Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region.

Chromosomal submicroscopic imbalances represent well-known causes of neurodevelopmental disorders. In some cases, these can cause specific autosomal dominant syndromes, with high-to-complete penetrance and de novo occurrence of the variant. In other cases, they result in non-syndromic neurodevelopmental disorders, often acting as moderate-penetrance risk factors, possibly inherited from unaffected parents. We describe a three-generation family with non-syndromic neuropsychiatric features segregating with a novel 19q13.32q13.33 microduplication. The propositus was a 28-month-old male ascertained for psychomotor delay, with no dysmorphic features or malformations. His mother had Attention-Deficit/Hyperactivity Disorder and a learning disability. The maternal uncle had an intellectual disability. Chromosomal microarray analysis identified a 969 kb 19q13.32q13.33 microduplication in the proband. The variant segregated in the mother, the uncle, and the maternal grandmother of the proband, who also presented neuropsychiatric disorders. Fragile-X Syndrome testing was negative. Exome Sequencing did not identify Pathogenic/Likely Pathogenic variants. Imbalances involving 19q13.32 and 19q13.33 are associated with neurodevelopmental delay. A review of the reported microduplications allowed to propose BICRA (MIM *605690) and KPTN (MIM *615620) as candidates for the neurodevelopmental delay susceptibility in 19q13.32q13.33 copy number gains. The peculiarities of this case are the small extension of the duplication, the three-generation segregation, and the full penetrance of the phenotype.

Prevenção de acidentes domésticos na primeira infância: uma revisão integrativa / Preventing domestic accidents in early childhood: an integrative review / Prevención de accidentes domésticos en la primera infancia: una revisión integradora

Introdução: A primeira infância é uma fase marcada por intenso desenvolvimento infantil, com o aperfeiçoamento de habilidades motoras, cognitivas e sensoriais. Em vista disso, as crianças são expostas a riscos e portanto, cuidados devem ser redobrados para prevenir acidentes, em especial no próprio lar. Objetivos: Identificar os riscos a que as crianças são expostas, bem como os trabalhos científicos que abordam a prevenção de acidentes domésticos na primeira infância. Métodos: Trata-se de uma revisão integrativa da literatura conduzida nas bases de dados: LILACS, MEDLINE, BDENF e SciELO. A avaliação, do nível de evidência dos artigos encontrados, foi obtida por meio do método Oxford Centre for Evidence-based Medicine. Resultados: Dez artigos atenderam aos critérios de busca estabelecidos. Os acidentes domésticos que se destacaram nos artigos foram: quedas, queimaduras, envenenamento e tombamento em aparelhos televisivos. Em relação ao ambiente familiar, foi notório que a maioria das famílias dos estudos analisados eram de baixa renda. Conclusão: Os pais ou responsáveis pelas crianças são essenciais para prevenir acidentes domésticos de variadas causas. Além disso, a atuação dos profissionais de saúde é primordial para desenvolver ou potencializar programas de prevenção, principalmente voltados para aqueles que são vulneráveis social ou economicamente, a fim de capacitar a população quanto à identificação e minimização dos riscos.

Introduction: Early childhood is a phase marked by intense child development, with improved motor, cognitive and sensory skills. Given this, children are exposed to risks and, therefore, must redouble care to prevent accidents, especially at home. Aim: To identify the risks to which children are exposed, as well as scientific works that address the prevention of domestic accidents in early childhood. Methods: This is an integrative literature review conducted in the following databases: LILACS, MEDLINE, BDENF, and SciELO. The level of evidence of the articles found was assessed using the Oxford Center for Evidence-based Medicine method. Results: Ten articles met the established search criteria. The domestic accidents that stood out in the articles were: falls, burns, poisoning, and tipping over television sets. Regarding the family environment, it was clear that most families in the analyzed studies were of low income. Conclusion: Parents or guardians of children are essential to prevent domestic accidents from various causes. In addition, the role of health professionals is necessary to develop or enhance prevention programs, mainly aimed at the socially or economically vulnerable, to train the population in identifying and minimizing risks.

