Clinical Characterization of Epilepsy in Children With Angelman Syndrome

Overview

Journal Pediatr Neurol

Specialties Neurology
Pediatrics

Date 2021 Sep 18

PMID 34536900

Citations 2

Authors

Daiana Cassater

Mariana Bustamante

Lisa Sach-Peltason

Alexander Rotenberg

Mark Nespeca

Wen-Hann Tan

Lynne M Bird

Joerg F Hipp

Affiliations

Soon will be listed here.

Abstract

Background: Epilepsy is highly prevalent in children with Angelman syndrome (AS), and its detailed characterization and relationship to the genotype (deletion vs nondeletion) is important both for medical practice and for clinical trial design.

Methods And Materials: We retrospectively analyzed the main clinical features of epilepsy in 265 children with AS who were enrolled in the AS Natural History Study, a multicenter, observational study conducted at six centers in the United States. Participants were prospectively followed up and classified by genotype.

Results: Epilepsy was reported in a greater proportion of individuals with a deletion than a nondeletion genotype (171 of 187 [91%] vs. 48 of 78 [61%], P < 0.001). Compared with participants with a nondeletion genotype, those with deletions were younger at the time of the first seizure (age: median [95% confidence interval]: 24 [21-24] months vs. 57 [36-85] months, P < 0.001) and had a higher prevalence of generalized motor seizures. Hospitalization following a seizure was reported in more children with a deletion than a nondeletion genotype (92 of 171 [54%] vs. 17 of 48 [36%], P = 0.04). The overall prevalence of absence seizures was not significantly different between genotype groups. Forty-six percent (102/219) of the individuals reporting epilepsy were diagnosed with AS concurrently or after their first seizure.

Conclusions: Significant differences exist in the clinical expression of epilepsy in AS according to the underlying genotype, with earlier age of onset and more severe epilepsy in individuals with AS due to a chromosome 15 deletion.

Citing Articles

Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS).

Tjeertes J, Bacino C, Bichell T, Bird L, Bustamante M, Crean R J Neurodev Disord. 2023; 15(1):22.

PMID: 37495977 PMC: 10373389. DOI: 10.1186/s11689-023-09494-w.

The role of whole exome sequencing in the UBE3A point mutation of Angelman Syndrome: A case report.

Triono A, Iskandar K, Nugrahanto A, Hadiyanto M, Gunadi , Herini E Ann Med Surg (Lond). 2022; 73:103170.

PMID: 34976390 PMC: 8683671. DOI: 10.1016/j.amsu.2021.103170.

References

Lossie A, Whitney M, Amidon D, Dong H, Chen P, Theriaque D . Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J Med Genet. 2001; 38(12):834-45. PMC: 1734773. DOI: 10.1136/jmg.38.12.834. View

Keute M, Miller M, Krishnan M, Sadhwani A, Chamberlain S, Thibert R . Angelman syndrome genotypes manifest varying degrees of clinical severity and developmental impairment. Mol Psychiatry. 2020; 26(7):3625-3633. PMC: 8505254. DOI: 10.1038/s41380-020-0858-6. View

Shaaya E, Grocott O, Laing O, Thibert R . Seizure treatment in Angelman syndrome: A case series from the Angelman Syndrome Clinic at Massachusetts General Hospital. Epilepsy Behav. 2016; 60:138-141. DOI: 10.1016/j.yebeh.2016.04.030. View

Sahoo T, Bacino C, German J, Shaw C, Bird L, Kimonis V . Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH: molecular characterization and genotype-phenotype correlations. Eur J Hum Genet. 2007; 15(9):943-9. DOI: 10.1038/sj.ejhg.5201859. View

Unterberger I, Trinka E, Kaplan P, Walser G, Luef G, Bauer G . Generalized nonmotor (absence) seizures-What do absence, generalized, and nonmotor mean?. Epilepsia. 2018; 59(3):523-529. DOI: 10.1111/epi.13996. View

