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BACKGROUND: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of genetic counselling legislation and practice across European Union (EU) Member States to serve as a foundation for future European recommendations and action. METHODS: National legislative databases of all 27 Member States were searched using terms relevant to genetic counselling, translated as appropriate. Interviews with relevant experts from each Member State were conducted to validate legislative search results and provide detailed insights into genetic counselling practice in each country. RESULTS: Genetic counselling is included in national legislative documents of 22 of 27 Member States, with substantial variation in legal mechanisms and prescribed details (i.e. the 'who, what, when and where' of counselling). Practice is similarly varied. Workforce capacity (25 of 27 Member States) and genetic literacy (all Member States) were common reported barriers. Recognition and/or better integration of genetic counsellors and updated legislation and were most commonly noted as the 'most important change' which would improve practice. CONCLUSIONS: This review highlights substantial variability in genetic counselling across EU Member States, as well as common barriers notwithstanding this variation. Future recommendations and action should focus on addressing literacy and capacity challenges through legislative, regulatory and/or strategic approaches at EU, national, regional and/or local levels.
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União Europeia , Aconselhamento Genético , Neoplasias , Humanos , Aconselhamento Genético/legislação & jurisprudência , Neoplasias/genética , Testes Genéticos/legislação & jurisprudênciaRESUMO
Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.
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Cardiomiopatia Dilatada , Adulto , Humanos , Pessoa de Meia-Idade , Romênia , Volume Sistólico , Função Ventricular Esquerda , Etnicidade , Morte Súbita CardíacaRESUMO
Background: Cardiomyopathies (CMs) represent a heterogeneous group of primary myocardial diseases characterized by structural and functional abnormalities. They represent one of the leading causes of cardiac transplantations and cardiac death in young individuals. Clinically they vary from asymptomatic to symptomatic heart failure, with a high risk of sudden cardiac death due to malignant arrhythmias. With the increasing availability of genetic testing, a significant number of affected people are found to have an underlying genetic etiology. However, the awareness of the benefits of incorporating genetic test results into the care of these patients is relatively low. Aim: The focus of this review is to summarize the current basis of genetic CMs, including the most encountered genes associated with the main types of cardiomyopathies: hypertrophic, dilated, restrictive arrhythmogenic, and non-compaction. Materials and Methods: For this narrative review, we performed a search of multiple electronic databases, to select and evaluate relevant manuscripts. Results: Advances in genetic diagnosis led to better diagnosis precision and prognosis prediction, especially with regard to the risk of developing arrhythmias in certain subtypes of cardiomyopathies. Conclusions: Implementing the genomic information to benefit future patient care, better risk stratification and management, promises a better future for genotype-based treatment.
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Cardiomiopatias , Humanos , Cardiomiopatias/genética , Cardiomiopatias/diagnóstico , Testes Genéticos/métodos , Genótipo , FenótipoRESUMO
Bardet-Biedl syndrome (BBS), is an emblematic ciliopathy hallmarked by pleiotropy, phenotype variability, and extensive genetic heterogeneity. BBS is a rare (~1/140,000 to ~1/160,000 in Europe) autosomal recessive pediatric disorder characterized by retinal degeneration, truncal obesity, polydactyly, cognitive impairment, renal dysfunction, and hypogonadism. Twenty-eight genes involved in ciliary structure or function have been implicated in BBS, and explain the molecular basis for ~75%-80% of individuals. To investigate the mutational spectrum of BBS in Romania, we ascertained a cohort of 24 individuals in 23 families. Following informed consent, we performed proband exome sequencing (ES). We detected 17 different putative disease-causing single nucleotide variants or small insertion-deletions and two pathogenic exon disruptive copy number variants in known BBS genes in 17 pedigrees. The most frequently impacted genes were BBS12 (35%), followed by BBS4, BBS7, and BBS10 (9% each) and BBS1, BBS2, and BBS5 (4% each). Homozygous BBS12 p.Arg355* variants were present in seven pedigrees of both Eastern European and Romani origin. Our data show that although the diagnostic rate of BBS in Romania is likely consistent with other worldwide cohorts (74%), we observed a unique distribution of causal BBS genes, including overrepresentation of BBS12 due to a recurrent nonsense variant, that has implications for regional diagnostics.
