"Unfortunately, we couldn't reach a definitive diagnosis": the interactional management of uncertainty in genetic counseling / "Infelizmente, não conseguimos chegar a um diagnóstico definitivo": a gestão interacional da incerteza no aconselhamento genético / "Lamentablemente no pudimos llegar a un diagnóstico definitivo": el manejo interaccional de la incertidumbre en el consejo genético"Lamentablemente no pudimos llegar a un diagnóstico definitivo": el manejo interaccional de la incertidumbre en el consejo genético

This paper examines how participants in genetic counseling sessions interactionally manage situations where the results of tests to investigate the causes of identified fetal malformations are inconclusive or missing. The dataset consists of 54 audio-recorded interactions at a unit specialized in moderate- and high-risk pregnancies at a Brazilian public hospital. Conversation analysis was used to examine the data, revealing that the participants deployed interactional actions that exhibited highly negative valence toward diagnostic inconclusiveness, demonstrating that when there is a motivation for a medical examination, insofar as its results will serve as a basis for subsequent decision-making (in this case about future pregnancies), there is a preference for bad diagnostic news over absent or inconclusive diagnostic news. These findings are consistent with prior interactional studies.

Este artigo examina como os participantes em sessões de aconselhamento genético gerenciam interacionalmente resultados de testes genéticos inconclusivos ou ausentes ­ testes para investigar as causas das malformações fetais identificadas. O conjunto de dados consiste em 54 interações gravadas em áudio em uma unidade de gestação de médio e alto risco de um hospital público brasileiro. A abordagem da Análise da Conversa utilizada para examinar os dados revela que os participantes desenvolvem ações interacionais que exibem uma orientação de valência altamente negativa em relação à inconclusividade diagnóstica, demonstrando que quando há motivação para um exame médico, ou seja, usando o resultado do teste diagnóstico como base para tomada de decisão, tal como acontece com futuras gestações, haja uma preferência por más notícias diagnósticas em detrimento de notícias diagnósticas ausentes ou inconclusivas. Tais resultados são consistentes com estudos interacionais anteriores.

Este artículo examina cómo los participantes en las sesiones de asesoramiento genético gestionan de forma interactiva los resultados de pruebas genéticas no concluyentes o faltantes, pruebas para investigar las causas de las malformaciones fetales identificadas. El conjunto de datos consta de 54 interacciones grabadas en audio en una unidad de embarazo de riesgo medio y alto de un hospital público brasileño. El enfoque de Análisis de Conversación utilizado para examinar los datos revela que los participantes desarrollan acciones interaccionales que exhiben una orientación de valencia altamente negativa hacia la falta de conclusión del diagnóstico, lo que demuestra que cuando hay motivación para un examen médico, es decir, utilizar el diagnóstico del resultado de la prueba como base para la toma de decisiones, como ocurre con futuros embarazos, se prefieran las malas noticias diagnósticas a las noticias diagnósticas ausentes o no concluyentes. Estos resultados son consistentes con estudios interaccionales previos.

Cribado prenatal de aneuploidías mediante análisis de ácido desoxirribonucleíco libre total circulante en plasma materno. Revisión narrativa / Prenatal screening for aneuploidies by analysis of circulating total free deoxyribonucleic acid in maternal plasma. Narrative review

La prueba prenatal no invasiva es un método de cribado de aneuploidías fetales y de resultar con riesgo alto debe ser confirmado a través de prueba genética diagnóstica. Es la prueba de detección más sensible y específica para las aneuploidías fetales comunes y minimiza la realización de técnicas invasivas, solo para las gestantes con riesgo elevado. Se debe realizar asesoramiento genético pre- y poscribado. Este estudio tiene como objetivo describir los fundamentos básicos de la prueba prenatal no invasiva mediante el análisis del ácido desoxirribonucleíco libre circulante en plasma materno para cribado de aneuploidías, y de los métodos primordiales y avances en biología molecular incluyendo las tecnologías de secuenciación de nueva generación, que lo han facilitado, considerando sus beneficios y limitaciones al aplicarla en la práctica clínica, en este campo que cambia con tanta rapidez(AU)

The non-invasive prenatal test is a screening method for fetal aneuploidies and if the result is at high risk, it must be confirmed through diagnostic genetic test. It is the most sensitive and specific detection test for common fetal aneuploidies and minimizes the use of invasive techniques, only for pregnant women at high risk. Genetic counseling should be performed before and after screening. This study aims to describe the basic fundamentals of non-invasive prenatal testing by analyzing free circulating deoxyribonucleic acid in maternal plasma for aneuploidy screening, and the primary methods and advances in molecular biology, including next-generation sequencing technologies, which have facilitated it, considering its benefits and limitations when applying it in clinical practice, in this rapidly changing field(AU)

Consenso de expertos basado en la evidencia: perfilamiento y manejo del carcinoma epitelial de ovario de alto grado avanzado / Expert consensus: Profiling and management of advanced or metastatic epithelial ovarian cancer

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ABSTRACT Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the "The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the "ESMO Standardized Operating Procedures Consensus Conference" were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/ IV BRCA1/2 positive EOC who received platinum-based chemotherapy and obtained complete response/ partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR, 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/ IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive "Arbeitsgemeinschaft Gynäkologische Onkologie - AGO" score or "I-model" positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: • Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/ paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. • Combination chemotherapy (carboplatin/ gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: • Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. • Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. • Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. • Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA ½ +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.

