Hemivertebra with pathogenic microdeletion of chromosome 9.

Hemivertebra is a rare congenital abnormality of the spinal column. Hemivertebra with other structural and cytogenetic abnormalities are reported. The prognosis is favorable with partial hemivertebra and with a single spinal defect as compared to a defect involving full segments and affecting different levels of the spines. The perinatal outcome is obscured when it is associated with other syndromes or cytogenetic abnormality. It is imperative to do serial thorough anatomical ultrasound scanning and to screen for chromosomal abnormality when hemivertebra is detected during pregnancy.

Retinoblastoma and polydactyly in a child with 46, XY, 15pstk+ karyotype-A case report and literature review.

BACKGROUND: Retinoblastoma (Rb) is the most common intraocular malignancy in childhood, originating from primitive retinal stem cells or cone precursor cells. It can be triggered by mutations of the RB1 gene or amplification of the MYCN gene. Rb may rarely present with polydactyly. METHODS: We conducted karyotype analysis, copy number variation sequencing, and whole-genome sequencing on the infant proband and his family. The clinical course and laboratory results of the proband's infant were documented and collected. We also reviewed the relevant literature. RESULTS: A 68-day-old boy presented with preaxial polydactyly and corneal edema. His intraocular pressure (IOP) was 40/19 mmHg, and color Doppler imaging revealed vitreous solid mass-occupying lesions with calcification in the right eye. Ocular CT showed flaky high-density and calcification in the right eye. This was classified as an International Retinoblastoma Staging System group E retinoblastoma with an indication for enucleation. Enucleation and orbital implantation were performed on the child's right eye. Karyotype analysis revealed an abnormal 46, XY, 15pstk+ karyotype, and the mother exhibited diploidy of the short arm of chromosome 15. The Alx-4 development factor, 13q deletion syndrome, and the PAPA2 gene have been reported as potential mechanisms for Rb combined with polydactyly. CONCLUSION: We report the case of a baby boy with Rb and polydactyly exhibiting a 46, XY, 15pstk+ Karyotype. We discuss potential genetic factors related to both Rb and polydactyly. Furthermore, there is a need for further exploration into the impact of chromosomal polymorphisms in Rb with polydactyly.

Does the Presence of Extended Jugular Lymphatic Sacs Add More Risk to Nuchal Thickness for Genetic and Structural Abnormality?

Background: The risks added by extended jugular lymphatic sacs (EJLS) to increased nuchal translucency (NT) including genetic and structural abnormalities and pregnancy outcomes have not been previously investigated, which this study aims to investigate. Methods: The data of 155 singleton pregnancies with increased fetal NT (≥95th percentile) of these 20 with fetal EJLS were evaluated retrospectively. Patients were stratified according to NT thickness such that ≥95th percentile - 3.5 mm, 3.6-4.4 mm, 4.5-5.4 mm, 5.5-6.4 mm, ≥6.5 mm, and grouped according to the presence of EJLS. Pregnancy outcomes, genetic and structural abnormalities were assessed by comparing EJLS with non-EJSL cases (n-EJLS). Results: Associated with NT, the incidence of the presence of EJLS increased with NT, from 4.5% at the ≥95th percentile - 3.5 mm to 30.8% when NT ≥5.5 mm. In the n-EJLS group, the proportion of fetuses with structural and genetic abnormalities increased as the measurement of NT increased. This correlation was not observed in the EJLS group. Compared to n-EJLS, cases with EJLS had a higher rate of fetal structural (38.5% vs. 75%, P = 0.003) and genetic (18.5% vs. 45%, P = 0.005) anomalies and a lower term live birth rate (59.3% vs. 15%, P < 0.001). Conclusion: The increasing rate of EJLS was seen as NT increased. Compared to n-EJLS, the EJLS cases had a higher rate poor pregnancy outcomes and fetal genetic and structural abnormalities.

Spontaneous abortion in the first trimester of pregnancy.

Spontaneous abortions in the first trimester of gravidity represent a clinically significant problem that can affect up to 15% of recognized pregnancies. The causes of early pregnancy loss are very heterogeneous and include genetic, environmental and immunological factors. Although the pathologist's main task is to exclude molar pregnancy, in some cases conventional histological examination can also contribute to the elucidation of the cause of miscarriage and the management of subsequent pregnancies, especially in the case of lesions with a high risk of recurrence that may lead to habitual abortion.

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.

Systematic review of subsequent pregnancy outcomes in couples with parental abnormal chromosomal karyotypes and recurrent pregnancy loss.