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Síndrome de Bardet-Biedl , Humanos , Romênia , Síndrome de Bardet-Biedl/diagnóstico , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/patologia , Sequenciamento do Exoma , Homozigoto , Mutação , Proteínas do Citoesqueleto/genética , Proteínas de Ligação a Fosfato/genéticaRESUMO
BACKGROUND: High empathy levels in health professionals represent an important factor in patient satisfaction and compliance, reducing patient anxiety and pain, enhancing diagnostic and clinical results and strengthening patient empowerment. Our purpose was to determine empathy level and to identify which of the socioeconomic status (SES) and psychological factors were able to predict highest empathy levels in a Romanian sample of community nurses. METHODS: Community nurses were invited in January-February 2023 to provide an answer to an online survey, using an advertisement in a professional network. 1580 participants voluntarily agreed to take part in this study, with a response rate of 85.8%. The survey included the Toronto Empathy Questionnaire, the Reading the Mind in the Eyes Test and socio-economic status items. A multivariate model for the prediction of belonging to the highest quartile of empathy as opposed to lowest quartile was constructed using SES and psychological variables as factors. RESULTS: The mean (SD) empathy level was 49.1 (6.7), with 74.7% of participants over the threshold of high empathy level. In the multivariate analysis, predictors of belonging to the highest quartile of TEQ, as opposed to the lowest quartile were: low self-perceived stress level (OR = 2.098, 95%CI 1.362-3.231), higher experience as a community nurse (OR = 1.561, 95%CI 1.120-2.175) and higher levels of the theory of mind (OR = 1.158, 95%CI 1.118-1.199), when controlling for gender, age, relationship status, presence of children in families, education, and income. CONCLUSIONS: Training programs targeting to increase emotional competences, reduce levels of stress and encourage personnel retention have the potential to increase the quality of community nursing in Romania.
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Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients' health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.
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Proteína BRCA1/genética , Distúrbios no Reparo do DNA/diagnóstico , Distúrbios no Reparo do DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação , Fenótipo , Alelos , Biomarcadores , Estudos de Associação Genética/métodos , Humanos , Masculino , Linhagem , Avaliação de SintomasRESUMO
BACKGROUND: Childhood overweight and obesity is a serious public health issue with an increase being observed in preschool-aged children. Treating childhood obesity is difficult and few countries use standardized treatments. Therefore, there is a need to find effective approaches that are feasible for both health care providers and families. Thus, the overall aim of this study is to assess the acceptance and effectiveness of a parent support program (the More and Less, ML) for the management of overweight and obesity followed by a mobile health (mHealth) program (the MINISTOP application) in a socially diverse population of families. METHODS/DESIGN: A two-arm, parallel design randomized controlled trial in 300 2-to 6-year-old children with overweight and obesity from Romania, Spain and Sweden (n = 100 from each). Following baseline assessments children are randomized into the intervention or control group in a 1:1 ratio. The intervention, the ML program, consists of 10-weekly group sessions which focus on evidence-based parenting practices, followed by the previously validated MINISTOP application for 6-months to support healthy eating and physical activity behaviors. The primary outcome is change in body mass index (BMI) z-score after 9-months and secondary outcomes include: waist circumference, eating behavior (Child Eating Behavior Questionnaire), parenting behavior (Comprehensive Feeding Practices Questionnaire), physical activity (ActiGraph wGT3x-BT), dietary patterns (based on metabolic markers from urine and 24 h dietary recalls), epigenetic and gut hormones (fasting blood samples), and the overall acceptance of the overweight and obesity management in young children (semi-structured interviews). Outcomes are measured at baseline and after: 10-weeks (only BMI z-score, waist circumference), 9-months (all outcomes), 15- and 21-months (all outcomes except physical activity, dietary patterns, epigenetics and gut hormones) post-baseline. DISCUSSION: This study will evaluate a parent support program for weight management in young children in three European countries. To boost the effect of the ML program the families will be supported by an app for 6-months. If the program is found to be effective, it has the potential to be implemented into routine care to reduce overweight and obesity in young children and the app could prove to be a viable option for sustained effects of the care provided. TRIAL REGISTRATION: ClinicalTrials.gov NCT03800823; 11 Jan 2019.
