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Abstract Background Neurofibromatosis type 1 (NF1) is a rare genetic disorder with a wide range of clinical manifestations, notably neurocutaneous features, that can lead to emotional and physical consequences. Objectives This study assessed the influence of sociodemographic factors and clinical features of the disease on the quality of life of Brazilian individuals with NF1. Methods This is a descriptive cross-sectional study. Data were collected from 101 individuals with NF1 using the Brazilian version of the Impact of NF1 on Quality of Life Questionnaire (INF1-QoL), a form with information on sociodemographic characteristics, and an NF1 visibility self-evaluation scale. The relationship between variables was evaluated through statistical testing, and the significance level was defined as 0.05. Results The study included 101 adults with NF1 aged 18 to 59 years, with a mean age of 35.54 years (±9.63) and a female predominance (n = 84, 83.17%). The mean total INF1-QoL score was 10.62 (±5.63), with a median of 10, minimum value of 0, and maximum of 31 points. Two characteristics of the participants were significantly associated with the quality of life: educational level (p = 0.003) and familial history of NF1 (p = 0.019). There was a statistically significant correlation between the INF1-QoL score and the degree of disease visibility (rho = 0.218; p = 0.028). Study limitations Cross-sectional study, conducted with a convenience sample and using self-reported measures. Conclusions The findings support the significant impact of NF1 on quality of life. The authors recommend multidisciplinary follow-up for patients, with adherence to anticipatory clinical care measures, adequate pain control, psychological assistance, and genetic counseling.
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BACKGROUND: Exercise-induced pulmonary haemorrhage (EIPH) in athletic horses is characterized by the presence of blood from the lungs in the tracheobronchial tree after intense exercise. Despite the high prevalence of EIPH in horses, the primary aetiology remains unknown. Variants in the genes encoding CD39 and CD39L1 (ENTPD1 and ENTPD2, respectively) were previously reported as potential genetic causes involved in EIPH pathogenesis. However, the role of these variants in haemostatic functions is unknown. RESULTS: To investigate the association between EIPH and missense variants in the ENTPD1 (rs1152296272, rs68621348, and rs68621347) and ENTPD2 genes (rs782872967), 76 Thoroughbred horses diagnosed with EIPH and 56 without clinical signs of EIPH (control group) by trachea-bronchial endoscopy were genotyped. The rs1152296272 and rs68621347 variants were linked, which explained why the same results were found in all horses. Approximately 96% and 95% of the EIPH and control horses, respectively, carried at least one nonreference allele for these variants. In contrast, 100% of the control horses and 96% of the EIPH horses were homozygous for the reference allele for the rs68621348 variant. In the EIPH group, 1.5% of the horses were homozygotes and 24% were heterozygous for the nonreference allele of the rs782872967 variant. In the control group, the nonreference allele of this variant was observed only in heterozygotes (16%). There were no significant differences between groups for any of the variants. CONCLUSIONS: The variants previously described in the genes encoding the CD39 and CD39L1 enzymes were highly present in the studied population. However, no association was found between the occurrence of EIPH and the presence of these variants in Thoroughbred horses in this study.
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Hemorragia , Doenças dos Cavalos , Pneumopatias , Condicionamento Físico Animal , Animais , Cavalos , Doenças dos Cavalos/genética , Hemorragia/veterinária , Hemorragia/genética , Pneumopatias/veterinária , Pneumopatias/genética , Masculino , Apirase/genética , Feminino , Predisposição Genética para Doença , Genótipo , Mutação de Sentido IncorretoRESUMO
BACKGROUND: The 22q11.2 Deletion Syndrome (22q11.2 DS) presents unique healthcare challenges for affected individuals, families, and healthcare systems. Despite its rarity, 22q11.2 DS is the most common microdeletion syndrome in humans, emphasizing the need to understand and address the distinctive healthcare requirements of those affected. This paper examines the multifaceted issue of health service access and caregivers' quality of life in the context of 22q11.2 DS in Brazil, a condition with diverse signs and symptoms requiring multidisciplinary care. This study employs a comprehensive approach to evaluate health service accessibility and the quality of life of caregivers of individuals with 22q11.2 DS. It utilizes a structured Survey and the WHOQOL-bref questionnaire for data collection. RESULTS: Individuals with 22q11.2 DS continue to receive incomplete clinical management after obtaining the diagnosis, even in the face of socioeconomic status that enabled an average age of diagnosis that precedes that found in sample groups that are more representative of the Brazilian population (mean of 3.2 years versus 10 years, respectively). In turn, caring for individuals with 22q11.2 DS who face difficulty accessing health services impacts the quality of life associated with the caregivers' environment of residence. CONCLUSIONS: Results obtained help bridge the research gap in understanding how caring for individuals with multisystem clinical conditions such as 22q11.2 DS and difficulties in accessing health are intertwined with aspects of quality of life in Brazil. This research paves the way for more inclusive healthcare policies and interventions to enhance the quality of life for families affected by this syndrome.
