Contemporary Trends in Cardiac Surgical Care for Trisomy 13 and 18 Patients Admitted to Hospitals in the United States.

OBJECTIVE: To assess rates of cardiac surgery and the clinical and demographic features that influence surgical vs nonsurgical treatment of congenital heart disease (CHD) in patients with trisomy 13 (T13) and trisomy 18 (T18) in the United States. STUDY DESIGN: A retrospective study was performed using the Pediatric Health Information System. All hospital admissions of children (<18 years of age) with T13 and T18 in the United States were identified from 2003 through 2022. International Classifications of Disease (ICD) codes were used to identify presence of CHD, extracardiac comorbidities/malformations, and performance of cardiac surgery. RESULTS: Seven thousand one hundred thirteen patients were identified. CHD was present in 62% (1625/2610) of patients with T13 and 73% (3288/4503) of patients with T18. The most common CHD morphologies were isolated atrial/ventricular septal defects (T13 40%, T18 42%) and aortic hypoplasia/coarctation (T13 21%, T18 23%). Single-ventricle morphologies comprised 6% (100/1625) of the T13 and 5% (167/3288) of the T18 CHD cohorts. Surgery was performed in 12% of patients with T13 plus CHD and 17% of patients with T18 plus CHD. For all cardiac diagnoses, <50% of patients received surgery. Nonsurgical patients were more likely to be born prematurely (P < .05 for T13 and T18). The number of extracardiac comorbidities was similar between surgical/nonsurgical patients with T13 (median 2 vs 2, P = .215) and greater in surgical vs nonsurgical patients with T18 (median 3 vs 2, P < .001). Hospital mortality was <10% for both surgical cohorts. CONCLUSIONS: Patients with T13 or T18 and CHD receive surgical palliation, but at a low prevalence (≤17%) nationally. Given operative mortality <10%, opportunity exists perhaps for quality improvement in the performance of cardiac surgery for these vulnerable patient populations.

Patau and Edwards Syndromes in a University Hospital: beyond palliative care.

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

Occurrence of mosaic trisomy 22 and pericentric inversion of chromosome 9 in a patient with a good prognosis.

Complete trisomy 22 is a rare chromosomal condition that is incompatible with life. However, mosaic trisomy 22 usually has prolonged survival compatibility and may present a good prognosis depending on the tissues affected. Herein, we described a male patient with the occurrence of mosaic trisomy 22 associated with the inversion of chromosome 9, with karyotype 47, XY, inv (9) (p11q13), + 22 [5] / 46, XY, inv(9) (p11q13) [45] and arr 22q11.1 ~ q13.33(16,417008-51,219,009)x2 ~ 3. It is not possible to infer, in general, the clinical characteristics associated with mosaic trisomy 22. However, the patient presented common clinical features observed in reported cases (in parentheses the percentage observed comparing all reported cases): facial dysmorphia (100%), delay in motor development/growth (82%), cardiac abnormalities (73%), ear abnormalities (55%) and facial and/or body asymmetry (55%), in addition to hypotonia, skin spots, hypoplastic nails. Given the survival and quality of life associated with multidisciplinary treatment, it can be concluded that the patient has a good prognosis. Conclusively, we're presenting the occurrence of mosaic trisomy 22 and chromosome 9 inversion in the patient with favorable prognosis. Thus, this study proposed a guide which should be inserted in databases of rare genetic conditions to help genetic counselors define mosaic trisomy 22 diagnosis.

Unusual Trisomy X Phenotype Associated with a Concurrent Heterozygous 16p11.2 Deletion: Importance of an Integral Approach for Proper Diagnosis.

Trisomy X is the most frequent sex chromosome anomaly in women, but it is often underdiagnosed postnatally because most patients do not show any clinical manifestation. It is estimated that only 10% of patients with trisomy X are diagnosed by clinical findings. Thus, it has been proposed that the clinical spectrum is not yet fully delimited, and additional uncommon or atypical clinical manifestations could be related to this entity. The present report describes a female carrying trisomy X but presenting atypical manifestations, including severe intellectual disability, short stature, thymus hypoplasia, and congenital hypothyroidism (CH). These clinical findings were initially attributed to trisomy X. However, chromosome microarray analysis (CMA) subsequently revealed that the patient also bears a heterozygous 304-kb deletion at 16p11.2. This pathogenic copy-number variant (CNV) encompasses 13 genes, including TUFM. Some authors recommend that when a phenotype differs from that described for an identified microdeletion, the presence of pathogenic variants in the non-deleted allele should be considered to assess for an autosomal recessive disorder; thus, we used a panel of 697 genes to rule out a pathogenic variant in the non-deleted TUFM allele. We discuss the possible phenotypic modifications that might be related to an additional CNV in individuals with sex chromosome aneuploidy (SCA), as seen in our patient. The presence of karyotype-demonstrated trisomy X and CMA-identified 16p11.2 deletion highlights the importance of always correlating a patient's clinical phenotype with the results of genetic studies. When the phenotype includes unusual manifestations and/or exhibits discrepancies with that described in the literature, as exemplified by our patient, a more extensive analysis should be undertaken to enable a correct diagnosis that will support proper management, genetic counseling, and medical follow-up.

Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome.

Down syndrome (DS) is characterized by the trisomy of chromosome 21 and by cognitive deficits that have been related to neuronal morphological alterations in humans, as well as in animal models. The gene encoding for amyloid precursor protein (APP) is present in autosome 21, and its overexpression in DS has been linked to neuronal dysfunction, cognitive deficit, and Alzheimer's disease-like dementia. In particular, the neuronal ability to extend processes and branching is affected. Current evidence suggests that APP could also regulate neurite growth through its role in the actin cytoskeleton, in part by influencing p21-activated kinase (PAK) activity. The latter effect is carried out by an increased abundance of the caspase cleavage-released carboxy-terminal C31 fragment. In this work, using a neuronal cell line named CTb, which derived from the cerebral cortex of a trisomy 16 mouse, an animal model of human DS, we observed an overexpression of APP, elevated caspase activity, augmented cleavage of the C-terminal fragment of APP, and increased PAK1 phosphorylation. Morphometric analyses showed that inhibition of PAK1 activity with FRAX486 increased the average length of the neurites, the number of crossings per Sholl ring, the formation of new processes, and stimulated the loss of processes. Considering our results, we propose that PAK hyperphosphorylation impairs neurite outgrowth and remodeling in the cellular model of DS, and therefore we suggest that PAK1 may be a potential pharmacological target.

Holoprosencephaly in Patau Syndrome.

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

Ultrassonografia morfológica de primeiro trimestre: importante ferramenta para rastreio de aneuploidias e pré-eclâmpsia / First-trimester morphological ultrasound: important tool for aneuploidy and pre-eclampsia screening

No início do século 20, as altas taxas de mortalidade materna e infantil estimularam o desenvolvimento de um modelo de atendimento pré-natal que mantivesse características parecidas até os dias atuais. Nesse modelo, haveria maior concentração de visitas durante o final do terceiro trimestre de gestação, devido às maiores taxas de complicações nas fases finais da gestação e à dificuldade de prever a ocorrência de resultados adversos durante o primeiro trimestre. Atualmente, a avaliação clínica durante o primeiro trimestre, com auxílio da ultrassonografia e marcadores bioquímicos, pode prever uma série de complicações que acometem a gestação, incluindo cromossomopatias, pré-eclâmpsia, restrição de crescimento fetal, anomalias fetais e trabalho de parto pré-termo.

At the beginning of the 20th century, the high rates of maternal and infant mortality stimulated the development of a model of prenatal care that maintained similar characteristics until the present day. In this model, there would be a greater concentration of visits during the end of the third trimester of pregnancy, due to the higher rates of complications in the final stages of pregnancy and the difficulty in predicting the occurrence of adverse outcomes during the first trimester. Currently, clinical evaluation during the first trimester, with the aid of ultrasound and biochemical markers, can predict a series of complications that affect pregnancy, including chromosomal disorders, preeclampsia, fetal growth restriction, fetal anomalies and preterm labor.

Perinatal Outcomes of Fetuses and Infants Diagnosed with Trisomy 13 or Trisomy 18.

OBJECTIVES: To identify factors associated with prenatal, perinatal, and postnatal outcomes, and determine medical care use for fetuses and infants with trisomy 13 (T13) and trisomy 18 (T18). STUDY DESIGN: This population-based retrospective cohort study included all prenatal and postnatal diagnoses of T13 or T18 in the greater Cincinnati area from January 1, 2012, to December 31, 2018. Overall survival, survival to hospital discharge, medical management, and maternal, fetal, and neonatal characteristics are analyzed. RESULTS: There were 124 pregnancies (125 fetuses) that were identified, which resulted in 72 liveborn infants. Male fetal sex and hydrops were associated with a higher rate of spontaneous loss. The median length of survival was 7 and 29 days, for infants with T13 and T18, respectively. Of the 27 infants alive at 1 month of age, 13 (48%) were alive at 1 year of age. Only trisomy type (T13), goals of care (comfort care), and extremely low birthweight were associated with a shorter length of survival. A high degree of variability existed in the use of medical services, with 28% of infants undergoing at least 1 surgical procedure and some children requiring repeated (≤29) or prolonged (>1 year) hospitalizations. CONCLUSIONS: Although many infants with T13 or T18 did not survive past the first week of life, nearly 20% lived for more than 1 year with varying degrees of medical support. The length of survival for an infant cannot be easily predicted, and surviving infants have high health care use throughout their lifespans.

