Asunto(s)

Epilepsia/genética , Eliminación de Gen , Proteína 2 de Unión a Metil-CpG/genética , Polimorfismo de Nucleótido Simple , Síndrome de Rett/genética , Femenino , Humanos

RESUMEN

OBJECTIVES: To describe the hospitalisation patterns in children with intellectual disability (ID) and/or autism spectrum disorder (ASD) after the first year of life and compare with those unaffected. DESIGN: Prospective cohort study using data linkage between health, ID and hospitalisation population-based datasets. SETTING: Western Australia. PARTICIPANTS: 416 611 individuals born between 1983 and 1999 involving 1 027 962 hospital admission records. Five case categories were defined (mild/moderate ID, severe ID, biomedically caused ID, ASD with ID and ASD without ID) and compared with the remainder of children and young people. PRIMARY AND SECONDARY OUTCOME MEASURES: Time to event analysis was used to compare time hospitalisation and rate of hospitalisation between the different case-groups by estimating HR, accounting for birth year and preterm birth status. RESULTS: ID and/or ASD were found to be associated with an increased risk of hospitalisation compared with the remainder of the population. The increase in risk was highest in those with severe ID and no ASD (HR=10.33, 95% CI 8.66 to 12.31). For those with ID of known biomedical cause or mild ID of unknown cause, the risk of hospitalisation was lower (HR=7.36, 95% CI 6.73 to 8.07 and HR=3.08, 95% CI 2.78 to 3.40, respectively). Those with ASDs had slightly increased risk (HR=2.82, 95% CI 2.26 to 3.50 for those with ID and HR=2.09, 95% CI 1.85 to 2.36 for those without ID). CONCLUSIONS: Children with an ID or ASD experience an increased risk of hospitalisation after the first year of life which varied from 2 to 10 times that of the rest of the population. Findings can inform service planning or resource allocation for these children with special needs.

RESUMEN

BACKGROUND: Rett syndrome is a severe genetic neurodevelopmental disorder mainly affecting females. The aim of this study was to describe pubertal development in a population-based cohort of females with Rett syndrome. METHODS: To assess pubertal trajectory we used six waves of data provided by parents of girls and women, recruited through the Australian population-based Rett Syndrome Database. The age at which adrenarche, thelarche or menarche occurred was used as the parameter for time to event (survival) analysis. The relationships between BMI, mutation type and the trajectories were investigated, using Cox proportional hazards. RESULTS: One quarter of girls reached adrenarche by 9.6 years, half by 11 years and three quarters by 12.6 years. Half reached menarche by 14 years (range 8-23). Being underweight was associated with later age at adrenarche, thelarche and menarche, while higher BMI (overweight) was associated with earlier onset. In general, girls with C-terminal deletions and early truncating mutations reached pubertal stages earlier and those with the p.R168X mutation reached them later. CONCLUSION: The pubertal course in Rett syndrome may be abnormal, sometimes with early adrenarche but delayed menarche. These features may be genotype dependent and may have varying relationships with growth and bone acquisition.

Asunto(s)

Pubertad , Síndrome de Rett/genética , Síndrome de Rett/fisiopatología , Australia , Índice de Masa Corporal , Niño , Estudios de Cohortes , Femenino , Humanos

RESUMEN

Multiplex ligation-dependent Probe Amplification (MLPA) has become available for the detection of a large deletion on the MECP2 gene allowing genetic confirmation of previously unconfirmed cases of clinical Rett syndrome. This study describes the phenotype of those with a large deletion and compares with those with other pathogenic MECP2 mutations. Individuals were ascertained from the Australian Rett Syndrome and InterRett databases with data sourced from family and clinician questionnaires, and two case studies were constructed from the longitudinal Australian data. Regression and survival analysis were used to compare severity and age of onset of symptoms in those with and without a large deletion. Data were available for 974 individuals including 51 with a large deletion and ages ranged from 1 year 4 months to 49 years (median 9 years). Those with a large deletion were more severely affected than those with other mutation types. Specifically, individuals with large deletions were less likely to have learned to walk (OR 0.42, 95% CI: 0.22-0.79, P=0.007) and to be currently walking (OR 0.53, 95% CI: 0.26-1.10, P=0.089), and were at higher odds of being in the most severe category of gross motor function (OR 1.84, 95% CI: 0.98-3.48, P=0.057) and epilepsy (OR 2.72, 95% CI: 1.38-5.37, P=0.004). They also developed epilepsy, scoliosis, hand stereotypies and abnormal breathing patterns at an earlier age. We have described the disorder profile associated with a large deletion from the largest sample to date and have found that the phenotype is severe with motor skills particularly affected.