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Obesidade Infantil/prevenção & controle , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Masculino , Poder Familiar/psicologia , Avaliação de Programas e Projetos de Saúde , TelemedicinaRESUMO
Introduction: Lifestyle factors, including inadequate eating patterns, emerge as a critical determinant of chronic disease. Apart from caring for patients, nurses should also take an active role in monitoring and managing their own health. Understanding the intricate relationship between nurses' eating behavior and managing their own health is crucial for fostering a holistic approach to healthcare, therefore our study aimed to evaluate eating behavior and demographic factors influencing chronic disease prevalence in a sample of community nurses from Romania. Methods: Between October-November 2023, 1920 community nurses were invited to answer an online survey, using an advertisement in their professional network. Of them, 788 responded. In the survey, which included a semi-quantitative food frequency questionnaire with 53 food items, the Intuitive Eating Survey 2 (IES-2), and demographic items were used. Results: A multivariate model was built for the prediction of the association between eating behavior and other factors associated with chronic diseases. The majority of participants were females (95.1%), with the largest age group falling between 40 and 49.9 years (48.2%). Regarding the EFSA criteria for adequate carbohydrate and fat intake, 20.2% of the group have a high intake of carbohydrates, respectively, 43.4% of the group have a high intake of fat. Analysis of chronic diseases indicated that 24.9% of individuals reported at least one diagnosis by a physician. The presence of chronic disease was associated with a low level of perceived health status, with an OR = 3.388, 95%CI (1.684-6.814), compared to those reporting excellent or very good perceived health status. High stress had an OR = 1.483, 95%CI (1.033-2.129). BMI had an OR = 1.069, 95%CI (1.032-1.108), while low carbohydrate diet score had an OR = 0.956, 95%CI (0.920-0.992). Gender and IES-2 did not significantly contribute to the model, but their effect was controlled. Discussion: By unraveling the intricate interplay between nutrition, lifestyle, and health outcomes in this healthcare cohort, our findings contribute valuable insights for the development of targeted interventions and support programs tailored to enhance the well-being of community nurses and, by extension, the patients they support.
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Comportamento Alimentar , Estilo de Vida , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Romênia/epidemiologia , Inquéritos e Questionários , Doença CrônicaRESUMO
Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the PLN p.Leu39* variant. A cohort including 11 PLN patients was identified among all patients with HCM (9/189, 4.8%) and DCM (2/62, 3.2%) who underwent genetic testing from two tertiary centers and five more were detected through cascade screening. Complete phenotyping was performed. PLN p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. We proceeded to compare these results to a similar analysis of a control cohort consisting of age-matched individuals that inherited pathogenic or likely pathogenic variants in common sarcomeric genes (MYBPC3/MYH7). Overall, the clinical characteristics and examination findings of patients carrying PLN p.Leu39* were not different from patients with cardiomyopathy related to sarcomeric mutations except for the presence of pathological Q waves and the incidence of non-sustained ventricular arrhythmias, which were higher in PLN patients than in those with MYBPC3/MYH7-related diseases.
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The ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as "maybe report" after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known.