Genetic counseling for hearing loss today / 临床耳鼻咽喉头颈外科杂志

Genetic counseling for hearing loss today originated from decoding the genetic code of hereditary hearing loss, which serves as an effective strategy for preventing hearing loss and constitutes a crucial component of the diagnostic and therapeutic framework. This paper described the main principles and contents of genetic counseling for hearing loss, the key points of counseling across various genetic models and its application in tertiary prevention strategies targeting hearing impairment. The prospects of an AI-assisted genetic counseling decision system and the envisions of genetic counseling in preventing hereditary hearing loss were introduced. Genetic counseling for hearing loss today embodies the hallmark of a new era, which is inseparable from the advancements in science and technology, and will undoubtedly contribute to precise gene intervention!

Splicing mutations of GSDME cause late-onset non-syndromic hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To dentify the genetic and audiological characteristics of families affected by late-onset hearing loss due to GSDMEgene mutations, aiming to explore clinical characteristics and pathogenic mechanisms for providing genetic counseling and intervention guidance. Methods:Six families with late-onset hearing loss from the Chinese Deafness Genome Project were included. Audiological tests, including pure-tone audiometry, acoustic immittance, speech recognition scores, auditory brainstem response, and distortion product otoacoustic emission, were applied to evaluate the hearing levels of patients. Combining with medical history and physical examination to analyze the phenotypic differences between the probands and their family members. Next-generation sequencing was used to identify pathogenic genes in probands, and validations were performed on their relatives by Sanger sequencing. Pathogenicity analysis was performed according to the American College of Medical Genetics and Genomics Guidelines. Meanwhile, the pathogenic mechanisms of GSDME-related hearing loss were explored combining with domestic and international research progress. Results:Among the six families with late-onset hearing loss, a total of 30 individuals performed hearing loss. The onset of hearing loss in these families ranged from 10 to 50 years（mean age: 27.88±9.74 years）. In the study, four splicing mutations of the GSDME were identified, including two novel variants: c. 991－7C>G and c. 1183+1G>T. Significantly, the c. 991－7C>G was a de novo variant. The others were previously reported variants: c. 991-1G>C and c. 991-15_991-13del, the latter was identified in three families. Genotype-phenotype correlation analysis revealed that probands with the c. 991－7C>G and c. 1183+1G>T performed a predominantly high-frequency hearing loss. The three families carrying the same mutation exhibited varying degrees of hearing loss, with an annual rate of hearing deterioration exceeding 0.94 dB HL/year. Furthermore, follow-up of interventions showed that four of six probands received intervention（66.67%）, but the results of intervention varied. Conclusion:The study analyzed six families with late-onset non-syndromic hearing loss linked to GSDME mutations, identifying four splicing variants. Notably, c. 991－7C>G is the first reported de novo variant of GSDME globally. Audiological analysis revealed that the age of onset generally exceeded 10 years,with variable effectiveness of interventions.

Genetic and phenotypic analysis of MYO15A rare variants associated with autosomal recessive hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by MYO15A gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Methods:Identification of MYO15A gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. Results:The probands of the two families have bilateral,severe or complete hearing loss.Four variants of MYO15A were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. Conclusion:This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the MYO15A gene is closely associated with autosomal recessive hearing loss, expanding the MYO15A variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.

Masculinidad hegemónica: factor negativo en la prevención de anemia falciforme en Matanzas

