RESUMO
Next generation sequencing based diagnosis has emerged as a promising tool for evaluating critically ill neonates and children. However, there is limited data on its utility in developing countries. We assessed its diagnostic rate and clinical impact on management of pediatric patients with a suspected genetic disorder requiring critical care. The study was conducted at a single tertiary hospital in Northern India. We analyzed 70 children with an illness requiring intensive care and obtained a precise molecular diagnosis in 32 of 70 probands (45.3%) using diverse sequencing techniques such as clinical exome, whole exome, and whole genome. A significant change in clinical outcome was observed in 13 of 32 (40.6%) diagnosed probands with a change in medication in 11 subjects and redirection to palliative care in two subjects. Additional benefits included specific dietary management (three cases), avoidance of a major procedure (one case) and better reproductive counseling. Dramatic therapeutic responses were observed in three cases with SCN1A, SCN2A and KCNQ2-related epileptic encephalopathy. A delayed turn-around for sequencing results was perceived as a major limiting factor in the study, as rapid and ultra-rapid sequencing was not available. Achieving a precise molecular diagnosis has great utility in managing critically ill patients with suspected genetic disorders in developing countries.
Assuntos
Estado Terminal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Feminino , Pré-Escolar , Lactente , Criança , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/terapia , Recém-Nascido , Testes Genéticos/métodos , Testes Genéticos/normas , Adolescente , Sequenciamento do Exoma/métodosAssuntos
Diagnóstico Pré-Natal , Humanos , Feminino , Gravidez , Diagnóstico Pré-Natal/métodos , Síndrome , Anormalidades Múltiplas , Recém-Nascido , MasculinoRESUMO
Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant skeletal dysplasia characterised by swelling and restriction of movement in the wrist and ankle joints, as well as osteolysis of the carpal and tarsal bones, that can be misdiagnosed as juvenile idiopathic arthritis. We describe five Indian families with heterozygous nonrecurrent missense pathogenic variants in exon 1 of MAF bZIP transcription factor B (MAFB).
Assuntos
Artrogripose , Osteólise , Humanos , Osteólise/diagnóstico por imagem , Osteólise/genética , Povo Asiático , ÉxonsRESUMO
To examine the impact of the COVID-19 pandemic, we interviewed 26 patients with lysosomal storage disorders receiving enzyme replacement therapy. 20 (77 %) had significant interruption in their treatment, with an average of 8 (range 2-28) missed doses. Alternate methods of delivering uninterrupted care including home therapy were used. Vulnerable patients with chronic genetic disorders require organization for their multidisciplinary needs of care.
Assuntos
COVID-19 , Terapia de Reposição de Enzimas/métodos , Acessibilidade aos Serviços de Saúde , Doenças por Armazenamento dos Lisossomos , Conduta do Tratamento Medicamentoso , Adolescente , COVID-19/epidemiologia , COVID-19/prevenção & controle , Defesa Civil/normas , Feminino , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/terapia , Acessibilidade aos Serviços de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/normas , Necessidades e Demandas de Serviços de Saúde , Humanos , Índia/epidemiologia , Controle de Infecções , Doenças por Armazenamento dos Lisossomos/epidemiologia , Doenças por Armazenamento dos Lisossomos/terapia , Masculino , Conduta do Tratamento Medicamentoso/organização & administração , Conduta do Tratamento Medicamentoso/normas , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
With the advent of next generation sequencing technology there has been a spurt of papers on genetics in epilepsy in children. Genetic testing has now become an essential part of clinical practice in epilepsy. It helps in reaching an etiological diagnosis, providing prognostic information, guiding therapy precisely indicated for the patient and avoiding drugs that may worsen the seizures. Once the pathogenic variant has been found, this enables determining and counseling the risk of recurrence to the patient and other relatives at risk. It also makes available different reproductive options such as prenatal diagnosis or pre-implantation diagnosis. The authors describe the benefits, the clinical situations that require genetic testing, the types of genetic tests that are available, and how to choose the appropriate test and their likely yields. Genetic counseling, both pre- and post-test that should be provided is described briefly. Two useful tables are included that depict the therapy for variants in different epilepsy genes.
