Abstract:Objective
We conducted a nationwide survey to determine the prevalence of common gastrointestinal and nutritional disorders in Rett syndrome (RTT) based on parental reporting and related the occurrence of these problems to age and methyl-CpG-binding protein 2 (MECP2) status.
Methods
We designed a questionnaire that probed symptoms, diagnoses, diagnostic tests, and treatment interventions related to gastrointestinal and nutritional problems in RTT. The International Rett Syndrome Foundation distributed the qu… Show more
“…Hand function and language skills regress in early childhood, in conjunction with the development of hand stereotypies and impaired mobility [Neul et al, 2010]. These functional deficits are further complicated by the development of comorbid conditions such as epilepsy [Bao et al, 2013], gastrointestinal disorders [Motil et al, 2012], and scoliosis [Downs et al, in press]. Some children can walk, negotiate stairs, self-feed or use eye gaze technology whereas others are unable to walk, require enteral feeding or engage in selfinjurious behaviors.…”
Rett syndrome is a neurodevelopmental disorder mainly affecting females and associated with a mutation on the MECP2 gene. There has been no systematic evaluation of the domains of quality of life (QOL) in Rett syndrome. The aims of this study were to explore QOL in school-aged children with Rett syndrome and compare domains with those identified in other available QOL scales. The sample comprised 21 families registered with the Australian Rett Syndrome Database whose daughter with Rett syndrome was aged 6-18 years. Semi-structured telephone interviews were conducted with each parent caregiver (19 mothers, 2 fathers) to investigate aspects of their daughter's life that were satisfying or challenging to her. Qualitative thematic analysis using a grounded theory framework was conducted, and emerging domains compared with those in two generic and three disability parent-report child QOL measures. Ten domains were identified: physical health, body pain, and discomfort, behavioral and emotional well-being, communication skills, movement and mobility, social connectedness, variety of activities, provision of targeted services, stability of daily routines, and the natural environment. The two latter domains were newly identified and each domain contained elements not represented in the comparison measures. Our data articulated important aspects of life beyond the genetic diagnosis. Existing QOL scales for children in the general population or with other disabilities did not capture the QOL of children with Rett syndrome. Our findings support the construction of a new parent-report measure to enable measurement of QOL in this group.
“…Hand function and language skills regress in early childhood, in conjunction with the development of hand stereotypies and impaired mobility [Neul et al, 2010]. These functional deficits are further complicated by the development of comorbid conditions such as epilepsy [Bao et al, 2013], gastrointestinal disorders [Motil et al, 2012], and scoliosis [Downs et al, in press]. Some children can walk, negotiate stairs, self-feed or use eye gaze technology whereas others are unable to walk, require enteral feeding or engage in selfinjurious behaviors.…”
Rett syndrome is a neurodevelopmental disorder mainly affecting females and associated with a mutation on the MECP2 gene. There has been no systematic evaluation of the domains of quality of life (QOL) in Rett syndrome. The aims of this study were to explore QOL in school-aged children with Rett syndrome and compare domains with those identified in other available QOL scales. The sample comprised 21 families registered with the Australian Rett Syndrome Database whose daughter with Rett syndrome was aged 6-18 years. Semi-structured telephone interviews were conducted with each parent caregiver (19 mothers, 2 fathers) to investigate aspects of their daughter's life that were satisfying or challenging to her. Qualitative thematic analysis using a grounded theory framework was conducted, and emerging domains compared with those in two generic and three disability parent-report child QOL measures. Ten domains were identified: physical health, body pain, and discomfort, behavioral and emotional well-being, communication skills, movement and mobility, social connectedness, variety of activities, provision of targeted services, stability of daily routines, and the natural environment. The two latter domains were newly identified and each domain contained elements not represented in the comparison measures. Our data articulated important aspects of life beyond the genetic diagnosis. Existing QOL scales for children in the general population or with other disabilities did not capture the QOL of children with Rett syndrome. Our findings support the construction of a new parent-report measure to enable measurement of QOL in this group.
