A Neurodevelopmental Survey of Angelman Syndrome With Genotype-Phenotype Correlations

Gentile, Jennifer; Tan, Wen‐Hann; Horowitz, Lucia; Bacino, Carlos A.; Skinner, Steven A.; Barbieri-Welge, Rene; Bauer-Carlin, Astrid; Beaudet, Arthur L.; Bichell, Terry Jo; Lee, Hye-Seung; Sahoo, Trilochan; Waisbren, Susan E.; Bird, Lynne M.; Peters, Sarika U.

doi:10.1097/dbp.0b013e3181ee408e

Cited by 131 publications

(171 citation statements)

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“…Those with identifi ed deletions on chromosome 15q11-q13 are referred to as deletion positive (DP), whereas those presenting other etiologies are labeled deletion negative, or non-deletion (ND). Previous investigators have reported individuals without deletions tend to present stronger cognitive, communicative, and linguistic skills than their counterparts with deletions (Didden, Korzilius, Duker, & Curfs, 2004;Didden et al, 2009;Gentile et al, 2010;Williams et al, 2009). The current investigation compared parents ' reports of AAC use across these two groups.…”

Section: Introductionmentioning

confidence: 92%

Parents’ Reports of Patterns of Use and Exposure to Practices Associated with AAC Acceptance by Individuals with Angelman Syndrome

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2013

Augmentative and Alternative Communication

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The primary purpose of this investigation was to enhance our understanding of AAC use by individuals with Angelman syndrome (AS) in relation to two broad genotypes: Deletion Positive (DP) and Non Deletion (ND). Previous investigators have suggested individuals without deletions typically exhibit stronger cognitive and communicative abilities than their DP counterparts. This investigation focused on several aspects of AAC use: communication systems used; exposure to, success with, and acceptance of electronic AAC devices; and exposure to practices associated with AAC acceptance. Results indicated that both groups rely heavily on unaided, nonsymbolic methods of communication, with the ND group more likely to use conventional, symbolic systems. While the two groups were similar with respect to exposure to an array of electronic devices, the DP group appeared more likely to have gone no further than low-tech devices such as the BIGmack™. There was strong evidence of both groups' capabilities for success with high-tech devices and overall acceptance of devices in terms of duration of use. This proved especially noteworthy in light of both groups' limited exposure to practices associated with AAC acceptance. Clinical implications of these findings are discussed along with future avenues of research.

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Section: Introductionmentioning

confidence: 92%

Parents’ Reports of Patterns of Use and Exposure to Practices Associated with AAC Acceptance by Individuals with Angelman Syndrome

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2013

Augmentative and Alternative Communication

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“…It is notable that overall, the most consistent finding is the uniformly poor expressive language skill in all participants regardless of their molecular sub-class. Since the single common molecular mechanism in all participants is the lack of UBE3A protein in parts of the brain where UBE3A is imprinted, a hypothesis can be developed that UBE3A may be essential in the development of expressive language skills (Gentile et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Applicability of genetic polymorphism analysis for the diagnosis of Angelman syndrome and the correlation between language difficulties and disease phenotype

Wang

Hou

2016

Genet. Mol. Res.

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ABSTRACT. Angelman syndrome (AS) is a neurogenetic disorder caused by a defect in the expression of the maternally inherited ubiquitin protein ligase E3A (UBE3A) gene in chromosome 15. The most common genetic defects include maternal deletions in chromosome 15q11-13; however, paternal uniparental disomy and imprinting defects allow for the identification of mutations in UBE3A in 10% of patients with AS. The aim of this study was to validate the clinical features and genetic polymorphisms of AS, and to discuss the relationship between functional language lateralization and the arcuate fasciculus in the Broca's and Wernicke's areas. Six children with AS (mean age = 32.57 months) presenting characteristic behavioral patterns of AS (frequent laughter and happy demeanor, hand flapping, and hypermotor behavior) were recruited to this study. The patients underwent a clinical evaluation (clinical history, dysmorphological and neurological examinations, and psychological evaluations) and paraclinical investigations [genetic tests (fluorescence in situ hybridization and methylation polymerase chain We conclude that AS diagnosis cannot rely solely on genetic testing for polymorphisms in UBE3A and must consider its clinical characteristics. Moreover, functional language lateralization and the arcuate fasciculus in the Broca's and Wernicke's areas were found to be closely correlated. Therefore, UBE3A gene mutation analysis combined with comprehensive clinical evaluations may be suitable for the diagnosis of AS.