Introducción: La primera infancia es una fase marcada por un intenso desarrollo infantil,con la mejora de las habilidades motoras, cognitivas y sensoriales. Así, los niños están expuestos a riesgos y, por lo tanto, los cuidados deben ser redoblados para prevenir accidentes, especialmente en el propio hogar. Objetivos: Identificar los riesgos a los que están expuestos los niños, así como trabajos científicos que aborden la prevención de accidentes domésticos en la primera infancia. Métodos: Se trata de una revisión integrativa de la literatura realizada en las siguientes bases de datos: LILACS, MEDLINE, BDENF y SciELO. La evaluación, del nivel de evidencia de los artículos encontrados se obtuvo por medio del método Oxford Center for Evidence-based Medicine. Resultados: Diez artículos cumplieron con los criterios de búsqueda establecidos. Los accidentes domésticos que se destacaron en los artículos fueron: caídas, quemaduras, envenenamiento y caídas de televisión. Con relación al ambiente familiar, fue notorio que la mayoría de las familias en los estudios analizados eran de bajos ingresos. Conclusión: Los padres o responsables de los niños son fundamentales para prevenir accidentes domésticos por diversas causas. Además, el papel de los profesionales de la salud es fundamental para desarrollar o potencializar programas de prevención, principalmente dirigidos a personas en situación de vulnerabilidad social o económica, con el fin de capacitar a la población en la identificación y minimización de riesgos.

Prenatal CFAP53-related laterality defect: case report and review of the literature.

Laterality defects include morphological anomalies with impaired left-right asymmetry induction, such as dextrocardia, situs inversus abdominis, situs inversus totalis and situs ambiguus. The different arrangement of major organs is called heterotaxy. We describe for the first time a fetus with situs viscerum inversus and azygos continuation of the inferior vena cava, due to previously unreported variants in compound heterozygosity in the CFAP53 gene, whose product is implied in cilial motility. Prenatal trio exome sequencing was performed with turn-around time during the pregnancy. The fetuses with laterality defects are suitable candidates for prenatal exome sequencing due to the emerging high diagnostic rate of this group of morphological anomalies. A timely molecular diagnosis plays a fundamental role in genetic counseling, regarding couple decisions on the ongoing pregnancy, providing recurrence risks, and in predicting possible respiratory complications due to ciliary dyskinesia.

Clinical variability in DYNC2H1-related skeletal ciliopathies includes Ellis-van Creveld syndrome.

Deleterious variants of DYNC2H1 gene are associated with a wide spectrum of skeletal ciliopathies (SC). We used targeted parallel sequencing to analyze 25 molecularly unsolved families with different SCs. Deleterious DYNC2H1 variants were found in six sporadic patients and two monozygotic (MZ) twins. Clinical diagnoses included short rib-polydactyly type 3 in two cases, and asphyxiating thoracic dystrophy (ATD) in one case. Remarkably, clinical diagnosis fitted with EvC, mixed ATD/EvC and short rib-polydactyly/EvC phenotypes in three sporadic patients and the MZ twins. EvC/EvC-like features always occurred in compound heterozygotes sharing a previously unreported splice site change (c.6140-5A>G) or compound heterozygotes for two missense variants. These results expand the DYNC2H1 mutational repertoire and its clinical spectrum, suggesting that EvC may be occasionally caused by DYNC2H1 variants presumably acting as hypomorphic alleles.

Mosaic genome-wide paternal uniparental disomy after discordant results from primary fetal samples and cultured cells.

Mosaic genome-wide paternal uniparental disomy (GWpUPD) is a rare condition in which two euploid cell lines coexist in the same individual, one with biparental content and one with genome-wide paternal isodisomy. We report a complex prenatal diagnosis with discordant results from cultured and uncultured samples. A pregnant woman was referred for placental mesenchymal dysplasia and fetal omphalocele. Karyotype, array-CGH and Beckwith-Wiedemann Syndrome (BWS) testing (methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of 11p15) performed on amniocytes were negative. After intrauterine fetal demise, the clinical suspicion persisted and BWS MS-MLPA was repeated on cultured cells from umbilical cord and amniotic fluid, revealing a mosaicism for KvH19 hypermethylation/KCNQ1OT1:TSS:DMR hypomethylation. These results, along with microsatellite analysis of the BWS region, were consistent with mosaic paternal 11p15 isodisomy. A concurrent maternal contamination exclusion test, analyzing polymorphic microsatellite markers on multiple chromosomes, showed an imbalance in favor of paternal alleles at all examined loci on cultured amniocytes and umbilical cord samples. This led to suspicion of mosaic GWpUPD, later confirmed by SNP-array, identifying a mosaic genome-wide paternal isodisomy affecting 60% of fetal cells. The assessment of mosaic GWpUPD requires multiple approaches beyond the current established diagnostic processes, also entertaining possible low-rate mosaicism. Clinical acumen and an integrated testing approach are the key to a successful diagnosis.