Introducción: En Cuba se le concede gran importancia a la atención de la madre y el niño, por lo cual se desarrollan programas de prevención de enfermedades como la anemia falciforme, condición hereditaria frecuente en el mundo. El asesoramiento genético de esta enfermedad pone de manifiesto rasgos de masculinidad hegemónica heredados de una cultura patriarcal, que conspiran contra el diagnóstico prenatal de la enfermedad. Objetivo: Describir los patrones de masculinidad hegemónica que inciden negativamente en la prevención de anemia falciforme en la provincia de Matanzas. Métodos: Se realizó una investigación descriptiva retrospectiva, a través de la revisión de las historias clínicas de anemia falciforme del Departamento de Genética Médica, de Matanzas, de 1981 a 2021. Se informatizó este registro genético en Excel y se procedió a examinar la información. Se analizó el número de esposos de gestantes portadoras negados a electroforesis de hemoglobina, así como el número de parejas negadas al diagnóstico prenatal y las causas en ambos casos. Se hizo un análisis porcentual presentado en tablas. Resultados: Fueron objeto de estudio 7140 esposos de gestantes portadoras de anemia falciforme; los negados a electroforesis de hemoglobina constituyeron 1088, por no aceptación de la paternidad ni de la morbimortalidad por esta enfermedad. De 428 parejas de riesgo, 252 se hicieron diagnóstico prenatal; 78,9 % de las 176 no estudiadas correspondió a negación masculina, donde imperaron: temor al aborto, inconformidad con la morbimortalidad, y rasgos de paternidad irresponsable. Conclusiones: Los patrones de masculinidad hegemónica se manifiestan de forma negativa en el asesoramiento genético de la anemia falciforme. Desmontarlos progresivamente ayuda a mejorar la prevención de esta enfermedad a través del diagnóstico prenatal.

Introduction: In Cuba, great importance is given to the care of mother and child, which is why programs are develop to prevent diseases such as sickle cell anemia, hereditary condition very frequent in the world. Genetic counseling of this disease reveals hegemonic masculinity traits inherited from a patriarchal culture, which conspire against prenatal diagnosis of the disease. Objective: To describe the patterns of hegemonic masculinity which negatively affect the prevention of sickle cell anemia in the province of Matanzas. Methods: A retrospective descriptive research was carried out, through the review of sickle cell anemia clinical records of the Medical Genetics Department of Matanzas, from 1981 to 2021.This genetic record was computerized in Excel and the information was examined. The number of husbands of carrying pregnant women who refused hemoglobin electrophoresis was analyzed, as well as the number of couples denied to prenatal diagnosis and the causes in both cases. A percentaje analysis was performed, presented in tables. Results: 7140 husbands of pregnant women carrying sickle cell anemia were studied; those who refused hemoglobin electrophoresis constituted 1088 due to non-acceptance of paternity and morbimortality for this disease. Of 428 risk couples, 252 were prenatally diagnosed; 78.9% of those 176 not studied corresponded to male denial, where fear of abortion, dissatisfaction with morbimortality, and irresponsible paternity traits prevailed. Conclusions: Patterns of hegemonic masculinity are negatively manifested in genetic counseling for sickle cell disease. Dismantling them progressively helps to improve the prevention of this disease through prenatal diagnosis.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer / Cenário de mutações germinativas em uma coorte do estado de Minas Gerais, Brasil, em pacientes submetidas ao aconselhamento genético para câncer ginecológico e de mama

Abstract Objective The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. Methods Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. Results We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. Conclusion This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

Resumo Objetivo O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. Métodos Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. Resultados Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. Conclusão Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.

Prenatal Diagnosis of 18q Deletion Syndrome / 中山大学学报(医学科学版)

ObjectiveTo explore the prenatal diagnostic methods of 18q deletion syndrome and improve understanding on the value of non-invasive prenatal testing （NIPT） in prenatal diagnosis of 18q deletion syndrome. Methods18q deletion syndrome was detected by conventional methods such as serological screening， ultrasonic imaging examination， chromosome karyotype analyses of both amniotic fluid cells and parental peripheral blood， and molecular biological techniques including NIPT， chromosomal microarray analysis （CMA） and copy number variation sequencing （CNV-Seq）. Genetic counseling was conducted based on these examination results. ResultsNIPT identified a 24 MB deletion on the chromosome 18 which contained 17 genes including BCL2 by karyotype analysis of amniotic fluid cells and CMA. Further ultrasonic imaging examination confirmed the diagnosis of 18q deletion syndrome and karyotype analysis of parental peripheral blood revealed a de novo deletion mutation. ConclusionsInterventional prenatal diagnosis is an integral standard for the diagnosis of 18q deletion syndrome. NIPT， as an important screening test in middle pregnancy， can indicate the early possible chromosome segment deletion and reduce the time and economic cost when no abnormality is found in ultrasonic imaging.

