Materiały źródłowe

• #1 Consensus guidelines on managing Rett syndrome across the lifespan | BMJ Paediatrics Open

  https://bmjpaedsopen.bmj.com/content/4/1/e000717

  Rett syndrome (RTT) is a severe neurodevelopmental disorder with an estimated worldwide prevalence of 1 in 20000-40000 people. […] The average age at RTT diagnosis of 2.5 years has been trending downward with increasing availability of diagnostic genetic testing. […] The multisystem nature of the disorder has been documented within multiple observational studies, with symptom risk evolving across the lifespan. […] The guidance for management by health professionals was grouped by relevant features and therapeutic approaches at different ages. […] Longitudinal supervision is required in RTT as physical, behavioural and cognitive limitations will not allow for independent living. […] The accumulating knowledge regarding the natural history of RTT serves as a vital resource to help providers anticipate the complexities of this disorder.

• #1 Global prevalence of Rett syndrome: systematic review and meta-analysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9841621/

  Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex. […] The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p 0.001). […] These findings may facilitate planning of therapeutic trials in this indication in terms of target sample size and accrual times. […] The aim of this systematic review and meta-analysis is to review the current literature pertaining to RTT and to estimate the prevalence of RTT in the general population, stratified by sex. […] The pooled prevalence estimate based on all eligible studies (random-effects model) was 7.1 cases per 100,000 females (95% CI: 4.8, 10.5). […] In summary, this is the first meta-analysis that estimates the prevalence of RTT. The results suggest that the prevalence remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability.

• #1 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10071755/

  Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. However, literature characterizing the real-world journey of patients with RTT is limited. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. […] In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. […] The annual prevalence of RTT between November 1, 2016 and October 31, 2019 in this dataset ranged from 0.30-0.32 per 10,000 enrollees overall, with higher prevalence ranges observed among female than male patients (female: 0.45-0.52; male: 0.08-0.10). […] Overall, the annual incidence of RTT in this dataset was an estimated 0.34 and 0.23 per 10,000 enrollees in 2018 and 2019, respectively (Table 2). Among female patients, the annual incidence was 0.43 and 0.31 per 10,000 female enrollees in 2018 and 2019, respectively, while among male patients, it was 0.22 and 0.13 per 10,000 male enrollees, respectively.

• #1 Rett Syndrome: Practice Essentials, Background, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/916377-overview

  The incidence of Rett syndrome (RS) has been reported to be approximately 1 per 23,000 live female births. […] Wide variations in incidence have been reported in various countries; rates as high as 1 per 10,000 live female births have been reported. […] One study in Japan found an incidence of 1 per 45,000 girls aged 6-14 years. […] Variations in incidence may be partly accounted for by the inclusion of atypical or variant forms of RS. These atypical forms include congenital RS, milder forms with later onset of regression, and preserved speech variants. […] RS generally becomes clinically evident by age 2-4 years; however, the underlying neurodevelopmental arrest probably starts in children aged 6-18 months or younger. […] Most patients identified are female because the disease is X-linked. […] Many males with RS are believed to die in utero. […] However, a few reports have detailed males with mutations in MECP2 and RS-like symptoms. […] Excess male fetal loss has not been demonstrated in families with a history of RS; thus, an alternative explanation for female predominance may be noted. […] No racial variations have been reported. In a study by Kozinetz et al, which included Latin Americans, Caucasians, and African Americans in Texas, no variations in the incidence or prevalence of RS were found.

• #1 Orphanet: Rett syndrome

  https://www.orpha.net/en/disease/detail/778

  The disorder affects approximately 1 in 10,000 live female births. The disease has been occasionally reported in males, usually with a lethal course before birth or in early infancy. […] Prevalence: 1-9 / 100 000.

• #1 Commentary: Are Developmental Skills Acquired Normally in Rett Syndrome?

  https://www.jneurology.com/articles/commentary-are-developmental-skills-acquired-normally-in-rett-syndrome.html

  In 2014, Neul et al. described the occurrence of developmental skills in more than 600 individuals with RTT, the largest reported to-date examined directly by teams consisting of a neurologist or geneticist and an experienced clinical coordinator. This allowed for a precise ascertainment of the timing of acquisition of specific developmental skills in this population. […] As we enter a period of increased clinical trial activity in this population, it is important to achieve accurate diagnosis as early as possible. Currently, data from the RTT NHS indicates that the average age of diagnosis is 2.7 years, down from about 4 years in the initial years of the study. Still, to effect a treatment as early as possible, age at diagnosis must be reduced even further. […] Coupling these factors with a closer examination of the abnormal pattern of acquisition of developmental skills adds further evidence for the possible establishment of a definitive diagnosis.

• #1 Trends in the Diagnosis of Rett Syndrome in Australia | Pediatric Research

  https://www.nature.com/articles/pr2011179

  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 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, 10.0312.45)] in comparison with 5 y of age [1/15,361 or 6.51 per 100,000 person-years (95% CI, 5.657.39)]. […] Changes in clinical practice resulting both from modifications to diagnostic criteria and the introduction of genetic testing have likely affected the pattern and timing of RTT diagnosis.

• #1 Twenty years of surveillance in Rett syndrome: what does this tell us? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-9-87

  The neurological disorder Rett syndrome (OMIM 312750) was first described in the English literature in 1983 and later found to be associated with mutations in the methyl CpG binding protein 2 gene (MECP2). Females are mostly affected with an incidence of diagnosis of 1:9000 by the age of 32 years. […] Using a population-based cohort we have shown that current survival to the age of 20 years is 77.6% with 59.8% surviving to early middle age. In women aged 18 years and older we found that epilepsy, breathing and sleep problems persisted, low weight and gastrointestinal issues were prevalent and although most have scoliosis loss of walking is not inevitable. […] Importantly, we can now report survival in the ARSD cohort of slightly less than 60% at 38 years of age although the current estimate of survival to 25 years (71.5%) is lower compared to our 2006 analysis. Death was most commonly caused by respiratory illnesses. […] The data contained in this paper represents twenty years of surveillance and highlights the consistent research effort required to understand rare disorders. Individuals with Rett syndrome have potential for prolonged survival with approximately 60% surviving to early middle age.

• #1 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10071755/

  The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. […] In light of the gaps in the literature regarding RTT, this study aimed to provide an overview of the epidemiology, patient characteristics, clinical manifestations, HRU, costs, and treatment patterns of patients with RTT in the US. […] The large clinical and economic burden of RTT observed in this study throughout patients’ lifespans suggests a substantial unmet need for treatment options that may modify the disease course and progression of RTT rather than managing its symptoms.

• #1 1st analysis of Rett syndrome prevalence may help in trial planning | New estimate set of 7.1 cases per 100,000 females worldwide | Rett Syndrome NewsEnvelope icon

  https://rettsyndromenews.com/news/1st-analysis-rett-syndrome-prevalence-may-help-trial-planning/

  Study sets new estimate of 7.1 cases per 100,000 females worldwide. The global prevalence of Rett syndrome is estimated to be 7.1 cases per 100,000 female individuals, according to the first known meta-analysis ever done to estimate the number of girls and women worldwide with the rare neurodevelopmental disorder. This finding “may facilitate planning of therapeutic trials in this disease, especially for target sample size and accrual times,” the researchers wrote, noting that “one of the rate-limiting factors in the development of new pharmacologic therapies for RTT [Rett syndrome] is the low prevalence of the disease.” […] The pooled prevalence estimate was 7.1 cases of Rett syndrome for each 100,000 female individuals, which is in line with previous estimates. […] Overall, the findings “suggest that the prevalence [of Rett] remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability,” the researchers concluded.