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Síndrome de DiGeorge , Acessibilidade aos Serviços de Saúde , Qualidade de Vida , Humanos , Brasil , Masculino , Feminino , Criança , Adulto , Adolescente , Cuidadores/psicologia , Pré-Escolar , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized. METHODS: We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases-deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes. RESULTS: From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization. CONCLUSION: Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.
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Síndromes Periódicas Associadas à Criopirina , Febre Familiar do Mediterrâneo , Doenças Hereditárias Autoinflamatórias , Meningite , Adulto Jovem , Humanos , Adulto , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Neurologistas , Adenosina Desaminase/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Febre Familiar do Mediterrâneo/genética , Síndromes Periódicas Associadas à Criopirina/genética , Febre , FenótipoRESUMO
BACKGROUND: Neurofibromatosis type 1 (NF1) is a rare genetic disorder with a wide range of clinical manifestations, notably neurocutaneous features, that can lead to emotional and physical consequences. OBJECTIVES: This study assessed the influence of sociodemographic factors and clinical features of the disease on the quality of life of Brazilian individuals with NF1. METHODS: This is a descriptive cross-sectional study. Data were collected from 101 individuals with NF1 using the Brazilian version of the Impact of NF1 on Quality of Life Questionnaire (INF1-QoL), a form with information on sociodemographic characteristics, and an NF1 visibility self-evaluation scale. The relationship between variables was evaluated through statistical testing, and the significance level was defined as 0.05. RESULTS: The study included 101 adults with NF1 aged 18 to 59 years, with a mean age of 35.54 years (±9.63) and a female predominance (n = 84, 83.17%). The mean total INF1-QoL score was 10.62 (±5.63), with a median of 10, minimum value of 0, and maximum of 31 points. Two characteristics of the participants were significantly associated with the quality of life: educational level (p = 0.003) and familial history of NF1 (p = 0.019). There was a statistically significant correlation between the INF1-QoL score and the degree of disease visibility (rho = 0.218; p = 0.028). STUDY LIMITATIONS: Cross-sectional study, conducted with a convenience sample and using self-reported measures. CONCLUSIONS: The findings support the significant impact of NF1 on quality of life. The authors recommend multidisciplinary follow-up for patients, with adherence to anticipatory clinical care measures, adequate pain control, psychological assistance, and genetic counseling.