“…This may be coupled with the appearance of dystonic positions, particularly at the ankles and wrists. Multiple neurologic or systemic issues often arise: 1) epilepsy beginning typically by the third year of life [30][31][32]; 2) periodic breathing consisting of breath-holding or hyperventilation or both [33][34][35]; 3) prominent gastrointestinal (GI) issues from top to bottom, including poor chewing and swallowing, gastroesophageal reflux, delayed stomach emptying, and constipation [36][37][38][39]; 4) decline in growth parameters in most, including height, weight, hands, and feet [28,40]; 5) scoliosis in most with up to 13% requiring surgical correction of the deformity [41]; 6) intolerance of warm temperatures; and 7) cool hands and feet. Ambulation is achieved initially in as many as 80% but is typically broad-based and nonpurposeful.…”
Rett syndrome (RTT) is a syndromic autism spectrum disorder caused by loss-of-function mutations in MECP2. The methyl CpG binding protein 2 binds methylcytosine and 5-hydroxymethycytosine at CpG sites in promoter regions of target genes, controlling their transcription by recruiting co-repressors and co-activators. Several preclinical studies in mouse models have identified rational molecular targets for drug therapies aimed at correcting the underlying neural dysfunction. These targeted therapies are increasingly translating into human clinical trials. In this review, we present an overview of RTT and describe the current state of preclinical studies in methyl CpG binding protein 2-based mouse models, as well as current clinical trials in individuals with RTT.
“…Scoliosis and osteoporosis are prominent (Chahrour and Zoghbi, 2007;Hagberg, 2002;Motil et al, 2014). In addition, gastrointestinal problems are common, including chewing difficulties, gastroesophageal reflux, constipation, and occasional biliary tract disorders (Hagberg, 2002;Motil et al, 2012). These gastrointestinal complications may significantly contribute to the general growth deficit and nutritional deficiencies observed in Rett syndrome patients (Motil et al, 2012).…”
Section: Clinical Features and Natural History Of Rett Syndromementioning
confidence: 99%
“…In addition, gastrointestinal problems are common, including chewing difficulties, gastroesophageal reflux, constipation, and occasional biliary tract disorders (Hagberg, 2002;Motil et al, 2012). These gastrointestinal complications may significantly contribute to the general growth deficit and nutritional deficiencies observed in Rett syndrome patients (Motil et al, 2012). Autonomic function is also disrupted, including peripheral vascular/vasomotor dysfunction and cardiac abnormalities, with prolonged QT interval and abnormal heart rate representing prominent manifestations of this aspect of disease (Chahrour and Zoghbi, 2007;Ellaway et al, 1999;Glaze, 2005;Hagberg, 2002;Neul et al, 2010;Sekul et al, 1994).…”
Section: Clinical Features and Natural History Of Rett Syndromementioning
confidence: 99%
“…However, patients with Rett syndrome may suffer from more subtle issues, such as chronic inflammatory disease. Indeed, Rett syndrome patients experience frequent bowel complications (Motil et al, 2012), which in theory could be related to a chronic inflammatory process. Additionally, Rett syndrome patients experience significant bone pathology, including scoliosis and osteopenia (Chahrour and Zoghbi, 2007;Motil et al, 2014).…”
Section: Mecp2 and The Immune System In Human Diseasementioning
Methyl-CpG binding protein 2 (MeCP2) was one of the first methyl-CpG binding proteins identified. Since its discovery, MeCP2 has been shown to be an essential regulator of gene transcription via its role in orchestrating transcriptional complexes associated with methylated CpG islands in the genome. In 1999, mutations in MeCP2 were identified as the primary cause of Rett syndrome. Several years later, another MeCP2-related neurodevelopmental disorder was identified, called MeCP2 duplication syndrome. Due to the clear association of both disorders with neurologic pathology, and the high levels of MeCP2 expressed by neurons, it was largely assumed that the complete etiology of disease in both disorders was explained by defects in neuronal function.
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