maneira significante estatisticamente no que se refere ao domínio de autocuidado e função social. Conclusão. A interpretação desses resultados revela haver um descompasso no domínio função social entre o desempenho das crianças e adolescentes e o grau de assistência prestada pelos cuidadores, que parece ser excessiva em relação às necessidades destas crianças e adolescentes. Com relação a outras variáveis apenas idade, frequência à escola e os cuidados de Fisioterapia e Fonoaudiologia mostraram que podem influenciar positiva ou negativamente o desempenho da criança e do adolescente e a relação entre estes e o cuidador, particularmente nos domínios de autocuidado e função social.

Background. Down syndrome (DS), also called trisomy 21 (T21), is the most common chromosomal disorders associated with intellectual disability. Information about the potential and functional difficulties of children with T21 can help parents, therapists, health managers and educators, favoring health support services and education for this population. Objective. Evaluate the functional abilities and the care provided by parents of school-age children and adolescents with T21 and explore the possible influence of some socio-environmental characteristics. Method. Observational, analytical, cross-sectional study with a convenience sample of 44 school-age children and adolescents, part of a previous study, whose data were collected through the application of the Pediatric Evaluation of Disability Inventory (PEDI) and answered by the parents of children and adolescents with T21 who agreed to participate in the study, after signing the informed consent form. Results. 45.5% were children and adolescents aged between 07 years old and 07 months to 12 years old, and 54.5% between 12 years old and 01 month to 19 years old and 06 months, predominantly male (63.5%). 36.6% were diagnosed with congenital heart disease, 93.0% attended schools. As per the caregivers, 47.6% had only an incomplete elementary school. As for therapeutic follow-up, some children and adolescents still receiving care: by physical therapists (9.1%), by speech therapists (31.8%) and by occupational therapists (13.6%). There was a statistically significant difference (p<0.005) in the social function domain and the degree of care assistance provided by the caregiver. The other relationships between the child's level of performance and the level of attention the caregiver pays in the different domains did not show statistically significant differences. As for the other variables, only the age and school attendance of the child and the adolescent, as well as the ones receiving physical therapy and speech therapy assistance, showed discrepancies between performance and the degree of care provided, in a statistically significant way concerning the domain of selfcare and social function. Conclusion. The interpretation of these results reveals a mismatch in the social function domain between the performance of the children and the adolescents and the degree of assistance provided by caregivers, which seems to be excessive to the needs of these children and adolescents. Regarding the other variables, only the age, the school attendance, and the Physical Therapy and Speech Therapy care showed that they can positively or negatively influence the performance of the child and the adolescent and the relationship between them and the caregiver, particularly in the domains of self-care and social function.

Preparation and evaluation of quality management samples for noninvasive prenatal screening / 中华医学遗传学杂志

OBJECTIVE@#To prepare a quality control sample for non-invasive prenatal screening (NIPS) and evaluate its quality and stability.@*METHODS@#According to the biological characteristics of cell-free fetal DNA derived from the plasma of pregnant women, the simulated samples were prepared by mixing genomic DNA fragments derived from individuals with trisomy 21, trisomy 18 and trisomy 13 and background plasma. The samples were then compared with commercially made quality control products tested on various NIPS platforms and stored at -80℃, -20℃, 4℃, 24℃ and 37℃ for various periods of time.@*RESULTS@#The simulated samples have attained the expected results and could be detected on various platforms and stored at -80℃and -20℃ for at least 30 days.@*CONCLUSION@#A simulated sample was successfully prepared and possessed good stability. It can be used as the quality control sample for NIPS.

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.

Síndrome de Edwards com elevada sobrevida - relato de caso / Edwards Syndrome with high survival - case report