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Neurofibromatose 1 , Qualidade de Vida , Fatores Socioeconômicos , Humanos , Feminino , Masculino , Estudos Transversais , Neurofibromatose 1/psicologia , Adulto , Brasil/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Inquéritos e Questionários , EscolaridadeRESUMO
Motor and somatosensory pathway dysfunction due to degeneration of long tracts in hereditary spastic paraplegias (HSP) indicates that postural abnormalities may be a relevant disease feature. However, balance assessments have been underutilized to study these conditions. How does the static balance of individuals with HSP with eyes open and closed differ from healthy controls, and how does it relate to disease severity? This cross-sectional case-control study assessed the static balance of 17 subjects with genetically confirmed HSP and 17 healthy individuals, evaluating the center of pressure (COP) variables captured by a force platform. The root-mean-square of velocities and mean of displacements amplitudes in mediolateral and anteroposterior axes were correlated with disease severity. All COP parameters' performances were significantly impaired in HSP subjects compared to controls (p < 0.001 for all comparisons). COP with eyes open and closed differed for all variables within the HSP group, whereas in the control group, differences were observed only for anteroposterior velocity and amplitude. Spastic Paraplegia Rating Scale presented moderate direct correlations with the most COP variables (Rho = - 0.520 to - 0.736). HSP individuals presented significant postural instability with eyes open and to a greater extent with eyes closed, corroborating the clinical findings of somatosensorial and proprioceptive pathways dysfunction. The degrees of proprioceptive and motor impairments are mutually correlated, suggesting that similar pathophysiological mechanisms operate for the degeneration of these long tracts. COP parameters can be seen as disease severity biomarkers of HSP, and they should be assessed in future clinical trials.
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Paraplegia Espástica Hereditária , Humanos , Estudos Transversais , Estudos de Casos e Controles , Equilíbrio Postural/fisiologia , PropriocepçãoRESUMO
El artículo expone conceptos actuales biológicos, así como algunos planteamientos filosóficos acerca del inicio de la vida, que se examinarán en relación con la necesidad del aborto eugenésico. Se presenta el concepto de "exdurantismo", en el que la combinación del nuevo genoma nuclear y mitocondrial hacen único al individuo; además, se concibe al complejo genómico como "integrador somático" que dirige el desarrollo embrionario, y se muestra la problemática en el caso de las violaciones que provocan embarazos, el aborto eugenésico en enfermedades genéticas incapacitantes o la utilización de embriones posterior a la fertilización in-vitro. Se plantea que la dignidad de la persona comienza desde la concepción. Frente a la detección de una enfermedad genética, grave o letal, se debe ofrecer soporte económico y social, de diagnóstico y tratamiento; además, desde la salud pública, una mayor inversión para plantear estrategias de tamizaje, diagnóstico, manejo e investigación.
The article presents current biological concepts, as well as some philosophical approaches to the beginning of life, which will be examined in relation to the need for eugenic abortion. The concept of "exdurantism" is presented, in which the combination of the new nuclear and mitochondrial genome makes the individual unique; furthermore, the genomic complex is conceived as a "somatic integrator" that directs embryonic development, and the problematic is shown in the case of rape that causes pregnancies, eugenic abortion in incapacitating genetic diseases or the use of embryos after in-vitro fertilization. The dignity of the person begins at conception. When a serious or lethal genetic disease is detected, economic and social support, diagnosis and treatment should be offered; in addition, public health should invest more in screening, diagnosis, management and research strategies.
O artigo apresenta conceitos biológicos atuais, bem como algumas abordagens filosóficas sobre o início da vida, que serão examinados em relação à necessidade do aborto eugênico. É apresentado o conceito de "exdurantismo", no qual a combinação do novo genoma nuclear e mitocondrial torna o indivíduo único; além disso, o complexo genômico é concebido como um "integrador somático" que dirige o desenvolvimento embrionário, e é mostrada a problemática no caso de estupro que resulta em gravidez, aborto eugênico em doenças geneticamente incapacitantes ou o uso de embriões após a fertilização in vitro. Argumenta-se que a dignidade da pessoa começa na concepção. Diante da detecção de uma doença genética, grave ou letal, devem ser oferecidos apoio econômico e social, diagnóstico e tratamento, bem como maior investimento em saúde pública em estratégias de triagem, diagnóstico, gestão e pesquisa.