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“…1) [7]. While there is variability with each molecular class of AS, in general those with deletion have a more severe phenotype, and those with UPD and imprinting defects a less severe phenotype [2,[8][9][10][11]. The diagnostic algorithm described in Fig.…”

Section: Genetic Etiology and Diagnosismentioning

confidence: 99%

“…Patients with AS with UPD and imprinting defects are predicted to have elevated [9,10,22,23]. One possibility is that the other genes located within 15q11-q13 play significant roles in brain development.…”

Section: Genetic Etiology and Diagnosismentioning

confidence: 99%

“…Treatment is supportive and includes 1) therapies to mitigate gross and fine motor delays; 2) augmentative communication strategies such as the use of communication devices, picture exchange cards, and modified sign language; and 3) intervention for comorbid ASD when present [2][3][4][8][9][10]. The remainder of treatment is limited to managing the problems associated with AS [66].…”

Section: Treatment Currentmentioning

confidence: 99%

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Angelman Syndrome

et al. 2015

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In this review we summarize the clinical and genetic aspects of Angelman syndrome (AS), its molecular and cellular underpinnings, and current treatment strategies. AS is a neurodevelopmental disorder characterized by severe cognitive disability, motor dysfunction, speech impairment, hyperactivity, and frequent seizures. AS is caused by disruption of the maternally expressed and paternally imprinted UBE3A, which encodes an E3 ubiquitin ligase. Four mechanisms that render the maternally inherited UBE3A nonfunctional are recognized, the most common of which is deletion of the maternal chromosomal region 15q11-q13. Remarkably, duplication of the same chromosomal region is one of the few characterized persistent genetic abnormalities associated with autistic spectrum disorder, occurring in >1-2 % of all cases of autism spectrum disorder. While the overall morphology of the brain and connectivity of neural projections appear largely normal in AS mouse models, major functional defects are detected at the level of context-dependent learning, as well as impaired maturation of hippocampal and neocortical circuits. While these findings demonstrate a crucial role for ubiquitin protein ligase E3A in synaptic development, the mechanisms by which deficiency of ubiquitin protein ligase E3A leads to AS pathophysiology in humans remain poorly understood. However, recent efforts have shown promise in restoring functions disrupted in AS mice, renewing hope that an effective treatment strategy can be found.Key Words Angelman syndrome . neurodevelopmental disorders . autism . ubiquitin ligase . Ube3a . Imprinting. Clinical OverviewIn 1965, the English physician Harry Angelman described 3 patients who presented with a stiff, jerky gait, absence of speech, excessive laughter, and seizures. The disorder that came to bear his name [Angelman syndrome (AS)] is now recognized to affect approximately 1 in 15,000 individuals and is characterized by motor dysfunction, severe intellectual disability, speech impairment, seizures, hyperactivity, and autism spectrum disorder (ASD) as a common comorbidity [1].Developmental delay in individuals with AS is usually observed within the first year of life. Though most individuals lack speech entirely, some who are mildly affected can acquire a few words. Receptive language is less impaired. Seizures occur in >80 % of patients, and onset is usually before the age of 3 years. Movement disorders include tremors, jerkiness, and ataxia. The characteristic behaviors of AS include mouthing of objects, happy demeanor with easily provoked laughter, attraction to water, hyperactivity, short attention span, and decreased sleeping (see recent reviews for more detailed description of the clinical phenotype [2][3][4]). These features of AS can be seen in other neurodevelopmental disorders, leading to a broad differential diagnosis [5], which has recently been reviewed (Table 1) [6]. Overlapping clinical features may indicate common neurophysiological pathways,

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A Neurodevelopmental Survey of Angelman Syndrome With Genotype-Phenotype Correlations

Cited by 131 publications

References 33 publications

Parents’ Reports of Patterns of Use and Exposure to Practices Associated with AAC Acceptance by Individuals with Angelman Syndrome

Parents’ Reports of Patterns of Use and Exposure to Practices Associated with AAC Acceptance by Individuals with Angelman Syndrome

Applicability of genetic polymorphism analysis for the diagnosis of Angelman syndrome and the correlation between language difficulties and disease phenotype

Angelman Syndrome

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