Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome

Molecular Genetics & Genomic Medicine

Ferrin Wheeler¹  Lynne Bird²  Jessica Duis³  Anna K. Childers³  Robert P. Carson⁴ 

[1] Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville Tennessee;Division of Genetics/Dysmorphology, Department of Pediatrics Rady Children’s Hospital, University of California San Diego San Diego California;Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center Nashville Tennessee;Divisions of Child Neurology and Epilepsy, Department of Pediatrics Vanderbilt Brain Institute, Vanderbilt University Medical Center Nashville Tennessee;

关键词: Angelman syndrome;    epilepsy;    imprinting;    mosaic Angelman syndrome;    mosaicism;   

DOI  :  10.1002/mgg3.837

来源: DOAJ

【 摘 要 】

Abstract Background Angelman Syndrome (AS) is a neurodevelopmental disorder with core features of intellectual disability, speech impairment, movement disorders, and a unique behavioral profile. Typically, AS results from absent maternal expression of UBE3A, but some individuals have imprinting defects in a portion of their cells. These individuals are mosaic for normal and defective UBE3A expression, resulting in mosaic AS (mAS) with a partial loss of gene expression. Methods This study aims to contrast the mAS phenotype to that of AS. Clinical characteristics of mAS were obtained from a parental survey of 22 mAS patients and from the Angelman Natural History study. These were contrasted with those of AS using historical data. Results Developmental delay was present in nearly all mAS patients, whereas the core features of AS were reported in less than 40%. While language and ability to manage activities of daily living were markedly improved over that expected in AS, mAS patients demonstrated a high incidence of behavioral challenges. Conclusion Clinical work‐up of an individual with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor should prompt methylation studies to rule out mAS. We expand the phenotypic spectrum of AS to include features that overlap with Prader‐Willi such as hyperphagia.

【 授权许可】

Unknown