Prenatal ultrasonographic characteristics of Beckwith-Wiedemann syndrome: analysis of six cases / 中华围产医学杂志

Objective:To summarize the prenatal ultrasonographic features of Beckwith- Wiedemann syndrome (BWS).Methods:This retrospective study retrieved the records of six cases with BWS from Women and Children's Hospital of Chongqing Medical University from January 2015 to December 2022, to analyze their ultrasonographic features, clinical features after birth or termination, and genetic test results using descriptive statistical analysis method.Results:Intrauterine overgrowth was found in all six fetuses by prenatal ultrasound, and the estimated fetal weights were higher for their gestational age. Prenatal ultrasound findings showed macroglossia and protrusion of tongue in five cases, hepatomegaly in four cases, enlarged kidney in four cases, thickened umbilical cord in three cases, and intestinal duplication in two cases. Genetic testing showed that all six cases were associated with genetic damage at the 11p15.5 chromosome region. Three pregnancies were terminated after the diagnosis, and the features of gross specimens were consistent with the prenatal diagnosis. The postnatal clinical manifestations of three live births were macrosomia and macroglossia, two of whom exhibited acromphalus.Conclusion:BWS should be considered when fetal overgrowth, visceral enlargement, macroglossia, and acromphalus are found by prenatal ultrasound.

Prenatal phenotypic analysis and genetic counseling for 22q11.21 microdeletion and microduplication syndrome / 中华围产医学杂志

Objective:To analyze the prenatal clinical phenotypes and pregnancy outcomes of fetuses with 22q11.21 microdeletion and microduplication syndrome to provide a basis for clinical genetic counseling.Methods:This retrospective study involved the cases diagnosed with 22q11.21 microdeletion or microduplication by chromosomal microarray analysis (CMA) due to abnormal ultrasound findings, advanced maternal age, or high-risk pregnancies indicated by serum screening in the Prenatal Diagnosis Center of the First Affiliated Hospital of Air Force Medical University from January 2015 to January 2022. Clinical phenotypes and pregnancy outcomes of the fetuses were analyzed and described.Results:Among 9 141 cases referred for CMA during the study period, 77 cases (0.8%) were diagnosed as 22q11.21 microdeletion or microduplication, including 62 (80.5%) with 22q11.21 microdeletion and 15 (19.5%) with microduplication. In the 22q11.21 microdeletion cases, 58 had typical deletion, and four had atypical deletions, but all fetuses carried TBX1 gene that was clearly associated with congenital heart disease. The 15 fetuses with 22q11.21 microduplication including 14 in the typical region and one in the atypical region. Forty-eight (77.4%) out of the 62 fetuses with 22q11.21 microdeletion were complicated by congenital heart defects, including 28 with conotruncal defects. Five of the 15 fetuses with 22q11.21 microduplication were complicated by congenital heart defects. The cases were followed up on telephone at three to six months after the expected date of delivery. Among the 62 cases with 22q11.21 microdeletion, 52 terminated pregnancies, five were lost to follow-up, and five were delivered (one died after one month of premature delivery, one was born with anal advancement and growth retardation, and three were followed up without obvious abnormality). Among the 15 cases with 22q11.21 microduplication, four terminated pregnancies, two were lost to follow-up, and nine gave birth (eight were followed up without obvious abnormality, one grew slowly). Conclusions:The application of CMA in the prenatal diagnosis of 22q11.21 microdeletion and microduplication fetuses, and the comprehensive analysis of clinical manifestations and pregnancy outcome combined with ultrasonic diagnosis are of great significance in guiding the treatment and rehabilitation after birth of an affected child. Genetic counseling for cases with 22q11.21 microdeletion and microduplication syndrome should be cautious and consider ultrasound findings.

Application of genetic counseling and preventive surgery in hereditary breast-ovarian cancer syndrome based on a rare family / 中华肿瘤杂志

Objective: To investigate the genetic, clinical and pathological characteristics of families with hereditary breast-ovarian cancer syndrome (HBOCS) and to explore the implementation of genetic counseling and preventive surgery. Methods: Four siblings with HBOCS in Cancer Hospital/Chinese Academy of Medical Sciences were selected as the study subjects. BRCA gene testing and genetic counseling were performed, family history was traced and family map was drawn. Results: There were 7 cancer patients (Ⅰ 2, Ⅱ 4, Ⅱ 8, Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) in three generations in the family. One patient (Ⅲ 7) had breast cancer and ovarian cancer successively. The first generation (Ⅰ 2) developed cancer at age 60, the second generation (Ⅱ4 and Ⅱ8) developed cancer at 55. The third generation (Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) developed cancer at the age of 42-50 years. Four HBOCS patients were treated in our hospital, and all of them were found to have deleterious BRCA1 mutation. Two had already developed ovarian cancer (Ⅲ 10, Ⅲ 12), while in one case (Ⅲ 11), tubal carcinoma was found during preventive total hysterectomy and pelvic lymph node metastasis was found after the supplementary staging surgery. The other patient without cancer underwent preventive bilateral salpingectomy(Ⅲ 15). Conclusion: The HBOCS family reported in this study is relatively rare, the onset time of tumor was younger generation by generation. It is very important to pay attention to the genetic counseling of ovarian cancer patients and to timely detect the HBOCS families for genetic testing and prophylactic surgery.