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Variação Genética , Humanos , Testes Genéticos/normas , Testes Genéticos/métodosRESUMO
AIM: To describe the current prevalence of paediatric hypertension and the relationships between body mass index, gender, place of residence, and blood pressure in a population of school-aged children from western Romania. MATERIAL AND METHOD: A total of 3626 children from Timisoara and the surrounding regions were examined by medical students from February, 2010 to June, 2011. Children's body mass index was interpreted on the basis of reference guidelines from Centers for Disease Control and Prevention. Blood pressure measurements were taken by the auscultation method. For defining elevated blood pressure, we used the standards published in the Fourth Report. RESULTS: Overall, the prevalence of overweight was 14% and 11.8% for obesity. Boys had a higher prevalence of both overweight and obesity compared with girls. The prevalence of hypertension on our screening was 9.1% higher in boys and urban residence. The prevalence of pre-hypertension was 6.5%. With regard to body mass index, 21.1% of obese, 12.8% of overweight, and 7.1% of normal weight children presented hypertension. The strongest determinant of hypertension was body mass index percentile. Significant odds ratio was found for obesity (3.93; confidence interval: 3.114.95), urban residence (1.68; confidence interval: 1.352.1), and male gender (1.34; confidence interval: 1.121.6). CONCLUSIONS: The results confirm a worrisome prevalence of overweight and obesity among children in Romania, accompanied by an alarming prevalence of hypertension. Overweight and obesity, male gender, and urban residence were the major contributing factors for the overall high prevalence of hypertension found. Our results point to the urgent need to adopt strategies aimed at preventing hypertension and obesity in children in Romania.
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Hipertensão/epidemiologia , Obesidade Infantil/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Sobrepeso/epidemiologia , Prevalência , Fatores de Risco , Romênia/epidemiologia , Distribuição por SexoRESUMO
Neonatal diffuse cutaneous mastocytosis (NDCM) is defined as the infiltration of the epidermis by a clonal proliferation of mast cells, observed at birth, without initial signs of systemic involvement. The typical driver mutation is in the KIT gene. We report a rare case of a boy, born at term, already presenting at birth with generalized subcutaneous nodules on the face, scalp, trunk, back, hands, and feet. The spleen, liver, and inflammatory markers were normal at birth. Tryptase was significantly elevated. A bone marrow biopsy showed no mast cell involvement at age 2 months. A punch biopsy at age 2 months revealed CD117-positive cells diffusely infiltrating the skin, with subsequent DNA NGS sequencing for the formalin-fixed paraffin embedded tissue (FFPE) identifying the pathogenic NM_000222.3:c.1504_1509dup; p.(Ala502_Tyr503dup) variant in the KIT gene previously associated with cutaneous mastocytosis. At 2 years follow-up, he had splenomegaly and multiple cervical and inguinal adenopathy, while the skin nodules persisted, especially on the scalp with accompanying pruritus. He received oral and local sodium cromoglycate, oral antihistamines, antibiotic cream for skin infection, and iron supplementation; however, compliance to treatment was relatively low. The prognosis is difficult to predict, as he developed systemic involvement, failure to thrive, and mild psychomotor delay. A case aggregation of NDCM reported in the literature was performed to provide a comprehensive overview of this rare pathology, to better understand the prognosis. NDCM is a life-threatening disease with severe complications. Almost half had severe complications, such as mast hepatosplenomegaly, adenopathy, bacterial infections, mast cell leukaemia, and systemic involvement.