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La neurofibromatosis tipo I o enfermedad de Von Recklinghausen es una de las enfermedades genéticas que afectan el sistema nervioso, denominada así por su origen común embrionario. Es una enfermedad autosómica dominante, progresiva, de evolución impredecible, que afecta la piel y el sistema nervioso central y periférico. Se presenta el caso de una escolar, femenina, de siete años de edad que ingresó en el Hospital Pediátrico Paquito Gonzáles Cueto debido a la presencia de varias manchas en la piel color "café con leche". Se recogió como antecedente familiar la presencia de neurofibromatosis tipo 1 en la abuela y bisabuela materna, esta última ya fallecida por dicha causa. Al examen físico se constataron nódulos de Lisch en espesor del iris del ojo izquierdo. Los estudios de imágenes evidenciaron varias lesiones nodulares hiperintensas en T2 y FLAIR, a nivel de la cápsula interna y externa bilateral y ventricular izquierda, la mayor de 20 x 11 mm, así como imagen hipointensa a nivel del nervio óptico izquierdo, de 7 mm. Se diagnosticó como neurofibromatosis tipo I. Por ser una de las enfermedades menos estudiadas en nuestro medio se decidió la publicación de este caso.
Neurofibromatosis type I or Von Recklinghausen's disease is one of the genetic diseases that affect the nervous system, named for its common embryonic origin. It is an autosomal dominant, progressive disease with an unpredictable course that affects the skin and the central and peripheral nervous system. The case of a seven-year-old female schoolchild who was admitted to the Paquito Gonzáles Cueto Pediatric Hospital due to the presence of several "coffee-with-milk" spots on her skin is presented. The presence of type 1 neurofibromatosis in her maternal grandmother and great-grandmother, the latter already deceased from said cause, was collected as a family history. On physical examination, Lisch nodules were found in the thickness of the iris of the left eye. Imaging studies revealed several hyperintense nodular lesions on T2 and FLAIR, at the level of the internal and external bilateral and left ventricular capsule, the largest measuring 20 x 11 mm, as well as a hypointense image at the level of the left optic nerve, measuring 7 mm. It was diagnosed as neurofibromatosis type I. Because it is one of the least studied diseases in our environment, it was decided to publish this case.
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This study reviews newly discovered insect peptide point mutations as new possible cancer research targets. To interpret newly discovered peptide point mutations in insects as new possible cancer research targets, we focused on the numerous peptide changes found in the 'CSP' family on the sex pheromone gland of the female silkworm moth Bombyx mori. We predict that the Bombyx peptide modifications will have a significant effect on cancer CUP (cancers of unknown primary) therapy and that bacterial peptide editing techniques, specifically Lactobacillus combined to CRISPR, will be used to regulate ribosomes and treat cancer in humans.
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Bombyx , Neoplasias , Animais , Feminino , Humanos , Bombyx/genética , Peptídeos , Ribossomos/genética , Neoplasias/genética , Neoplasias/terapiaRESUMO
Abstract Hypertrichosis and dental anomalies may occur alone or in combination in the spectrum of many syndromes. To identify genetic entities characterized by hypertrichosis and dental anomalies, a search was performed in the Mendelian Inheritance in Man database with the terms "hypertrichosis" or "hirsutism" and "tooth" or "dental abnormalities." Nondependent androgen metabolism disturbances were classified as hypertrichosis. Genetic entities with hypertrichosis and dental anomalies were included in the study. Additional searches were performed in the PubMed and Orphanet databases, when necessary, in order to include data from scientific articles. An integrative analysis of the genes associated with the identified syndromes was conducted using STRING to characterize biological processes, pathways, and interactive networks. The p-values were subjected to the false discovery rate for the correction of multiple tests. Thirty-nine syndromes were identified, and dental agenesis was the most frequent dental anomaly present in 41.02% (n = 16) of the syndromes. Causative genes were identified in 33 out of 39 genetic syndromes. Among them, 39 genes were identified, and 38 were analyzed by STRING, which showed 148 biological processes and three pathways that were statistically significant. The most significant biological processes were the disassembly of the nucleosome (GO:0006337, p = 1.09e-06), chromosomal organization (GO:0051276, p = 1.09e-06) and remodeling of the chromatin (GO: 0006338, p = 7.86e-06), and the pathways were hepatocellular carcinoma (hsa05225, p = 5.77e-05), thermogenesis (hsa04714, p = 0.00019), and cell cycle (hsa04110, p = 0.0433). Our results showed that the identification of hypertrichosis and dental anomalies may raise the suspicion of one of the thirty-nine syndromes with both phenotypes.