Application of genetic counseling and preventive surgery in hereditary breast-ovarian cancer syndrome based on a rare family / 中华肿瘤杂志

Objective: To investigate the genetic, clinical and pathological characteristics of families with hereditary breast-ovarian cancer syndrome (HBOCS) and to explore the implementation of genetic counseling and preventive surgery. Methods: Four siblings with HBOCS in Cancer Hospital/Chinese Academy of Medical Sciences were selected as the study subjects. BRCA gene testing and genetic counseling were performed, family history was traced and family map was drawn. Results: There were 7 cancer patients (Ⅰ 2, Ⅱ 4, Ⅱ 8, Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) in three generations in the family. One patient (Ⅲ 7) had breast cancer and ovarian cancer successively. The first generation (Ⅰ 2) developed cancer at age 60, the second generation (Ⅱ4 and Ⅱ8) developed cancer at 55. The third generation (Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) developed cancer at the age of 42-50 years. Four HBOCS patients were treated in our hospital, and all of them were found to have deleterious BRCA1 mutation. Two had already developed ovarian cancer (Ⅲ 10, Ⅲ 12), while in one case (Ⅲ 11), tubal carcinoma was found during preventive total hysterectomy and pelvic lymph node metastasis was found after the supplementary staging surgery. The other patient without cancer underwent preventive bilateral salpingectomy(Ⅲ 15). Conclusion: The HBOCS family reported in this study is relatively rare, the onset time of tumor was younger generation by generation. It is very important to pay attention to the genetic counseling of ovarian cancer patients and to timely detect the HBOCS families for genetic testing and prophylactic surgery.

Toma de decisión compartida en la asesoría preprueba de la ecografía de las 11 a las 13 semanas de gestación: revisión bibliográfica / Shared decision making in pretest counseling at the 11 to 13 weeks ultrasound scan: bibliographic review

Resumen ANTECEDENTES: En el diagnóstico prenatal confluye un grupo de tecnologías enfocadas a la detección de defectos o anomalías congénitas de origen genético y multifactorial. Con independencia del tipo de prueba de que se trate, cualquier tecnología de diagnóstico prenatal debe ir acompañada de asesorías pre y posprueba. La sustentación ética de estas asesorías es de primordial interés para la Medicina prenatal y ha sido tarea de diversas organizaciones. METODOLOGÍA: Estudio retrospectivo, de búsqueda en las bases de datos PubMed, Web of Science y Google Scholar, con los términos MeSH: "Pregnancy", "Prenatal Diagnosis", "Genetic Conuseling", "Relational Autonomy" y "Decision Making". RESULTADOS: Se encontraron 909 referencias de las que se eliminaron las de más de 20 años de publicación, las que no contaban con textos completos y las duplicadas por la búsqueda en distintas bases de datos. Al final se analizaron 25 artículos en texto completo que sirvieron de base para la revisión bibliográfica. CONCLUSIONES: En la actualidad, el ultrasonido es la principal puerta de entrada al mundo del diagnóstico prenatal. Aludir a la indicación y uso éticos de cualquier tecnología de diagnóstico prenatal previene daño al embarazo en su conjunto y desincentiva la necesidad de una normatividad jurídica detallada que, por el momento, no existe en muchos países, incluido el nuestro. Hoy en día se dispone de lineamientos éticos claros para la asesoría de la ecografía como técnica de diagnóstico prenatal.

Abstract BACKGROUND: Prenatal diagnosis brings together a group of technologies that focus on the detection of congenital defects or anomalies of genetic and multifactorial origin. Irrespective of the type of test, any prenatal diagnostic technology must be accompanied by pre- and post-test counselling. The ethical underpinning of such counselling is of paramount interest to prenatal medicine and has been the task of several organisations. METHODOLOGY: Retrospective study, searching PubMed, Web of Science and Google Scholar databases using the MeSH terms: "pregnancy", "prenatal diagnosis", "genetic counselling", "relational autonomy" and "decision making". RESULTS: We found 909 references from which we eliminated those older than 20 years of publication, those without full text and those duplicated by searching in different databases. In the end, 25 full-text articles were analysed and served as the basis for the literature review. CONCLUSIONS: Ultrasound is currently the main gateway to the world of prenatal diagnosis. The ethical indication and use of any prenatal diagnostic technology prevents harm to the pregnancy as a whole and avoids the need for detailed legal regulation, which currently does not exist in many countries, including our own. Clear ethical guidelines are now available for advice on ultrasound as a prenatal diagnostic technique.

