Current and emerging treatment options for Angelman syndrome

References

• Oiglane-Shlik E, Talvik T, Zordania R, et al. Prevalence of Angelman syndrome and Prader–Willi syndrome in Estonian children: sister syndromes not equally represented. Am J Med Genet Part A. 2006;140(18):1936–1943. doi: 10.1002/ajmg.a.31423
   PubMedGoogle Scholar
• Luk HM, Lo IF. Angelman syndrome in Hong Kong Chinese: a 20 years’ experience. Eur J Med Genet. 2016;59(6–7):315–319. doi: 10.1016/j.ejmg.2016.05.003
   PubMed Web of Science ®Google Scholar
• Angelman H. ‘Puppet’ children a report on three cases. Dev Med Child Neurol. 1965;7(6):681–688. doi: 10.1111/j.1469-8749.1965.tb07844.x
   Web of Science ®Google Scholar
• Sadhwani A, Wheeler A, Gwaltney A, et al. Developmental skills of individuals with Angelman syndrome assessed using the Bayley-III. J Autism Dev Disord. 2023;53(2):720–737. doi: 10.1007/s10803-020-04861-1
   PubMed Web of Science ®Google Scholar
• Larson AM, Shinnick JE, Shaaya EA, et al. Angelman syndrome in adulthood. Am J Med Genet A. 2015;167A(2):331–344. doi: 10.1002/ajmg.a.36864
   PubMedGoogle Scholar
• Cassater D, Bustamante M, Sach-Peltason L, et al. Clinical characterization of epilepsy in children with Angelman syndrome. Pediatr Neurol. 2021;124:42–50. DOI:10.1016/j.pediatrneurol.2021.08.007
   PubMed Web of Science ®Google Scholar
• Williams CA, Driscoll DJ, Dagli AI. Clinical and genetic aspects of Angelman syndrome. Genet Med. 2010;12(7):385–395. doi: 10.1097/GIM.0b013e3181def138
   PubMed Web of Science ®Google Scholar
• Williams CA, Beaudet AL, Clayton-Smith J, et al. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet A. 2006;140(5):413–418. doi: 10.1002/ajmg.a.31074
   PubMedGoogle Scholar
• Frohlich J, Miller MT, Bird LM, et al. Electrophysiological phenotype in Angelman syndrome differs between genotypes. Biol Psychiatry. 2019;85(9):752–759. doi: 10.1016/j.biopsych.2019.01.008
   PubMed Web of Science ®Google Scholar
• Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet. 1997;15(1):70–73. doi: 10.1038/ng0197-70
   PubMed Web of Science ®Google Scholar
• Minassian BA, DeLorey TM, Olsen RW, et al. Angelman syndrome: correlations between epilepsy phenotypes and genotypes. Ann Neurol. 1998;43(4):485–493. doi: 10.1002/ana.410430412
   PubMed Web of Science ®Google Scholar
• Jiang YH, Beaudet AL. Human disorders of ubiquitination and proteasomal degradation. Curr Opin Pediatr. 2004;16(4):419–426. doi: 10.1097/01.mop.0000133634.79661.cd
   PubMed Web of Science ®Google Scholar
• Low KS, Chen D. Genome-wide gene expression profiling of the Angelman syndrome mice with Ube3a mutation. Eur J Hum Genet. 2010;18(11):1228–1235. doi: 10.1038/ejhg.2010.95
   PubMed Web of Science ®Google Scholar
• Jiang YH, Armstrong D, Albrecht U, et al. Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. Neuron. 1998;21(4):799–811. doi: 10.1016/S0896-6273(00)80596-6
   PubMed Web of Science ®Google Scholar
• Cheron G, Servais L, Wagstaff J, et al. Fast cerebellar oscillation associated with ataxia in a mouse model of Angelman syndrome. Neuroscience. 2005;130(3):631–637. doi: 10.1016/j.neuroscience.2004.09.013
   PubMed Web of Science ®Google Scholar
• DiStefano RB, Wilson C, Hyde EH, et al. Behavioral characterization of dup15q syndrome: toward meaningful endpoints for clinical trials. Am J Med Genet. 2020;182(1):71–84. doi: 10.1002/ajmg.a.61385
   PubMed Web of Science ®Google Scholar
• Willgoss T, Cassater D, Connor S, et al. Measuring what matters to individuals with Angelman syndrome and their families: development of a patient-centered disease concept model. Child Psychiatry Hum Dev. 2021;52(4):654–668. doi: 10.1007/s10578-020-01051-z
   PubMed Web of Science ®Google Scholar
• Buoni S, Grosso S, Pucci L, et al. Diagnosis of Angelman syndrome: clinical and EEG criteria. Brain Dev. 1999;21(5):296–302. doi: 10.1016/S0387-7604(99)00007-8
   PubMed Web of Science ®Google Scholar
• Thibert RL, Larson AM, Hsieh DT, et al. Neurologic manifestations of Angelman syndrome. Pediatr Neurol. 2013;48(4):271–279. doi: 10.1016/j.pediatrneurol.2012.09.015
   PubMed Web of Science ®Google Scholar
• Lossie AC, Whitney MM, Amidon D, et al. Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J Med Genet. 2001;38(12):834–845. doi: 10.1136/jmg.38.12.834
   PubMed Web of Science ®Google Scholar
• Shaaya EA, Grocott OR, Laing O, et al. Seizure treatment in Angelman syndrome: a case series from the Angelman syndrome clinic at Massachusetts general Hospital. Epilepsy Behav. 2016;60:138–141.