• #1 Phenotypes in adult patients with Rett syndrome: results of a 13-year experience and insights into healthcare transition | Journal of Medical Genetics

  https://jmg.bmj.com/content/59/1/39

  The major limitation of our previous study was that data were obtained from the patients’ parents in most cases, introducing a bias in the interpretation of some clinical details. Nevertheless, that study taught us that the complex phenotype of individuals with RTT requires more careful and extensive medical care, although guidelines for clinical management of adolescents and adults with RTT are not available. The majority of adults with RTT are treated in paediatric centres because specialised adult clinics are rare. […] In conclusion, we have discussed the main clinical issues that should be considered when transitioning patients with RTT to adult care, based on data from our study and from the literature. We underline the importance of establishing a multidisciplinary team and educating the adult team members about RTT. Larger international studies assessing the medical problems of adult women with RTT and experiences from other adult clinics are highly encouraged.

• #2 Multidisciplinary Management of Rett Syndrome: Twenty Years’ Experience

  https://www.mdpi.com/2073-4425/14/8/1607

  Over the last 20 years, the understanding and natural history of Rett syndrome has advanced, but to date no cure has emerged, with multidisciplinary management being symptomatic and supportive. […] Rett Syndrome (RTT; OMIM entry #312750) is one of the most common genetic causes of developmental and intellectual disability in females, affecting up to 1:10,000 females under the age of 12 years. […] The average age at RTT diagnosis has trended downwards with the improvement and increasing availability of diagnostic genetic testing. […] The median age of diagnosis was three years of age and reflects the increasing knowledge and awareness of RTT, as well as greater access to diagnostic genetic testing. […] This study analysed a cohort of females with classical RTT who attended the RTT multidisciplinary management clinic at the Children’s Hospital at Westmead, Sydney, Australia, over a 20 year period and aims to provide a comprehensive review of their clinical features, comorbidities and multidisciplinary management.

• #2 Global prevalence of Rett syndrome: systematic review and meta-analysis | springermedizin.de

  https://www.springermedizin.de/global-prevalence-of-rett-syndrome-systematic-review-and-meta-an/23925946

  Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex. […] The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p 0.001). […] Despite greatly variable precision of estimation, all estimates were compatible with a prevalence range of approximately 5 to 10 cases per 100,000 females based on their respective 95% CIs. […] The aim of this systematic review and meta-analysis is to review the current literature pertaining to RTT and to estimate the prevalence of RTT in the general population, stratified by sex. These results may facilitate planning of future clinical trials for this indication in terms of target sample size and accrual times.

• #2 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-023-03181-y

  Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. […] This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. […] In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. […] The annual prevalence of RTT between November 1, 2016 and October 31, 2019 in this dataset ranged from 0.30-0.32 per 10,000 enrollees overall, with higher prevalence ranges observed among female than male patients (female: 0.45-0.52; male: 0.08-0.10). […] Overall, the annual incidence of RTT in this dataset was an estimated 0.34 and 0.23 per 10,000 enrollees in 2018 and 2019, respectively.

• #2 Trends in the Diagnosis of Rett Syndrome in Australia | Pediatric Research

  https://www.nature.com/articles/pr2011179

  The birth prevalence varied by birth year, peaking for those born in the early to mid-1990s. […] The point prevalence of RTT in Australia on June 30, 2009, was 8.6 per 100,000 females (95% CI, 7.410.1) aged 518 y and 5.8 per 100,000 females (95% CI, 4.86.9) aged 1932 y. […] The cumulative risk (likelihood of a female child being diagnosed with RTT by a certain age) was estimated using survival analysis. […] The change in cumulative risk before and after 1999 shows a clear increase in the risk of RTT diagnosis and a parallel decrease in age of diagnosis.

• #2

  https://www.orthobullets.com/pediatrics/4107/rett-syndrome

  Rett Syndrome is a congenital condition caused by an X-linked dominant mutation in the MECP2 gene that affects girls between 6-18 months of age. […] Epidemiology […] Incidence […] 1 in 10,000 births. […] Demographics […] male fetuses (only 1 X chromosome) do not survive to term. […] female fetuses (1 mutated gene, 1 normal gene) survive and manifest disease.

• #2 Rett Syndrome in Ireland: A demographic study | medRxiv

  https://www.medrxiv.org/content/10.1101/2023.02.13.23285763v1.full-text

  This missing information would be crucial for the proper diagnosis and characterization of the Irish RTT population and for advancing RTT research. […] This study analyses data from the Irish RTT population on the basis of information provided by the caregivers of patients with RTT. […] The average age of RTT diagnosis in Ireland is 5.21 years, which is higher than in Poland, the UK, the US, and Denmark, but lower than in Australia and the Netherlands. […] Despite limited access to RTT diagnosis in Ireland, the average age of diagnosis seems to be comparable to that of other populations. […] The results show a milder phenotype of scoliosis in patients who can walk unassisted and a trend of scoliosis not progressing in the p.Arg306Cys mutant patient. […] We plan to increase the number of participants in the study in order to better characterise the RTT population in Ireland. […] The literature suggests that Irish individuals with RTT are currently not included in international studies or clinical trials. […] The inclusion of Irish patients in such databases would be beneficial for RTT patients, scientists, healthcare professionals and the Irish community.

• #2 Global prevalence of Rett syndrome: systematic review and meta-analysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9841621/

  Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex. […] The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p 0.001). […] These findings may facilitate planning of therapeutic trials in this indication in terms of target sample size and accrual times. […] The aim of this systematic review and meta-analysis is to review the current literature pertaining to RTT and to estimate the prevalence of RTT in the general population, stratified by sex. […] The pooled prevalence estimate based on all eligible studies (random-effects model) was 7.1 cases per 100,000 females (95% CI: 4.8, 10.5). […] In summary, this is the first meta-analysis that estimates the prevalence of RTT. The results suggest that the prevalence remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability.

• #2 Twenty years of surveillance in Rett syndrome: what does this tell us? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-9-87

  The neurological disorder Rett syndrome (OMIM 312750) was first described in the English literature in 1983 and later found to be associated with mutations in the methyl CpG binding protein 2 gene (MECP2). Females are mostly affected with an incidence of diagnosis of 1:9000 by the age of 32 years. […] Using a population-based cohort we have shown that current survival to the age of 20 years is 77.6% with 59.8% surviving to early middle age. In women aged 18 years and older we found that epilepsy, breathing and sleep problems persisted, low weight and gastrointestinal issues were prevalent and although most have scoliosis loss of walking is not inevitable. […] Importantly, we can now report survival in the ARSD cohort of slightly less than 60% at 38 years of age although the current estimate of survival to 25 years (71.5%) is lower compared to our 2006 analysis. Death was most commonly caused by respiratory illnesses. […] The data contained in this paper represents twenty years of surveillance and highlights the consistent research effort required to understand rare disorders. Individuals with Rett syndrome have potential for prolonged survival with approximately 60% surviving to early middle age.