OBJECTIVE: To evaluate the current evidence of pregnancy outcomes among couples with recurrent pregnancy loss (RPL) with abnormal karyotypes vs. those with normal karyotypes and among couples with RPL and abnormal karyotypes after receiving expectant management vs. preimplantation genetic diagnosis (PGD). DESIGN: Systematic review and meta-analysis. SETTING: Academic medical centers. PATIENT(S): Pregnancy outcomes in 6,301 couples with RPL who conceived without medical intervention in 11 studies were analyzed. However, only 2 studies addressed the outcomes of couples with RPL and abnormal karyotypes after expectant management (75 cases) vs. PGD (50 cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The pregnancy outcomes in couples with RPL with abnormal and normal karyotypes across included studies were evaluated. RESULT(S): Compared with those with a normal karyotype, a significantly lower first pregnancy live birth rate (LBR) was found in couples with RPL with abnormal karyotypes (58.5% vs. 71.9%; odds ratio [OR], 0.55; 95% confidence interval [CI], 0.46-0.65; I2 =27%). A markedly decreased first pregnancy LBR was found in couples with a translocation (52.9% vs. 72.4%; OR, 0.44; 95% CI, 0.31-0.61; I2 =33%) but not in couples with an inversion. However, the differences in accumulated LBR (81.4% vs. 74.8%; OR, 0.96; 95% CI, 0.90-1.03; I2 = 0) were nonsignificant, whereas the miscarriage rate was distinctly higher in couples with RPL and abnormal karyotypes (53.0% vs. 34.7%; OR, 2.21; 95% CI, 1.69-2.89; I2 = 0). Compared with those who chose expectant management, differences in accumulated LBR were nonsignificant (60% vs. 68%; OR, 0.55; 95% CI, 0.11-2.62; I2 =71%), whereas the miscarriage rate (24% vs. 65.3%; OR, 0.15; 95% CI, 0.04-0.51; I2 = 45) was markedly low in couples with RPL and abnormal karyotypes who chose PGD. CONCLUSION(S): Couples with RPL and abnormal karyotypes had a higher miscarriage rate than couples with normal karyotypes but achieved a noninferior accumulated LBR through multiple conception attempts. In couples with RPL and abnormal karyotypes, PGD treatment did not increase the accumulated LBR but markedly reduced miscarriage rate compared with expectant management.

Marrow changes and reduced proliferative capacity of mesenchymal stromal cells from patients with "no-option" critical limb ischemia; observations on feasibility of the autologous approach from a clinical trial.

BACKGROUND AIMS: Approximately 1 in 3 patients with critical limb ischemia (CLI) are not suitable for surgical or endovascular revascularization. Those "no-option" patients are at high risk of amputation and death. Autologous bone marrow mesenchymal stromal cells (MSCs) may provide a limb salvage option. In this study, bone marrow characteristics and expansion potentials of CLI-derived MSCs produced during a phase 1b clinical trial were compared with young healthy donor MSCs to determine the feasibility of an autologous approach. Cells were produced under Good Manufacturing Practice conditions and underwent appropriate release testing. METHODS: Five bone marrow aspirates derived from patients with CLI were compared with six young healthy donor marrows in terms of number of colony-forming units-fibroblast (CFUF) and mononuclear cells. The mean population doubling times and final cell yields were used to evaluate expansion potential. The effect of increasing the volume of marrow on the CFUF count and final cell yield was evaluated by comparing 5 CLI-derived MSCs batches produced from a targeted 30 mL of marrow aspirate to five batches produced from a targeted 100 mL of marrow. RESULTS: CLI-derived marrow aspirate showed significantly lower numbers of mononuclear cells with no difference in the number of CFUFs when compared with healthy donors' marrow aspirate. CLI-derived MSCs showed a significantly longer population doubling time and reduced final cell yield compared with young healthy donors' MSCs. The poor growth kinetics of CLI MSCs were not mitigated by increasing the bone marrow aspirate from 30 to 100 mL. CONCLUSIONS: In addition to the previously reported karyotype abnormalities in MSCs isolated from patients with CLI, but not in cells from healthy donors, the feasibility of autologous transplantation of bone marrow MSCs for patients with no-option CLI is further limited by the increased expansion time and the reduced cell yield.

45,X/46,XY Mosaicism with Male Phenotype: Case Report.

Mixed gonadal dysgenesis is the most common chromosomal abnormality with ambiguous genitalia, defined as a 45,X/46,XY mosaicism. It can present with a normal male phenotype, ambiguous genitalia, or features of Turner syndrome. A 14-year-old patient was referred to the genetics clinic due to hypospadia, cryptorchidism, and aortic coarctation. During the physical examination, short stature, webbed neck, and Blashko lines on his back were noted. He had a previous karyotype reported as normal. However, due to an inadequate evolution and a low resolution on the previous test, a higher resolution karyotype was performed, identifying a mosaicism 45,X/46,XY. A multidisciplinary board examined the case, and follow-up with tumor markers was carried out to evaluate the presence of gonadoblastoma, one of the main complications in these patients. Treatment should be transdisciplinary and focused on the particular characteristics of each case. Other treatment alternatives include corrective surgery and hormonal therapy.

Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison.

We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement by Q-FISH. An abnormal karyotype was detected in 12 out of 32 cultured UL samples. In five karyotypically abnormal ULs, MED12 mutations were found. The chromosomal abnormalities in ULs were present mostly by complex rearrangements, including chromothripsis. In both karyotypically normal and abnormal ULs, telomeres were ~40% shorter than in the corresponding myometrium, being possibly prerequisite to chromosomal rearrangements. The uncultured samples of six karyotypically abnormal ULs were checked for the detected chromosomal abnormalities through interphase FISH with individually designed DNA probe sets. All chromosomal abnormalities detected in cultured ULs were found in corresponding uncultured samples. In all tumors, clonal spectra were present by the karyotypically abnormal cell clone/clones which coexisted with karyotypically normal ones, suggesting that chromosomal abnormalities acted as drivers, rather than triggers, of the neoplastic process. In vitro propagation did not cause any changes in the spectrum of the cell clones, but altered their ratio compared to uncultured sample. The alterations were unique for every UL. Compared to its uncultured counterpart, the frequency of chromosomally abnormal cells in the cultured sample was higher in some ULs and lower in others. To summarize, ULs are characterized by both inter- and intratumor genetic heterogeneity. Regardless of its MED12 status, a tumor may be comprised of clones with and without chromosomal abnormalities. In contrast to the clonal spectrum, which is unique and constant for each UL, the clonal frequency demonstrates up or down shifts under in vitro conditions, most probably determined by the unequal ability of cells with different genetic aberrations to exist outside the body.

Segmental Cervical Aplasia in a Colombian Creole Mare with Mosaic X-Chromosome Aneuploidy.

A 4-year-old Colombian Creole mare was presented for diagnosis because the external orifice of her cervix was not detectable when a uterine lavage as therapy for uterine fluid accumulation was attempted. Clinical and ultrasonographic evaluation of the genital tract revealed that ovaries were of normal size and showed structures suggestive of regular ovarian activity. However, granular free-floating fluid material distending the uterus was detected by ultrasound. Upon vaginal examination, the normal external cervical morphology was not evident. The vagina ended in a blind bag with a small papilla with no evident external cervical os. Cytology of uterine fluid obtained by transvaginal aspiration showed findings compatible with mucometra. Cytogenetic analysis revealed an abnormal karyotype (63,X and 64,XX both 45% and 65,XXX 10%). A diagnosis of congenital segmental cervical aplasia was proposed possibly related to the mosaicism detected. To our knowledge, this is the first case of this reproductive pathology in a mare with regular ovarian activity and confirmed aneuploidy in mosaic form of the X sex chromosome.

Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report.

BACKGROUND: Fetoplacental discrepancies occur in approximately 1-2% of analyzed prenatal cases. They are typically due to confined placental mosaicism, where an aberration is observed in the placental cells but not found in the fetal cells. Confined placental mosaicism usually involves aneuploidies and more sparsely structural chromosomal aberrations. To the best of our knowledge, this is the first reported case of a discrepancy in the analyses of chorionic villus sampling and amniocentesis involving two different structural chromosomal aberrations of chromosome 21. CASE PRESENTATION: We report a 33-year-old woman who was referred for a non-invasive prenatal testing due to an increased risk of trisomy 21 gleaned from a combined ultrasound and blood test. The non-invasive prenatal testing showed an increased risk of trisomy 21 with a normalized coverage signal that did not match the fetal cell-free DNA fraction. Rapid aneuploidy detection performed on uncultured chorionic villi indicated mosaicism for trisomy 21. The follow-up analyses revealed discordant chromosomal aberrations: 46,XY,der(21)t(10;21)(p11.21;q10) in the analysis of the chorionic villus sampling and 46,XY, + 21,der(21;21)(q10;q10) in the analysis of the amniocentesis. Thus, the analyses indicated mosaicism for a cell line containing trisomy 21 and a cell line containing a partially duplicated short arm of chromosome 10 in the chorionic villi and complete trisomy 21 resulting from an isochromosome 21 in the amniotic fluid. The analyses of the lymphocytes and the fibroblasts of the woman were normal. CONCLUSIONS: We propose a multiple-step mechanism as a possible theoretical explanation for the formation of these discordant structural chromosomal aberrations in the chorionic villi and amniotic fluid. With this case report, we want to highlight the importance of understanding the possible underlying embryological mechanisms when interpreting results from different prenatal analyses.