Asunto(s)

Secuencia de Bases , Proteína 2 de Unión a Metil-CpG/genética , Síndrome de Rett/epidemiología , Síndrome de Rett/genética , Eliminación de Secuencia , Adolescente , Adulto , Edad de Inicio , Australia/epidemiología , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa Multiplex , Fenotipo , Síndrome de Rett/diagnóstico , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios

RESUMEN

OBJECTIVE: To assess the direct annual health care costs for children and adolescents with Down syndrome in Western Australia and to explore the variation in health care use including respite, according to age and disease profile. STUDY DESIGN: Population-based data were derived from a cross-sectional questionnaire that was distributed to all families who had a child with Down syndrome as old as 25 years of age in Western Australia. RESULTS: Seventy-three percent of families (363/500) responded to the survey. Mean annual cost was $4209 Australian dollars ($4287 US dollars) for direct health care including hospital, medical, pharmaceutical, respite and therapy, with a median cost of $1701. Overall, costs decreased with age. The decline in costs was a result of decreasing use of hospital, medical, and therapy costs with age. Conversely, respite increased with age and also with dependency. Health care costs were greater in all age groups with increasing dependency and for an earlier or current diagnosis of congenital heart disease. Annual health care costs did not vary with parental income, including cost of respite. CONCLUSIONS: Direct health care costs for children with Down syndrome decrease with age to approximate population costs, although costs of respite show an increasing trend.

Asunto(s)

Síndrome de Down/economía , Costos de la Atención en Salud/estadística & datos numéricos , Adolescente , Factores de Edad , Australia/epidemiología , Niño , Preescolar , Estudios Transversales , Evaluación de la Discapacidad , Personas con Discapacidad , Síndrome de Down/epidemiología , Femenino , Cardiopatías Congénitas/economía , Cardiopatías Congénitas/epidemiología , Humanos , Hidroterapia/economía , Lactante , Recién Nacido , Masculino , Terapia Ocupacional/economía , Visita a Consultorio Médico/economía , Visita a Consultorio Médico/estadística & datos numéricos , Modalidades de Fisioterapia/economía , Cuidados Intermitentes/economía , Logopedia/economía , Encuestas y Cuestionarios , Natación/economía , Adulto Joven

RESUMEN

Rett syndrome is a rare but severe neurological disorder typically associated with a mutation in the MECP2 gene. We describe change in gross motor function over 3 to 4 years for 70 subjects participating in the Australian Rett Syndrome Database. Linear regression was used to assess relationships with age, genotype, and general and complex gross motor skills scores measured on the Gross Motor Scale for Rett syndrome. Skills were slightly better or maintained in approximately 40% of subjects and slightly decreased in approximately 60%. Teenagers and women who walked in 2004 were less likely to lose complex skills than those younger. Girls with a p.R294X mutation were more likely to lose complex motor skills, otherwise skill changes were spread across the mutation categories. In conclusion, small changes were observed over this period with greater stability of skills in teenagers and women with the ability to walk.

Asunto(s)

Destreza Motora/fisiología , Trastornos del Movimiento/etiología , Síndrome de Rett/complicaciones , Adolescente , Adulto , Factores de Edad , Arginina/genética , Australia , Progresión de la Enfermedad , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Proteína 2 de Unión a Metil-CpG/genética , Trastornos del Movimiento/genética , Mutación/genética , Estudios Retrospectivos , Síndrome de Rett/genética , Adulto Joven

RESUMEN

Modifications to diagnostic criteria and introduction of genetic testing have likely affected the pattern and timing of Rett syndrome diagnosis. The trends in incidence and prevalence of Rett syndrome in Australia were examined; the cumulative risk of a female being diagnosed was determined; and the impact of changes to diagnostic criteria and availability of genetic testing on these frequencies was investigated. The population-based Australian Rett Syndrome Database was used to identify a total of 349 verified Rett syndrome females born 1976-2006 and diagnosed 1982-2008. The proportion of female cases born and diagnosed per year and the cumulative risk of a diagnosis were determined. The median age of Rett syndrome diagnosis decreased from 4.5 y if diagnosed before 2000 to 3.5 y if diagnosed after 1999. The cumulative risk of diagnosis had almost doubled by 32 y of age [1/8,905 or 11.23 per 100,000 person-years (95% CI, 10.03-12.45)] in comparison with 5 y of age [1/15,361 or 6.51 per 100,000 person-years (95% CI, 5.65-7.39)]. Earlier age of diagnosis may result in families experiencing less stress and emotional strain compared with those with delayed diagnosis.

