Chromosomal abnormalities detected by karyotyping among patients with secondary amenorrhea: a retrospective study

ABSTRACT BACKGROUND: Chromosomal abnormalities (CAs) have been described in patients with secondary amenorrhea (SA). However, studies on this association are scarce. OBJECTIVES: To evaluate the frequency and types of CAs detected by karyotyping in patients with SA. DESIGN AND SETTING: This retrospective study was performed in a reference clinical genetic service in South Brazil. METHODS: Data were obtained from the medical records of patients with SA who were evaluated between 1975 and 2022. Fisher's bicaudate exact test and Student's t-test were used, and P < 0.05 was considered significant. RESULTS: Among 43 patients with SA, 14 (32.6%) had CAs, namely del (Xq) (n = 3), 45,X (n = 2), 46,X,r(X)/45,X (n = 2), 46,XX/45,X (n = 1), 46,X,i(q10)/45,X (n = 1), 47,XXX (n = 1), 46,XX/47,XXX (n = 1), 46,XX/47,XX,+mar (n = 1), 45,XX,trob(13;14)(q10;q10)/46,XXX,trob(13;14)(q10;q10) (n = 1), and 46,XX,t(2;21)(q23;q11.2) (n = 1). Additional findings were observed mostly among patients with CA compared with those without CA (P = 0.0021). No difference in the mean age was observed between the patients with SA with or without CAs (P = 0.268025). CONCLUSIONS: CAs are common among patients with SA, especially those with short stature and additional findings. They are predominantly structural, involve the X chromosome in a mosaic, and are compatible with the Turner syndrome. Patients with SA, even if isolated, may have CAs, particularly del (Xq) and triple X.

Array-based comparative genomic hybridization combined with quantitative fluorescence-polymerase chain reaction analysis of spontaneous abortion tissue / 中国医师进修杂志

Objective:To detect and analyze the spontaneous abortion tissue by Array-based comparative genomic hybridization (Array-CGH) combined with quantitative fluorescence polymerase chain reaction (QF-PCR), and provide genetic guidance for spontaneous abortion prevention and prenatal testing.Methods:A total of 345 patients who were diagnosed with spontaneous abortion at Dalian Women′s and Children′s Medical Center between July 2016 to September 2019 were continuously collected. Array-CGH combined with QF-PCR technology was used to analyze and collect abortion tissues that met the inclusion criteria.Results:QF-PCR detected a total of 213 cases of abnormal chromosome number, and Array-CGH supplemented the detection of 24 cases of abnormal chromosome structure. The genetic abnormality detection rate reached 68.7% (237/345) , and common abortion tissues′ chromosomal abnormalities in this area were detected. The incidence of abortion tissues′ chromosomal abnormalities in the elder pregnant women (≥ 35 years) and earlier trimester pregnant women (<10 weeks) was significantly increased: 84.43% (141/167) vs. 53.93% (96/178), 59.42% (205/284) vs. 9.28% (32/61).Conclusions:Array-CGH combined with QF-PCR is comprehensive and complementary. Some karyotype abnormalities are more common in abortion tissues. The elder and earlier trimester pregnant women should accept genetic counseling.

Malformaciones congénitas en óbitos fetales / Congenital malformations in fetal stillbirth

INTRODUCCIÓN. Las malformaciones congénitas son defectos estructurales o funcionales producidos en el desarrollo embrionario o fetal, de diversa etiología, algunas son prevenibles por lo que el diagnóstico prenatal es indispensable para determinar pronóstico y futuro obstétrico. OBJETIVO. Describir las malformaciones congénitas prevalentes en óbitos fetales y destacar la importancia de completar el diagnóstico prenatal. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo y retrospectivo. De una población de 276 Historias Clínicas con diagnóstico de pérdidas fetales espontáneas, se tomó muestra de 41 con malformaciones congénitas del Centro Obstétrico, en el Hospital de Especialidades Carlos Andrade Marín, de enero 2017 a diciembre 2018. Criterios de inclusión: diagnóstico óbitos con malformaciones congénitas menores de 34 semanas de gestación identificadas por estudio ecográfico, cromosómico y de necropsia. Criterios de exclusión: óbitos con estudio de necropsia normal. Los datos se obtuvieron del sistema MIS-AS400. El análisis se realizó con el programa Microsoft Excel. RESULTADOS. Se encontró prevalencia de malformaciones congénitas en óbitos fetales del 14,85% (41; 276), el hidrops representó el 41,46% (17; 41), de estos en el 53% (9; 17) se hallaron malformaciones mayores y en el 47% (8; 17) otras malformaciones asociadas. Se encontraron 17 cariotipos, 76,47% (13; 17) fueron anormales y 23,52% (4; 17) normales. DISCUSIÓN. Las comorbilidades maternas y antecedentes familiares, fueron factores relevantes para la aparición de malformaciones congénitas cuya prevalencia aún se debe investigar en el Ecuador. CONCLUSIÓN. Se describieron malformaciones congénitas prevalentes y la importancia de realizar el control prenatal con estudios complementarios para precisar el diagnóstico y determinar el futuro obstétrico.