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Linfadenopatia , Mastocitose Cutânea , Mastocitose Sistêmica , Humanos , Recém-Nascido , Masculino , Linfadenopatia/complicações , Linfadenopatia/patologia , Mastócitos/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/genética , Mastocitose Cutânea/complicações , Mastocitose Sistêmica/complicações , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/patologiaRESUMO
Background: The COVID-19 pandemic had a major impact on the mental health and well-being of children with neurodevelopmental conditions (NDCs) and of their families worldwide. However, there is insufficient evidence to understand how different factors (e.g., individual, family, country, children) have impacted on anxiety levels of families and their children with NDCs developed over time. Methods: We used data from a global survey assessing the experience of 8043 families and their children with NDCs (mean of age (m) = 13.18 years, 37% female) and their typically developing siblings (m = 12.9 years, 45% female) in combination with data from the European Centre for Disease Prevention and Control, the University of Oxford, and the Central Intelligence Agency (CIA) World Factbook, to create a multilevel data set. Using stepwise multilevel modelling, we generated child-, family- and country-related factors that may have contributed to the anxiety levels of children with NDCs, their siblings if they had any, and their parents. All data were reported by parents. Results: Our results suggest that parental anxiety was best explained by family-related factors such as concerns about COVID-19 and illness. Children's anxiety was best explained by child-related factors such as children's concerns about loss of routine, family conflict, and safety in general, as well as concerns about COVID-19. In addition, anxiety levels were linked to the presence of pre-existing anxiety conditions for both children with NDCs and their parents. Conclusions: The present study shows that across the globe there was a raise in anxiety levels for both parents and their children with NDCs because of COVID-19 and that country-level factors had little or no impact on explaining differences in this increase, once family and child factors were considered. Our findings also highlight that certain groups of children with NDCs were at higher risk for anxiety than others and had specific concerns. Together, these results show that anxiety of families and their children with NDCs during the COVID-19 pandemic were predicted by very specific concerns and worries which inform the development of future toolkits and policy. Future studies should investigate how country factors can play a protective role during future crises.
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COVID-19 , Pandemias , Humanos , Feminino , Adolescente , Masculino , Família/psicologia , Pais/psicologia , Ansiedade/epidemiologiaRESUMO
BACKGROUND: Developmental delay and intellectual disability represent a common pathology in general population, involving about 3% of the pediatric age population, the genetic etiology being often involved. The aim of this study was to determine the clinically relevant copy number variants in patients diagnosed with global developmental delay/intellectual disability in our population, using the chromosomal microarray analysis. METHODS: We analyzed 189 patients diagnosed with global developmental delay/intellectual disability, presented in Clinical Emergency Hospital for Children, Cluj-Napoca. The patients were completely clinically investigated, including dysmorphic and internal malformations evaluation, psychiatric, neuropsychological and metabolic evaluation, standard karyotyping. Genomic analysis was done using chromosomal microarray analysis. RESULTS: Pathogenic findings (including uniparental disomy) and variants of unknown significance were detected in 53 of 189 patients (28.04%). Pathogenic copy number variants and uniparental disomy were observed in 35 of 189 patients (18.51%). Two patients presented uniparental disomy for chromosome 15, one with clinical phenotype of Prader-Willi syndrome and the other with clinical phenotype with Angelman syndrome. Within the category of pathogenic findings, the recurrent copy number variants were seen in 21 of 35 patients (60%). CONCLUSIONS: The increased percentage of pathogenic structural variants observed in patients with global developmental delay/intellectual disability analyzed by chromosomal microarray technique supports its use in patients with a non-specific phenotype such as these neurodevelopmental disorders. The high percentage of recurrent pathogenic variants between these findings is a finding that support their initial evaluation when a genetic testing algorithm could be a useful option.