• #2 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10071755/

  The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. […] In light of the gaps in the literature regarding RTT, this study aimed to provide an overview of the epidemiology, patient characteristics, clinical manifestations, HRU, costs, and treatment patterns of patients with RTT in the US. […] The large clinical and economic burden of RTT observed in this study throughout patients’ lifespans suggests a substantial unmet need for treatment options that may modify the disease course and progression of RTT rather than managing its symptoms.

• #2 Validating the Rett Syndrome Gross Motor Scale | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147555

  Rett syndrome is a neurodevelopmental disorder usually caused by a mutation on the X-linked methyl-CpG-binding protein 2 (MECP2) gene. The condition affects females approximately 1 per 9,000 live female births, and is characterized by a loss of functional hand use and language skills in early childhood with the development of hand stereotypies and impaired mobility. […] The Australian Rett Syndrome Database (ARSD) is a population-based register established in 1993 of confirmed individuals with Rett syndrome born 1976 and subsequently. […] The National Center for Rett syndrome in Denmark was established in 2007 and offers counselling and annual follow-up by a multidisciplinary team. Currently, there are 109 known confirmed individuals (age two to 61 years) with Rett syndrome in Denmark of whom 96 (88%) have a MECP2 mutation.

• #2 Addgene: Rett Syndrome

  https://www.addgene.org/collections/rett-syndrome/

  Rett syndrome is a neurodevelopmental disorder that presents in early toddlerhood primarily affecting females at an incidence of approximately 1:10,000. […] Diagnosis of Rett syndrome is currently based on specific clinical diagnostic criteria, defined as the presence of relatively normal early development, regression with a loss of spoken language and hand skills, development of repetitive hand stereotypies, and gait dysfunction or absence of gait. […] Greater than 95% of individuals who meet diagnostic criteria have disease-causing mutations in the gene methyl-CpG binding protein 2 (MECP2). […] While there is wide variability in symptoms even within patients with the same mutation, the location and type of MECP2 mutation can be a strong predictor of symptom severity. […] A large number of mutations are known to cause Rett syndrome, however, eight recurrent missense and nonsense mutations (R106W, R133C, T158M, R168X, R255X, R270X, R294X, and R306C) account for almost 46% of all Rett syndrome cases. […] Laurvick et al. 2006. Rett syndrome in Australia: a review of the epidemiology.

• #2 Phenotypes in adult patients with Rett syndrome: results of a 13-year experience and insights into healthcare transition | Journal of Medical Genetics

  https://jmg.bmj.com/content/59/1/39

  The major limitation of our previous study was that data were obtained from the patients’ parents in most cases, introducing a bias in the interpretation of some clinical details. Nevertheless, that study taught us that the complex phenotype of individuals with RTT requires more careful and extensive medical care, although guidelines for clinical management of adolescents and adults with RTT are not available. The majority of adults with RTT are treated in paediatric centres because specialised adult clinics are rare. […] In conclusion, we have discussed the main clinical issues that should be considered when transitioning patients with RTT to adult care, based on data from our study and from the literature. We underline the importance of establishing a multidisciplinary team and educating the adult team members about RTT. Larger international studies assessing the medical problems of adult women with RTT and experiences from other adult clinics are highly encouraged.

• #3 Global prevalence of Rett syndrome: systematic review and meta-analysis | springermedizin.de

  https://www.springermedizin.de/global-prevalence-of-rett-syndrome-systematic-review-and-meta-an/23925946

  The pooled prevalence estimate based on all eligible studies (random-effects model) was 7.1 cases per 100,000 females (95% CI: 4.8, 10.5). […] The results suggest that the prevalence remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability.

• #3 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-023-03181-y

  Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. […] This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. […] In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. […] The annual prevalence of RTT between November 1, 2016 and October 31, 2019 in this dataset ranged from 0.30-0.32 per 10,000 enrollees overall, with higher prevalence ranges observed among female than male patients (female: 0.45-0.52; male: 0.08-0.10). […] Overall, the annual incidence of RTT in this dataset was an estimated 0.34 and 0.23 per 10,000 enrollees in 2018 and 2019, respectively.

• #3 Trends in the Diagnosis of Rett Syndrome in Australia | Pediatric Research

  https://www.nature.com/articles/pr2011179

  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 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, 10.0312.45)] in comparison with 5 y of age [1/15,361 or 6.51 per 100,000 person-years (95% CI, 5.657.39)]. […] Changes in clinical practice resulting both from modifications to diagnostic criteria and the introduction of genetic testing have likely affected the pattern and timing of RTT diagnosis.

• #3 Orphanet: Rett syndrome

  https://www.orpha.net/en/disease/detail/778

  The disorder affects approximately 1 in 10,000 live female births. The disease has been occasionally reported in males, usually with a lethal course before birth or in early infancy. […] Prevalence: 1-9 / 100 000.

• #3 Rett Syndrome | CheckRare

  https://checkrare.com/rett-syndrome/

  Rett syndrome is most common in girls, and it is one of the most common genetic causes of developmental and intellectual impairment in girls. […] Worldwide, the prevalence of Rett syndrome is 1 in 20,000 to 40,000 people, affecting up to 1 in 10,000 girls aged 12 years or younger. […] One estimate specific to the United States calculated approximately 6,000 to 9,000 children and adults living with Rett syndrome. […] The presentation is heterogenous, at least partly because of the number of potential point mutations and their locations involved, as well as the randomness of X-chromosome inactivation. […] The average age of patients with typical Rett syndrome at the time of diagnosis is 2.5 years; however, as genetic testing becomes more prevalent, earlier diagnostic confirmation may be possible in the future.

• #3 Global prevalence of Rett syndrome: systematic review and meta-analysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9841621/

  Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex. […] The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p 0.001). […] These findings may facilitate planning of therapeutic trials in this indication in terms of target sample size and accrual times. […] The aim of this systematic review and meta-analysis is to review the current literature pertaining to RTT and to estimate the prevalence of RTT in the general population, stratified by sex. […] The pooled prevalence estimate based on all eligible studies (random-effects model) was 7.1 cases per 100,000 females (95% CI: 4.8, 10.5). […] In summary, this is the first meta-analysis that estimates the prevalence of RTT. The results suggest that the prevalence remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability.

• #3 Rett Syndrome Market Size, Share & Trends 2035

  https://www.imarcgroup.com/rett-syndrome-market

  Rett syndrome affects around one in every 10,000 girls in the United States by the age of twelve. […] The global prevalence of Rett syndrome is estimated to be 7.1 cases per 100,000 females. […] Scoliosis is the most common orthopedic co-morbidity, occurring by age 15 in nearly 75% of people with Rett syndrome. […] Rett syndrome almost predominantly affects girls. […] 70% of children with Rett syndrome live to at least 50 years of age. […] IMARC Group’s new report provides an exhaustive analysis of the Rett syndrome market in the United States, EU4 (Germany, Spain, Italy, and France), United Kingdom, and Japan. This includes treatment practices, in-market, and pipeline drugs, share of individual therapies, market performance across the seven major markets, market performance of key companies and their drugs, etc.

