RESUMO
Mutations in methyl-CpG-binding protein 2 (MECP2) in males can lead to various phenotypes, ranging from neonatal encephalopathy to intellectual disability. In this study, using Nord's method of next-generation sequencing in three siblings, we identified a 0.6â¯kb deletion involving the transcriptional repression domain (TRD). Two males and one female had intellectual disability and apnea, but none met the criteria of Rett syndrome. Both males had sick sinus syndrome and severe tracheomalacia that resulted in early death. The mother, with skewed X-inactivation, had no symptoms. Therefore, this mutation is pathological for both males and females, resulting in sick sinus syndrome and severe tracheomalacia with strong reproducibility in males. Deletions involving major domains in MECP2 can result in a severe phenotype, and deletion of the TRD domain can cause severe autonomic nervous system dysregulation in males in these cases.
Assuntos
Doenças do Sistema Nervoso Autônomo/genética , Cromossomos Humanos X/metabolismo , Deficiência Intelectual/genética , Proteína 2 de Ligação a Metil-CpG/genética , Síndrome do Nó Sinusal/genética , Traqueomalácia/genética , Apneia/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Deficiência Intelectual/fisiopatologia , Masculino , Linhagem , Domínios Proteicos , Deleção de Sequência , Irmãos , Síndrome do Nó Sinusal/mortalidade , Síndrome do Nó Sinusal/fisiopatologia , Traqueomalácia/patologia , Sequenciamento do ExomaRESUMO
OBJECTIVE: A subset of children with repaired congenital heart disease (CHD) may require tracheostomy for ongoing ventilatory support. Data on outcomes of children with CHD and tracheostomy are scarce. Our objectives were to describe indications for tracheostomy and outcomes, including readmission data in this population. METHODS: This is a retrospective chart review of children (<18 years old) with CHD who underwent tracheostomy at a single center over a 12-year period. Exclusion criteria were prematurity with isolated patent ductus arteriosus ligation. Outcomes until discharge and data on all readmissions after the initial discharge were reviewed. RESULTS: A total of 21 subjects with CHD underwent tracheostomy at a median (range) age of 4 (1-84) months and mean (standard deviation) weight of 7.2 (5.9) kg. The most common indication for tracheostomy was tracheomalacia with ventilator-dependent respiratory failure (14/21 subjects), followed by subglottic stenosis (5) and vocal cord palsy (2). Genetic syndromes were present in 13 (62%) subjects. The mean (standard deviation) post-tracheostomy length of stay was 55 (35) days. All subjects survived to discharge; 17 (81%) required home ventilation. A total of 11 (52%) subjects died during follow-up, all of whom were mechanically ventilated while three (14%) children underwent successful decannulation. The mean number of nonelective readmissions decreased from 2.4/patient-year in the first year to 1.4/patient-year in the second year, respectively. The commonest reasons for readmission were respiratory deterioration, infections, and mechanical tracheostomy-related problems. CONCLUSIONS: The majority of children with CHD who underwent tracheostomy did so for ventilator dependence and tracheomalacia and had coexisting genetic syndromes. About half the cohort died; among survivors, readmissions were common but decreased after the first year. These results underscore the ongoing mortality and morbidity risks faced by this vulnerable population.