Asunto(s)

Síndrome de Rett/diagnóstico , Adolescente , Adulto , Australia/epidemiología , Niño , Preescolar , Bases de Datos Factuales , Femenino , Pruebas Genéticas , Humanos , Síndrome de Rett/epidemiología , Síndrome de Rett/genética , Adulto Joven

RESUMEN

The early developmental history prior to the manifestation of Rett syndrome features is of clinical interest. This study describes the attainment of gross developmental milestones and regression, and assesses the relationships between genotype and age at diagnosis. The Australian Rett Syndrome Database and International Rett Syndrome Phenotype Database were used to source a total of 293 confirmed female subjects. Most girls learned to sit, were able to babble or use words, and approximately half learned to walk. Altered milestone attainment was associated with earlier diagnosis. There was variation in the acquisition of milestones, the age of regression, and the age of diagnosis by genotype. Most parents expressed concerns about unusual behaviors or development during infancy, and a more subtle atypical development during infancy was reported for most girls. It is important for clinicians to be aware of variable early development in Rett syndrome and that timely genetic testing is not precluded on this account.

Asunto(s)

Desarrollo Infantil , Síndrome de Rett/diagnóstico , Síndrome de Rett/genética , Habla , Caminata , Factores de Edad , Niño , Preescolar , Diagnóstico Precoz , Femenino , Genotipo , Humanos , Lactante , Síndrome de Rett/psicología , Encuestas y Cuestionarios

RESUMEN

BACKGROUND: Research findings investigating the sociodemographics of autism spectrum disorder (ASD) have been inconsistent and rarely considered the presence of intellectual disability (ID). METHODS: We used population data on Western Australian singletons born from 1984 to 1999 (n = 398,353) to examine the sociodemographic characteristics of children diagnosed with ASD with or without ID, or ID without ASD compared with non-affected children. RESULTS: The profiles for the four categories examined, mild-moderate ID, severe ID, ASD without ID and ASD with ID varied considerably and we often identified a gradient effect where the risk factors for mild-moderate ID and ASD without ID were at opposite extremes while those for ASD with ID were intermediary. This was demonstrated clearly with increased odds of ASD without ID amongst older mothers aged 35 years and over (odds ratio (OR) = 1.69 [CI: 1.18, 2.43]), first born infants (OR = 2.78; [CI: 1.67, 4.54]), male infants (OR = 6.57 [CI: 4.87, 8.87]) and increasing socioeconomic advantage. In contrast, mild-moderate ID was associated with younger mothers aged less than 20 years (OR = 1.88 [CI: 1.57, 2.25]), paternal age greater than 40 years (OR = 1.59 [CI: 1.36, 1.86]), Australian-born and Aboriginal mothers (OR = 1.60 [CI: 1.41, 1.82]), increasing birth order and increasing social disadvantage (OR = 2.56 [CI: 2.27, 2.97]). Mothers of infants residing in regional or remote areas had consistently lower risk of ASD or ID and may be linked to reduced access to services or under-ascertainment rather than a protective effect of location. CONCLUSIONS: The different risk profiles observed between groups may be related to aetiological differences or ascertainment factors or both. Untangling these pathways is challenging but an urgent public health priority in view of the supposed autism epidemic.