• #3 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-023-03181-y

  The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. […] Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. […] RTT-related healthcare costs comprised 45% of all-cause healthcare costs. […] The large clinical and economic burden of RTT observed in this study throughout patients’ lifespans suggests a substantial unmet need for treatment options that may modify the disease course and progression of RTT rather than managing its symptoms.

• #3 Validating the Rett Syndrome Gross Motor Scale | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147555

  Rett syndrome is a neurodevelopmental disorder usually caused by a mutation on the X-linked methyl-CpG-binding protein 2 (MECP2) gene. The condition affects females approximately 1 per 9,000 live female births, and is characterized by a loss of functional hand use and language skills in early childhood with the development of hand stereotypies and impaired mobility. […] The Australian Rett Syndrome Database (ARSD) is a population-based register established in 1993 of confirmed individuals with Rett syndrome born 1976 and subsequently. […] The National Center for Rett syndrome in Denmark was established in 2007 and offers counselling and annual follow-up by a multidisciplinary team. Currently, there are 109 known confirmed individuals (age two to 61 years) with Rett syndrome in Denmark of whom 96 (88%) have a MECP2 mutation.

• #3 Multidisciplinary Management of Rett Syndrome: Twenty Years’ Experience

  https://www.mdpi.com/2073-4425/14/8/1607

  Over the last 20 years, the understanding and natural history of Rett syndrome has advanced, but to date no cure has emerged, with multidisciplinary management being symptomatic and supportive. […] Rett Syndrome (RTT; OMIM entry #312750) is one of the most common genetic causes of developmental and intellectual disability in females, affecting up to 1:10,000 females under the age of 12 years. […] The average age at RTT diagnosis has trended downwards with the improvement and increasing availability of diagnostic genetic testing. […] The median age of diagnosis was three years of age and reflects the increasing knowledge and awareness of RTT, as well as greater access to diagnostic genetic testing. […] This study analysed a cohort of females with classical RTT who attended the RTT multidisciplinary management clinic at the Children’s Hospital at Westmead, Sydney, Australia, over a 20 year period and aims to provide a comprehensive review of their clinical features, comorbidities and multidisciplinary management.

• #3 1st analysis of Rett syndrome prevalence may help in trial planning | New estimate set of 7.1 cases per 100,000 females worldwide | Rett Syndrome NewsEnvelope icon

  https://rettsyndromenews.com/news/1st-analysis-rett-syndrome-prevalence-may-help-trial-planning/

  Study sets new estimate of 7.1 cases per 100,000 females worldwide. The global prevalence of Rett syndrome is estimated to be 7.1 cases per 100,000 female individuals, according to the first known meta-analysis ever done to estimate the number of girls and women worldwide with the rare neurodevelopmental disorder. This finding “may facilitate planning of therapeutic trials in this disease, especially for target sample size and accrual times,” the researchers wrote, noting that “one of the rate-limiting factors in the development of new pharmacologic therapies for RTT [Rett syndrome] is the low prevalence of the disease.” […] The pooled prevalence estimate was 7.1 cases of Rett syndrome for each 100,000 female individuals, which is in line with previous estimates. […] Overall, the findings “suggest that the prevalence [of Rett] remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability,” the researchers concluded.

• #4 1st analysis of Rett syndrome prevalence may help in trial planning | New estimate set of 7.1 cases per 100,000 females worldwide | Rett Syndrome NewsEnvelope icon

  https://rettsyndromenews.com/news/1st-analysis-rett-syndrome-prevalence-may-help-trial-planning/

  Study sets new estimate of 7.1 cases per 100,000 females worldwide. The global prevalence of Rett syndrome is estimated to be 7.1 cases per 100,000 female individuals, according to the first known meta-analysis ever done to estimate the number of girls and women worldwide with the rare neurodevelopmental disorder. This finding “may facilitate planning of therapeutic trials in this disease, especially for target sample size and accrual times,” the researchers wrote, noting that “one of the rate-limiting factors in the development of new pharmacologic therapies for RTT [Rett syndrome] is the low prevalence of the disease.” […] The pooled prevalence estimate was 7.1 cases of Rett syndrome for each 100,000 female individuals, which is in line with previous estimates. […] Overall, the findings “suggest that the prevalence [of Rett] remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability,” the researchers concluded.

• #4 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10071755/

  Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. However, literature characterizing the real-world journey of patients with RTT is limited. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. […] In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. […] The annual prevalence of RTT between November 1, 2016 and October 31, 2019 in this dataset ranged from 0.30-0.32 per 10,000 enrollees overall, with higher prevalence ranges observed among female than male patients (female: 0.45-0.52; male: 0.08-0.10). […] Overall, the annual incidence of RTT in this dataset was an estimated 0.34 and 0.23 per 10,000 enrollees in 2018 and 2019, respectively (Table 2). Among female patients, the annual incidence was 0.43 and 0.31 per 10,000 female enrollees in 2018 and 2019, respectively, while among male patients, it was 0.22 and 0.13 per 10,000 male enrollees, respectively.

• #4 Rett Syndrome: Practice Essentials, Background, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/916377-overview

  The incidence of Rett syndrome (RS) has been reported to be approximately 1 per 23,000 live female births. […] Wide variations in incidence have been reported in various countries; rates as high as 1 per 10,000 live female births have been reported. […] One study in Japan found an incidence of 1 per 45,000 girls aged 6-14 years. […] Variations in incidence may be partly accounted for by the inclusion of atypical or variant forms of RS. These atypical forms include congenital RS, milder forms with later onset of regression, and preserved speech variants. […] RS generally becomes clinically evident by age 2-4 years; however, the underlying neurodevelopmental arrest probably starts in children aged 6-18 months or younger. […] Most patients identified are female because the disease is X-linked. […] Many males with RS are believed to die in utero. […] However, a few reports have detailed males with mutations in MECP2 and RS-like symptoms. […] Excess male fetal loss has not been demonstrated in families with a history of RS; thus, an alternative explanation for female predominance may be noted. […] No racial variations have been reported. In a study by Kozinetz et al, which included Latin Americans, Caucasians, and African Americans in Texas, no variations in the incidence or prevalence of RS were found.

• #4 Rett Syndrome | CheckRare

  https://checkrare.com/rett-syndrome/

  The average age of diagnosis for patients with atypical Rett syndrome is 3.8 years. […] Patients with Rett syndrome often survive into their fifth decade and require lifelong, intensive care. […] As a result, the health (physical, mental, and financial) of caregivers must be a consideration. […] Overall, the clinical status of patients with Rett syndrome tends to stabilize as patients enter young adulthood; for example, the incidence of scoliosis in patients with Rett syndrome generally lessens after the onset of puberty. […] However, these patients are at higher risk than the general population for osteopenia and contractures, and consensus guidelines recommend surveillance for these musculoskeletal issues.