RESUMO Introdução: A Síndrome de Edwards, é a segunda alteração genética mais comum no recém-nascido, caracteriza-se por apresentar três cromossomos no par 18. Essa trissomia com baixa expectativa de vida, apresenta diversas malformações, principalmente alterações cardíacas, ortopédicas, neurológicas e pulmonares, afetando principalmente fetos do sexo feminino. Objetivo: Descrever um caso clínico de uma criança com Síndrome de Edwards com elevada sobrevida, 7 anos, uma exceção ao que é descrito na literatura. Relato de caso: Paciente feminina, 7 anos de idade, que nasceu com Síndrome de Edwards, diagnosticada no pré-natal. A gestação foi sem intercorrência e a criança nasceu a termo apresentando cardiopatias congênitas, como dupla via de saída do ventrículo direito, comunicação interventricular, permanência do canal arterial e estenose pulmonar. Apresenta também disfunção cerebral e alterações esqueléticas. Faz acompanhamento multidisciplinar com fonoaudióloga e fisioterapeuta duas vezes por semana e periodicamente com pediatra e neurologista. Conclusão: Por se tratar de um caso raro e pouco documentado na literatura a existência de crianças com mais de 7 anos de idade, como nesse caso, mostra que é possível superar a expectativa de vida documentada na literatura. Alguns fatores, como ter o diagnóstico no período pré-natal, não ter apresentado intercorrências na gestação, ter nascido a termo, apresentar cardiopatias congênitas que se compensam, somando-se a cuidados multiprofissionais semanalmente, podem ter contribuído para que esta criança tenha conseguido viver até os 7 anos. PALAVRA-CHAVE: Trissomia, síndrome da trissomia do cromossomo 18, sobrevida

ABSTRACT Introduction: Edwards Syndrome, the second most common genetic alteration in newborns, is characterized by having three chromosomes in pair 18. This trisomy with low life expectancy, presents several malformations, mainly cardiac, orthopedic, neurological and mainly affecting female fetuses. Objective: To describe a clinical case of a child with Edwards Syndrome with high survival, 7 years, an exception to what is described in the literature. Case report: Female patient, 7 years old, who was born with Edwards Syndrome, diagnosed prenatally. The pregnancy was uneventful and the child was born at term with congenital heart disease, such as right ventricular double outlet, ventricular septal defect, permanence of the ductus arteriosus, and pulmonary stenosis. She also presents brain dysfunction and skeletal changes. She undergoes multidisciplinary follow-up with a speech therapist and physiotherapist twice a week and periodically with a pediatrician and neurologist. Conclusion: As this is a rare case and the existence of children over 7 years of age, as in this case, is little documented in the literature, it shows that it is possible to exceed the life expectancy documented in the literature. Some factors, such as having the diagnosis in the prenatal period, not having had complications during pregnancy, being born at term, having congenital heart diseases that compensate, adding to weekly multiprofessional care, may have contributed to this child having managed to live up to 7 years old. KEYWORDS: Trisomy, trisomy 18 syndrome, survival

Radioterapia en tumor de células gigantes tenosinovial (sinovitis villonodular pigmentada) / Radiation therapy in tenosynovial giant cell tumor (pigmented villonodular synovitis)

Presentar nuestra experiencia de 18 años en el tratamiento con radioterapia y evaluar cifras de control tumoral local en pacientes con diagnóstico de tumor de células gigantes tenosinovial difuso sinovitis villonodular pigmentada difusa. 33 pacientes, tratados durante el período 2000-2018. En 19 (57,6 %) se practicó sinovectomía parcial, 10 (30,3 %) fueron tratados con artroplastia y sinovectomía, 4 (12,2 %) con sinovectomía total. 32 pacientes recibieron radioterapia posoperatoria, 1 paciente preoperatoria. Técnica más empleada fue planificación 2D 51,5 % seguida de conformada con planificación 3D (RTC3D) 48,5 %. La dosis total promedio administrada 44 Gy (rango 10,5 - 50). Tiempo promedio de tratamiento radiante 28 días (8-35). Tiempo de seguimiento entre 0,7 - 240,8 meses, mediana 12 meses, promedio 52,1 meses. 26 pacientes (79 %) presentaron mejoría de la sintomatología inicial y 6 (18 %) refirieron estabilidad de los síntomas. La respuesta clínica al tratamiento en relación al tiempo de seguimiento, 12 pacientes (36,4 %) estaban asintomáticos, 10 con un seguimiento mayor a 60 meses; 14 (42,4 %) refieren respuesta clínica satisfactoria, (2 con un seguimiento mayor a 60 meses) 6 pacientes presentaban enfermedad estable, para un control local del 97 %. El 87,9 % presentaron dermatitis grado I, 1 desarrolló dermatitis grado II, 3 no presentaron efectos adversos. La radioterapia es una modalidad de tratamiento muy efectiva como adyuvante a la sinovectomía, observándose altas tasas de control local de la enfermedad con una baja morbilidad(AU)