Prevención de hemoglobinopatías en el Policlínico 28 de septiembre, municipio Santiago de Cuba / Hemoglobinopathy Prevention in 28 de Septiembre Outpatient Polyclinic, of Santiago de Cuba Municipality

Introducción: La anemia de células falciformes es un defecto funcional que afecta la hemoglobina, tiene carácter hereditario y una elevada frecuencia en la población cubana. Objetivo: Caracterizar el programa de prevención de hemoglobinopatías en el Policlínico 28 de septiembre, municipio Santiago de Cuba. Métodos: Se realizó un estudio descriptivo, retrospectivo de corte longitudinal en 6055 gestantes, estudiadas por electroforesis de hemoglobina o cuya condición era conocida con anterioridad durante el período enero 2011 a diciembre 2020 hemoglobinopatías en el Policlínico 28 de septiembre del municipio Santiago de Cuba. Se analizaron las variantes de hemoglobinas, su frecuencia, la proporción de esposos estudiados, parejas de alto riesgo detectadas, diagnósticos prenatales realizados y sus resultados. Se utilizó la estadística descriptiva para el análisis de los datos. Resultados: De las gestantes, 7,18 por ciento resultó portadora de alguna variante de hemoglobina. Se logró estudiar 92,64 por ciento de los cónyuges, donde el aborto resultó la causa más significativa de no estudio. Se detectaron 27 parejas de alto riesgo, fueron realizados 22 diagnósticos prenatales (81,50 por ciento) y se diagnosticaron cuatro fetos portadores de hemoglobinopatía SS por estudio molecular, cuyos progenitores optaron por la terminación de la gestación en el marco del asesoramiento genético. Conclusiones: La caracterización del programa de hemoglobina en gestantes nos permitió identificar la frecuencia de portadoras dentro del grupo estudiado, así como la efectividad del asesoramiento genético ofrecido a las parejas de alto riesgo en el primer nivel de atención al no reportarse nacidos vivos con la enfermedad en el área de salud durante el decenio(AU)

Introduction: Sickle cell anemia is a functional defect that affects hemoglobin. It is of a hereditary nature and highly frequent among the Cuban population. Objective: To characterize the hemoglobinopathies prevention program in 28 de Septiembre outpatient Polyclinic, of Santiago de Cuba Municipality. Methods: A descriptive, retrospective and longitudinal study was carried out, during the period from January 2011 to December 2020, with 6055 pregnant women, studied by hemoglobin electrophoresis or whose condition was previously known. The hemoglobin variants, their frequency, the proportion of studied spouses, the identified high-risk couples, the performed prenatal diagnoses and their results were analyzed. Descriptive statistics were used for data analysis. Results: Of the pregnant women, 7.18 percent presented some hemoglobin variant. It was possible to study 92.64 percent of the spouses, while abortion was the most significant unstudied cause. Twenty-seven high-risk couples were identified, 22 prenatal diagnoses were performed (81.50 percent), and four fetuses were diagnosed, by molecular study, to present sickle cell anemia as a hemoglobinopathy, whose parents opted for pregnancy termination within the framework of genetic counseling. Conclusions: The characterization of the hemoglobin program in pregnant women allowed us to identify the frequency of carriers within the studied group, as well as the effectiveness of genetic counseling offered to high-risk couples at the first level of care, since no live births were reported with the disease in the health area during the decade(AU)

Shared decision-making in genetic counseling: A scoping review / La toma de decisiones compartida en el asesoramiento genético: una revisión del ámbito de aplicación / Tomada de decisão compartilhada em aconselhamento genético: uma revisão de propósito

Abstract: Background: It is challenging to make informed decision in genetic counseling. Shared decision-making provides a chance in balancing the information and preferences between counselors and counselees. However, the status and prescriptions of shared decision-making have not been extensively studied in genetic counseling. Aim: To develop an up-to-date literature review of the shared decision-making in genetic counseling, identify knowledge gaps, and provide inspiration and suggestions for the development and practice of genetic counseling. Methods: "Genetic Counseling" and "Shared decision-making" were used to search in PubMed, Web of Science, Embase, Wanfang, CNKI and CBM databases. The search deadline was March 26, 2021. Results: A total of 22 articles were included, and four themes were identified: how people involved in genetic counseling, different stakeholders involved in SDM, multiple facilitators and barriers to SDM and the effectiveness of SDM in genetic counseling. Conclusion: Each participant needs to recognize their boundaries and make the best effort to involve in the shared decision-making. In the future, multinational studies should be considered for bringing shared decision-making to the global scale and well-designed studies are required to explore the long-term impact of shared decision-making in genetic counseling.

