Altered Attainment of Developmental Milestones Influences the Age of Diagnosis of Rett Syndrome

Fehr, Stephanie; Bebbington, Ami; Ellaway, Carolyn; Rowe, Peter W; Leonard, Helen; Downs, Jenny

doi:10.1177/0883073811401396

Cited by 39 publications

(50 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 & 3A, B, C & D). 128 The large deletion group, not included in the initial InterRett study, was subsequently described separately confirming earlier US findings 127 of phenotypic severity (see Figs 2 & 3E). 129 In a later publication, also studied separately were the C terminal deletions, a milder group which, due to their comparatively later loss of skills and onset of stereotypies, 120 fit with the initial "late regression" descriptor (see Figs.…”

Section: Overall Severity and Relationship With Genotypesupporting

confidence: 74%

Clinical and biological progress over 50 years in Rett syndrome

2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Overall Severity and Relationship With Genotypesupporting

confidence: 74%

Clinical and biological progress over 50 years in Rett syndrome

2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Early development was more severely impaired in those with the CDKL5 disorder, with approximately half learning to sit and 10% learning to walk in comparison with B80% learning to sit and just under half learning to walk in a recent study of 293 females with RTT. 48 Those with the CDKL5 disorder were less likely to use words whereas use of some words was acquired by nearly 90% of females with RTT before regression. 48 Females with the CDKL5 disorder were also less likely to develop hand stereotypies, breathing disturbances, gastrointestinal problems and a spinal curvature, but were much more likely to develop seizures and have sleep disturbances.…”

Section: Discussionmentioning

confidence: 95%

“…48 Those with the CDKL5 disorder were less likely to use words whereas use of some words was acquired by nearly 90% of females with RTT before regression. 48 Females with the CDKL5 disorder were also less likely to develop hand stereotypies, breathing disturbances, gastrointestinal problems and a spinal curvature, but were much more likely to develop seizures and have sleep disturbances. These findings again suggest that the CDKL5 disorder is clinically separate to RTT, indicating the need to develop independent clinical criteria for the identification of the CDKL5 disorder.…”

Section: Discussionmentioning

confidence: 95%

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

et al. 2012

Self Cite

View full text Add to dashboard Cite

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n ¼ 86) and females with MECP2 mutations (n ¼ 920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

show abstract

“…Hand stereotypies such as wringing, mouthing and clapping develop in almost all girls and women, with the number of different types of movements and their frequency decreasing as the girls grow older [24]. Population data from Australia has found that nearly half the girls and women had never learned to walk [25]. Rett syndrome is also associated with other co-morbidities, such as breathing disturbances, scoliosis, epilepsy and poor growth [26].…”

Section: Introductionmentioning

confidence: 99%

Caring for a child with severe intellectual disability in China: The example of Rett syndrome

Lim

Downs

et al. 2012

Disability and Rehabilitation

Self Cite

View full text Add to dashboard Cite

Implications for rehabilitation Little is known about the lives of girls with Rett syndrome in China, a genetic condition associated with severe disability.  Most girls experienced home-based care with limited access to appropriate equipment, education and rehabilitation.  Limited information and discrimination and stigma from some community members reduced families' abilities to meet their child's needs.  Greater access to health, education and information services in China should be supported.

show abstract

Altered Attainment of Developmental Milestones Influences the Age of Diagnosis of Rett Syndrome

Cited by 39 publications

References 22 publications

Clinical and biological progress over 50 years in Rett syndrome

Clinical and biological progress over 50 years in Rett syndrome

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

Caring for a child with severe intellectual disability in China: The example of Rett syndrome

Contact Info

Product

Resources

About