Asunto(s)

Trastorno Autístico/complicaciones , Trastorno Autístico/epidemiología , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/epidemiología , Parto , Adulto , Demografía , Femenino , Humanos , Masculino , Edad Materna , Análisis Multivariante , Prevalencia , Factores Socioeconómicos , Australia Occidental/epidemiología , Adulto Joven

RESUMEN

PURPOSE: To describe leisure participation for school-aged children with Down syndrome and to investigate how factors, classified by the World Health Organisation's International Classification of Functioning, Disability and Health, influence their leisure participation. METHOD: Families in Western Australia with a child aged 5-18 years with Down syndrome were surveyed in a population-based study (n = 208) in 2004. RESULTS: One-third of parents reported that their child with Down syndrome had no friends although half reported two or more friends. Factors affecting number of friendships included the child's functional ability, behavioural issues and parent's availability of time. Those children with higher functional independence scores in daily tasks were more likely to have two or more friends than those with lower functional independence scores (OR: 1.02, 95% CI 1.01-1.04 for a single point increase in WeeFIM score). All children participated in predominantly solitary and sedentary leisure activities. CONCLUSIONS: Leisure participation was affected by complex factors both within and external to the child with Down syndrome. Further investigation of the relevance of these factors to leisure may enable more satisfying and meaningful participation in leisure for school-aged children with Down syndrome.

Asunto(s)

Síndrome de Down/psicología , Actividades Recreativas , Calidad de Vida , Actividades Cotidianas , Adolescente , Niño , Preescolar , Niños con Discapacidad/clasificación , Niños con Discapacidad/psicología , Síndrome de Down/complicaciones , Familia , Femenino , Amigos , Humanos , Masculino , Vigilancia de la Población , Características de la Residencia , Instituciones Académicas , Conducta Social , Australia Occidental

RESUMEN

This study aimed to investigate the trajectories over time of health status and health service use in Rett syndrome by mutation type. Data were obtained from questionnaires administered over six years to 256 participants from the Australian Rett Syndrome Database. Health status (episodes of illness and medication load) and health service use (general practitioner and specialist visits and hospital stays) were summarized into composite scores with Principal Component Analysis. Linear and mixed regression models examined effects of mutation type and other variables on these scores over time. For some mutations (such as p.R255X, p.R168X) health status was poorer at a younger age and improved over time, while for p.R133C it was better at a younger age and deteriorated with time. For those with p.R133C health service use was lowest at a younger age and highest at 25 years. With other mutations, such as p.R255X, p.R270X, p.R294X, C terminal and p.R306C, health service use was higher at a younger age, but dropped off considerably by 25 years of age. Health service use generally declined in parallel with deterioration in health status, although this pattern differed by mutation type, demonstrating important variability in the course of Rett syndrome.

RESUMEN

Loss of hand function is a core feature of Rett syndrome. This article describes longitudinal hand function at 3 time points for 72 subjects participating in the Australian Rett Syndrome Database. Approximately 40% of subjects with some grasping abilities lost skill over the 3- to 4-year period between video assessments. In these subjects, a decrease in hand function was seen less frequently in girls 13 to 19 years old than in those younger than 8 years, in subjects with some mobility compared with those who were wheelchair bound, and in those who had previously been able to finger feed. Relationships with the magnitude of change reflected these findings. Change in hand function did not vary with clinical severity. The results for all subjects were similar to results obtained when analysis was restricted to those with a pathogenic mutation. Variability in the longitudinal course of hand function in Rett syndrome was observed.

Asunto(s)

Mano/fisiopatología , Síndrome de Rett/patología , Adolescente , Adulto , Factores de Edad , Australia/epidemiología , Niño , Preescolar , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Estudios Longitudinales , Proteína 2 de Unión a Metil-CpG/genética , Mutación/genética , Síndrome de Rett/genética , Síndrome de Rett/fisiopatología , Grabación en Video , Adulto Joven

RESUMEN

OBJECTIVES: To compare the prevalence of parent reported medical conditions and rates of health service utilization in school-aged children with Down syndrome in Western Australia in 1997 and 2004. STUDY DESIGN: We compared two cross-sectional surveys completed by parents of children with Down syndrome identified from population-based sources in 1997 (n = 210) and 2004 (n = 208). Surveys collected information on family demographics, medical conditions, health issues, and service utilization. The analysis described medical conditions in 2004 and compared frequencies in both years. Regression analyses compared medical conditions and health utilisation in the two cohorts. RESULTS: In 2004, children with Down syndrome had greater odds of having a bowel condition (OR, 1.69; 95%, 1.16 to 2.45; P = .01), were less likely to have a current problem due to their cardiac condition (OR, 0.32; 95% CI, 0.15 to 0.68, P = .003), and demonstrated an overall reduction in episodic illnesses and infections. The use of GP services (incidence rate ratio [IRR] = 0.91; 95% CI, 0.83 to 1.00, P = .05) and combined medical specialist visits (IRR = 0.92; 95% CI, 0.84 to 1.01; P = .09) were reduced in 2004, as were overnight hospital admissions (IRR = 0.60; 95% CI, 0.37 to 0.96; P = .03) and length of stay (IRR = 0.33; 95% CI, 0.24 to 0.44; P < .001). CONCLUSIONS: The health status of children with Down syndrome has varied over time with reductions in current cardiac problems, episodic illnesses, and health service use. Research is now needed to investigate the impact of these changes on the overall health and quality of life of children and families living with Down syndrome.