Resumen: Antecedentes: Es un reto tomar una decisión informada en el asesoramiento genético. La toma de decisiones compartida ofrece una oportunidad para equilibrar la información y las preferencias entre los asesores y los pacientes. Sin embargo, el estado y las prescripciones de la toma de decisiones compartida no se han estudiado ampliamente en el asesoramiento genético. Objetivo: Desarrollar una revisión bibliográfica actualizada de la toma de decisiones compartida en el asesoramiento genético, identificar las lagunas de conocimiento y proporcionar inspiración y sugerencias para el desarrollo y la práctica del asesoramiento genético. Métodos: "Genetic Counseling" y "Shared decision-making" se utilizaron para buscar en las bases de datos PubMed, Web of Science, Embase, Wanfang, CNKI y CBM. La fecha límite de búsqueda fue el 26 de marzo de 2021. Resultados: Se incluyó un total de 22 artículos y se identificó cuatro temas: cómo se involucran las personas en el asesoramiento genético, las diferentes partes interesadas involucradas en la GDS, los múltiples facilitadores y barreras para la GDS y la efectividad de la GDS en el asesoramiento genético. Conclusión: Cada participante necesita reconocer sus límites y hacer el mejor esfuerzo para involucrarse en la toma de decisiones compartida. En el futuro, se debe considerar la realización de estudios multinacionales para llevar la toma de decisiones compartida a la escala global y se requieren estudios bien diseñados para explorar el impacto a largo plazo de la toma de decisiones compartida en el asesoramiento genético.

Resumo Antecedentes: Tomar uma decisão informada em aconselhamento genético é um desafio. A tomada de decisão compartilhada (SDM) fornece uma oportunidade para contrabalançar a informação e preferências entre conselheiros e aconselhados. Entretanto, o status e prescrições da tomada de decisão compartilhada não têm sido extensivamente estudados em aconselhamento genético. Objetivo: Desenvolver uma revisão de literatura atualizada sobre a tomada de decisão compartilhada em aconselhamento genético, identificar lacunas no conhecimento e fornecer inspiração e sugestões para o desenvolvimento e prática do aconselhamento genético. Métodos: "Genetic Counseling" e "Shared decision-making" foram usados para pesquisar nos bancos de dados PubMed, Web of Science, Embase, Wanfang, CNKI e CBM. A data limite para a pesquisa foi 26 de março de 2021. Resultados: Um total de 22 artigos foram incluídos e quatro temas foram identificados: como pessoas se envolveram em aconselhamento genético, diferentes interessados envolvidos em SDM, facilitadores e barreiras múltiplas à SDM e efetividade da SDM em aconselhamento genético. Conclusão: Cada participante necessita reconhecer seus limites e fazer os melhores esforços para se envolver em tomada de decisão compartilhada. No futuro, estudos multinacionais devem ser considerados para trazer a tomada de decisão compartilhada a uma escala global e estudos bem desenhados são requeridos para explorar o impacto a longo prazo da tomada de decisão compartilhada em aconselhamento genético.

Histological and Immunohistochemical Characteristics for Hereditary Breast Cancer Risk in a Cohort of Brazilian Women / Características histológicas e imunohistoquímicas para risco hereditário de câncer de mama em uma coorte de mulheres brasileiras

Abstract Objective The study aimed to characterize the clinical, histological, and immunohistochemical profile of women with invasive breast cancer, according to the risk for Hereditary Predisposition Breast and Ovarian Cancer Syndrome in a Brazilian population. Methods This is a retrospective study performed from a hospital-based cohort of 522 women, diagnosed with breast cancer treated at an oncology referral center in the Southeast region of Brazil, between 2014 and 2016. Results Among the 430 women diagnosed with invasive breast cancer who composed the study population, 127 (29.5%) were classified as at increased risk for hereditary predisposition to breast and ovarian cancer syndrome. There was a lower level of education in patients at increased risk (34.6%) when compared with those at usual risk (46.0%). Regarding tumor characteristics, women at increased risk had higher percentages of the disease diagnosed at an advanced stage (32.3%), and with tumors > 2cm (63.0%), with increased prevalence for both characteristics, when compared with those at usual risk. Furthermore, we found higher percentages of HG3 (43.3%) and Ki-67 ≥ 25% (64.6%) in women at increased risk, with prevalence being about twice as high in this group. The presence of triple-negative tumors was observed as 25.2% in women at increased risk and 6.0% in women at usual risk, with the prevalence of absence of biomarkers being 2.5 times higher among women in the increased risk group. Conclusion From the clinical criteria routinely used in the diagnosis of breast cancer, the care practice of genetic counseling for patients at increased risk of hereditary breast cancer in contexts such as Brazil is still scarce.