Brigo F, Trinka E, Lattanzi S, Bragazzi N, Nardone R, Martini M . A brief history of typical absence seizures - Petit mal revisited. Epilepsy Behav. 2018; 80:346-353. DOI: 10.1016/j.yebeh.2018.01.007. View

Scheffer I, Berkovic S, Capovilla G, Connolly M, French J, Guilhoto L . ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; 58(4):512-521. PMC: 5386840. DOI: 10.1111/epi.13709. View

Meeren H, van Luijtelaar G, Lopes da Silva F, Coenen A . Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory. Arch Neurol. 2005; 62(3):371-6. DOI: 10.1001/archneur.62.3.371. View

Bindels-de Heus K, Mous S, Hooven-Radstaake M, van Iperen-Kolk B, Navis C, Rietman A . An overview of health issues and development in a large clinical cohort of children with Angelman syndrome. Am J Med Genet A. 2019; 182(1):53-63. PMC: 6916553. DOI: 10.1002/ajmg.a.61382. View

10.

Williams C, Beaudet A, Clayton-Smith J, Knoll J, Kyllerman M, Laan L . Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet A. 2006; 140(5):413-8. DOI: 10.1002/ajmg.a.31074. View

11.

Luk H, Lo I . Angelman syndrome in Hong Kong Chinese: A 20 years' experience. Eur J Med Genet. 2016; 59(6-7):315-9. DOI: 10.1016/j.ejmg.2016.05.003. View

12.

Sueri C, Ferlazzo E, Elia M, Bonanni P, Randazzo G, Gasparini S . Epilepsy and sleep disorders improve in adolescents and adults with Angelman syndrome: A multicenter study on 46 patients. Epilepsy Behav. 2017; 75:225-229. DOI: 10.1016/j.yebeh.2017.07.041. View

13.

Williams C, Driscoll D, Dagli A . Clinical and genetic aspects of Angelman syndrome. Genet Med. 2010; 12(7):385-95. DOI: 10.1097/GIM.0b013e3181def138. View

14.

Clayton-Smith J, Laan L . Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet. 2003; 40(2):87-95. PMC: 1735357. DOI: 10.1136/jmg.40.2.87. View

15.

Mertz L, Christensen R, Vogel I, Hertz J, Ostergaard J . Epilepsy and cataplexy in Angelman syndrome. Genotype-phenotype correlations. Res Dev Disabil. 2016; 56:177-82. DOI: 10.1016/j.ridd.2016.06.002. View

16.

Moncla A, Malzac P, Voelckel M, Auquier P, Girardot L, Mattei M . Phenotype-genotype correlation in 20 deletion and 20 non-deletion Angelman syndrome patients. Eur J Hum Genet. 1999; 7(2):131-9. DOI: 10.1038/sj.ejhg.5200258. View

17.

Thibert R, Larson A, Hsieh D, Raby A, Thiele E . Neurologic manifestations of Angelman syndrome. Pediatr Neurol. 2013; 48(4):271-9. DOI: 10.1016/j.pediatrneurol.2012.09.015. View

18.

Grieco J, Romero B, Flood E, Cabo R, Visootsak J . A Conceptual Model of Angelman Syndrome and Review of Relevant Clinical Outcomes Assessments (COAs). Patient. 2018; 12(1):97-112. PMC: 6335381. DOI: 10.1007/s40271-018-0323-7. View

19.

Le Fevre A, Beygo J, Silveira C, Kamien B, Clayton-Smith J, Colley A . Atypical Angelman syndrome due to a mosaic imprinting defect: Case reports and review of the literature. Am J Med Genet A. 2017; 173(3):753-757. DOI: 10.1002/ajmg.a.38072. View

20.

Varela M, Kok F, Otto P, Koiffmann C . Phenotypic variability in Angelman syndrome: comparison among different deletion classes and between deletion and UPD subjects. Eur J Hum Genet. 2004; 12(12):987-92. DOI: 10.1038/sj.ejhg.5201264. View