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Deficiência Intelectual , Criança , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Deficiência Intelectual/diagnóstico , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/genética , Dissomia Uniparental , Romênia , Aberrações CromossômicasRESUMO
Bone marrow failure represents an umbrella diagnosis for several life-threatening disorders. In many people, the etiology remains unknown for a long time, leading to an odyssey to diagnosis, with numerous tests performed and sometimes inappropriate treatment. Biallelic pathogenic variants in the DNAJC21 gene were recently discovered to cause bone marrow failure syndrome type 3, having phenotypic overlap with Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and Diamond-Blackfan anemia. Herein, we report an 8-year-old boy, with normal intellect, presenting bone marrow failure; growth retardation; failure to thrive; recurrent infections (including sepsis); cryptorchidia; skeletal, skin, teeth, and hair abnormalities; joint hypermobility; eczema; palpebral ptosis; high myopia; rod-cone retinal dystrophy; and short telomeres. He underwent several tests and evaluations, including genetic investigations (panel and exome sequencing), before the DNAJC21 gene was known to cause disease. Whole-genome sequencing performed at the age of 7 years, identified two novel, pathogenic, and compound heterozygous variants in the DNAJC21 gene: NM_001012339.3:c.148C>T (stopgain-maternal origin), p.Gln50∗ and c.643_644delinsTTT (frameshift paternal origin), and p.Lys215Phefs∗71. He received aggressive treatments for his multisystem disease: blood cell transfusions, high-dose corticosteroids, immunoglobulins, multiple antibiotics, vitamins, growth hormone, and others. However, allogeneic hematopoietic stem cell transplantation was avoided. The clinical evolution of bone marrow failure and recurrent infections stabilized with age, yet the myopia progressed. Exocrine pancreatic insufficiency was not detected. This report widens the molecular and clinical understanding of bone marrow failure syndrome type 3. Genome sequencing directed a precise diagnosis that improved patient management and enabled family genetic counseling.
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Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.
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Epilepsia , Testes Genéticos , Humanos , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Estudos Transversais , Testes Genéticos/métodos , Epilepsia/tratamento farmacológico , Epilepsia/genética , Convulsões/genéticaRESUMO
In Romania, one in four children has excess weight. Because childhood obesity is a sensitive topic, many healthcare professionals find it difficult to discuss children's excess weight with parents. This study aims to identify barriers and facilitators in childhood obesity-related communication, as perceived by healthcare professionals in Romania. As part of the STOP project, healthcare professionals (family physicians, pediatricians, and dieticians) who treat children with excess weight were invited to a telephone interview. The semi-structured questions were translated from a questionnaire previously used at the Swedish study site of the STOP project. Interviews were transcribed and then used for thematic analysis. Fifteen doctors and three dieticians (16 females and 2 males), with average 18.2 ± 10.1 years of experience, were interviewed. Four main themes were identified. Professionals reported that when children began experiencing obesity-related stigma or comorbidities, this became the tipping point of weight excess, where parents felt motivated to begin treatment. Barriers in communication were part of several layers of distrust, recognized as tension between professionals and caregivers due to conflicting beliefs about excess weight, as well as lack of trust in medical studies. Most respondents felt confident using models of good practice, consisting of a gentle approach and patient-centered care. Nonetheless, professionals noted systemic barriers due to a referral system and allocation of clinical time that hinder obesity treatment. They suggested that lack of specialized centers and inadequate education of healthcare professional conveys the system does not prioritize obesity treatment and prevention. The interviewed Romanian doctors and dieticians identified patient-centered care as key to treating children with obesity and building trust with their caregivers. However their efforts are hindered by healthcare system barriers, including the lack of specialized centers, training, and a referral system. The findings therefore suggest that, to improve childhood obesity prevention and treatment, systemic barriers should be addressed. Trial Registration: ClinicalTrials.gov, NCT03800823; 11 Jan 2019.