Resumo Objetivo O presente estudo buscou caracterizar o perfil clínico, histológico e imunohistoquímico de mulheres com câncer de mama invasivo segundo o risco para a Síndrome de Predisposição Hereditária ao Câncer de Mama e Ovário em uma população brasileira. Métodos Trata-se de um estudo retrospectivo realizado a partir de uma coorte hospitalar composta por 522 mulheres diagnosticadas com câncer de mama entre 2014 e 2016 assistidas em um centro de referência oncológica localizado na região sudeste brasileira. Resultados Entre as 430 mulheres diagnosticadas com câncer de mama invasivo que compuseram a população de estudo, 127 (29,5%) foram classificadas como de risco aumentado para a síndrome de predisposição hereditária ao câncer de mama e ovário. Verificou-se menor nível de escolaridade nas pacientes com risco aumentado (34,6%) quando comparadas àquelas consideradas como de risco habitual (46,0%). Quanto às características do tumor, as mulheres de risco aumentado apresentaram maiores percentuais de doença diagnosticada em estádio avançado (32,3%) e com tumores > 2cm (63,0%), com prevalência aumentada para ambas as características, quando comparadas àquelas de risco habitual. Ainda nas mulheres de risco aumentado, foram encontrados maiores percentuais de GH3 (43,3%) e Ki-67 ≥ 25% (64,6%), com prevalência cerca de duas vezes maior neste grupo. A presença de tumores triplo-negativos foi observada em 25,2% nas mulheres de risco aumentado e 6,0% nas mulheres de risco habitual, com prevalência de ausência de biomarcadores 2,5 vezes maior entre as mulheres do grupo de risco aumentado. Conclusão A partir dos critérios clínicos rotineiramente utilizados no diagnóstico do câncer de mama, a prática assistencial do aconselhamento genético para as pacientes com risco aumentado de câncer de mama hereditário em contextos como o do Brasil ainda é escarça.

Cross-sectional observational analysis of the genetic referral practices across pediatric ophthalmology outpatient departments in an urban setting

Purpose: To analyze the genetic referral practices of pediatric ophthalmologists in an urban setting. Methods: (1) The first limb of the study: cross?sectional, observational study among children visiting the outpatient department of pediatric ophthalmology across five centers in Mumbai. All pediatric patients were screened separately by pediatric ophthalmologists and a clinical geneticist for their ophthalmic and systemic complaints. Children were marked for referral to genetics (RTG) by both the specialists based on identification of distinctive features (red flag) and were requested to meet a local geneticist. (2a) Twenty?three months later, patients who had been marked for RTG were contacted telephonically to follow?up if they had met the geneticist. (2b) Additionally, the last 20 proformas from each center were checked retrospectively to note the RTG marked by the ophthalmologist alone. Results: (1) In the first aspect of the study, 126 patients (male: female = 1.2:1) were included. Forty?nine (38.3%) patients were referred for genetic evaluation, of which three (6.1%), 31 (63.26%), and 15 (30.6%) cases were referred by the ophthalmologist alone, geneticist alone, and by both the specialists, respectively. Glaucoma (100%), nystagmus (86%), and leukocoria (83%) were the most prominent ocular diagnoses in cases referred for genetic evaluation. Facial dysmorphism (55.1%) and neurodevelopmental delays (51%) were among the most common systemic red flags found in patients referred to genetics. (2a) Twenty?three months later, on contacting the 49 patients marked for RTG, only one family had met the geneticist. (2b) Retrospective evaluation of 100 proformas: only three patients were marked for RTG by ophthalmologist alone. Conclusion: This study found that the genetic referrals by pediatric ophthalmologist were far lesser than those by geneticist. The study highlights an area of knowledge gap among pediatric ophthalmologists, prompting a need for heightened awareness in this area.

Exploiting Genetic Counseling as a Tool for the Analysis of Dissociative Behavior and Sub-normality from Conception to Birth among Maladjusted Blind, Deaf and Dumb Infants

This paper analyzes the dissociation behavior of children from pregnancy to birth and resultant sub-normality using genetic counseling in an attempt to mainstream children with birth disabilities and the challenges of the genetic counselor. Genetic counseling is a process of communication to provide information about a genetic condition, or inheritance, and support decision making and adjustment in families with the inheritance gene. It uses children that need special needs, the blind, deaf and dumb. Genetic counseling approach, re-affirmation, care and integration, and confidence-building institutionalized in school and family life remains some of the vital tools needed to support these children using genetic guidance and counseling as the best approach to adjusting the different maladaptive behavior of children. The genetic counseling approach includes information about the implications of testing positive for the genetic disorder, including the psychological impact and other consequences, whether to inform relatives of your intention to test, or not to test and the usual pattern of progression of the sub-normality identified tested for and its potential treatments. Thus, the paper seems to analyze sub-normality as classified within the adequacy of social adaptation. Analysis of dissociation behavior associated with sub mentality shows discouragement, contempt, and neglect from an early age, emotionally and maladjusted social growth. Therefore, the counselor must experience sub-normality by getting involved and clarifying their feeling toward the children with these disabilities.