Asunto(s)

Síndrome de Down/epidemiología , Síndrome de Down/terapia , Servicios de Salud/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Factores de Edad , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/terapia , Niño , Comorbilidad , Intervalos de Confianza , Estudios Transversales , Síndrome de Down/diagnóstico , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Musculoesqueléticas/terapia , Oportunidad Relativa , Prevalencia , Calidad de la Atención de Salud , Análisis de Regresión , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/terapia , Medición de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Australia Occidental/epidemiología

RESUMEN

This study used densitometry to investigate the areal bone mineral density (aBMD) and bone mineral content (BMC) in an Australian Rett syndrome cohort and to assess how factors such as genotype, epilepsy, BMI, and mobility affect these parameters. The influence of lean tissue mass (LTM) and bone area (BA) on total body BMC (TBBMC) was also investigated. Participants, recruited from the Australian Rett Syndrome Database (ARSD), had TBBMC and lumbar spine (LS) and femoral neck (FN) aBMD measured using Dual energy x-ray absorptiometry. Mean height standardized Z scores and CIs for the bone outcomes were obtained from multiple regression models. The mean height Z score for the FN aBMD was low at -2.20, while the LS aBMD was -0.72. The TBBMC mean height Z score was -0.62, although once adjusted for BA and LTM, the mean was above zero, suggesting that low BMC can be explained by narrow bones and decreased muscle mass, likely secondary to decreased mobility. Multiple linear regression identified the p.R168× and p.T158M mutations as the strongest predictors of low aBMC and BMD for all bone outcomes. The strong relationship between genotype, BMC, and aBMD is likely underpinned by the strong relationship between LTM, mobility, and bone outcome measures.

Asunto(s)

Densidad Ósea/fisiología , Síndrome de Rett/fisiopatología , Absorciometría de Fotón/métodos , Adulto , Australia , Composición Corporal , Estatura , Niño , Bases de Datos Factuales , Femenino , Humanos , Síndrome de Rett/patología , Encuestas y Cuestionarios

RESUMEN

There is often delay between onset of Rett syndrome symptoms and its diagnosis, possibly related to symptom presentation or socio-demographic factors. We hypothesized that girls with an atypical presentation or whose family had a lower socio-economic status would receive a later diagnosis. Female subjects with a confirmed diagnosis of Rett syndrome were sourced from the Australian Rett Syndrome and InterRett Databases. Variables analyzed included timing and development of symptoms; MECP2 mutation type; parental occupation and education; maternal age and birth order. Residential location and socio-economic status were also analyzed for the Australian cases. Linear regression was used to determine relationships between these factors and age at diagnosis. A total of 909 cases were included. An older age of diagnosis was associated with later loss of hand function and speech, later onset of hand stereotypies and the presence of the p.R133C or p.R294X MECP2 mutation. Socio-economic factors did not predict age of diagnosis for Australian families. For families participating in the InterRett database, a younger age of diagnosis was associated with higher levels of parental education or occupation. A clinical picture consistent with the classic presentation of Rett syndrome is associated with an earlier diagnosis. Clinicians need to be alerted to the variable presentation of Rett syndrome including the milder phenotypes of cases with the p.R133C or p.R294X mutation. Educational resources to assist this understanding including guidance on when to request genetic testing could be useful to streamline the process of diagnosis in Rett syndrome.

