Trends in the Diagnosis of Rett Syndrome in Australia

Fehr, Stephanie; Bebbington, Ami; Nassar, Natasha; Downs, Jenny; Ronen, Gabriel M.; Klerk, Nicholas de; Leonard, Helen

doi:10.1203/pdr.0b013e3182242461

Cited by 130 publications

(103 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several studies showed a mild-to-moderate increase in RTT incidence over previous decades [14,23], which was also observed in our study. Such tendency could be explained by advances in clinical and molecular diagnosis of RTT.…”

Section: Discussionsupporting

confidence: 90%

Epidemiology of Rett Syndrome in Serbia: Prevalence, Incidence and Survival

Sarajlija

Kisić-Tepavčević²,

Nikolic³

et al. 2015

Neuroepidemiology

View full text Add to dashboard Cite

Background: Rett syndrome (RTT) is a severe neurodevelopmental disorder that represents the second most common cause of mental retardation in females. However, incidence and prevalence of RTT are scarcely reported. Methods: A retrospective study included all patients with RTT diagnosed between 1981 and 2012 in Serbia. Estimation of incidence and prevalence was calculated on the basis of vital statistics reported by Statistical Office of Republic of Serbia. Results: From 1981 to 2012, RTT hasbeen diagnosed in 102 girls in Serbia. Incidence of RTT in Serbia is estimated at 0.586:10,000 female live births. We estimated the prevalence of RTT in population of females younger than 19 years at 1:8,439. Death occurred in 19 patients (18.63%), with pneumonia as the most common cause. The lethal outcome by the age of 12 years could be expected for 11% of patients. The mean age at diagnosis was 3.5 years and we have confirmed a significant trend towards earlier dianosis during studied period. Conclusions: Rett syndrome incidence in Serbia is in accordance with reports from other countries. Serbian RTT patients have increased risk for early death when compared to patients in more developed countries, most commonly due to pneumonia. There was significant trend towards early diagnosis of RTT in Serbia over recent decades.

show abstract

Section: Discussionsupporting

confidence: 90%

Epidemiology of Rett Syndrome in Serbia: Prevalence, Incidence and Survival

Sarajlija

Kisić-Tepavčević²,

Nikolic³

et al. 2015

Neuroepidemiology

View full text Add to dashboard Cite

show abstract

“…206 Further studies in 2011 demonstrated that the cumulative incidence was increasing with age and that the median age at diagnosis had fallen from 4.5 before to 3.5 years after 1999. 207 …”

Section: Global Efforts To Study a Rare Disorder Epidemiologymentioning

confidence: 99%

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

“…Combining data collected as part of InterRett, 11 an international Rett syndrome phenotype database, with data from the Australian Rett Syndrome Database (ARSD), 12 a population-based cohort, the phenotype associated with a large deletion is described in detail and compared with the phenotype of cases with other common mutations.…”

Section: Introductionmentioning

confidence: 99%

The phenotype associated with a large deletion on MECP2

et al. 2012

Self Cite

View full text Add to dashboard Cite

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, P¼0.007) and to be currently walking (OR 0.53, 95% CI: 0.26-1.10, P¼0.089), 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, P¼0.057) and epilepsy (OR 2.72, 95% CI: 1.38-5.37, P¼0.004). 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.

show abstract

Trends in the Diagnosis of Rett Syndrome in Australia

Cited by 130 publications

References 36 publications

Epidemiology of Rett Syndrome in Serbia: Prevalence, Incidence and Survival

Epidemiology of Rett Syndrome in Serbia: Prevalence, Incidence and Survival

Clinical and biological progress over 50 years in Rett syndrome

The phenotype associated with a large deletion on MECP2

Contact Info

Product

Resources

About