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Diagnoses offered prior to a formal Angelman syndrome diagnosis, according to age at diagnosis of participants within the Global Angelman Syndrome Registry (n = 393). Autism χ² (5, 393) = 13.073, p = .023, V = .182; global developmental delay χ² (3, 393) = 37.805, p < .001, V = .310; cerebral palsy χ² (5, 393) = 19.715, p = .001, V = .224; seizure disorder χ² (5, 393) = 41.120, p < .001, V = .323
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Objectives
Angelman syndrome (AS) and is typically diagnosed in children under the age of three based upon early behavioural concerns identified by parents, or genetic links with other family members. For some families however, the pathway to diagnosis is not so clear, particularly when children demonstrate differential characteristics, commonly se...
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Background:
Developmental delay and intellectual disability represent a common pathology in general population, involving about 3% of the pediatric age population, the genetic etiology being often involved. The aim of this study was to determine the clinically relevant copy number variants in patients diagnosed with global developmental delay/inte...
Angelman syndrome (AS) is caused by the functional absence of the maternal ubiquitin-protein ligase E3A (UBE3A) gene. Approximately 5% of AS is caused by paternal uniparental disomy of chromosome 15 (UPD(15)pat), most of which is considered to result from monosomy rescue. However, little attention has focused on how UPD(15)pat occurs. We suggest th...
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are genetic imprinting disorders resulting from absent or reduced expression of paternal or maternal genes in chromosome 15q11q13 region, respectively. The most common etiology is deletion of the maternal or paternal 15q11q13 region. Methylation is the first line for molecular diagnostic testin...
Angelman syndrome is a rare neurodevelopmental disorder caused by mutations affecting the chromosomal 15q11-13 region, either by contiguous gene deletions, imprinting defects, uniparental disomy, or mutations in the UBE3A gene itself. Phenotypic abnormalities are driven primarily, but not exclusively (especially in 15q11-13 deletion cases) by loss...
Anxiety is being increasingly identified in Angelman syndrome (AS). Qualitative questions and quantitative assessments were used to evaluate for anxiety in 50 subjects with AS. In-person evaluations assessed behaviors concerning for anxiety and circumstances wherein they occurred. Caregivers completed anxiety and other behavioral rating scales. Car...
Citations
... The genetic diagnoses (Table S1) were deletion in 58.1%, with the remaining showing paternal uniparental disomy and mutation (~34.0%), an imprinting defect, or abnormal DNA methylation/undefined cases (~8.0%). The distribution of genotype classes was also comparable to more recent results [35] and data collected by previous studies [18,36]. ...
... (2) the deletion subtype showed a trend toward the highest rates of severe epilepsy and multiple seizures. These results were in line with the literature [11,[35][36][37][38]. 3 The table compares the frequencies of positive cases (seizure types) observed between groups. For p-Value(*), the "Non-Deletion" group has ≤ 5 cases; therefore, the p-Value should be interpreted as indicative of a trend. ...
... Despite the underrepresentation of the Italian population in the Global Registry at the time of the report [34], the demographic and genetic data were aligned with the broader outcomes observed in the global initiative. The registry data confirmed the diagnostic delay of approximately 2 years and the distribution of genetic subtypes, with the distribution of genotypes showing that recent advances in genomics have improved the diagnosis of non-deletion subtypes, which is supported by existing studies [18,34,35]. ...
Background: The Angelman Syndrome Registry (RISA) was developed as a retrospective study with the following objectives: to evaluate the clinical history of individuals with Angelman Syndrome (AS) in Italy and compare it with the existing literature; to investigate the feasibility of gathering data by directly involving participants in the data collection process; and to explore the relationship between different symptoms and genotypes. Methods: Established in 2018, RISA enrolled a total of 82 participants, with 62 (75.6%) providing complete data. Demographic, clinical, and genetic information was collected using electronic case report forms. Descriptive statistics characterized the sample, while associations between genotype and clinical characteristics were examined. Results: Descriptive analysis revealed a median participant age of 8.0 years, with males comprising 48.8% of the sample. Deletion (58.1%) was the most common genotype. The majority (82.2%) experienced epilepsy, with seizures typically onset before 3 years of age. Most patients (86.2%) required multiple anti-epileptic drugs for control, with generalized tonic–clonic seizures and atypical absence seizures being most prevalent. The deletion group exhibited more severe developmental delays and a trend towards higher seizure severity. Sleep problems affected 69.4% of participants, characterized by difficulties in sleep onset and maintenance. Conclusions: This study offers valuable insights into the clinical history and genetic characteristics of AS in Italy, consistent with the prior literature. Additionally, it underscores the efficacy of patient registries in capturing comprehensive data on rare diseases such as AS, highlighting their potential to advance research and enhance patient care.