INTRODUCTION. Congenital malformations are structural or functional defects produced in embryonic or fetal development, of diverse etiology, some are preventable, so prenatal diagnosis is essential to determine prognosis and obstetric future. OBJECTIVE. Describe the prevalent congenital malformations in stillbirths and highlight the importance of completing the prenatal diagnosis. MATERIALS AND METHODS. Observational, descriptive and retrospective study. From a population of 276 Clinical Histories with a diagnosis of spontaneous fetal losses, a sample of 41 with congenital malformations was taken from the Obstetric Center, at the Carlos Andrade Marín Specialty Hospital, from January 2017 to December 2018. Inclusion criteria: diagnosis of deaths with malformations congenital less than 34 weeks of gestation identified by ultrasound, chromosomal and necropsy study. Exclusion criteria: deaths with normal autopsy study. The data were obtained from the MIS AS400 system. The analysis was carried out with the Microsoft Excel program. RESULTS. The prevalence of congenital malformations in stillbirths was 14,85% (41; 276), hydrops represented 41,46% (17; 41), of these, 53% (9; 17) found major malformations and in 47% (8; 17) other associated malformations. 17 karyotypes were found, 76,47% (13; 17) were abnormal and 23,52% (4; 17) were normal. DISCUSSION. Maternal comorbidities and family history were relevant factors for the appearance of congenital malformations whose prevalence has yet to be investigated in Ecuador. CONCLUSION. Prevalent congenital malformations and the importance of carrying out prenatal control with complementary studies to clarify the diagnosis and determine the obstetric future were described.

Detección de un mosaico de trisomía 21 en líquido amniótico / Detection of a mosaicism of trisomy 21 in amniotic liquid

Resumen Se analizó un resultado con alteración cromosómica tomado de una base de datos conformada por un total de 4755 muestras de líquido amniótico extraídos mediante amniocentesis con indicación de su médico tratante, riesgo sérico y edad materna avanzada. En este reporte se presenta la detección de un mosaico de trisomía 21 en líquido amniótico, mediante la técnica de Banda G donde se analizaron 20 metafases. Los resultados obtenidos documentan una composición cromosómica 47, XY+21 y 46, XY con una relación 9:11 respecto a las metafases analizadas, confirmándose así el diagnóstico del Síndrome de Down secundario a mosaico.

Abstract A result with chromosomal alteration was analyzed from a database consisting of a total of 4755 samples of amniotic fluid extracted by amniocentesis with indication of the attending physician, serum risk and advanced maternal age. This report presents the detection of a mosaicism of trisomy 21 in amniotic fluid, using G- Banding where 20 metaphases were analyzed. The results obtained document a chromosomal composition 47, XY + 21 and 46, XY with a 9:11 ratio with respect to the metaphases analyzed, confirming the diagnosis of Down syndrome secondary to mosaicism.

Síndrome de Edwards con cardiopatía congénita de larga supervivencia: reporte de caso y revisión de literatura / Prolonged survival in Edwards syndrome with congenital heart disease: a case report and literature review