Gestação, Vírus da Imunodeficiência Adquirida (HIV) e COVID-19: desafios na assistência ao pré-natal / Embarazo, virus de la inmunodeficiencia adquirida y COVID-19: desafíos en la atención prenatal / Pregnancy, acquired immunodeficiency virus and COVID-19: challenges in prenatal care

Objetivo: evidenciar os desafios existentes durante o pré-natal em mulheres grávidas soropositivas para o Vírus da Imunodeficiência Adquirida durante um período pandêmico. Método: Trata-se de uma pesquisa quantitativa exploratória de caráter descritivo, utilizando-se de levantamento de dados através de entrevistas em campo com 19 gestantes com Vírus da Imunodeficiência Adquirida de um serviço de assistência especializada, entre julho de 2021 e julho de 2022. Resultados: apontaram dificuldades para agendar consultas, realizar exames e acesso aos resultados, dificuldades para conseguir transporte devido a distância da unidade de infectologia e dificuldade para agendar consultas na unidade básica de saúde. Conclusão:o serviço de assistência especializada realizou a reorganização da assistência para diminuir os desafios presentes, que foram dificuldade de acesso a unidade, marcação e acesso a resultado de exames pré-natal.

Objectives: to highlight the existing challenges during prenatal care in pregnant women seropositive for the Acquired Immunodeficiency Virus during a pandemic period. Method: This is a descriptive exploratory quantitative research, using data collection through field interviews with 19 pregnant women with Acquired Immunodeficiency Virus from a specialized assistance service, between July 2021 and July 2022. Results: they pointed out difficulties in scheduling consultations, performing tests and accessing the results, difficulties in getting transportation due to the distance from the infectology unit and difficulty in scheduling consultations at the basic health unit. Conclusion: the specialized assistance service carried out the reorganization of assistance to reduce the present challenges, which were difficulty in accessing the unit, scheduling and access to prenatal exam results.

Objetivos:resaltar los desafíos existentes durante la atención prenatal en gestantes seropositivas para el Virus de la Inmunodeficiencia Adquirida en período de pandemia. Método: Se trata de una investigación cuantitativa exploratoria descriptiva, utilizando la recolección de datos a través de entrevistas de campo con 19 gestantes con Virus de la Inmunodeficiencia Adquirida de un servicio de asistencia especializada, entre julio de 2021 y julio de 2022. Resultados:señalaron dificultades en la programación de consultas, realización de pruebas y acceso a los resultados, dificultades para conseguir transporte debido a la distancia de la unidad de infectología y dificultad para programar consultas en la unidad básica de salud. Conclusión: el servicio de asistencia especializada realizó la reorganización de la asistencia para reducir los desafíos presentes, que fueron la dificultad de acceso a la unidad, la programación y el acceso a los resultados del examen prenatal.

Complete Pseudo-Anodontia in an Adult Woman with Pseudo-Hypoparathyroidism Type 1a: A New Additional Nonclassical Feature?

Pseudo-anodontia consists in the clinical, not radiographic, absence of teeth, due to failure in their eruption. It has been reported as part of an extremely rare syndrome, named GAPO syndrome. Pseudo-hypoparathyroidism type 1a (PHPT-1a) is a rare condition, characterized by resistance to the parathyroid hormone (PTH), as well as to many other hormones, and resulting in hypocalcemia, hyperphosphatemia, and elevated PTH. We report here the case of a 32-year-old woman with a long-standing history of non-treated hypocalcemia, in the context of an undiagnosed PHPT-1a. She had an intellectual disability, showed clinical features of the Albright hereditary osteodystrophy (AHO) and presented signs of multiple hormone resistances. She received treatment for seizures since the age of six. Examination of her mouth revealed a complete absence of teeth. Treatment of hypocalcemia and hormone deficiencies were started only at 29 years of age. Genetic testing demonstrated the presence of a frameshift variant in the GNAS gene in the proband as well as in her mother. A Single Nucleotide Polymorphism (SNP) array analysis failed to demonstrate pathogenic copy number variants (CNVs) but showed several regions with loss of heterozygosity (LOHs) for a final percentage of 1.75%, compatible with a fifth degree of relationship. Clinical exome sequencing (CES) ruled out any damaging variants in all the teeth agenesis-related genes. In conclusion, although we performed an extensive genetic analysis in search of possible additional gene alterations that could explain the presence of the peculiar phenotypic characteristics observed in our patient, we could not find any additional genetic defects. Our results suggest that the association of genetically confirmed PHPT-1a and complete pseudo-anodontia associated with persistent patchy alopecia areata is a new additional nonclassical feature related to the GNAS pathogenic variant.

Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, and sleep disturbance, and no therapy has been developed to alleviate its symptoms or delay disease onset. SMS occurs due to haploinsufficiency of the retinoic acid-induced-1 (RAI1) gene caused by either chromosomal deletion (SMS-del) or RAI1 missense/nonsense mutation. The molecular mechanisms underlying SMS are unknown. Here, we generated and characterized primary cells derived from four SMS patients (two with SMS-del and two carrying RAI1 point mutations) and four control subjects to investigate the pathogenetic processes underlying SMS. By combining transcriptomic and lipidomic analyses, we found altered expression of lipid and lysosomal genes, deregulation of lipid metabolism, accumulation of lipid droplets, and blocked autophagic flux. We also found that SMS cells exhibited increased cell death associated with the mitochondrial pathology and the production of reactive oxygen species. Treatment with N-acetylcysteine reduced cell death and lipid accumulation, which suggests a causative link between metabolic dyshomeostasis and cell viability. Our results highlight the pathological processes in human SMS cells involving lipid metabolism, autophagy defects and mitochondrial dysfunction and suggest new potential therapeutic targets for patient treatment.

3'UTR Deletion of NONO Leads to Corpus Callosum Anomaly, Left Ventricular Non-Compaction and Ebstein's Anomaly in a Male Fetus.

NONO (Non-Pou Domain-Containing Octamer-Binding Protein) gene maps on chromosome Xq13.1 and hemizygous loss-of-function nucleotide variants are associated with an emerging syndromic form of intellectual developmental disorder (MRXS34; MIM #300967), characterized by developmental delay, intellectual disability, poor language, dysmorphic facial features, and microcephaly. Structural brain malformation, such as corpus callosum and cerebellar abnormalities, and heart defects, in particular left ventricular non-compaction (LVNC), represent the most recurrent congenital malformations, recorded both in about 80% of patients, and can be considered the distinctive imaging findings of this disorder. We present on a further case of NONO-related disease; prenatally diagnosed in a fetus with complete corpus callosum agenesis; absence of septum pellucidum; pericallosal artery; LVNC and Ebstein's anomaly. A high-resolution microarray analysis demonstrated the presence of a deletion affecting the NONO 3'UTR; leading to a marked hypoexpression of the gene and the complete absence of the protein in cultured amniocytes. This case expands the mutational spectrum of MRXS34, advises to evaluate NONO variants in pre- and postnatal diagnosis of subjects affected by LVNC and other heart defects, especially if associated with corpus callosum anomalies and confirm that CNVs (Copy Number Variants) represent a non-negligible cause of Mendelian disorders.

Exome sequencing efficacy and phenotypic expansions involving esophageal atresia/tracheoesophageal fistula plus.

Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a life-threatening birth defect that often occurs with other major birth defects (EA/TEF+). Despite advances in genetic testing, a molecular diagnosis can only be made in a minority of EA/TEF+ cases. Here, we analyzed clinical exome sequencing data and data from the DECIPHER database to determine the efficacy of exome sequencing in cases of EA/TEF+ and to identify phenotypic expansions involving EA/TEF. Among 67 individuals with EA/TEF+ referred for clinical exome sequencing, a definitive or probable diagnosis was made in 11 cases for an efficacy rate of 16% (11/67). This efficacy rate is significantly lower than that reported for other major birth defects, suggesting that polygenic, multifactorial, epigenetic, and/or environmental factors may play a particularly important role in EA/TEF pathogenesis. Our cohort included individuals with pathogenic or likely pathogenic variants that affect TCF4 and its downstream target NRXN1, and FANCA, FANCB, and FANCC, which are associated with Fanconi anemia. These cases, previously published case reports, and comparisons to other EA/TEF genes made using a machine learning algorithm, provide evidence in support of a potential pathogenic role for these genes in the development of EA/TEF.

Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet-Biedl Syndrome-Like Phenotype.

Fibrillin proteins are extracellular matrix glycoproteins assembling into microfibrils. FBN1, FBN2, and FBN3 encode the human fibrillins and mutations in FBN1 and FBN2 cause connective tissue disorders called fibrillinopathies, affecting cardiovascular, dermal, skeletal, and ocular tissues. Recently, mutations of the less characterized fibrillin family member, FBN3, have been associated in a single family with Bardet-Biedl syndrome (BBS). Here, we report on a patient born from two first cousins and affected by developmental delay, cognitive impairment, obesity, dental and genital anomalies, and brachydactyly/syndactyly. His phenotype was very similar to that reported in the previous FBN3-mutated family and fulfilled BBS clinical diagnostic criteria, although lacking polydactyly, the most recurrent clinical feature, as the previous siblings described. A familial SNP-array and proband's WES were performed prioritizing candidate variants on the sole patient's runs of homozygosity. This analysis disclosed a novel homozygous missense variant in FBN3 (NM_032447:c.5434A>G; NP_115823:p.Ile1812Val; rs115948457), inherited from the heterozygous parents. This study further supports that FBN3 is a candidate gene for a BBS-like syndrome characterized by developmental delay, cognitive impairment, obesity, dental, genital, and skeletal anomalies. Anyway, additional studies are necessary to investigate the exact role of the gene and possible interactions between FBN3 and BBS proteins.

Chromosomal Microarray Analysis in Fetuses Detected with Isolated Cardiovascular Malformation: A Multicenter Study, Systematic Review of the Literature and Meta-Analysis.

Cardiovascular malformations (CVM) represent the most common structural anomalies, occurring in 0.7% of live births. The CVM prenatal suspicion should prompt an accurate investigation with fetal echocardiography and the assessment through genetic counseling and testing. In particular, chromosomal microarray analysis (CMA) allows the identification of copy number variations. We performed a systematic review and meta-analysis of the literature, studying the incremental diagnostic yield of CMA in fetal isolated CVM, scoring yields for each category of heart disease, with the aim of guiding genetic counseling and prenatal management. At the same time, we report 59 fetuses with isolated CVM with normal karyotype who underwent CMA. The incremental CMA diagnostic yield in fetuses with isolated CVM was 5.79% (CI 5.54-6.04), with conotruncal malformations showing the higher detection rate (15.93%). The yields for ventricular septal defects and aberrant right subclavian artery were the lowest (2.64% and 0.66%). Other CVM ranged from 4.42% to 6.67%. In the retrospective cohort, the diagnostic yield was consistent with literature data, with an overall CMA diagnostic yield of 3.38%. CMA in the prenatal setting was confirmed as a valuable tool for investigating the causes of fetal cardiovascular malformations.

Diagnóstico de la superación en farmacovigilancia de productos naturales en Servicios Farmacéuticos, en Pinar del Río / Analysis of the training in pharmacovigilance of natural products in Pharmaceutical Services, Pinar del Rio

RESUMEN Introducción: la superación en farmacovigilancia de los produtos naturales es importante para el conocimiento y habilidades en el desempeño de los profesionales en servicios farmacéuticos comunitario por su vínculo en el desarrollo científico en la identificación, cuantificación, manejo de la documentación, vigilancia y reporte de reacciones adversas de los produtos tradicionales. Objetivo: diagnosticar el estado actual de la superación en farmacovigilancia de los productos naturales dirigidos a profesionales en servicios farmacéuticos en Pinar del Río en el periodo de enero de 2019 a marzo de 2020 Métodos: se realizó una investigación desarrollo de tipo educacional en los profesionales en servicios farmacéuticos en Pinar del Río. El universo lo constituyeron 78 profesionales, y la muestra seleccionada correspondió a 58 profesionales en los servicios farmacéuticos. Se utilizó como método general el dialéctico materialista, como métodos teóricos, histórico lógico, como métodos empíricos las encuesta, el análisis documental, la entrevista y la observación. En los métodos estadísticos se utilizó la estadística descriptiva. Resultados: según las necesidades de aprendizaje se encontró insuficiente en un 93,10 %, la utilización de la documentación fue bajo en un 65,5 % y el nivel de superación fue baja en un 75,86 %. Conclusiones: se constató la insuficiente preparación que existe en los profesionales de servicios farmacéuticos en farmacovigilancia de los productos naturales y déficit en la utilización de la cuantificación, evaluación y notificación de las reacciones adversas de los productos naturales.