To report our eighteen-year experience with radiation therapy in the treatment of diffuse tenosinovial giant cell tumor / diffuse pigmented villonodular synovitis and to assess local control of the disease. A review of 33 patients with treated with radiation therapy during the period 2000-2018 was done. 19 (57.6 %) partial synovectomy was performed, 10 (30.3 %) underwent arthroplasty plus synovectomy, 4 (12.2 %) total synovectomy. 32 patients received radiotherapy postoperative and 1 pre-operative. Most common technique employed was conventional (2D) in 51.5 % and 3D conformal (3DCRT) in 48.5 %. The average total dose was 44 Gy (range 10.5-50), with a mean treatment time of 28 days (8-35). Follow-up time ranged from 0.7- 240.8 months, median time and mean time of 12 and 52.1 months respectively After RT 26 (79 %) of the patients obtained improvement of the initial symptoms and 6 (18 %) were stable. 12 patients (36.4 %) were asymptomatic with follow-up time longer than 36 months (10 of 12 had follow-up time >60 months), 14 (42.4 %) had significant clinical improvement (2 of 14 had follow-up time >60 months), and 6 had stable disease, local control of 97 %. Complications were few, acute skin toxicity was grade I in 29 (87.9%) and grade II in 1 patient. There was no significant chronic toxicity. Radiation therapy is an effective adjuvant treatment modality after synovectomy in patients with high local control rates and low morbidity(AU)

Cariótipos possíveis na síndrome de Klinefelter: uma revisão narrativa / Possible karyotypes in the syndrome Klinefelter: A Narrative Review

Os sinais clínicos da síndrome de Klinefelter foram observados pela primeira vez em 1942, mas sua etiologia só foi definida em 1959. Trata-se de uma condição genética na qual pelo menos um cromossomo X extra é adicionado ao cariótipo masculino normal (46,XY) e acomete cerca de 1 em cada 500 homens. É caracterizada por variabilidade fenotípica que leva a atraso ou ausência de diagnóstico, com uma estimativa de 50% a 75% de homens com Síndrome de Klinefelter nunca obterem o diagnóstico correto. Apesar de o cariótipo clássico (47,XXY) ser encontrado em 80%-90% dos pacientes e o mosaicismo (46,XY/47,XXY) nos 10% restantes, outros cariótipos podem ser encontrados menos frequentemente. Nesse sentido, este estudo tem por finalidade descrever os possíveis cariótipos identificados nos pacientes com Síndrome de Klinefelter. Os resultados mostram que a Síndrome de Klinefelter é usualmente diagnosticada na vida adulta e caracterizada por uma heterogeneidade citogenética quanto aos cariótipos possíveis apresentados pelos pacientes afetados. A condição foi diagnosticada precocemente quando associada à anomalia dos cromossomos autossomos, excesso de cromossomos X extra ou quando foi realizado diagnóstico pré-natal por idade materna avançada. É imprescindível que os profissionais de saúde, em especial os médicos, se familiarizem mais com essa condição, pois o diagnóstico correto e precoce permite a intervenção e tratamento adequados visando melhorar a qualidade de vida desses indivíduos.

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.

Clinical effect of expanded non-invasive prenatal testing for serological screening of fetuses with high-risk for Down's syndrome / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical effect of expanded non-invasive prenatal testing (NIPT-plus) for serological screening of fetuses with high-risk for Down's syndrome.@*METHODS@#To retrospectively study the screening results, prenatal diagnosis and pregnancy outcomes of 1561 midterm pregnant women underwent NIPT-plus in our center from September 2018 to December 2019 due to serological screening with high-risk for Down's syndrome(≥ 1/270).@*RESULTS@#45 pregnant women had a high-risk with a detection rate of 2.88% (45/1561) of 1561 pregnant women who performed NIPT-plus. 40 pregnant women underwent invasive prenatal diagnosis and 20 cases were confirmed with a positive predictive value of 50.0% (20/40). Statistical analysis showed that NIPT-plus has a high detection rate for trisomy 21, sex chromosomal aneuploidy, and MMS in the 0.1/90 group, but with a positive predictive value lower than the other two groups.@*CONCLUSION@#The detection rate and PPVs of NIPT-plus in different groups of Down's high-risk pregnant women was different. NIPT-plus can reduce the pressure of prenatal diagnosis and can be used as a screening method for Down's syndrome with high risk in pregnant women.

