RESUMO
Many studies have attempted to establish the genotype-phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well-defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype-phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non-invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence-based management in RTT. © 2016 Wiley Periodicals, Inc.
Assuntos
Estudos de Associação Genética , Genótipo , Proteína 2 de Ligação a Metil-CpG/genética , Mutação , Fenótipo , Síndrome de Rett/diagnóstico , Síndrome de Rett/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Fever is common in children aged 0-4 years old and often leads to parental worries and in turn, high use of healthcare services. Educating parents may have beneficial effects on their sense of coping and fever management. Most parents receive information when their child is ill but it might be more desirable to educate parents in the setting of well-child clinics prior to their child becoming ill, in order to prepare parents for future illness management. This study aims to explore experiences of well-child clinic professionals when dealing with childhood fever and current practices of fever information provision to identify starting points for future interventions. METHODS: We held four focus group discussions based on naturalistic enquiry among 22 well-child clinic professionals. Data was analysed using the constant comparative technique. RESULTS: Well-child clinic professionals regularly received questions from parents about childhood fever and felt that parental worries were the major driving factor behind these contacts. These worries were assumed to be driven by: (1) lack of knowledge (2) experiences with fever (3) educational level and size social network (4) inconsistencies in paracetamol administration advice among healthcare professionals. Well-child clinic professionals perceive current information provision as limited and stated a need for improvement. For example, information should be consistent, easy to find and understand. CONCLUSIONS: Fever-related questions are common in well-child care and professionals perceive that most of the workload is driven by parental worries. The focus group discussions revealed a desire to optimise the current limited information provision for childhood fever. Future interventions aimed at improving information provision for fever in well-child clinics should consider parental level of knowledge, experience, educational level and social network and inconsistencies among healthcare providers. Future fever information provision should focus on improving fever management and practical skills.
Assuntos
Serviços de Saúde da Criança , Febre , Enfermeiras e Enfermeiros , Médicos , Adulto , Pré-Escolar , Emoções , Feminino , Grupos Focais , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , Pais/psicologia , Relações Profissional-Família , Carga de TrabalhoRESUMO
Rett syndrome (RTT; OMIM 312750) is an X-linked dominant neurodevelopmental disorder leading to cognitive and motor impairment, epilepsy, and autonomic dysfunction in females. Since the discovery that RTT is caused by mutations in MECP2, large retrospective genotype-phenotype correlation studies have been performed. A number of general genotype-phenotype relationships were confirmed and specific disorder profiles were described. Nevertheless, conflicting results are still under discussion, partly due to the variability in classification of mutations, assessment tools, and structure of the data sets. The aim of this study was to investigate relationships between genotype and specific clinical data collected by the same experienced physician in a well-documented RTT cohort, and evaluate its prognostic value in counseling young parents with a newly diagnosed RTT girl regarding her future outcome. The Maastricht-Leuven Rett Syndrome Database is a register of 137 molecularly confirmed clinical RTT cases, containing both molecular and clinical data on examination and follow up by the same experienced physician. Although the general genotype-phenotype relationships were confirmed, the clinical severity was still found to be very variable. We therefore recommend caution in using genotype-phenotype data in the prognosis of outcome for children in Rett syndrome. Early diagnosis, early intervention, and preventive management are imperative for better outcomes and better quality of daily life for RTT females and their families.
Assuntos
Estudos de Associação Genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Proteína 2 de Ligação a Metil-CpG/genética , Síndrome de Rett/genética , Síndrome de Rett/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Bases de Dados Genéticas , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Genótipo , Humanos , Pessoa de Meia-Idade , Mutação , Fenótipo , Prognóstico , Estrutura Terciária de Proteína/genética , Síndrome de Rett/diagnóstico , Análise de Sequência de DNARESUMO
The aging process of people with intellectual disabilities has been a topic of interest in recent years. Good knowledge of the specific healthcare problems in adults with intellectual disabilities and anticipating on these problems are important issues in providing support and healthcare for these persons. Nevertheless little is known about the aging process of people with specific syndromes, like Rett syndrome. In association with the Dutch Rett syndrome parent association, 70 postal questionnaires were sent to the contact persons of the females aged at least 16 years with a clinical diagnosis of Rett syndrome. The questionnaire consisted of general questions, questions about living conditions, skills, physical and psychiatric morbidity. The response rate was 76% (n = 53). In general adults with Rett syndrome seemed to be reasonably healthy, whereas neurological, respiratory and behavioral morbidity appeared to be of great influence. High care dependency was confirmed. In contrast with underweight, overweight showed to be an under-ascertained feature. The general disorder profile was confirmed, considering the increase with age regarding kyphosis and the better communication and autonomic dysfunction in the oldest age group compared to the younger age groups. Features of autonomic dysfunction deserve more medical attention, especially the interrelation between quality of sleep, respiration and behavior in Rett syndrome. Longitudinal studies including genotype-phenotype analyses are needed for insight in individual changes in support needs and health.
Assuntos
Envelhecimento , Nível de Saúde , Síndrome de Rett/fisiopatologia , Inquéritos e Questionários , Adolescente , Adulto , Análise de Variância , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Feminino , Genótipo , Humanos , Cifose/epidemiologia , Cifose/genética , Cifose/fisiopatologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Comunicação não Verbal , Sobrepeso/epidemiologia , Sobrepeso/genética , Sobrepeso/fisiopatologia , Síndrome de Rett/epidemiologia , Síndrome de Rett/genéticaRESUMO
Despite their good appetite, many females with Rett syndrome (RTT) meet the criteria for moderate to severe malnutrition. Although feeding difficulties may play a part in this, other constitutional factors such as altered metabolic processes are suspected. Irregular breathing is a common clinical feature, leading to chronic respiratory alkalosis or acidosis. We assumed that these changes in intracellular pH cause disturbances in the metabolic equilibrium, with important nutritional consequences. The study population consisted of a group of thirteen well-defined RTT girls with extended clinical, molecular and neurophysiological assessments. Despite normal levels of total dietary energy and protein intakes, malnutrition was confirmed based on significantly low fat-free mass index (FFMI) values. Biochemical screening of multiple metabolic pathways showed significantly elevated plasma creatine concentrations and increased urinary creatine/creatinine ratio in five RTT girls. Four girls, 10 years and older, were forceful breathers, one 13-year-old girl had an undetermined cardiorespiratory phenotype. An isolated increase of the urinary creatine/creatinine ratio was seen in two girls, a 9-year old forceful and a 4-year old feeble breather. Given that the young girls are feeble breathers and the older girls are forceful breathers, it is impossible to determine whether the elevated creatine concentrations are due to increasing age or cardiorespiratory phenotype. Furthermore, MeCP2 deficiency may cause epigenetic aberrations affecting the expression of the creatine-transporter gene, which is located at Xq28. Further studies are required to confirm these findings and to provide greater insight into the pathogenesis of the abnormal creatine metabolism in RTT.