Asunto(s)

Síndrome de Rett/genética , Adulto , Australia , Escolaridad , Femenino , Genotipo , Humanos , Lactante , Masculino , Edad Materna , Proteína 2 de Unión a Metil-CpG/genética , Mutación , Síndrome de Rett/diagnóstico , Factores Socioeconómicos

RESUMEN

AIM: rett syndrome is a severe neurodevelopmental disorder that typically affects females. Little is known about the natural history and survival time of these females. METHOD: we compared the survival of all Austrian female participants from Rett's historical cohort (1966) with that of affected females registered in the Australian Rett Syndrome Database. The analysis included both Kaplan-Meier analysis and a log-rank test for equality of survivor functions. RESULTS: of females in the original Austrian group, three are still alive. The median age at death was 13 years 4.8 months. The probability of survival up to the age of 25 years was 21%, compared with 71% in the Australian cohort (p<0.001). We found no practical or statistically significant differences in survival between the various birth year groups within the Australian cohort. INTERPRETATION: our data indicate that survival of females with Rett syndrome has improved since the late 1960s but that there has been shown no change in survival over the last 30 years, possibly because the follow-up time has been too short.

Asunto(s)

Proteína 2 de Unión a Metil-CpG/genética , Síndrome de Rett/mortalidad , Adolescente , Adulto , Australia/epidemiología , Austria/epidemiología , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Mutación , Síndrome de Rett/diagnóstico , Síndrome de Rett/genética , Adulto Joven

RESUMEN

Recent animal studies suggest links between MeCP2 function and sensitivity to pain. This study investigated the nature and prevalence of atypical pain responses in Rett syndrome and their relationships with specific MECP2 mutations. Families enrolled in the Australian Rett Syndrome Database (ARSD) and InterRett database participated in this study. Cases with a known MECP2 pathogenic mutation, whose families had completed a questionnaire on registration and had answered questions on pain sensitivity were included (n = 646). Logistic regression was used to analyze relationships between the atypical pain responses and genotype. Descriptions of decreased pain sensitivity were content analyzed. The prevalence estimate of reporting an abnormal pain response was 75.2% and a decreased sensitivity to pain was 65.0% in the population-based ARSD. Families of ARSD and InterRett subjects with a C-terminal (OR 2.6; 95% CI 0.8-8.0), p.R168X (OR 2.1; 95% CI 0.7-6.1), or p.R306C (OR 2.7; 95% CI 0.8-9.6) mutation were more likely to report decreased sensitivity to pain. Parents and carers described decreased and delayed responses in situations judged likely to cause pain such as injections, falls, trauma, and burns. This study has provided the first precise estimate of the prevalence of abnormal sensitivity to pain in Rett syndrome but specific relationships with genotype are not yet clear. Clinical practice should include a low threshold for the clinical assessment of potential injuries in Rett syndrome.

Asunto(s)

Proteína 2 de Unión a Metil-CpG/genética , Dolor/complicaciones , Dolor/genética , Síndrome de Rett/complicaciones , Síndrome de Rett/genética , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , Humanos , Análisis Multivariante , Mutación/genética

RESUMEN

AIM: We investigated relationships between hand function and genotype and aspects of phenotype in Rett syndrome. METHOD: Video assessment in naturalistic settings was supplemented by parent-reported data in a cross-sectional study of 144 females with a mean age of 14 years 10 months (SD 7 y 10 mo; range 2 y-31 y 10 mo), 110 of whom had a mutation of the methyl CpG binding protein 2 (MECP2) gene. Ordinal logistic regression was used to assess relationships between hand function and MECP2 mutation, age, a modified Kerr score, Functional Independence Measure for Children (WeeFIM), ambulation level, and frequency of hand stereotypies. RESULTS: Approximately two-thirds of participants demonstrated purposeful hand function, ranging from simple grasping skills to picking up and manipulating small objects. In participants with a confirmed MECP2 mutation, those with the p.R168X mutation had the poorest hand function on multivariate analysis with C-terminal deletion as the baseline (odds ratio [OR] 0.19; 95% confidence interval [CI] 0.04-0.95), whereas those with the p.R133C or p.R294X mutation had better hand function. Participants aged 19 years or older had lower hand function than those aged less than 8 years (OR 0.36; 95% CI 0.14-0.92). Factors that were associated with better hand function were lower Kerr scores for a 1-point increase in score (OR 0.77; 95% CI 0.69-0.86), higher WeeFIM scores for a 1-point increase in score (OR 1.08; 95% CI 1.04-1.12), and greater ambulation than those completely dependent on carers for mobility (OR 22.64; 95% CI 7.02-73.08). The results for participants with a confirmed pathogenic mutation were similar to results obtained when participants without a mutation were also included. INTERPRETATION: Our novel assessment of hand function in Rett syndrome correlated well with known profiles of common MECP2 mutations and overall clinical severity. This promising assessment could measure clinical responses to therapy.