Integrated Quantitative Neuro-Transcriptome Analysis of Several Brain Areas in Human Trisomy 21.

BACKGROUND: Although Down syndrome (DS) is the most frequent human chromosomal disorder and it causes mainly intellectual disability, its clinical presentation is complex and variable. OBJECTIVE: We aimed to analyze and compare the transcriptome disruption in several brain areas from individuals with DS and euploid controls as a new approach to consider a global systemic differential disruption of gene expression beyond chromosome 21. METHODS: We used data from a DNA microarray experiment with ID GSE59630 previously deposited in the GEO DataSet of NCBI database. The array contained log2 values of 17,537 human genes expressed in several aeras of the human brain. We calculated the differential gene expression (Z-ratio) of all genes. RESULTS: We found several differences in gene expression along the DS brain transcriptome, not only in the genes located at chromosome 21 but in other chromosomes. Moreover, we registered the lowest Z-ratio correlation between the age ranks of 16-22 weeks of gestation and 39-42 years (R2 = 0.06) and the highest Z-ratio correlation between the age ranks of 30-39 years and 40-42 years (R2 = 0.89). The analysis per brain areas showed that the hippocampus and the cerebellar cortex had the most different gene expression pattern when compared to the brain as a whole. CONCLUSIONS: Our results support the hypothesis of a systemic imbalance of brain protein homeostasis, or proteostasis network of cognitive and neuroplasticity process, as new model to explain the important effect on the neurophenotype of trisomy that occur not only in the loci of chromosome 21 but also in genes located in other chromosomes.

Cytogenetic Patterns, Congenital Heart Disease, and Thyroid Dysfunction in Children with Down Syndrome.

OBJECTIVES: To study the cytogenetic patterns, congenital heart disease, and thyroid dysfunction in children with Down syndrome. STUDY DESIGN: This was a retrospective observational study of children with Down syndrome over a period of 20 years, from a major referral institution in Kerala state, South India. The cytogenetic patterns, echocardiography reports, and thyroid profiles were analyzed using SPSS, version 20, software. The prevalence of heart disease and thyroid status in the various cytogenetic patterns also were analyzed. RESULTS: The prevalence of translocation (9.45%) was high compared with the reported 4% in the literature. More of the younger mothers had translocation with a greater, but not statically significant, incidence of heart disease. Mosaic karotypes (3.04%) were also greater than reported (1%) in the literature, with female preponderance. Heart disease was seen in 58% of cases, with atrial septal defect being the most common lesion, compared with atrioventricular septal defect noted in literature. Hypothyroidism was noted in 31.2% with no difference among the cytogenetic groups. There was no case of hyperthyroidism. CONCLUSIONS: The high prevalence of translocation and mosaic Down syndrome stresses the need for routine karyotyping in children with Down syndrome. The need for routine screening and regular follow up of heart diseases and thyroid status should be emphasized.

Trisomy 21 and Assisted Reproductive Technologies: A review.

Trisomy 21 is the most common genetic disorder seen among infants, and it causes spontaneous abortions, abnormal neural development and other pathologies associated with newborn development. In newborns with this trisomy, 90-95% have full trisomy, 1.4-1.9% have mosaicism, and 1-4.7% have translocations. The principal cause of trisomy 21 is advanced maternal age, in which recombination errors may occur during fetal development, age-related accumulation of damaged DNA, cohesin degradation producing the premature loss of chromosomes or sister chromatids, and alterations during the spindle formation process. The paternal age has also an effect on trisomy 21, specifically during male aging, when there is higher risk of chromosomal breaking in spermatozoa. Epigenetics is also an important risk factor of trisomy 21 through changes in the DNA methylation process, histone modification and non-coding RNAs. Assisted reproductive technologies (ART) have emerged in recent years as a safe alternative for couples with fertility problems. These techniques, which include controlled ovarian stimulation (COS), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and vitrification, decrease the incidence of aneuploidy in human preimplantation embryos, and are widely used. The following study aims to review and discuss the available literature on trisomy 21 in the field of assisted human reproduction.

Prenatal cytogenetic diagnosis: results obtained in the specialized laboratory of Clínica Universitaria Colombia from 2013 to 2019.