Assuntos
Epilepsia , Testes Genéticos , Criança , Aconselhamento , Epilepsia/diagnóstico , Epilepsia/genética , Aconselhamento Genético , Sequenciamento de Nucleotídeos em Larga Escala , HumanosRESUMO
Gerstmann-Sträussler-Scheinker (GSS) syndrome is a devastating hereditary prion disease, presenting in 4th-5th decade with progressive ataxia and dementia. Pathogenic variants in the PRNP gene lead to aggregation of misfolded prion protein which results in neurodegeneration and death within a few years of onset. A key feature of prion disorders is conversion of normal prion protein (PrPc) into its misfolded form (PrPSc). Genetic modifiers include methionine at position 129 in prion protein and octapeptide repeats. We present an Indian kindred with c. 305C > T, p.Pro102Leu mutation in PRNP gene causing GSS in multiple members and discuss the impact of the polymorphism at position 129 on the severity of illness.
Assuntos
Doença de Gerstmann-Straussler-Scheinker , Doenças Priônicas , Príons , Doença de Gerstmann-Straussler-Scheinker/genética , Humanos , Índia , Mutação , Doenças Priônicas/genética , Proteínas Priônicas/genética , Príons/genéticaAssuntos
Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Insuficiência de Crescimento/genética , Ataxia/genética , Criança , Esmalte Dentário/metabolismo , Deficiências do Desenvolvimento/genética , Humanos , Masculino , Hipotonia Muscular/genética , Mutação/genética , SíndromeRESUMO
BACKGROUND: Preexamination period is an exceptionally stressful time for schoolgoing children and adolescents, and the propensity of having anxiety symptoms increases. AIM: This study aimed to assess the presence of anxiety symptoms in students in preexamination period. MATERIALS AND METHODS: The study was carried on 619 children from Class VIII to XI. All of them were given a structured questionnaire for sociodemographic profile and Screen for Child Anxiety Related Emotional Disorders questionnaire. Association of various variables with presence of anxiety symptoms was assessed. Statistics was analyzed with SPSS version 17.0 software. RESULTS: Totally 170 children (27.5%) had anxiety symptoms, similarly the various subgroups had increased frequency compared to the known prevalence in this age group. Age, years spent in the current school, living with parents, presence of domestic stressors, and grade deterioration, all were significantly associated with increased frequency of these symptoms. Similarly, association with various subgroups is described. CONCLUSION: This study attempts to give evidence of increased anxiety symptoms, during preexamination phase, compared to the reported prevalence in this age group, and thus to address this becomes imperative which will improve their performance and also the mental health preventing distress along with psychological and behavioral problems.
Assuntos
Aterosclerose/cirurgia , Prótese Vascular , Artéria Femoral/cirurgia , Sobrevivência de Enxerto , Doenças Vasculares Periféricas/cirurgia , Artéria Poplítea/cirurgia , Stents , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico por imagem , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doenças Vasculares Periféricas/diagnóstico por imagem , Artéria Poplítea/diagnóstico por imagem , Resultado do Tratamento , UltrassonografiaAssuntos
Comportamento Cooperativo , Cooperação Internacional , Medicina/organização & administração , Política Organizacional , Radiologia Intervencionista/organização & administração , Especialização , Canadá , Credenciamento , Humanos , Medicina/tendências , Radiologia Intervencionista/tendências , Sociedades MédicasRESUMO
Yunis-Varon syndrome is a rare, autosomal recessive syndrome characterized by growth retardation, defective growth of the cranial bones along with complete or partial absence of the clavicles (cleidocranial dysplasia), characteristic facial features, and/or abnormalities of the fingers and/or toes.