Communicative and cognitive functioning in Angelman syndrome with UBE3A mutation: a case report (original) (raw)
Related papers
Cognitive and adaptive behavior profiles of children with Angelman syndrome
American Journal of Medical Genetics, 2004
Angelman syndrome (AS) is a neurodevelopmental disorder caused by maternal deficiency of the UBE3A gene that encodes E6-AP ubiquitinprotein ligase. Expression of the UBE3A gene from the maternal chromosome is essential to prevent AS. AS is characterized by severe mental retardation, ataxia, and a defined behavioral pattern characterized mainly by happy/sociable disposition. This study used the Bayley Scales of Infant Development and the Vineland Adaptive Behavior Scales to examine the cognitive abilities and adaptive behavior of children (n ¼ 20) with the four known molecular classes of AS, including patterns of strengths and weaknesses across adaptive behavior domains, and the relationship between adaptive behavior and overall cognitive abilities. Cognitive skills fell within the severe to profound range of mental deficiency. Differences in cognitive skills according to genetic subtype only partially supported previous research and suggest that there is overlap in abilities across genetic subtypes of AS. Adaptive behavior skills were also significantly delayed, with participants demonstrating a significant strength in socialization, and a weakness in motor skills. Strong, positive correlations emerge between cognitive ability scores and adaptive behaviors scores. These results provide further delineation of a cognitive/behavioral phenotype in AS.
Phenotypic and behavioral variability within Angelman Syndrome group with UPD
Genetics and Molecular Biology, 2002
The Angelman syndrome (AS) (developmental delay, mental retardation, speech impairment, ataxia, outbursts of laughter, seizures) can result either from a 15q11-q13 deletion, or from paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. We describe here the phenotypic and behavioral variability detected in eight UPD patients out of a group of 58 AS patients studied. All of them presented developmental delay, mental retardation, ataxia, speech impairment, and frequent drooling. Only one had microcephaly, whereas in two of them the OFC (head circumference) was above the 98 th percentile. The weight of all patients was above the 50 th percentile, and in three of them the height was above the 90 th percentile. Three were able to say a few words and to communicate by gestures. Two patients presented hyperphagia, and three presented skin picking, common features in the Prader-Willi syndrome (PWS). Four patients (4/7) had wide-spaced teeth. Five presented seizures, and two others did not manifest frequent laughter. One patient was very different from the others, as he showed a better understanding and abilities to communicate, to play video games and to draw. We suggest here that there seems to be an extreme phenotypic and behavioral variability within the UPD group, and that both typical patients and those with mental retardation, language impairment, happy disposition, and hyperactivity should be tested for AS.
Molecular Psychiatry
Angelman Syndrome (AS) is a severe neurodevelopmental disorder due to impaired expression of UBE3A in neurons. There are several genetic mechanisms that impair UBE3A expression, but they differ in how neighboring genes on chromosome 15 at 15q11–q13 are affected. There is evidence that different genetic subtypes present with different clinical severity, but a systematic quantitative investigation is lacking. Here we analyze natural history data on a large sample of individuals with AS (n = 250, 848 assessments), including clinical scales that quantify development of motor, cognitive, and language skills (Bayley Scales of Infant Development, Third Edition; Preschool Language Scale, Fourth Edition), adaptive behavior (Vineland Adaptive Behavioral Scales, Second Edition), and AS-specific symptoms (AS Clinical Severity Scale). We found that clinical severity, as captured by these scales, differs between genetic subtypes: individuals with UBE3A pathogenic variants and imprinting defects (...