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Obesidade Infantil , Criança , Comunicação , Atenção à Saúde , Feminino , Humanos , Masculino , Obesidade Infantil/epidemiologia , Romênia , SuéciaRESUMO
Background: Atrioventricular septal defect (AVSD) is a cardiac malformation that accounts for up to 5% of total congenital heart disease, occurring with high frequency in people with Down Syndrome (DS). We aimed to establish the surgical challenges and outcome of medical care in different types of AVSD in children with DS compared to those without DS (WDS). Methods: The study included 62 children (31 with DS) with AVSD, evaluated over a 5 year period. Results: Complete AVSD was observed in 49 (79%) children (27 with DS). Six children had partial AVSD (all WDS) and seven had intermediate types of AVSD (4 with DS). Eight children had unbalanced complete AVSD (1 DS). Median age at diagnosis and age at surgical intervention in complete AVSD was not significantly different in children with DS compared to those WDS (7.5 months vs. 8.6). Median age at surgical intervention for partial and transitional AVSDs was 10.5 months for DS and 17.8 months in those without DS. A large number of patients were not operated: 13/31 with DS and 8/31 WDS. Conclusion: The complete form of AVSD was more frequent in DS group, having worse prognosis, while unbalanced AVSD was observed predominantly in the group without DS. Children with DS required special attention due to increased risk of pulmonary hypertension. Late diagnosis was an important risk factor for poor prognosis, in the setting of suboptimal access to cardiac surgery for patients in Romania. Although post-surgery mortality was low, infant mortality before surgery remains high. Increased awareness is needed in order to provide early diagnosis of AVSD and enable optimal surgical treatment.
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Cardiofaciocutaneous (CFC) syndrome [Online Mendelian Inheritance in Man (OMIM) #115150] is characterized by craniofacial dysmorphism, heart malformation, ectodermal abnormalities, neuromotor delay and intellectual disability. It is not a frequent disease, about 300 cases have been reported in the medical literature. We describe the case of a 34-year-old patient presenting with CFC syndrome phenotype, monitored since the age of 1 1∕2 years. Clinical findings included craniofacial dysmorphism, development delay, heart malformation and severe intellectual disability. The evolution was with progressive intellectual disability, hypogonadism, hypertrophic cardiomyopathy, wrinkled palms and soles. Molecular analysis showed a heterozygous variant in the B-Raf proto-oncogene, serine∕threonine kinase (BRAF) gene (7q34): NM_001354609.2:c.1502A>G, with pathogenic significance. We report this case, observed along a period of 33 years, for illustration of clinical evolutive particularities, and for difficulties in establishing the positive diagnosis.
Assuntos
Displasia Ectodérmica , Cardiopatias Congênitas , Deficiência Intelectual , Adulto , Displasia Ectodérmica/genética , Fácies , Insuficiência de Crescimento , Cardiopatias Congênitas/genética , Humanos , Deficiência Intelectual/genética , Estudos Longitudinais , Proteínas Proto-Oncogênicas B-rafRESUMO
Background: Urinary tract infections (UTI) are common in children worldwide. Congenital anomalies of kidney and urinary tract (CAKUT) increase the risk of UTI and consequently antibiotic resistance. Antibiotic resistance represents an important public health issue worldwide. We aimed to evaluate the local trend in terms of bacterial uropathogen resistance in the western part of Romania in children with CAKUT and UTI. Methods: 252 children with CAKUT were admitted to our hospital over a five-year period. Of them, 91 developed at least one UTI episode, with a total number of 260 positive urine cultures. We collected data about age at diagnosis of CAKUT, sex, origin environment, type and side of CAKUT, number of UTIs, type of uropathogen, and uropathogens antibiotic resistance. Results: Distribution of uropathogens was Escherichia coli (38.84%), Klebsiella spp. (21.15%), Enterococcus spp. (15.76%), Proteus spp. (8.07%), Pseudomonas spp. (8.07%), Enterobacter spp. (2.3%), other Gram-negative bacteria (2.3%), and other Gram-positive bacteria (3.45%). High antibiotic resistance was detected for ampicillin, amoxicillin, and second-generation cephalosporins. Escherichia coli presented high resistance for cefepime and ceftriaxone. Pseudomonas spp. remained susceptible to amikacin, quinolones, and colistin. Vancomycin, teicoplanin, linezolid, and piperacillin/tazobactam remained effective in treating Gram-positive UTI. Conclusions: High antibiotic resistance was identified for frequently used antibiotics. Lower antibiotic resistance was observed for some broad-spectrum antibiotics. Understanding uropathogens' antibiotic resistance is important in creating treatment recommendations, based on international guidelines, local resistance patterns, and patient particularities.