• #4 Global prevalence of Rett syndrome: systematic review and meta-analysis | springermedizin.de

  https://www.springermedizin.de/global-prevalence-of-rett-syndrome-systematic-review-and-meta-an/23925946

  The pooled prevalence estimate based on all eligible studies (random-effects model) was 7.1 cases per 100,000 females (95% CI: 4.8, 10.5). […] The results suggest that the prevalence remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability.

• #4 Twenty years of surveillance in Rett syndrome: what does this tell us? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-9-87

  The neurological disorder Rett syndrome (OMIM 312750) was first described in the English literature in 1983 and later found to be associated with mutations in the methyl CpG binding protein 2 gene (MECP2). Females are mostly affected with an incidence of diagnosis of 1:9000 by the age of 32 years. […] Using a population-based cohort we have shown that current survival to the age of 20 years is 77.6% with 59.8% surviving to early middle age. In women aged 18 years and older we found that epilepsy, breathing and sleep problems persisted, low weight and gastrointestinal issues were prevalent and although most have scoliosis loss of walking is not inevitable. […] Importantly, we can now report survival in the ARSD cohort of slightly less than 60% at 38 years of age although the current estimate of survival to 25 years (71.5%) is lower compared to our 2006 analysis. Death was most commonly caused by respiratory illnesses. […] The data contained in this paper represents twenty years of surveillance and highlights the consistent research effort required to understand rare disorders. Individuals with Rett syndrome have potential for prolonged survival with approximately 60% surviving to early middle age.

• #4 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-023-03181-y

  The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. […] Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. […] RTT-related healthcare costs comprised 45% of all-cause healthcare costs. […] The large clinical and economic burden of RTT observed in this study throughout patients’ lifespans suggests a substantial unmet need for treatment options that may modify the disease course and progression of RTT rather than managing its symptoms.

• #4 Validating the Rett Syndrome Gross Motor Scale | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147555

  Rett syndrome is a neurodevelopmental disorder usually caused by a mutation on the X-linked methyl-CpG-binding protein 2 (MECP2) gene. The condition affects females approximately 1 per 9,000 live female births, and is characterized by a loss of functional hand use and language skills in early childhood with the development of hand stereotypies and impaired mobility. […] The Australian Rett Syndrome Database (ARSD) is a population-based register established in 1993 of confirmed individuals with Rett syndrome born 1976 and subsequently. […] The National Center for Rett syndrome in Denmark was established in 2007 and offers counselling and annual follow-up by a multidisciplinary team. Currently, there are 109 known confirmed individuals (age two to 61 years) with Rett syndrome in Denmark of whom 96 (88%) have a MECP2 mutation.

• #4 Rett Syndrome | CheckRare

  https://checkrare.com/rett-syndrome/

  Rett syndrome is most common in girls, and it is one of the most common genetic causes of developmental and intellectual impairment in girls. […] Worldwide, the prevalence of Rett syndrome is 1 in 20,000 to 40,000 people, affecting up to 1 in 10,000 girls aged 12 years or younger. […] One estimate specific to the United States calculated approximately 6,000 to 9,000 children and adults living with Rett syndrome. […] The presentation is heterogenous, at least partly because of the number of potential point mutations and their locations involved, as well as the randomness of X-chromosome inactivation. […] The average age of patients with typical Rett syndrome at the time of diagnosis is 2.5 years; however, as genetic testing becomes more prevalent, earlier diagnostic confirmation may be possible in the future.

• #4 Global prevalence of Rett syndrome: systematic review and meta-analysis | springermedizin.de

  https://www.springermedizin.de/global-prevalence-of-rett-syndrome-systematic-review-and-meta-an/23925946

  Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex. […] The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p 0.001). […] Despite greatly variable precision of estimation, all estimates were compatible with a prevalence range of approximately 5 to 10 cases per 100,000 females based on their respective 95% CIs. […] The aim of this systematic review and meta-analysis is to review the current literature pertaining to RTT and to estimate the prevalence of RTT in the general population, stratified by sex. These results may facilitate planning of future clinical trials for this indication in terms of target sample size and accrual times.

• #5 Multidisciplinary Management of Rett Syndrome: Twenty Years’ Experience

  https://www.mdpi.com/2073-4425/14/8/1607

  Over the last 20 years, the understanding and natural history of Rett syndrome has advanced, but to date no cure has emerged, with multidisciplinary management being symptomatic and supportive. […] Rett Syndrome (RTT; OMIM entry #312750) is one of the most common genetic causes of developmental and intellectual disability in females, affecting up to 1:10,000 females under the age of 12 years. […] The average age at RTT diagnosis has trended downwards with the improvement and increasing availability of diagnostic genetic testing. […] The median age of diagnosis was three years of age and reflects the increasing knowledge and awareness of RTT, as well as greater access to diagnostic genetic testing. […] This study analysed a cohort of females with classical RTT who attended the RTT multidisciplinary management clinic at the Children’s Hospital at Westmead, Sydney, Australia, over a 20 year period and aims to provide a comprehensive review of their clinical features, comorbidities and multidisciplinary management.

• #5

  https://www.orthobullets.com/pediatrics/4107/rett-syndrome

  Rett Syndrome is a congenital condition caused by an X-linked dominant mutation in the MECP2 gene that affects girls between 6-18 months of age. […] Epidemiology […] Incidence […] 1 in 10,000 births. […] Demographics […] male fetuses (only 1 X chromosome) do not survive to term. […] female fetuses (1 mutated gene, 1 normal gene) survive and manifest disease.

• #5 1st analysis of Rett syndrome prevalence may help in trial planning | New estimate set of 7.1 cases per 100,000 females worldwide | Rett Syndrome NewsEnvelope icon

  https://rettsyndromenews.com/news/1st-analysis-rett-syndrome-prevalence-may-help-trial-planning/

  Study sets new estimate of 7.1 cases per 100,000 females worldwide. The global prevalence of Rett syndrome is estimated to be 7.1 cases per 100,000 female individuals, according to the first known meta-analysis ever done to estimate the number of girls and women worldwide with the rare neurodevelopmental disorder. This finding “may facilitate planning of therapeutic trials in this disease, especially for target sample size and accrual times,” the researchers wrote, noting that “one of the rate-limiting factors in the development of new pharmacologic therapies for RTT [Rett syndrome] is the low prevalence of the disease.” […] The pooled prevalence estimate was 7.1 cases of Rett syndrome for each 100,000 female individuals, which is in line with previous estimates. […] Overall, the findings “suggest that the prevalence [of Rett] remained stable for the last 20 years in the range of 5 to 10 cases per 100,000 females, without substantial regional variability,” the researchers concluded.

• #5 Complexities of Rett Syndrome and MeCP2 | Journal of Neuroscience

  https://www.jneurosci.org/content/31/22/7951

  Rett syndrome (RTT, MIM 312750), originally described by the Austrian pediatrician Andreas Rett, is an X-linked neurodevelopmental disorder that primarily affects girls at a frequency of 1:10,000 live female births (Rett, 1966; Hagberg, 1985; Laurvick et al., 2006; Neul et al., 2010). […] Longevity studies suggest that despite the overwhelming number of debilitating symptoms, some RTT women may survive until at least the sixth decade of life (Hagberg, 2005; Freilinger et al., 2010; Kirby et al., 2010). Conversely, there clearly is excess mortality in affected individuals, with a yearly death rate of between 1 and 2%, with 25% of all deaths characterized as sudden and unexpected (Kerr et al., 1997). […] In addition to those individuals who display the clinically defined classic or typical RTT, there are other atypical or variant RTT individuals who present with some but not all RTT features (Neul et al., 2010).