46XX Testicular Disorder of Sex Development.

In this case report, we present the case of a 31-year-old man who presented with primary infertility, azoospermia and occasional sexual dysfunction. History and general physical examination were unremarkable. Local examination showed bilateral low volume testes and remaining aspects of the male reproductive tract were unremarkable. Detailed investigation showed a hypergonadotropic hypogonadism suggestive of primary testicular failure. Genetic screening showed a 46XX karyotype and Y chromosome testing was positive for sex-determining region (SRY) gene. Ultrasound abdomen was normal renal system and adrenal glands. A diagnosis of 46XX testicular disorders of sex development (DSD) was made. The incidence of this disorder is estimated to be 1:20,000 males. Such syndromic male partners generally have normal external genitalia and discover this disorder only in adulthood because of infertility. Such men have small volume testes, azoospermia and hypergonadotropic hypogonadism. Genetic and endocrine consultations are necessary to manage hypergonadotropic hypogonadism. Testicular sperm extraction is not recommended as there are deletions in all regions of Y chromosome, and adoption or assisted reproduction technology with a sperm donor are fertility options.

Coronary plaque burden in Turner syndrome a coronary computed tomography angiography study.

Turner syndrome (TS) is associated with coronary artery disease (CAD), an important cause of premature death in TS. However, the determinants of CAD in women with TS remain unknown. In a cross-sectional study design, 168 women without clinical evidence of CAD (115 with TS and 53 without TS) were assessed for the presence and volume of subclinical CAD using coronary CT angiography. Karyotype, the presence of congenital heart defects and conventional cardiovascular risk factors were also registered. Comparative analyses were performed (1) between women with and without TS and (2) in the TS group, between women with and without subclinical CAD. The prevalence of CAD, in crude and adjusted analyses, was not increased for women with TS (crude prevalence: 40 [35%] in TS vs. 25 [47%] in controls, p = 0.12). The volume of atherosclerosis was not higher in women with TS compared with controls (median and interquartile range 0 [0-92] in TS vs. 0 [0-81]mm3 in controls, p = 0.29). Among women with TS, women with subclinical CAD were older (46 ± 13 vs. 37 ± 11 years, p < 0.001), had higher blood pressure (systolic blood pressure 129 ± 16 vs. 121 ± 16 mmHg, p < 0.05) and were more frequently diagnosed with type 2 diabetes (5 [13%] vs. 2 [3%], p < 0.05). Karyotype or congenital heart defects were not associated with subclinical CAD. Some women with TS show early signs of CAD, however overall, not more than women without TS. Conventional cardiovascular risk factors were the principal determinants of CAD also in TS, and CAD prevention strategies should be observed.ClinicalTrial.gov Identifier: NCT01678261 ( https://clinicaltrials.gov/ct2/show/NCT01678261 ).

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.

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

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.

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.

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.

Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities.

BACKGROUND: Critical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%-40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI. METHODS: Twelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs. RESULTS: A high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 106 MSCs and one with a mid-dose of 40 × 106 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy. CONCLUSIONS: The results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.

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.

Increased nuchal translucency and pregnancy outcomes: experience of Baskent University Ankara Hospital.

OBJECTIVE: First trimester nuchal translucency (NT) measurement is considered to be an important tool in antenatal follow-up. This study aimed to evaluate the outcomes of pregnancies with increased NT at Baskent University Ankara Hospital between 2004 and 2016. MATERIALS AND METHODS: Patients with NT measurements ≥1.5 multiples of median (MoM) were divided into two groups; group I included increased NT cases without fetal anomalies (either abnormal fetal karyotype or congenital structural anomalies) or loss (intrauterine fetal death), and group II included increased NT cases with fetal anomalies or loss. The groups were compared with each other with respect to maternal demographic features and NT measurements. RESULTS: Karyotype analyses were normal in 73.1% of cases with increased NT (57/78). Among those, 21.1% (12/57) had structural anomalies, and to specify, 9.6% (5/52 over 18 weeks) had cardiac anomalies. Although maternal demographic features did not differ significantly, NT measurements, both as millimeters and MoM, were significantly higher in group II (p<0.05). According to the receiver operating characteristic (ROC) curves, the optimal cut-off values for NT measurements for predicting fetal anomalies or loss were 3.05 mm and 2.02 MoM. NT measurement >7 millimeters or NT MoM >4.27 resulted in poor fetal outcomes without exception. CONCLUSION: Higher NT measurements indicate poorer pregnancy outcomes. Our study indicates that fetal echocardiography must be considered for all cases with increased NT.