Angelman syndrome 2005: Updated consensus for diagnostic criteria

Williams, Charles A.; Beaudet, Arthur L.; Clayton‐Smith, Jill; Knoll, Joan H.M.; Kyllerman, M; Laan, L.A.E.M.; Magenis, R. Ellen; Moncla, A.; Schinzel, Albert; Summers, Jim; Wagstaff, Joseph

doi:10.1002/ajmg.a.31074

Cited by 513 publications

(492 citation statements)

References 47 publications

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“…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].…”

Section: Clinical Overviewmentioning

confidence: 99%

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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Section: Clinical Overviewmentioning

confidence: 99%

Angelman Syndrome

et al. 2015

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“…7 Newborns typically have a normal phenotype. Developmental delays are first noted at around age 6 months.…”

Section: Clinical Criteria For Diagnosismentioning

confidence: 99%

Clinical and genetic aspects of Angelman syndrome

Williams

Driscoll

Dagli

2010

Genetics in Medicine

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“…29 For children who lack speech, DNA methylation analysis is performed to exclude Angelman syndrome, with sequencing of the Angelman gene (UBE3A ligase) in classic cases if a normal pattern of DNA methylation is found. 30 Sequencing of the MECP2 gene is performed in girls with features of Rett syndrome as well as in males or females with suspicion of "atypical Rett" syndrome, which can include mild mental retardation or autism. 31,32 Included in this group would be girls with autism and preserved speech, normal head circumference, or some use of their hands; girls with no speech and features similar to those found in Angelman syndrome; and girls with autism, mental retardation, and seizures.…”

Section: Genetic Testing In Autismmentioning

confidence: 99%

Genetic testing in autism: how much is enough?

Herman

Henninger

Ratliff-Schaub

et al. 2007

Genetics in Medicine

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Purpose: To evaluate the yield of genetic testing in children with autism spectrum disorders. Methods: We performed a retrospective chart review of 71 unrelated patients with a diagnosis of an isolated autism spectrum disorder seen in a genetics clinic over a period of 14 months. For most, referrals occurred after evaluation by a developmental pediatrician and/or psychologist to establish the diagnosis. Tiered laboratory testing for the majority of the patients followed a guideline that was developed in collaboration with clinicians at The Autism Center at Children's Hospital, Columbus, OH. Results: The patients included 57 males and 14 females; 57 met DSM-IV criteria for autism, with the rest being Asperger or pervasive developmental disorder not otherwise specified.

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Angelman syndrome 2005: Updated consensus for diagnostic criteria

Cited by 513 publications

References 47 publications

Angelman Syndrome

Angelman Syndrome

Clinical and genetic aspects of Angelman syndrome

Genetic testing in autism: how much is enough?

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