• #5 Epidemiology and Patient Journey of Rett Syndrome in the United States: A Real-World Evidence Study – Analysis Group

  https://www.analysisgroup.com/Insights/publishing/epidemiology-and-patient-journey-of-rett-syndrome-in-the-united-states-a-real-world-evidence-study/

  Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. […] In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. Among 5,940 female patients (pediatric: 3,078; adult: 2,862) with mean observation period of 2.04 years, the most prevalent clinical manifestations were neurological disorders (72.8%), gastrointestinal/nutritional disorders (41.9%), and orthopedic disorders (34.6%). The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. RTT-related healthcare costs comprised 45% of all-cause healthcare costs.

• #5 Multidisciplinary Management of Rett Syndrome: Twenty Years’ Experience

  https://www.mdpi.com/2073-4425/14/8/1607

  The clinic has a diverse team of medical practitioners, including a Pediatrician, Clinical Geneticist and Dentist, along with Allied Health professionals such as a Genetic Counsellor, Dietitian, Physiotherapist, Occupational Therapist, Speech Therapist and a Music Therapist. […] This study provides a comprehensive review of the clinical features, comorbidities and multidisciplinary management of a well-characterized cohort of females with classical Rett syndrome.

• #5 Addgene: Rett Syndrome

  https://www.addgene.org/collections/rett-syndrome/

  Rett syndrome is a neurodevelopmental disorder that presents in early toddlerhood primarily affecting females at an incidence of approximately 1:10,000. […] Diagnosis of Rett syndrome is currently based on specific clinical diagnostic criteria, defined as the presence of relatively normal early development, regression with a loss of spoken language and hand skills, development of repetitive hand stereotypies, and gait dysfunction or absence of gait. […] Greater than 95% of individuals who meet diagnostic criteria have disease-causing mutations in the gene methyl-CpG binding protein 2 (MECP2). […] While there is wide variability in symptoms even within patients with the same mutation, the location and type of MECP2 mutation can be a strong predictor of symptom severity. […] A large number of mutations are known to cause Rett syndrome, however, eight recurrent missense and nonsense mutations (R106W, R133C, T158M, R168X, R255X, R270X, R294X, and R306C) account for almost 46% of all Rett syndrome cases. […] Laurvick et al. 2006. Rett syndrome in Australia: a review of the epidemiology.

• #5 Proof-of-concept trial for Rett treatment expected soon in ColombiaEnvelope icon

  https://rettsyndromenews.com/news/proof-concept-trial-rett-treatment-expected-soon-colombia/

  Unravel Biosciences is asking authorities in Colombia to allow the launch — which could be as early as this summer, if cleared — of proof-of-concept clinical trials in the country to test RVL001, its treatment candidate for Rett syndrome. […] The trial is expected to enroll 15 people with Rett syndrome and will test the experimental therapy against a placebo, according to a company press release. […] Both applications were submitted under a pilot program from the National Food and Drug Surveillance Institute (INVIMA) that aims to accelerate development of treatments designed to fill unmet needs in rare diseases. This means that Unravel’s applications will get priority review, however no time frame was specified by the company.

• #6 Rett Syndrome | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-60327-161-5_158

  Rett syndrome, a neurodevelopmental disorder affecting girls almost exclusively, was first described by Rett in 1966. The prevalence is estimated to be 1/10,000 1/15,000 female births; over 95% of cases arise de novo due to the fact that most females with Rett syndrome do not reproduce. Rett syndrome is considered to be one of the most common genetic causes of mental retardation in girls, second only to Down syndrome. […] Kozinetz CA, Skender ML, MacNaughton N, et al.: Epidemiology of Rett syndrome: a population-based registry. Pediatrics 91:445450, 1993.

• #6 Rett Syndrome: Practice Essentials, Background, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/916377-overview

  The incidence of Rett syndrome (RS) has been reported to be approximately 1 per 23,000 live female births. […] Wide variations in incidence have been reported in various countries; rates as high as 1 per 10,000 live female births have been reported. […] One study in Japan found an incidence of 1 per 45,000 girls aged 6-14 years. […] Variations in incidence may be partly accounted for by the inclusion of atypical or variant forms of RS. These atypical forms include congenital RS, milder forms with later onset of regression, and preserved speech variants. […] RS generally becomes clinically evident by age 2-4 years; however, the underlying neurodevelopmental arrest probably starts in children aged 6-18 months or younger. […] Most patients identified are female because the disease is X-linked. […] Many males with RS are believed to die in utero. […] However, a few reports have detailed males with mutations in MECP2 and RS-like symptoms. […] Excess male fetal loss has not been demonstrated in families with a history of RS; thus, an alternative explanation for female predominance may be noted. […] No racial variations have been reported. In a study by Kozinetz et al, which included Latin Americans, Caucasians, and African Americans in Texas, no variations in the incidence or prevalence of RS were found.

• #6 Trends in the Diagnosis of Rett Syndrome in Australia | Pediatric Research

  https://www.nature.com/articles/pr2011179

  The birth prevalence varied by birth year, peaking for those born in the early to mid-1990s. […] The point prevalence of RTT in Australia on June 30, 2009, was 8.6 per 100,000 females (95% CI, 7.410.1) aged 518 y and 5.8 per 100,000 females (95% CI, 4.86.9) aged 1932 y. […] The cumulative risk (likelihood of a female child being diagnosed with RTT by a certain age) was estimated using survival analysis. […] The change in cumulative risk before and after 1999 shows a clear increase in the risk of RTT diagnosis and a parallel decrease in age of diagnosis.

• #6 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-023-03181-y

  The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. […] Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. […] RTT-related healthcare costs comprised 45% of all-cause healthcare costs. […] The large clinical and economic burden of RTT observed in this study throughout patients’ lifespans suggests a substantial unmet need for treatment options that may modify the disease course and progression of RTT rather than managing its symptoms.

• #6 Commentary: Are Developmental Skills Acquired Normally in Rett Syndrome?

  https://www.jneurology.com/articles/commentary-are-developmental-skills-acquired-normally-in-rett-syndrome.html

  In 2014, Neul et al. described the occurrence of developmental skills in more than 600 individuals with RTT, the largest reported to-date examined directly by teams consisting of a neurologist or geneticist and an experienced clinical coordinator. This allowed for a precise ascertainment of the timing of acquisition of specific developmental skills in this population. […] As we enter a period of increased clinical trial activity in this population, it is important to achieve accurate diagnosis as early as possible. Currently, data from the RTT NHS indicates that the average age of diagnosis is 2.7 years, down from about 4 years in the initial years of the study. Still, to effect a treatment as early as possible, age at diagnosis must be reduced even further. […] Coupling these factors with a closer examination of the abnormal pattern of acquisition of developmental skills adds further evidence for the possible establishment of a definitive diagnosis.

