Parent perceptions, beliefs, and fears around genetic treatments and cures for children with Angelman syndrome

Adams, Dawn; Roche, Laura; Heussler, Helen

doi:10.1002/ajmg.a.61631

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…Developmental studies indicate that children with AS caused by a deletion are developmentally more delayed across all domains compared with those due to a UBE3A pathogenic variant or UPD [ 14 , 54 , 60 ]. Cognitive skills are much lower in the deletion group than in the non-deletion group [ 14 , 60 ]. Delayed gross and fine motor skills are more severe in the deletion group [ 14 , 53 , 60 , 61 , 62 ].…”

Section: Genotype–phenotype Correlation In Angelman Syndromementioning

confidence: 99%

“…Cognitive skills are much lower in the deletion group than in the non-deletion group [ 14 , 60 ]. Delayed gross and fine motor skills are more severe in the deletion group [ 14 , 53 , 60 , 61 , 62 ]. Seizure and microcephaly have been reported to be more common and severe in the deletion group [ 53 , 63 , 64 , 65 ].…”

Section: Genotype–phenotype Correlation In Angelman Syndromementioning

confidence: 99%

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Genotype–Phenotype Correlations in Angelman Syndrome

Yang

Shu

Mao

et al. 2021

Genes

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Angelman syndrome (AS) is a rare neurodevelopmental disease that is caused by the loss of function of the maternal copy of ubiquitin–protein ligase E3A (UBE3A) on the chromosome 15q11–13 region. AS is characterized by global developmental delay, severe intellectual disability, lack of speech, happy disposition, ataxia, epilepsy, and distinct behavioral profile. There are four molecular mechanisms of etiology: maternal deletion of chromosome 15q11–q13, paternal uniparental disomy of chromosome 15q11–q13, imprinting defects, and maternally inherited UBE3A mutations. Different genetic types may show different phenotypes in performance, seizure, behavior, sleep, and other aspects. AS caused by maternal deletion of 15q11–13 appears to have worse development, cognitive skills, albinism, ataxia, and more autistic features than those of other genotypes. Children with a UBE3A mutation have less severe phenotypes and a nearly normal development quotient. In this review, we proposed to review genotype–phenotype correlations based on different genotypes. Understanding the pathophysiology of the different genotypes and the genotype–phenotype correlations will offer an opportunity for individualized treatment and genetic counseling. Genotype–phenotype correlations based on larger data should be carried out for identifying new treatment modalities.

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Section: Genotype–phenotype Correlation In Angelman Syndromementioning

confidence: 99%

Section: Genotype–phenotype Correlation In Angelman Syndromementioning

confidence: 99%

Genotype–Phenotype Correlations in Angelman Syndrome

Yang

Shu

Mao

et al. 2021

Genes

View full text Add to dashboard Cite

show abstract

“…Parents of children with Angelman syndrome, a genetic disorder causing severe intellectual and physical disability, overwhelmingly identified cure as a research priority. 13 By contrast, a survey of parents of children with Down syndrome found that while 61% favoured treatment that would reduce symptoms, only 41% supported a curative approach. 14 Parents of children with…”

Section: Discussionmentioning

confidence: 97%

“…Parental views about gene therapy for life‐threatening genetic disorders are influenced by the severity of the condition and available treatment. Parents of children with Angelman syndrome, a genetic disorder causing severe intellectual and physical disability, overwhelmingly identified cure as a research priority 13 . By contrast, a survey of parents of children with Down syndrome found that while 61% favoured treatment that would reduce symptoms, only 41% supported a curative approach 14 .…”

Section: Discussionmentioning

confidence: 99%

Parental perspectives on gene therapy for children with haemophilia: The Exigency study

Khair¹,

Steadman²,

Chaplin³

et al. 2020

Haemophilia

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Introduction Gene therapy is used in life‐limiting conditions of childhood. While not a current therapeutic option for children with haemophilia, it may be considered in the future especially for those where access to treatment is limited. Aim To assess the attitudes and opinions of parents of children with haemophilia about gene therapy as a potential future treatment, by understanding their awareness about gene therapy and what they need to know now and in the future; gauging levels of interest in gene therapy for their children; and exploring perceived current motivations and barriers. Methods A mixed methods study with an online questionnaire and in‐depth qualitative interviews in focus groups which were analysed using thematic analysis. Results One hundred and fifty‐eight participants commenced the online survey; 63 were fully completed (39%). 60 had heard of gene therapy but few (17/60 [28.3%]) felt they had a good understanding. 38/60 (63.3%) respondents did not know that gene therapy is not available for children. However, most held positive views: 53/60 (88.3%) saying they would consider it for their child. In the interviews, participants (N = 10, all mothers) discussed their awareness and understanding of gene therapy and opinions about it for children, including how this should be communicated to the child and parents. Conclusion A coherent, community‐wide strategy for communicating information and news about gene therapy should now be provided for children and families living with haemophilia. This should come primarily from trusted haemophilia nursing teams, who can give tailored, age‐appropriate, factual advice.

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“…The decision to enroll a child into a clinical trial requires serious deliberation from consenting parents and guardians; these are weighty decisions that can impact their child's health, well-being, and the well-being of their family-and the potential promise of an otherwise unobtainable disease-modifying therapy may have an unintended coercive appeal. Moreover, the depth of understanding of genetic disease, inheritance, genetic therapies, and research trials is highly variable across parents with children with a variety of genetic syndromes [75]. It is critical that for such trials, the purpose, procedures, and expected outcomes be clearly discussed and explained.…”

Section: Safety and Ethical Considerationsmentioning

confidence: 99%

Clinical Trial Design for Disease-Modifying Therapies for Genetic Epilepsies

2021

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Although trials with anti-seizure medications (ASMs) have not shown clear anti-epileptogenic or disease-modifying activity in humans to date, rapid advancements in genomic technology and emerging gene-mediated and gene replacement options offer hope for the successful development of disease-modifying therapies (DMTs) for genetic epilepsies. In fact, more than 26 potential DMTs are in various stages of preclinical and/or clinical development for genetic syndromes associated with epilepsy. The scope of disease-modification includes but is not limited to effects on the underlying pathophysiology, the condition's natural history, epilepsy severity, developmental achievement, function, behavior, sleep, and quality of life. While conventional regulatory clinical trials for epilepsy therapeutics have historically focused on seizure reduction, similarly designed trials may prove ill-equipped to identify these broader disease-modifying benefits. As we look forward to this pipeline of DMTs, focused consideration should be given to the challenges they pose to conventional clinical trial designs for epilepsy therapeutics. Just as DMTs promise to fundamentally alter how we approach the care of patients with genetic epilepsy syndromes, DMTs likewise challenge how we traditionally construct and measure the success of clinical trials. In the following, we briefly review the historical and preclinical frameworks for DMT development for genetic epilepsies and explore the many novel challenges posed for such trials, including the choice of suitable outcome measures, trial structure, timing and duration of treatment, feasible follow-up period, varying safety profile, and ethical concerns.

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Parent perceptions, beliefs, and fears around genetic treatments and cures for children with Angelman syndrome

Cited by 8 publications

References 37 publications

Genotype–Phenotype Correlations in Angelman Syndrome

Genotype–Phenotype Correlations in Angelman Syndrome

Parental perspectives on gene therapy for children with haemophilia: The Exigency study

Clinical Trial Design for Disease-Modifying Therapies for Genetic Epilepsies

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