Behavior and neuropsychiatric manifestations in Angelman syndrome
Neuropsychiatric Disease and Treatment, 2008
Angelman syndrome has been suggested as a disease model of neurogenetic developmental condition with a specifi c behavioral phenotype. It is due to lack of expression of the UBE3A gene, an imprinted gene located on chromosome 15q. Here we review the main features of this phenotype, characterized by happy demeanor with prominent smiling, poorly specifi c laughing and general exuberance, associated with hypermotor behavior, stereotypies, and reduced behavioral adaptive skills despite proactive social contact. All these phenotypic characteristics are currently diffi cult to quantify and have been subject to some differences in interpretation. For example, prevalence of autistic disorder is still debated. Many of these features may occur in other syndromic or nonsyndromic forms of severe intellectual disability, but their combination, with particularly prominent laughter and smiling may be specifi c of Angelman syndrome. Management of problematic behaviors is primarily based on behavioral approaches, though psychoactive medication (eg, neuroleptics or antidepressants) may be required.
A Neurodevelopmental Survey of Angelman Syndrome With Genotype-Phenotype Correlations
Journal of Developmental & Behavioral Pediatrics, 2010
Objective-Angelman syndrome (AS) is a neurodevelopmental disorder caused by a deletion on chromosome 15, uniparental disomy (UPD), imprinting defect, or UBE3A mutation. It is characterized by intellectual disability with minimal speech and certain behavioral characteristics. We used standardized measures to characterize the developmental profile and to analyze genotype-phenotype correlations in AS.
BMC medical genetics, 2017
Patients with Angelman syndrome (AS) are affected by severe intellectual disability with absence of speech, distinctive dysmorphic craniofacial features, ataxia and a characteristic behavioral phenotype. AS is caused by the lack of expression in neurons of the UBE3A gene, which is located in the 15q11.2-q13 imprinted region. Functional loss of UBE3A is due to 15q11.2-q13 deletion, mutations in the UBE3A gene, paternal uniparental disomy and genomic imprinting defects. We report here two patients with clinical features of AS referred to our hospital for clinical follow-up and genetic diagnosis. Methylation Specific-Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) of the 15q11.2-q13 region was carried out in our laboratory as the first diagnostic tool detecting two novel UBE3A intragenic deletions. Subsequently, the MLPA P336-A2 kit was used to confirm and determine the size of the UBE3A deletion in the two patients. A review of the clinical features of previously reported p...
Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome
Molecular Genetics & Genomic Medicine
Angelman Syndrome (AS) (OMIM #105830) is a neurodevelopmental disorder with clinical features characterized by severe developmental delay/intellectual disability, speech impairment, movement disorders or ataxia, and a unique behavioral profile with an excitable, smiling, and happy demeanor. In addition, the majority of AS patients are noted to be microcephalic by 2 years of age and exhibit epilepsy and characteristically abnormal electroencephalogram (EEG) patterns (Fiumara, Pittala, Cocuzza,
American journal of medical genetics. Part A, 2018
We present three children from two unrelated families with Angelman syndrome (AS) whose developmental skills are far more advanced than any other non-mosaic AS individual ever reported. All have normal gait and use syntactic language spontaneously to express their needs. All of them have a c.2T > C (p.Met1Thr) variant in UBE3A, which abrogates the start codon of isoform 1, but not of isoforms 2 and 3. This variant was maternally inherited in one set of siblings, but de novo in the other child from the unrelated family. This report underscores the importance of considering AS in the differential diagnosis even in the presence of syntactic speech.
Genomic imprinting and mental retardation: Angelman and Prader-Willi syndromes
2007
Genomic imprinting is a prime example of epigenetic change leading to variable gene expression. Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are disorders associated with failure of genomic imprinting at the same locus but exhibiting different clinical presentations.. The loss of maternal imprint at the chr15q11-q13 locus leads to AS, while lack of paternal patterning results in PWS. Individuals with AS exhibit severe to profound mental retardation (MR) in combination with epilepsy, abnormal EEG patterns, movement disorders, inappropriate smiling or laughter, a happy demeanor, minimal speech, and an easily excitable personality. People with PWS typically present with mild MR, behavior problems, hypotonia, hyperphagia and obesity, and delayed or incomplete sexual development.