• #6 Addgene: Rett Syndrome

  https://www.addgene.org/collections/rett-syndrome/

  Rett syndrome is a neurodevelopmental disorder that presents in early toddlerhood primarily affecting females at an incidence of approximately 1:10,000. […] Diagnosis of Rett syndrome is currently based on specific clinical diagnostic criteria, defined as the presence of relatively normal early development, regression with a loss of spoken language and hand skills, development of repetitive hand stereotypies, and gait dysfunction or absence of gait. […] Greater than 95% of individuals who meet diagnostic criteria have disease-causing mutations in the gene methyl-CpG binding protein 2 (MECP2). […] While there is wide variability in symptoms even within patients with the same mutation, the location and type of MECP2 mutation can be a strong predictor of symptom severity. […] A large number of mutations are known to cause Rett syndrome, however, eight recurrent missense and nonsense mutations (R106W, R133C, T158M, R168X, R255X, R270X, R294X, and R306C) account for almost 46% of all Rett syndrome cases. […] Laurvick et al. 2006. Rett syndrome in Australia: a review of the epidemiology.

• #6 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10071755/

  The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. […] In light of the gaps in the literature regarding RTT, this study aimed to provide an overview of the epidemiology, patient characteristics, clinical manifestations, HRU, costs, and treatment patterns of patients with RTT in the US. […] The large clinical and economic burden of RTT observed in this study throughout patients’ lifespans suggests a substantial unmet need for treatment options that may modify the disease course and progression of RTT rather than managing its symptoms.

• #7 Validating the Rett Syndrome Gross Motor Scale | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147555

  Rett syndrome is a neurodevelopmental disorder usually caused by a mutation on the X-linked methyl-CpG-binding protein 2 (MECP2) gene. The condition affects females approximately 1 per 9,000 live female births, and is characterized by a loss of functional hand use and language skills in early childhood with the development of hand stereotypies and impaired mobility. […] The Australian Rett Syndrome Database (ARSD) is a population-based register established in 1993 of confirmed individuals with Rett syndrome born 1976 and subsequently. […] The National Center for Rett syndrome in Denmark was established in 2007 and offers counselling and annual follow-up by a multidisciplinary team. Currently, there are 109 known confirmed individuals (age two to 61 years) with Rett syndrome in Denmark of whom 96 (88%) have a MECP2 mutation.

• #7 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10071755/

  Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. However, literature characterizing the real-world journey of patients with RTT is limited. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. […] In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. […] The annual prevalence of RTT between November 1, 2016 and October 31, 2019 in this dataset ranged from 0.30-0.32 per 10,000 enrollees overall, with higher prevalence ranges observed among female than male patients (female: 0.45-0.52; male: 0.08-0.10). […] Overall, the annual incidence of RTT in this dataset was an estimated 0.34 and 0.23 per 10,000 enrollees in 2018 and 2019, respectively (Table 2). Among female patients, the annual incidence was 0.43 and 0.31 per 10,000 female enrollees in 2018 and 2019, respectively, while among male patients, it was 0.22 and 0.13 per 10,000 male enrollees, respectively.

• #7 Epidemiology and Patient Journey of Rett Syndrome in the United States: A Real-World Evidence Study – Analysis Group

  https://www.analysisgroup.com/Insights/publishing/epidemiology-and-patient-journey-of-rett-syndrome-in-the-united-states-a-real-world-evidence-study/

  Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. […] In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. Among 5,940 female patients (pediatric: 3,078; adult: 2,862) with mean observation period of 2.04 years, the most prevalent clinical manifestations were neurological disorders (72.8%), gastrointestinal/nutritional disorders (41.9%), and orthopedic disorders (34.6%). The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. RTT-related healthcare costs comprised 45% of all-cause healthcare costs.

• #7 Rett Syndrome in Ireland: A demographic study | medRxiv

  https://www.medrxiv.org/content/10.1101/2023.02.13.23285763v1.full-text

  RTT is X-linked, predominantly affecting females; males with RTT typically do not survive past a year. […] RTT has several subtypes including classic/typical RTT, atypical RTT, and Rett-like. […] The classification of RTT and its subtypes is continually evolving, exhibiting a diverse clinical and genetic spectrum. […] Overall, there is significant clinical and phenotypic variability associated with RTT. […] The barriers resulting from the variability of RTT have led to the development of several RTT databases as a means to categorise and analyse different RTT cohorts. […] The primary advantage of recognizing a population cohort is to advance the criteria for patients selection in clinical studies. […] However, the genetic information is not always available for patients with RTT in Ireland.

• #7 Rett Syndrome in Ireland: A demographic study | medRxiv

  https://www.medrxiv.org/content/10.1101/2023.02.13.23285763v1.full-text

  Rett syndrome (RTT) is a rare neuropsychiatric condition associated to mutations in the gene coding for the methyl-CpG-binding protein 2 (MECP2). It is primarily observed in girls and affects individuals globally. […] However, in Ireland, there is a scarcity of data regarding patients with RTT, which impedes the ability to fully characterize the Irish RTT population. […] The main finding of this study is the limited number of genetic tests conducted to support the clinical diagnosis of RTT. […] The results shows that Irish patients with RTT have comparable presentation with respect to patients in other countries, however, they had a better response to anti-epileptic drugs and fewer skeletal deformities were reported. […] Despite the limited sample size, this study is the first to characterise the RTT population in Ireland and highlights the importance of genetic testing for patients with RTT in order to sharpen the characterization of the phenotype and increase the visibility of Irish patients in the international RTT community.

• #7 Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-023-03181-y

  The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. […] Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. […] RTT-related healthcare costs comprised 45% of all-cause healthcare costs. […] The large clinical and economic burden of RTT observed in this study throughout patients’ lifespans suggests a substantial unmet need for treatment options that may modify the disease course and progression of RTT rather than managing its symptoms.

• #8 Consensus guidelines on managing Rett syndrome across the lifespan | BMJ Paediatrics Open

  https://bmjpaedsopen.bmj.com/content/4/1/e000717

  Rett syndrome (RTT) is a severe neurodevelopmental disorder with an estimated worldwide prevalence of 1 in 20000-40000 people. […] The average age at RTT diagnosis of 2.5 years has been trending downward with increasing availability of diagnostic genetic testing. […] The multisystem nature of the disorder has been documented within multiple observational studies, with symptom risk evolving across the lifespan. […] The guidance for management by health professionals was grouped by relevant features and therapeutic approaches at different ages. […] Longitudinal supervision is required in RTT as physical, behavioural and cognitive limitations will not allow for independent living. […] The accumulating knowledge regarding the natural history of RTT serves as a vital resource to help providers anticipate the complexities of this disorder.

• #8 Rett Syndrome Market Size, Share & Trends 2035

  https://www.imarcgroup.com/rett-syndrome-market

  Rett syndrome affects around one in every 10,000 girls in the United States by the age of twelve. […] The global prevalence of Rett syndrome is estimated to be 7.1 cases per 100,000 females. […] Scoliosis is the most common orthopedic co-morbidity, occurring by age 15 in nearly 75% of people with Rett syndrome. […] Rett syndrome almost predominantly affects girls. […] 70% of children with Rett syndrome live to at least 50 years of age. […] IMARC Group’s new report provides an exhaustive analysis of the Rett syndrome market in the United States, EU4 (Germany, Spain, Italy, and France), United Kingdom, and Japan. This includes treatment practices, in-market, and pipeline drugs, share of individual therapies, market performance across the seven major markets, market performance of key companies and their drugs, etc.