El síndrome de Edwards o trisomía 18 es una entidad compleja, con afectaciones en los sistemas musculoesquelético, craneofacial, cardiovascular y neurológico. Su genética es variada, presentándose tanto de manera completa como en mosaicismo. Es infrecuente que la supervivencia supere el primer año de vida. Su caracterización fenotípica no es patognomónica, por lo cual el cariotipo es fundamental para el diagnóstico prenatal por medio de amniocentesis y cordocentesis mediante técnica de hibridación fluorescente in situ. Se presenta el caso de una paciente de ocho años que ha sobrevivido con esta condición, a pesar de presentar tetralogía de Fallot acompañada de malformaciones cardíacas graves. El diagnóstico comenzó por ecografía de tamizaje prenatal a las 16 semanas y ecografía de detalle, con amniocentesis y cariotipo de líquido amniótico, con resultado 47 XX+18. Ha sido tratada por múltiples especialidades médicas, debido a complicaciones osteomusculares, articulares, neurológicas, metabólicas y cardiovasculares que han limitado su calidad de vida. El manejo de estos pacientes requiere un equipo médico multidisciplinario. La consejería a los padres debe incluir aspectos relativos a la sobrevida, complicaciones frecuentes y riesgo-beneficio a evaluar antes de someter al menor a intervenciones quirúrgicas complejas o correctivas.

Edwards syndrome or trisomy 18 is a complex entity that involves the musculoskeletal, craniofacial, cardiovascular, and neurological systems. Its genetics are varied, presenting both in a complete and mosaic type. Survival rarely exceeds the first year of life. Its phenotype characterization is not pathognomonic, so karyotype is essential for diagnosis, prenatally by amniocentesis and cordocentesis by FISH technique. We present the case of an eight-year-old girl who has survived with this condition despite presenting tetralogy of Fallot and serious cardiac malformations. Diagnosis began with prenatal screening ultrasound at 16 weeks and detailed ultrasound, with amniocentesis and amniotic fluid karyotype, with a result of 47 XX+18. She has been treated by multiple medical specialties, due to musculoskeletal, joint, neurological, metabolic, and cardiovascular complications that have limited her quality of life. The management of these patients requires a multidisciplinary medical team, and counseling for parents should include aspects related to survival, frequent complications, and risk-benefit to be evaluated before subjecting the minor to complex or corrective surgical interventions.

Acute myeloid leukemia patients with CD7 positive: analyses of cytogenetic and clinical characteristics / 白血病·淋巴瘤

Objective To investigate the cytogenetic and clinical features of acute myeloid leukemia (AML) with CD7 positive. Methods Among 788 AML patients in the First Affiliated Hospital of USTC from January 2008 to December 2012, a total of 140 AML patients with CD7 positive were enrolled, and their clinical and cytogenetic characteristics were analyzed respectively. Results According to French-American-British (FAB) classification systems, M5[47.1 % (66/140)] and M2[27.1 % (38/140)] were often detected in 140 AML patients with CD7 positive. The positive rate of CD7 in M0patients [(60.9±13.2) %] was the highest, followed by (53.1±29.5) % in M1patient. Karyotype analysis showed that 72 (51.4 %) AML patients with CD7 positive had unfavorable karyotypes. Thirty-one (22.1 %) AML patients with CD7 positive simultaneously showed the expressions of lymphoid antigens. Clinically, some AML patients with CD7 positive was accompanied by hyperleukocytosis [75.0 % (105/140)] (white blood count ≥20×109/L) and hepatosplenomegaly [82.1 % (115/140)]. The proportion of elder patients (above 65 years old) and complete remission rate of AML with CD7 positive were lower than those of AML with CD7 negative [25.7 % (36/140) vs. 39.4 % (255/648);12.1 % (17/140) vs. 24.7 % (160/648), respectively], and there were statistical differences (χ 2＝ 8.62, P＝0.03; χ 2＝ 9.70, P＝ 0.01, respectively). Conclusion AML patients with CD7 positive have specific cytogenetic and clinical characteristics, and poor prognosis.

Azacitidine and lenalidomide as an alternative treatment for refractory acute myeloid leukemia: a case report / Azacitidina e lenalidomida como alternativa de tratamento para leucemia mieloide aguda refratária: um relato de caso

CONTEXT: Refractory acute myeloid leukemia (AML) is a difficult disease to control with second or third-line chemotherapy regimens. In this report, we describe using azacitidine in combination with lenalidomide as salvage therapy. CASE REPORT: 52-year-old female was diagnosed with refractory AML and high-risk cytogenetics: complex monosomal karyotype consisting of t (3, 3) in association with monosomy 7 and del 5q. Morphological remission associated with maintenance of the cytogenetic abnormality of chromosome 3 and disappearance of the abnormalities relating to chromosomes 5 and 7 was achieved after three cycles of combination therapy with azacitidine and lenalidomide. CONCLUSION: Azacitidine plus lenalidomide can be a therapeutic option for patients with refractory AML, as illustrated in this case. .