Is it necessary to choose NIPT-plus for pregnant women who opt for non-invasive prenatal testing? A study of 50 cases / 中华医学遗传学杂志

OBJECTIVE@#To explore whether it is necessary to choose NIPT-plus for the prenatal screening of pregnant women.@*METHODS@#The results of NIPT and NIPT-plus sequencing data, fetal DNA concentration, prenatal diagnosis and pregnancy outcome of 50 pregnant women were compared.@*RESULTS@#Compared with NIPT, NIPT-plus attained similar fetal DNA concentration and a 4.4-fold increase in sequencing data. NIPT was able to detect 4 cases of 21-trisomy, 2 cases of 18-trisomy, and 9 cases of sex chromosome aneuploidies (SCAs) signaled by NIPT-plus, but missed one 18-trisomy, and failed to detect rare chromosome aneuploidies (RCAs) and microdeletion/microduplication syndromes (MMS). The PPVs of NIPT-plus for 21-trisomy, 18-trisomy, SCAs, MMS and RCAs were 100%, 100%, 44.4%, 30.4% and 0%, respectively. And those of NIPT for 21-trisomy, 18-trisomy, and SCAs were 100%, 100%, and 44.4%, respectively.@*CONCLUSION@#It is necessary for pregnant women to select NIPT-plus to improve the detection rate of common trisomies, SCAs and disease-specific MMS, therefore reduce the occurrene of birth defect.

Prenatal diagnosis of a rare case with de novo partial 21q(21q22.1→ qter) trisomy syndrome and absent nasal bone / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis for a fetus with absent nasal bone by using cytogenetic and molecular techniques.@*METHODS@#Chromosomal karyotyping, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) assays were applied for the diagnoses. Peripheral blood samples were also taken from the parents for chromosomal karyotyping and FISH analysis.@*RESULTS@#The fetus was found to have a 46,XX,add(21)(p11.2) karyotype, and SNP-array has revealed a 11.3 Mb duplication at 21q22.12q22.3 (hg19: 36 762 648-48 093 361), which was confirmed by FISH. Both parents were found to be normal by chromosomal karyotyping and FISH analysis. The fetus was ultimately found to have a karyotype of 46,XX,der(21)t(21;21)(p11.2;q22.1), resulting a de novo partial trisomy of 21q22.1.@*CONCLUSION@#Combined use of various techniques has enabled accurate prenatal diagnosis and genetic counseling for the fetus.

Prenatal cytogenetic and molecular genetic analysis of a fetus with confined placenta mosaicism for trisomy 16 / 中华医学遗传学杂志

OBJECTIVE@#To review the clinical data of a fetus with false positive result of non-invasive prenatal testing (NIPT) due to confined placental mosaicism (CPM).@*METHODS@#Amniotic fluid sample was taken from a pregnant women with high risk for chromosome 16 aneuploidy for karyotyping analysis, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH). Genetic testing was also conducted on the fetal and maternal surface of the placenta, root of umbilical cord and fetal skin tissue after induced abortion.@*RESULTS@#Cytogenetic analysis of the amniotic fluid sample yielded a normal karyotype. SNP array revealed mosaicism (20%) of trisomy 16 in the fetus. FISH confirmed the presence of mosaicism (25%) for trisomy 16. After induced labor, all sampled sites of placenta were confirmed to contain trisomy 16 by SNP array, while the analysis of fetal skin tissue yielded a negative result.@*CONCLUSION@#CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.

Analysis of Clinical Characteristics and Prognosis in Children with Acute Megakaryoblastic Leukemia without Down Syndrome / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL).@*METHODS@#The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment.@*RESULTS@#The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×10@*CONCLUSION@#Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.