Asunto(s)

Mano , Actividad Motora , Síndrome de Rett/diagnóstico , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Estudios Transversales , Bases de Datos como Asunto , Femenino , Genotipo , Mano/fisiología , Humanos , Proteína 2 de Unión a Metil-CpG/genética , Actividad Motora/fisiología , Mutación , Fenotipo , Sistema de Registros , Síndrome de Rett/genética , Síndrome de Rett/fisiopatología , Índice de Severidad de la Enfermedad , Grabación en Video , Caminata , Adulto Joven

RESUMEN

Stereotypic hand movements are a feature of Rett Syndrome but few studies have observed their nature systematically. Video data in familiar settings were obtained on subjects (n = 144) identified from an Australian population-based database. Hand stereotypies were demonstrated by most subjects (94.4%), 15 categories were observed and midline wringing was seen in approximately 60% of subjects. There was a median of two stereotypies per subject but this number decreased with age. Clapping and mouthing of hands were more prevalent in girls younger than 8 years and wringing was more prevalent in women 19 years or older. Clapping was commoner in those with p.R306C and early truncating mutations, and much rarer in those with p.R106W, p.R270X, p.R168X, and p.R255X. Stereotypies tended to be less frequent in those with more severe mutations. Otherwise, there were no clear relationships between our categories of stereotypies and mutation. Approximately a quarter each had predominantly right and left handed stereotypies and for the remaining half, no clear laterality was seen. Results were similar for all cases and when restricted to those with a pathogenic mutation. Hand stereotypies changed with increasing age but limited relationships with MECP2 mutations were identified.

Asunto(s)

Mano/fisiopatología , Síndrome de Rett/complicaciones , Trastorno de Movimiento Estereotipado/etiología , Trastorno de Movimiento Estereotipado/patología , Adolescente , Adulto , Factores de Edad , Australia/epidemiología , Niño , Preescolar , Planificación en Salud Comunitaria , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Proteína 2 de Unión a Metil-CpG/genética , Mutación/genética , Síndrome de Rett/genética , Trastorno de Movimiento Estereotipado/genética , Adulto Joven

RESUMEN

STUDY DESIGN: Modified Delphi technique. OBJECTIVE: To develop guidelines for the clinical management of scoliosis in Rett syndrome through evidence review and consensus expert panel opinion. SUMMARY OF BACKGROUND DATA: Rett syndrome is a rare disorder and clinical expertise is thus with small case series. Scoliosis is a frequent association and the evidence base dealing with scoliosis management in this syndrome is limited. Parents of affected girls and women have expressed needs for more information about scoliosis and Rett syndrome. METHODS: An initial draft of scoliosis guidelines was created based on literature review and open-ended questions where the literature was lacking. Perspectives of four parents of Rett syndrome patients informed this initial draft. Access to an online and a Microsoft Word formatted version of the draft were then sent to an international, multidisciplinary panel of clinicians via e-mail with input sought using a 2-stage modified Delphi process to reach consensus agreement. Items included clinical monitoring and intervention before the diagnosis of scoliosis; monitoring after the diagnosis of scoliosis; imaging; therapy and conservative management; bracing; and preoperative, surgical, and postoperative considerations. RESULTS: The first draft contained 71 statements, 65 questions. The second draft comprised 88 items with agreement to strong agreement achieved on 85, to form the final guideline document. A comprehensive, life-span approach to the management of scoliosis in Rett syndrome is recommended that takes into account factors such as physical activity, posture, nutritional and bone health needs. Surgery should be considered when the Cobb angle is approximately 40 degrees to 50 degrees and must be supported by specialist management of anesthesia, pain control, seizures, and early mobilization. CONCLUSION: Evidence- and consensus-based guidelines were successfully created and have the potential to improve care of a complex comorbidity in a rare condition and stimulate research to improve the current limited evidence base.

Asunto(s)

Síndrome de Rett/complicaciones , Escoliosis/terapia , Niño , Medicina Basada en la Evidencia , Femenino , Humanos , Cooperación Internacional , Escoliosis/etiología , Escoliosis/fisiopatología