CONTEXTO: A leucemia mieloide aguda (LMA) refratária é considerada doença de difícil controle com regime quimioterápico de segunda ou terceira linha. Neste relato, é descrito o uso de azacitidina em combinação com lenalidomida como esquema de resgate. RELATO DE CASO: Paciente de 52 anos, do sexo feminino, com o diagnóstico de LMA refratária de alto risco citogenético, apresentava cariótipo complexo e monossômico, com t (3, 3), associado à monosomia do 7 e del 5q. Destaca-se que, após três ciclos da terapia combinada com azacitidina e lenalidomida, houve remissão morfológica, com manutenção da anormalidade citogenética relacionada ao cromossomo 3 e desaparecimento da anormalidade relacionada aos cromossomos 5 e 7. CONCLUSÃO: Azacitidina e lenalidomida podem ser opção terapêutica para pacientes com LMA refratária, como demonstrado neste caso. .

Relationship between absent or hypoplastic fetal nasal bone and chromosome abnormalities: analysis of 187 cases / 中华围产医学杂志

Objective To investigate the relationship between absent or hypoplastic fetal nasal bone and chromosome abnormalities.Methods From January 2010 to April 2014,187 fetuses were found to have absent or hypoplastic nasal bone by prenatal ultrasound scanning in Guangzhou Maternal and Children's Hospital.All the pregnant women should undergo interventional prenatal diagnosis for fetal chromosome abnormalities,and should be followed up for three months after the expected delivery date.The correlation between absent or hypoplastic fetal nasal bone and chromosome abnormalities,and the effects of complicating structural defects were analyzed by descriptive analysis and the Chi-square test.Results Of the 187 pregnant women,126 underwent interventional prenatal diagnostic tests,and fetal chromosome abnormalities were detected in 36 cases (28.6％),including 26 cases (20.6％) of trisomy 21,6 cases (4.8％) of trisomy 18,three cases (2.4％) of trisomy 13 and one sex chromosome chimerism.In the 126 cases received prenatal diagnosis,the incidence of chromosome abnormalities in fetuses without other structural defects was significantly lower than that with structural defects [12.7％ (8/63) vs 44.4％ (28/63),x2=15.556,P=0.000].Among 63 cases without other structural defects,seven fetuses were confirmed to have chromosome abnormalities in 14 women with high risk by Down syndrome screening,no chromosome abnormalities were found in 39 pregnant women with low risk by Down syndrome screening,and one sex chromosome chimerism was found in the other ten women who did not undergo Down syndrome screening.Absent or hypoplastic nasal bone detected in the first trimester resulted in a higher risk of chromosome abnormalities than that detected in the second and the third trimester [25.5％ (28/110) vs 10.4％ (8/77),x2=6.613,P=0.007].Conclusions When a fetus is found to have absent or hypoplastic nasal bone,it is necessary to perform Down syndrome screening and a detailed morphology scan.Women shown to have fetuses with absent or hypoplastic nasal bone with other structural defects or high risk by Down syndrome screening should undergo prenatal diagnostic tests to exclude fetal chromosome abnormalities.

Chromosomal analysis of 394 couples with recurrent spontaneous abortion / 国际检验医学杂志

Objective To explore the relationship between recurrent spontaneous abortion and the chromosome abnormality by analyzing the 394 couples′chromosome karyotypes.Methods Peripheral blood lymphocytes in 394 couples of recurrent spontane-ous abortion in Guangzhou area were cultured and performed the chromosome karyotype analysis.Results Among 394 couples of recrudescence abortion,41 cases (5.2%)of abnormal chromosome karyotypes were detected including 1 case(2.44%)of chromo-some number abnormality,8 cases (19.51 %)of balanced translocation,3 cases (7.32%)of Robertsonian translocation,1 case (2.44%)of chromosome inversion and 28 cases (68.29%)of chromosomal polymorphism.Conclusion The chromosomal abnor-mality is an important reason for recurrent spontaneous abortion.Recurrent spontaneous abortion is not only associated with anoma-lies of chromosome structure,and could have a certain relationship with chromosome polymorphism.