• #8 Rett Syndrome in Ireland: A demographic study | medRxiv

  https://www.medrxiv.org/content/10.1101/2023.02.13.23285763v1.full-text

  This missing information would be crucial for the proper diagnosis and characterization of the Irish RTT population and for advancing RTT research. […] This study analyses data from the Irish RTT population on the basis of information provided by the caregivers of patients with RTT. […] The average age of RTT diagnosis in Ireland is 5.21 years, which is higher than in Poland, the UK, the US, and Denmark, but lower than in Australia and the Netherlands. […] Despite limited access to RTT diagnosis in Ireland, the average age of diagnosis seems to be comparable to that of other populations. […] The results show a milder phenotype of scoliosis in patients who can walk unassisted and a trend of scoliosis not progressing in the p.Arg306Cys mutant patient. […] We plan to increase the number of participants in the study in order to better characterise the RTT population in Ireland. […] The literature suggests that Irish individuals with RTT are currently not included in international studies or clinical trials. […] The inclusion of Irish patients in such databases would be beneficial for RTT patients, scientists, healthcare professionals and the Irish community.

• #8 Multidisciplinary Management of Rett Syndrome: Twenty Years’ Experience

  https://www.mdpi.com/2073-4425/14/8/1607

  The clinic has a diverse team of medical practitioners, including a Pediatrician, Clinical Geneticist and Dentist, along with Allied Health professionals such as a Genetic Counsellor, Dietitian, Physiotherapist, Occupational Therapist, Speech Therapist and a Music Therapist. […] This study provides a comprehensive review of the clinical features, comorbidities and multidisciplinary management of a well-characterized cohort of females with classical Rett syndrome.

• #9 SciELO Brazil – Rett syndrome: clinical and epidemiological aspects in a Brazilian institution Rett syndrome: clinical and epidemiological aspects in a Brazilian institution

  https://www.scielo.br/j/anp/a/ZJBMrgLpG4G68gSsNZs9cfg/

  Rett syndrome (RS) is a neurodevelopmental disorder, preferentially found in females and specifically involving the functions on which intelligence and its expression depend – learning, hand use and speech – leaving many others intact. This is a study on clinical, diagnostic and epidemiological aspects of RS in a Brazilian sample. It included 33 female patients with chronic encephalopathy without known etiology. RS was diagnosed in 24 patients (72.7%): 17 (70.8%) had classical RS; 5 (20.8%), atypical RS and 2 (8.4%), potential RS. In 9 girls clinical data and/or laboratory studies excluded diagnosis of RS. […] Prevalence is estimated between 1:10.000 and 1:15.000 girls. […] The present study has the purpose of performing a clinical analysis of a cohort of girls with chronic encephalopathy without a recognizable evident etiology, who were referred to our neuropediatric service, in order to 1) establish, within this Brazilian sample, the prevalence of RS, 2) determine the frequency of its different variants, 3) identify the etiology of the non-RS cases, and 4) discuss the limits of the current RS diagnostic criteria in view of the clinical and laboratory particularities found in some of our cases.

• #9 Consensus guidelines on managing Rett syndrome across the lifespan | BMJ Paediatrics Open

  https://bmjpaedsopen.bmj.com/content/4/1/e000717

  Rett syndrome (RTT) is a severe neurodevelopmental disorder with an estimated worldwide prevalence of 1 in 20000-40000 people. […] The average age at RTT diagnosis of 2.5 years has been trending downward with increasing availability of diagnostic genetic testing. […] The multisystem nature of the disorder has been documented within multiple observational studies, with symptom risk evolving across the lifespan. […] The guidance for management by health professionals was grouped by relevant features and therapeutic approaches at different ages. […] Longitudinal supervision is required in RTT as physical, behavioural and cognitive limitations will not allow for independent living. […] The accumulating knowledge regarding the natural history of RTT serves as a vital resource to help providers anticipate the complexities of this disorder.

• #10 Rett Syndrome – CAGS

  https://cags.org.ae/en/ctga-details/913/rett-syndrome

  Rett syndrome (RTT) is a neurodevelopmental disorder characterised by early onset developmental stagnation (6 months-1.5 year) followed by developmental regression and motor deterioration. […] RTT appears to occur predominantly in females with a prevalence rate of 1/10,000-1/15,000 female births. […] Rett Syndrome results from a mutation on the X chromosome that is transmitted as an X-linked trait. […] Koul and Al Gheilani (1997) reported four cases of Rett syndrome seen over a period of four years. […] Al-Jarallah et al. (1996) described five Saudi girls (age 3.5-12 years) with Rett Syndrome. […] Al-Jarallah et al. (1996) examined a Sudanese girl with Rett Syndrome.

• #10 About Rett Syndrome, Symptoms, Causes, Diagnosis and Treatments

  https://reverserett.org/about-rett-syndrome/

  Rett syndrome is a severe neurological disorder that is diagnosed primarily in girls and begins to manifest during the toddler years. […] Rett is caused by errors in a gene called MECP2, which is located on the X chromosome. […] Many studies have provided evidence that the vast majority of MECP2 mutations originate in the sperm. […] Rett syndrome is a clinical diagnosis given by a physician based on the child’s history and symptoms. […] Since most primary care doctors have limited experience with Rett syndrome, a consensus on guidelines about how to care for individuals with Rett syndrome was published in 2020. […] Although Rett syndrome remains a clinical diagnosis based on the child’s symptoms and history, the identification of MECP2 has made DNA testing and confirmation possible for affected individuals and their families.

• #11 Rett Syndrome | CheckRare

  https://checkrare.com/rett-syndrome/

  Rett syndrome is most common in girls, and it is one of the most common genetic causes of developmental and intellectual impairment in girls. […] Worldwide, the prevalence of Rett syndrome is 1 in 20,000 to 40,000 people, affecting up to 1 in 10,000 girls aged 12 years or younger. […] One estimate specific to the United States calculated approximately 6,000 to 9,000 children and adults living with Rett syndrome. […] The presentation is heterogenous, at least partly because of the number of potential point mutations and their locations involved, as well as the randomness of X-chromosome inactivation. […] The average age of patients with typical Rett syndrome at the time of diagnosis is 2.5 years; however, as genetic testing becomes more prevalent, earlier diagnostic confirmation may be possible in the future.

• #12 Rett Syndrome: Healthcare Professionals | Acadia Pharmaceuticals

  https://acadia.com/en-us/healthcare-professionals/areas-of-focus/rett-syndrome

  Rett syndrome is a rare, neurodevelopmental disorder that affects approximately 6,000 9,000 patients in the U.S. […] RTT is diagnosed based on clinical evaluation, typically by 3 years of age, with confirmatory genetic testing used to determine the presence and type of underlying mutations. […] Although underlying mutations in genes such as MECP2 are neither necessary nor sufficient for diagnosis, mutational analysis can help predict severity in order to better prepare for the needs of individuals with RTT. […] Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis.

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