Genetic analysis of a case with Pierre-Robin sequence due to partial 1q trisomy and partial 4q monosomy / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a neonate with Pierre-Robin sequence.@*METHODS@#The child was subjected to chromosomal karyotyping, single nucleotide polymorphism array (SNP-array)-based comparative genomic hybridization and fluorescence in situ hybridization (FISH) analysis.@*RESULTS@#The child has featured microgthnia, glossoptosis, upper airway obstruction, mandible dehiscence and short neck. He was found to have a karyotype of 46,XY,der(4)add(4)(q34). Her mother's karyotype was determined as 46,XX,t(1;4)(q43;q34), while his father was 46,XY. SNP-array analysis suggested the child to be arr [hg19] 1q42.2q44 (232 527 958-249 202 755)× 3; 4q34.3q35.2 (168 236 901-190 880 409)× 1. The result of SNP-array for both parents was normal. FISH analysis confirmed that his mother has carried a balanced t(1;4)(q42;34) translocation. The aberrant chromosome 4 in the child has derived from his mother's translocation, which gave rise to partial 1q trisomy and 4q monosomy.@*CONCLUSION@#The 1q42.2q44 duplication and 4q34.3q35.2 deletion of the child probably underlay his abnormal phenotype of Pierre-Robin sequence.

Impact of confined placental mosaicism on non-invasive prenatal testing and pregnancy outcomes / 中华医学遗传学杂志

OBJECTIVE@#To assess the impact of confined placental mosaicism (CPM) on non-invasive prenatal testing (NIPT) and pregnancy outcomes.@*METHODS@#Copy number variation sequencing (CNV-seq) and single nucleotide polymorphism array (SNP-array) were carried out on placental specimen sampled from eight pregnancies with confirmed false-positive NIPT results. The impact of CPM on NIPT and pregnancy outcomes were analyzed based on the laboratory tests and clinical characteristics.@*RESULTS@#Five of the eight cases with false-positive NIPT results were proven to be CPM involving trisomy 9, 13, 21, 22, and X, respectively. The mosaic ratios for different placental regions have varied from 4% to 80%. Two fetuses with confirmed CPM showed fetal growth restriction (FGR) and additional ultrasound abnormalities, 1 fetus showed only FGR. The remaining two fetuses showed normal growth.@*CONCLUSION@#NIPT is highly sensitive to CPM, whilst CPM is an important cause for false-positive NIPT result. CPM may be associated with FGR. Investigation of the presence of CPM is important for both pre- and post-test genetic counseling and management of the pregnancy.

Value of non-invasive prenatal testing for the detection of fetal chromosomal copy number variations / 中华医学遗传学杂志

OBJECTIVE@#To explore the value of non-invasive prenatal testing (NIPT) for the detection of fetal chromosome copy number variations (CNVs).@*METHODS@#Clinical data of 18 661 pregnant women who underwent NIPT were collected. For fetuses suspected for carrying CNVs, amniotic fluid samples were collected for chromosomal karyotyping and/or chromosomal microarray analysis (CMA).@*RESULTS@#Among all samples, NIPT suggested that 58 fetuses carried trisomy 21, 18 carried trisomy 18, 19 carried trisomy 13, 1 carried trisomies 18 and 21. Eighty eight women accepted invasive prenatal diagnosis. The results of CMA in 59 cases were consistent with those of NIPT, which yielded a consistency rate of 67.05%. In addition, 37 cases of fetal CNVs were detected by NIPT, of which 19 (15 microdeletions and 4 microduplications) have accepted invasive prenatal diagnosis. In 14 cases, the results were consistency with those of NIPT, with a consistent rate of 73.68%.@*CONCLUSION@#NIPT features high sensitivity and accuracy. Invasive prenatal diagnosis should be considered for CNVs detected by NIPT, and by tracing its parental origin, it can provide guidance for clinical practice.