Variedad de la presentación citogenética en el síndrome de turner, prenatal y postnatal / Cytogenetics variety of presentation turner syndrome, prenatal and postnatal

Antecedentes: El síndrome de Turner (ST) es causado por la ausencia total o parcial del cromosoma X y posee una gran variedad en su presentación citogenética. Objetivos: Determinar la variedad de presentación citogenética y la existencia de diferencias entre los casos diagnosticados in útero y los de diagnóstico postnatal, en pacientes con ST en dos laboratorios de referencia de Cali, Colombia. Métodos: Se realizó un estudio observacional descriptivo de corte transversal, se incluyeron pacientes con diagnóstico de ST, cuyo cariotipo se realizó entre los años 2000 y 2012, en los laboratorios de citogenética de la Universidad del Valle y un instituto de genética de Cali, Colombia. Se recolectó información del reporte del cariotipo, tipo de muestra y tiempo de realización del diagnóstico y se determinó frecuencias y asociaciones estadísticas entre las variables a estudiar. Resultados: Se incluyeron 181 pacientes con fórmula cromosómica compatible con ST; 69 fueron diagnosticados in útero, los demás, en recién nacidos vivos, infantes o adultos. La fórmula cromosómica 45 X0 se encontró en el 95,6 por ciento de los casos de diagnóstico prenatal y 58 por ciento de los de diagnóstico postnatal. Se aplicó la prueba del test exacto de Fisher, comparando los múltiples subgrupos de la variedad de presentación citogenética de diagnóstico prenatal y postnatal, encontrándose diferencias estadísticamente significativas en la distribución de las dos poblaciones evaluadas (p<0,001). Conclusiones: Existen diferencias significativas en los cariotipos de los pacientes con ST diagnosticados in útero, respecto a los diagnosticados en vida extrauterina. Se postula que esa diferencia tendría una explicación biológica sobre la posibilidad de muerte in útero por la ausencia total del cromosoma X.

Background: Turner syndrome is caused by the complete or partial absence of chromosome X and has a great variety in their cytogenetic presentation. Objectives: To determine the variety of cytogenetic presentation and the presence of differences between cases diagnosed in uterus and postnatally, in patients with Turner syndrome at two reference laboratories of Cali, Colombia. Methods: A descriptive cross-sectional study was performed. We included patients with cytogenetic diagnosis of Turner syndrome performed between 2000 and 2012 at cytogenetic laboratories of Universidad del Valle and a genetic institute in Cali, Colombia. The information of karyotype result, type of sample and the diagnosis moment was collected, determining frequencies and statistical associations. Results: 181 patients with Turner's chromosomic presentation; 69 were diagnosed in uterus, the other as live newborns, infants or adults. Chromosomal formula 45X0 was found in 95.6 percent of cases with prenatal diagnosis and 58 percent of postnatal diagnosis. Fisher's test was applied, comparing the cytogenetic presentations of prenatal and postnatal diagnosis, statistically significant difference in the distribution of the two populations evaluated was found (p<0.001). Conclusions: There are significant differences in the karyotypes of patients with ST diagnosed in utero, compared to those diagnosed in postnatal life. We hypothesize that this difference would have a biological explanation due to a higher probability of death in utero by the complete absence of chromosome X.

Cytogenetic analysis and its significance of 4628 children for genetic counseling in Chongqing / 重庆医科大学学报

Objective:To investigate the distribution characteristics of the abnormal karyotpye in Children of Chongqing, to provide the information for management, prenatal diagnosis and intervention. Methods:Samples of the peripheral blood lymphocyte from 4 628 children were prepared with routine cytogenetic methods,G-bangding was employed for karyotype analysis, and C-banding was used when necessary. Results:A total of 22.67%(1 049/4 628) patients were identified to have abnormalities with 73 kinds of karyotypes. Among these aberrations, 874(83.32%) cases were euchromosome malformation,159(15.16%)were sex chromosome malformation,and Down’s syndrome,Turner’s syndrome were the most common. Mental retardation,short stature and congenital malformation were the three main causes of genetic counseling,and the major age grades were infants,school children and preschool children in-sequence,42.57%(742/1 743)with mental retardation,9.98%(98/982) with short stature,and 8.10%(56/691)with congenital malformation were detected to have abnormalities,which were coincided with clinical diagnosis,respectively. Conclusion:The abnormal karyotypes are various and complex in Chongqing,routine karyotyping is necessary for children of mental retardation,congenital malformation and growth retardation with unknown reason,since it can benefit for early management and intervention of genetic diseases.