ABSTRACT Introduction: training in pharmacovigilance of natural products is important for developing knowledge and skills in the performance of professionals in the community pharmaceutical services, because of its link in the scientific development, identification, quantification, documentation management and observation as well as reporting adverse reactions of traditional products. Objective: to analyze the current status of the training in pharmacovigilance of natural products aimed at professionals of the pharmaceutical services in Pinar del Rio during January 2019 to March 2020. Methods: a development-educational type research was carried out among professionals in pharmaceutical services in Pinar del Rio. The target group comprised 78 professionals, and the chosen sample corresponded to 58 professionals in pharmaceutical services. The general method applied was the dialectical materialist, along with historical-logical as theoretical methods; the empirical methods were the survey, documentary analysis, interview and observation. Results: considering the learning needs, it was found that 93,10 % as insufficient, the use of documents was low in 65,5 % and the level of training was low in 75,86 %. Conclusions: the insufficient training of professionals from the pharmaceutical services qualified to carry out pharmacovigilance of natural products and the deficit in the application of quantification, evaluation and reports of adverse reactions of natural products were proved.

3-Methylglutaconic Aciduria Type I Due to AUH Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature.

3-Methylglutaconic aciduria type I (MGCA1) is an inborn error of the leucine degradation pathway caused by pathogenic variants in the AUH gene, which encodes 3-methylglutaconyl-coenzyme A hydratase (MGH). To date, MGCA1 has been diagnosed in 19 subjects and has been associated with a variable clinical picture, ranging from no symptoms to severe encephalopathy with basal ganglia involvement. We report the case of a 31-month-old female child referred to our center after the detection of increased 3-hydroxyisovalerylcarnitine levels at newborn screening, which were associated with increased urinary excretion of 3-methylglutaconic acid, 3-hydroxyisovaleric acid, and 3-methylglutaric acid. A next-generation sequencing (NGS) panel for 3-methylglutaconic aciduria failed to establish a definitive diagnosis. To further investigate the strong biochemical indication, we measured MGH activity, which was markedly decreased. Finally, single nucleotide polymorphism array analysis disclosed the presence of two microdeletions in compound heterozygosity encompassing the AUH gene, which confirmed the diagnosis. The patient was then supplemented with levocarnitine and protein intake was slowly decreased. At the last examination, the patient showed mild clumsiness and an expressive language disorder. This case exemplifies the importance of the biochemical phenotype in the differential diagnosis of metabolic diseases and the importance of collaboration between clinicians, biochemists, and geneticists for an accurate diagnosis.

Neurodevelopmental Impairment As the Main Phenotypic Hallmark Associated with the Translocation t(7;10)(7p22.3;q26.11).

Reported here is a novel patient carrying an unbalanced t (10q26.11-q26.3; 7p22.3) and presenting with a severe intellectual disability with autistic features, abnormalities of muscle tone, and a drug-responsive epilepsy. The prominence of neurological and neurodevelopmental abnormalities in the clinical phenotype highlights a possible pathogenic role for different genes in the involved regions. Hypothetical mechanisms may include a possible gene dosage effect for DOCK1 and/or haploinsufficiency of PRKAR1B SUN1, ADAP1 , and GPER1 .

Koolen-de Vries syndrome in a 63-year-old woman: Report of the oldest patient and a review of the adult phenotype.