... In 2020, the registry was moved to the Trial Ready Registry Framework (TRRF) [30,32,[34][35][36][37][38][39]. The new platform incorporated significant revisions based on feedback from families, clinicians and researchers. ...
Global disease registries are critical to capturing common patient related information on rare illnesses, allowing patients and their families to provide information about their condition in a safe, accessible, and engaging manner that enables researchers to undertake critical research aimed at improving outcomes. Typically, English is the default language of choice for these global digital health platforms. Unfortunately, language barriers can significantly inhibit participation from non-English speaking participants. In addition, there is potential for compromises in data quality and completeness. In contrast, multinational commercial entities provide access to their websites in the local language of the country they are operating in, and often provide multiple options reflecting ethnic diversity. This paper presents a case study of how the Global Angelman Syndrome Registry (GASR) has used a novel approach to enable multiple language translations for its website. Using a “semi-automated language translation” approach, the GASR, which was originally launched in English in September 2016, is now available in several other languages. In 2020, the GASR adopted a novel approach using crowd-sourcing and machine translation tools leading to the availability of the GASR in Spanish, Traditional Chinese, Italian, and Hindi. As a result, enrolments increased by 124% percent for Spain, 67% percent for Latin America, 46% percent for Asia, 24% for Italy, and 43% for India. We describe our approach here, which we believe presents an opportunity for cost-effective and timely translations responsive to changes to the registry and helps build and maintain engagement with global disease communities.
... Between 5 and 20% of individuals with characteristic physical and behavioural features show no identifiable abnormalities in the 15q 11-13 region (Clayton-Smith & Laan, 2003;Lossie et al., 2001;Williams et al., 2001). The UBE3A gene is specifically imprinted in neurons, and as such, the behavioural phenotype of AS results in significant central nervous system deficits such as severe to profound intellectual disability, motor impairment with an unsteady gait, significant impairment in expressive communication skills (compared with receptive communication skills), frequently reported epilepsy disorders, and gastrointestinal complications (Clayton-Smith & Laan, 2003;Horsler & Oliver, 2006;Roche et al., 2021). Individuals with AS also demonstrate an apparent general happy demeanour with frequent laughing and smiling (Horsler & Oliver, 2006b); however, they can develop more challenging behaviours over time. ...
... Reports of developmental milestones including communication and motor skills from parental reports may provide a reliable overview of an individual's functioning and may improve the accuracy of clinical judgements (Glascoe, 2000;Roche et al., 2021). Parental accuracy has been demonstrated in identifying specific behavioural characteristics of disorders in children. ...
Objectives
Angelman syndrome (AS) is a rare genetic disorder that affects the expression of the UBE3A gene within the central nervous system that profoundly impacts neurodevelopment. Individuals with AS experience significant challenges across multiple adaptive behaviour domains including communication, motor skills, and the ability to independently perform daily functions such as feeding, and toileting. Furthermore, persons with AS can demonstrate specific behaviours that limit their ability to participate within their social environment that vary with age. The aim of this paper is to explore the adaptive behaviour profile through parent report from the Global Angelman Syndrome Registry.
Methods
Specific parent report data from the Global Angelman Syndrome Registry were analysed to explore the adaptive profile of 204 young children, under the age of 6 years old, with formal diagnoses of AS. Analysis of data focused on communication skills, gross and fine motor skills, daily self-care skills (feeding, toileting, and dressing), and behavioural characteristics. Several relationships were explored: (a) the age at which certain skills were first performed based on genotype; (b) abilities in motor and adaptive behaviours, according to age and genotype, and (c) the frequency at which children performed specific communication skills and the presence and frequency of challenging behaviours, across age and genotype.
Results
We visually present the ages at which frequent speech, walking, and independent dressing and toileting were first mastered by children. Additionally, we provide in-depth descriptives of expressive and receptive communication skills (including the use of alternative communication forms), fine and gross motor skills, eating, dressing, toileting, anxiety, aggression, and other behavioural characteristics.
Conclusions
This cross-sectional profile of adaptive skills in 204 young children with AS showcases that although many communication, motor and adaptive skills were determined by age, children with a non-deletion aetiology exhibited advantages in communication skills, which may have impacted upon subsequent adaptive skills. The use of parent report in the present study provides valuable insight into the adaptive behaviour profile of young children with AS.
