Twenty years of surveillance in Rett syndrome: what does this tell us?

Anderson, Alison; Wong, Kingsley; Jacoby, Peter; Downs, Jenny; Leonard, Helen

doi:10.1186/1750-1172-9-87

Cited by 101 publications

(96 citation statements)

References 27 publications

(49 reference statements)

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“…219 Recent population data using longitudinal follow-up over more than two decades suggest that approximately 60% will survive to their late thirties. 137 This is considerably lower than the estimates of 50% at 50 years using the North American Database (data derived from 50% response to questionnaires administered to IRSA family members) 220 and 75% at 45 years using nine years follow-up of the US Natural History sample. 221 Both samples are large but select groups likely to be better resourced than the general US population.…”

Section: Role Of Advocacy Groupsmentioning

confidence: 77%

“…Similarly the Rett Syndrome Behaviour Questionnaire 200 was developed for the purpose of differentiating individuals with RTT from those with other causes of intellectual disability before genetic testing became available. It has been used successfully in genotype phenotype studies to assess some aspects of behavior such as mood and anxiety 137,201 but again may not appropriately measure behavior as an outcome in a clinical trial. There is a clear need for the further development of such instruments and work is currently underway in that regard.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

“…Following Dr Alison Kerr's use of the British Paediatric Surveillance Unit to launch the British Isles RTT Survey in 1990, 208 the Australian database (see Fig 1), established three years later, took advantage of the newly formed Australian Paediatric Surveillance Unit to ascertain cases. 206 Now maintained for over two decades, each additional year of follow-up increases its value, 137 providing capacity to follow children into adulthood and identify trajectories of functioning and comorbidities. 209 Population-based longitudinal follow-up with minimisation of attrition is essential for studies of life expectancy but is uncommon in the field of rare disorders.…”

Section: Infrastructuresmentioning

confidence: 99%

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Clinical and biological progress over 50 years in Rett syndrome

2016

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It is fifty years since Andreas Rett first described Rett syndrome, a disorder now known to be caused by a mutation in the MECP2 gene. A compelling blend of astute clinical observations, clinical and laboratory research has already built our understanding of Rett syndrome and its biological underpinnings. We document the contributions of the early pioneers and describe the evolution of knowledge in terms of diagnostic criteria, clinical variation and the interplay with other Rett-related disorders. We provide a synthesis of what is known about the neurobiology of MeCP2, the lessons from both cell and animal models and how they may inform future clinical trials. With a focus on the core criteria, we examine the relationships that have been demonstrated between genotype and clinical severity. We review what is known about the many comorbidities that occur in this disorder and how genotype may also modify their presentation. We acknowledge the important drivers that are accelerating this research program including the roles of research infrastructure, international collaboration and advocacy groups. Finally, we conclude by highlighting the major milestones since 1966 and what they mean for the day-to-day lives of those with Rett syndrome and their families. Key pointsThere has been an explosion of knowledge about Rett syndrome in relation to its genetic basis, clinical characteristics and their relationships during the fifty years since the disorder was first described by Andreas Rett.Whilst initially the diagnosis of Rett syndrome was based only on clinical criteria, identifying its genetic cause has had a major positive impact on how clinicians diagnose the disorder but also provides new challenges as we enter the era of next generation sequencing.

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Section: Role Of Advocacy Groupsmentioning

confidence: 77%

Section: Therapeutic Strategiesmentioning

confidence: 99%

Section: Infrastructuresmentioning

confidence: 99%

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Clinical and biological progress over 50 years in Rett syndrome

2016

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“…Seizure onset varied widely from 1 to 16 years, and a high proportion suffered drug-resistant frequent seizures (36%). The large Australian study (423 subjects) combined data from the Australian database and an international cohort, and found a history of seizures in only 45% (Anderson et al, 2014). Again, drug-resistant epilepsy was present in 36% of those with a history of seizures who were taking antiseizure drugs.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal course of epilepsy in Rett syndrome and related disorders

Tarquinio

Hou

Berg

et al. 2016

Brain

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Epilepsy is common in Rett syndrome, an X-linked dominant disorder caused by mutations in the MECP2 gene, and in Rett-related disorders, such as MECP2 duplication. However, neither the longitudinal course of epilepsy nor the patterns of seizure onset and remission have been described in Rett syndrome and related conditions. The present study summarizes the findings of the Rett syndrome Natural History study. Participants with clinical Rett syndrome and those with MECP2 mutations without the clinical syndrome were recruited through the Rett Natural History study from 2006 to 2015. Clinical details were collected, and cumulative lifetime prevalence of epilepsy was determined using the Kaplan-Meier estimator. Risk factors for epilepsy were assessed using Cox proportional hazards models. Of 1205 participants enrolled in the study, 922 had classic Rett syndrome, and 778 of these were followed longitudinally for 3939 person-years. The diagnosis of atypical Rett syndrome with a severe clinical phenotype was associated with higher prevalence of epilepsy than those with classic Rett syndrome. While point prevalence of active seizures ranged from 30% to 44%, the estimated cumulative lifetime prevalence of epilepsy using Kaplan-Meier approached 90%. Specific MECP2 mutations were not significantly associated with either seizure prevalence or seizure severity. In contrast, many clinical features were associated with seizure prevalence; frequency of hospitalizations, inability to walk, bradykinesia, scoliosis, gastrostomy feeding, age of seizure onset, and late age of diagnosis were independently associated with higher odds of an individual having epilepsy. Aggressive behaviour was associated with lower odds. Three distinct patterns of seizure prevalence emerged in classic Rett syndrome, including those who did not have seizures throughout the study, those who had frequent relapse and remission, and those who had relentless seizures. Although 248 of those with classic Rett syndrome and a history of seizures were in terminal remission at last contact, only 74 (12% of those with a history of epilepsy) were seizure free and off anti-seizure medication. When studied longitudinally, point prevalence of active seizures is relatively low in Rett syndrome, although lifetime risk of epilepsy is higher than previously reported. While daily seizures are uncommon in Rett syndrome, prolonged remission is less common than in other causes of childhood onset epilepsy. Complete remission off anti-seizure medications is possible, but future efforts should be directed at determining what factors predict when withdrawal of medications in those who are seizure free is propitious.

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“…For most mutations, clinical severity increases with age [7]. Whilst mortality is increased, many live into adulthood and some into older age [8,9].…”

Section: Introductionmentioning

confidence: 99%