Koolen-de Vries syndrome (KdVS) is a rare genetic disorder caused by a de novo microdeletion in chromosomal region 17q21.31 encompassing KANSL1 or by a de novo intragenic pathogenic variant of KANSL1. KdVS is typically characterized by intellectual disability (ID), variable from mild to severe, developmental psychomotor delay, especially of expressive language development, friendly disposition, and multiple systemic abnormalities. So far, most of the individuals affected by KdVS are diagnosed in infancy or in adolescence; to the best of our knowledge, only 34 (including ours) adults have been reported in literature. Here we present the adult phenotype of a 63-year-old Italian woman affected by KdVS, caused by a 17q21.31 microdeletion. She is, to our knowledge, the oldest affected individual reported so far. We collected her clinical history and photographs, as well as those of other 26 adult patients described so far and compared her to them. We propose that the cardinal features of KdVS in adulthood are ID (ranging from mild to severe, usually moderate), friendly behavior, musculoskeletal abnormalities (especially scoliosis), and facial dysmorphism (a long face and a pronounced pear-shape nose with bulbous overhanging nasal tip). Therefore, we suggest considering KdVS in differential diagnosis in adult patients characterized by these features.

Germline Predisposition to Pediatric Cancer, from Next Generation Sequencing to Medical Care.

Knowledge about genetic predisposition to pediatric cancer is constantly expanding. The categorization and clinical management of the best-known syndromes has been refined over the years. Meanwhile, new genes for pediatric cancer susceptibility are discovered every year. Our current work shares the results of genetically studying the germline of 170 pediatric patients diagnosed with cancer. Patients were prospectively recruited and studied using a custom panel, OncoNano V2. The well-categorized predisposing syndromes incidence was 9.4%. Likely pathogenic variants for predisposition to the patient's tumor were identified in an additional 5.9% of cases. Additionally, a high number of pathogenic variants associated with recessive diseases was detected, which required family genetic counseling as well. The clinical utility of the Jongmans MC tool was evaluated, showing a high sensitivity for detecting the best-known predisposing syndromes. Our study confirms that the Jongmans MC tool is appropriate for a rapid assessment of patients; however, the updated version of Ripperger T criteria would be more accurate. Meaningfully, based on our findings, up to 9.4% of patients would present genetic alterations predisposing to cancer. Notably, up to 20% of all patients carry germline pathogenic or likely pathogenic variants in genes related to cancer and, thereby, they also require expert genetic counseling. The most important consideration is that the detection rate of genetic causality outside Jongmans MC et al. criteria was very low.

Vulnerabilidade do trabalhador rural em tempos de pandemia da COVID19 / Vulnerability of rural workers in times of the COVID-19 pandemic / Vulnerabilidad de los trabajadores rurales en tiempos de pandemia de COVID-19

Objetivo: Abordar, frente à literatura, a vulnerabilidade do trabalhador rural em tempos de pandemia da COVID-19. Método: trata-se de uma análise qualitativa, através de revisão integrativa realizada no período de maio de 2020, a partir da seguinte questão norteadora: "Quão vulneráveis estão os trabalhadores rurais em tempos de pandemia?". A pesquisa foi realizada nas bases de dados Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE) e Scientific Electronic Library Online (SciELO). Resultados: foram encontrados 129 artigos, mas apenas oito foram pertinentes ao estudo. Um dos setores mais afetados com o distanciamento social foi a agricultura familiar, assim como o setor pesqueiro. Conclusão: o distanciamento social é uma medida de saúde pública indispensável, mas afeta os determinantes e condicionantes de saúde atrelados aos pequenos agricultores, pescadores e marisqueiros, uma vez que ocorre drástica redução ou nulidade de obtenção de renda das famílias. Portanto, são necessárias políticas públicas de assistência para essa população.(AU)

Objective: To approach the content in the literature regarding the vulnerability of rural workers in times ofthe COVID-19 pandemic. Method: This qualitative analysis was developed as an integrative review carried outin May 2020, based on the following research question: "How vulnerable are rural workers in times ofthe pandemic?". We searched the databases ofthe Latin American and Caribbean Health Sciences Literature (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), and Scientific Electronic Library Online (SciELO). Results: We found 129 articles, but only eight were relevant to the study. Family farming, along with fishing, was one ofthe most affected sectors by social distancing. Conclusion: Social distancing is an indispensable public health measure. However, it affects the health determinants and conditioning factors related to small-scale farmers, fishers, and shellfishers, as their family income is drastically reduced or altogether lost. Therefore, there is a need for public policies to aid this population.(AU)

