RESUMO
OBJECTIVES: Genetic disorders are a leading contributor to mortality in the neonatal ICU and PICU in the United States. Although individually rare, there are over 6,200 single-gene diseases, which may preclude a genetic diagnosis prior to ICU admission. Rapid whole genome sequencing is an emerging method of diagnosing genetic conditions in time to affect ICU management of neonates; however, its clinical utility has yet to be adequately demonstrated in critically ill children. This study evaluates next-generation sequencing in pediatric critical care. DESIGN: Retrospective cohort study. SETTING: Single-center PICU in a tertiary children's hospital. PATIENTS: Children 4 months to 18 years admitted to the PICU who were nominated between July 2016 and May 2018. INTERVENTIONS: Rapid whole genome sequencing with targeted phenotype-driven analysis was performed on patients and their parents, when parental samples were available. MEASUREMENTS AND MAIN RESULTS: A molecular diagnosis was made by rapid whole genome sequencing in 17 of 38 children (45%). In four of the 17 patients (24%), the genetic diagnoses led to a change in management while in the PICU, including genome-informed changes in pharmacotherapy and transition to palliative care. Nine of the 17 diagnosed children (53%) had no dysmorphic features or developmental delay. Eighty-two percent of diagnoses affected the clinical management of the patient and/or family after PICU discharge, including avoidance of biopsy, administration of factor replacement, and surveillance for disorder-related sequelae. CONCLUSIONS: This study demonstrates a retrospective evaluation for undiagnosed genetic disease in the PICU and clinical utility of rapid whole genome sequencing in a portion of critically ill children. Further studies are needed to identify PICU patients who will benefit from rapid whole genome sequencing early in PICU admission when the underlying etiology is unclear.
Assuntos
Doenças Genéticas Inatas/diagnóstico , Sequenciamento Completo do Genoma , Adolescente , Criança , Pré-Escolar , Estado Terminal/terapia , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Medicina de Precisão/métodos , Estudos RetrospectivosAssuntos
Mordeduras e Picadas/complicações , Peixes , Prepúcio do Pênis/lesões , Adulto , Animais , Humanos , MasculinoAssuntos
Moléculas de Adesão Celular Neuronais/genética , Deleção Cromossômica , Cromossomos Humanos Par 2/genética , Deficiências do Desenvolvimento/genética , Deleção de Genes , Hérnias Diafragmáticas Congênitas , Proteínas do Tecido Nervoso/genética , Anormalidades Múltiplas/genética , Estatura/genética , Proteínas de Ligação ao Cálcio , Criança , Hibridização Genômica Comparativa , Feminino , Hérnia Diafragmática/genética , Humanos , Moléculas de Adesão de Célula NervosaRESUMO
BACKGROUND: Hypertensive encephalopathy is one of the few neurologic emergencies in which prompt diagnosis and treatment can prevent permanent neurological damage. This syndrome is rarely seen in children. OBJECTIVES: To discuss the recognition of hypertensive encephalopathy as a cause of acute neurological changes in children. CASE REPORT: We present the case of a 3-year-old boy who presented to the Emergency Department with seizures due to hypertensive encephalopathy. A review of the literature on the subject follows the case report. CONCLUSIONS: Hypertensive encephalopathy is a rare cause of acute neurological changes in children that can cause permanent damage if not recognized early. This case illustrates the importance of considering this syndrome as a potential cause of neurological symptoms, especially as neuroimaging can initially be misleading.