Effectiveness of non-invasive prenatal screening for the detection of fetal sex chromosome anomalies / 中华医学遗传学杂志

OBJECTIVE@#To evaluate the efficacy of non-invasive prenatal screening (NIPS) for fetal sex chromosome anomalies.@*METHODS@#A retrospective analysis was carried out for 20 802 women undergoing NIPS screening. For 165 cases suspected for fetal sex chromosomal anomalies, the results of invasive prenatal diagnosis were obtained.@*RESULTS@#Among the 165 cases suspected for fetal sex chromosome anomalies, 129 have accepted invasive prenatal diagnosis, and 45 were confirmed, which yielded a positive predictive value of 34.88%. These included 16 cases of 47,XYY, 10 cases of 47,XXY, 6 cases of 45,X/46,XX, 5 cases of 47,XXX, 3 cases of 45,X, 1 case of 45,X/46,X,i(X)(q10), 1 case of 45,X/46,X,del(X)(q22), 1 case of 46,X,del(X)(q22), 1 case of 46,X,del(X)(p11) and 1 case of Xp22.31 1.2 Mb deletion.@*CONCLUSION@#NIPS has limited value for detecting fetal sex chromosome anomalies. Karyotyping analysis combined with other diagnostic techniques can offer effective prenatal diagnosis for suspected cases.

Clinical characteristics and prenatal diagnosis of fetuses with sex chromosomal aneuploidies detected by non-invasive prenatal testing during early and midterm pregnancies / 中华医学遗传学杂志

OBJECTIVE@#To analyze the indication, karyotyping result, ultrasound finding, pregnancy decision and follow-up of fetuses with sex chromosome aneuploidies (SCA) detected by non-invasive prenatal testing (NIPT) during early and midterm pregnancies.@*METHODS@#The results of 225 singleton pregnancies with fetal SCA detected by NIPT were reviewed and analyzed.@*RESULTS@#The 225 cases included 45,X (n=37), 47,XXY (n=74), 47,XXX (n=50), 47,XYY (n=56) and mosaicisms (n=8), among which 121 (53.8%) have opted to terminate the pregnancy, including 45,X (n=31), 47,XXY (n=61), 47,XXX (n=14), 47,XYY (n=12) and 3 mosaicisms. The remainder 104 (46.2%) have elected to continue with the pregnancy, among which three have opted to terminate due to abnormalities detected by ultrasonography, and two had spontaneous abortions.@*CONCLUSION@#NIPT as a first-tier screening method can effectively detect fetal trisomies 21, 13 and 18 as well as SCA. The types of fetal SCA and presence of ultrasound abnormalities are critical factors for the termination of pregnancy.

Results of non-invasive prenatal testing for 2473 women with twin pregnancy / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the detection of fetal chromosomal aneuploidies in women with twin pregnancy.@*METHODS@#A total of 2473 women with twin pregnancy underwent the NIPT test to assess the risk for fetal chromosomal aneuploidies from January 2016 to September 2019. Those with a high risk by NIPT were confirmed by amniocentesis or chorionic villus sampling. All cases were followed up to evaluate the positive prediction value of NIPT for twin pregnancies.@*RESULTS@#Among the 2473 women, the NIPT test has identified 31 cases (1.25%) with a high risk for fetal chromosomal aneuploidies, which included 5 cases of trisomy 21, 1 case of chromosome 21 deletion, 4 cases of trisomy 18, 7 cases of sex chromosome abnormality and 14 cases of microdeletion and microduplication. By invasive prenatal diagnosis or chromosomal karyotyping analysis of neonates, 5 cases of trisomy 21, 3 cases of trisomy 18, 1 case of sex chromosome abnormality, and 2 cases of microdeletion and microduplication were confirmed, which yielded a positive predictive value of 100%, 75%, 25% and 25%, respectively.@*CONCLUSION@#NIPT can be used for the screening of fetal chromosomal aneuploidies in women with twin pregnancy with high accuracy. The method is non-invasive, safe and effective for the screening of fetal chromosomal aneuploidies, in particular trisomy 21.

Genetic analysis of a pedigree with atypical partial 4q trisomy / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with mental retardation.@*METHODS@#G-banded karyotyping analysis and single nucleotide polymorphism microarray (SNP array) were used to detect the genetic variants within the family, and the origin of the variants was analyzed using UPDtool Statistics software.@*RESULTS@#The patient, a 26-year-old female, was found to have a chromosomal karyotype of 46,XX,dup(4)(q28.2q31.3),and SNP array revealed a 25.71 Mb duplication at 4q28.2-q31.3. The duplication was inherited from her father, and her fetus was found to carry the same duplication.@*CONCLUSION@#The duplication of the patient probably underlay the mental retardation. The gender of the carrier and parental origin of the duplication might have led to the variation in their clinical phenotype.