OBJECTIVE: Prenatal cytogenetic evaluation is a key tool for identifying alterations in pregnant women with high risk for fetal chromosomal abnormalities (CA). In Colombia, there are not large-scale reports about the prevalence and pattern of CA in prenatal cytogenetic analysis. METHOD: A descriptive study was performed from registers of prenatal cytogenetic analysis on amniotic fluid (AF), chorionic villus biopsy (CVS), and fetal blood (FB) samples sent to the specialized laboratory of the Clínica Universitaria Colombia between 2013 and 2019. RESULTS: The prevalence of CA was 20.9%. The trisomies 21, 18, 13, and monosomy X were the most frequent aneuploidies, and the derivative chromosomes were the most frequent structural abnormalities. Although the rate of CA was higher in women over the age of 35 years old; monosomy X, unbalanced rearrangements, and microduplications were associated with the group of women under the age of 35 (p < .05). Trisomies 21 and 18 were the most common aneuploidies identified by FISH and were found to be altered in 52% of the aCGH studies. Ultrasonographic markers associated with CA were the most frequent clinical indication. CONCLUSION: In Colombia, the invasive prenatal cytogenetic analysis continues being an important diagnostic tool available for pregnant women with high risk for fetal CA.

Attitudes of Argentinean Neonatologists toward Resuscitation of Infants with Trisomies 21, 18, and 13: A Multicenter Survey.

OBJECTIVE: This study was aimed to explore the attitude of Argentinean neonatologists in the delivery room on resuscitating infants with trisomies. STUDY DESIGN: An anonymous questionnaire was completed by neonatologists staffing level-III neonatal intensive care units (NICUs) on resuscitation of children with trisomies 21, 18, and 13. Potential sociocultural factors influencing the decision to resuscitate were included. RESULTS: Overall, 314 neonatologists in 34 units in the Buenos Aires region participated (response rate of 54%). The position of neonatologists regarding the resuscitation in the delivery room was that 98% would resuscitate newborns with trisomy 21, and 47% with trisomy 18 or trisomy 13. Resuscitation of newborns with trisomy 18 or trisomy 13 by neonatologists was significantly associated with working in the public sector, religious beliefs, and legal framework. CONCLUSION: With improvement in the management and treatment of infants with trisomies 18 and 13, Argentinean neonatologists showed a favorable attitude toward resuscitating them in the delivery room. KEY POINTS: · We explored the attitudes of Argentinean neonatologists on resuscitation of children with trisomies.. · Half of neonatologists would resuscitate newborns with trisomies18 and 13.. · These results suggest an ongoing paradigm shift of the most severe trisomies..

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.

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

Inherited unbalanced reciprocal translocation with 3q duplication and 5p deletion in a foetus revealed by cell-free foetal DNA (cffDNA) testing: a case report.

BACKGROUND: Since 2011, screening maternal blood for cell-free foetal DNA (cffDNA) fragments has offered a robust clinical tool to classify pregnancy as low or high-risk for Down, Edwards, and Patau syndromes. With recent advances in molecular biology and improvements in data analysis algorithms, the screening's scope of analysis continues to expand. Indeed, screening now encompassess additional conditions, including aneuploidies for sex chromosomes, microdeletions and microduplications, rare autosomal trisomies, and, more recently, segmental deletions and duplications called copy number variations (CNVs). Yet, the ability to detect CNVs creates a new challenge for cffDNA analysis in couples in which one member carries a structural rearrangement such as a translocation or inversion. CASE PRESENTATION: We report a segmental duplication of the long arm of chromosome 3 and a segmental deletion of the short arm of chromosome 5 detected by cffDNA analysis in a 25-year-old pregnant woman. The blood sample was sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay. G-band karyotyping in amniotic fluid only detected an abnormality in chromosome 5. Next-generation sequencing in amniocytes confirmed both abnormalities and identified breakpoints in 3q26.32q29 and 5p13.3p15. The foetus died at 21 weeks of gestation due to multiple abnormalities, and later G-band karyotyping in the parents revealed that the father was a carrier of a balanced reciprocal translocation [46,XY,t(3;5)(q26.2;p13)]. Maternal karyotype appeared normal. CONCLUSION: This case provides evidence that extended cffDNA can detect, in addition to aneuploidies for whole chromosomes, large segmental aneuploidies. In some cases, this may indicate the presence of chromosomal rearrangements in a parent. Such abnormalities are outside the scope of standard cffDNA analysis targeting chromosomes 13, 18, 21, X, and Y, potentially leading to undiagnosed congenital conditions.

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.