Objetivo: abordarla vulnerabilidad de los trabajadores rurales en tiempos de la pandemia COVID-19 en la literatura. Método: se trata de un análisis cualitativo, a través de una revisión integradora realizada en el período de mayo de 2020, a partir de la siguiente pregunta orientadora: "¿Hubo un aumento de la vulnerabilidad de los trabajadores rurales en tiempos de pandemia" ?. La búsqueda se realizó en las bases de datos Medical Literature Analysis and Retrieval System Online (MEDLINE) y Scientific Electronic Library Online (SciELO). Resultados: se encontraron catorce artículos, pero solo cuatro fueron relevantes para el estudio. Uno de los sectores más afectados por el distanciamiento socialfue la agricultura familiar, así como el sector pesquero. Conclusión: el distanciamiento social es una medida de salud pública indispensable, pero afecta los determinantes y condiciones de salud vinculados a los pequeños agricultores, pescadores y marisqueros, ya que existe una drástica reducción o nulidad en la obtención de ingresos para las familias, requiriendo de políticas públicas asistenciales para esa población.(AU)

Generation of an induced pluripotent stem cell line (CSS012-A (7672)) carrying the p.G376D heterozygous mutation in the TARDBP protein.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative condition with phenotypic and genetic heterogeneity. It is characterized by the selective vulnerability and the progressive loss of the neural population. Here, an induced pluripotent stem cell (iPSC) line was generated from dermal fibroblasts of an individual carrying the p.G376D mutation in the TDP-43 protein. Fibroblasts were reprogrammed using non-integrating episomal plasmids. There were no karyotype abnormalities, and iPSCs successfully differentiated into all three germ layers. This cell line may prove useful in the study of the pathogenic mechanisms that underpin ALS syndrome.

Práticas integrativas e complementares no cuidado em saúde de crianças: revisão integrativa / Integrative and Complementary Practices in children's health care: Integrative Review

Objetivos: Identificar trabalhos científicos que abordem a utilização das Práticas Integrativas e Complementares em crianças, como forma do cuidado em saúde. Métodos: Revisão integrativa conduzida nas bases de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online e Base de Dados de Enfermagem em maio de 2020. A avaliação, do nível de evidência, foi obtida por meio do método Oxford Centre for Evidence-based Medicine. Resultados: Onze estudos atenderam aos critérios estabelecidos. A literatura científica carece de dados que permitam caracterizar o uso das terapias complementares, no público infantil, com uma maior consistência. Mesmo assim, foi possível detectar a variedade dessas, bem como a prevalência. Conclusões: As práticas Integrativas e Complementares fundamentam-se em um reducionismo biológico e constituem hoje um importante aliado no fortalecimento das políticas públicas de saúde. Em virtude disso, é bastante usada em crianças devido ao impacto benéfico em suas vidas. (AU)

Objectives: To identify scientific works that address the use of Integrative and Complementary Practices in children, as a form of health care. Methods: Integrative review conducted in the databases of Latin American and Caribbean Literature in Health Sciences, Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online and Nursing Database in May 2020. The assessment, of the level of evidence, was obtained using the Oxford Center for Evidence-based Medicine method. Results: Eleven studies met the established criteria. The scientific literature lacks data to characterize the use of complementary therapies, in children, with greater consistency. Even so, it was possible to detect the variety of these, as well as the prevalence. Conclusions: Integrative and Complementary practices are based on biological reductionism and today constitute an important ally in strengthening public health policies. As a result, it is widely used in children due to the beneficial impact on their lives. (AU)

Objetivos: identificar trabajos científicos que aborden el uso de prácticas integradoras y complementarias en los niños, como una forma de atención médica. Métodos: Revisión integradora realizada en las bases de datos de Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Sistema de Análisis y Recuperación de Literatura Médica en línea, Biblioteca electrónica científica en línea y Base de datos de enfermería en mayo de 2020. La evaluación, del nivel de La evidencia se obtuvo utilizando el método del Centro de Oxford para la Medicina basada en la Evidencia. Resultados: Once estudios cumplieron los criterios establecidos. La literatura científica carece de datos para caracterizar el uso de terapias complementarias, en niños, con mayor consistencia. Aun así, fue posible detectar la variedad de estos, así como la prevalencia. Conclusiones: las prácticas integradoras y complementarias se basan en el reduccionismo biológico y hoy son un aliado importante para fortalecer las políticas de salud pública. Como resultado, se usa ampliamente en niños debido al impacto beneficioso en sus vidas. (AU)