   PubMed Web of Science ®Google Scholar
• Sueri C, Ferlazzo E, Elia M, et al. 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
   PubMed Web of Science ®Google Scholar
• Thibert RL, Conant KD, Braun EK, et al. Epilepsy in Angelman syndrome: a questionnaire-based assessment of the natural history and current treatment options. Epilepsia. 2009;50(11):2369–2376. doi: 10.1111/j.1528-1167.2009.02108.x
   PubMed Web of Science ®Google Scholar
• Elia M. Myoclonic status in nonprogressive encephalopathies: an update. Epilepsia. 2009;50:41–44. doi: 10.1111/j.1528-1167.2009.02119.x
   PubMed Web of Science ®Google Scholar
• Pollack SF, Grocott OR, Parkin KA, et al. Myoclonus in Angelman syndrome. Epilepsy Behav. 2018;82:170–174. DOI:10.1016/j.yebeh.2018.02.006
   PubMed Web of Science ®Google Scholar
• Worden L, Grocott O, Tourjee A, et al. Diazepam for outpatient treatment of nonconvulsive status epilepticus in pediatric patients with Angelman syndrome. Epilepsy Behav. 2018;82:74–80. DOI:10.1016/j.yebeh.2018.02.027
   PubMed Web of Science ®Google Scholar
• Prasad A, Grocott O, Parkin K, et al. Angelman syndrome in adolescent and adulthood: a retrospective chart review of 53 cases. Am J Med Genet A. 2018;176(6):1327–1334. doi: 10.1002/ajmg.a.38694
   PubMed Web of Science ®Google Scholar
• Duis J, Bindels-de Heus GCB, Valstar MJ, et al. A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome. Mol Gene Genomic Med. 2022;10(3):e1843. doi: 10.1002/mgg3.1843
   PubMed Web of Science ®Google Scholar
• Franz DN, Glauser TA, Tudor C, et al. Topiramate therapy of epilepsy associated with Angelman’s syndrome. Neurology. 2000;54(5):1185–1188. doi: 10.1212/WNL.54.5.1185
   PubMed Web of Science ®Google Scholar
• Ascoli M, Elia M, Gasparini S, et al. Therapeutic approach to neurological manifestations of Angelman syndrome. Expert Rev Clin Pharmacol. 2022;15(7):843–850. doi: 10.1080/17512433.2022.2109463
   PubMed Web of Science ®Google Scholar
• Valente KD, Koiffmann CP, Fridman C, et al. Epilepsy in patients with Angelman syndrome caused by deletion of the chromosome 15q11-13. Arch Neurol. 2006;63(1):122–128. doi: 10.1001/archneur.63.1.122
   PubMedGoogle Scholar
• Nolt DH, Mott JM, Lopez WL. Assessment of anticonvulsant effectiveness and safety in patients with Angelman’s syndrome using an Internet questionnaire. Am J Health Syst Pharm. 2003;60(24):2583–2587. doi: 10.1093/ajhp/60.24.2583
   PubMed Web of Science ®Google Scholar
• Sugiura C, Ogura K, Ueno M, et al. High-dose ethosuximide for epilepsy in Angelman syndrome: implication of GABA(A) receptor subunit. Neurology. 2001;57(8):1518–1519. doi: 10.1212/WNL.57.8.1518
   PubMed Web of Science ®Google Scholar
• Kawano O, Egawa K, Shiraishi H. Perampanel for nonepileptic myoclonus in Angelman syndrome. Brain Dev. 2020;42(5):389–392. doi: 10.1016/j.braindev.2020.02.007
   PubMed Web of Science ®Google Scholar
• Groesbeck DK, Blum RM, Kossoff EH. Long-term use of the ketogenic diet in the treatment of epilepsy. Dev Med Child Neurol. 2006;48(12):978–981. doi: 10.1017/S0012162206002143
   PubMed Web of Science ®Google Scholar
• Pfeifer HH, Thiele EA. Low-glycemic-index treatment: a liberalized ketogenic diet for the treatment of intractable epilepsy. Neurology. 2005;65(11):1810–1812. doi: 10.1212/01.wnl.0000187071.24292.9e
   PubMed Web of Science ®Google Scholar
• Grocott OR, Herrington KS, Pfeifer HH, et al. Low glycemic index treatment for seizure control in Angelman syndrome: a case series from the center for dietary therapy of epilepsy at the Massachusetts general Hospital. Epilepsy Behav. 2017;68:45–50. DOI:10.1016/j.yebeh.2016.12.018
   PubMed Web of Science ®Google Scholar
• Clarke, Marston, Clarke DJ, et al. Problem behaviors associated with 15q-Angelman syndrome. Am J Ment Retard. 2000;105(1):25–31. doi: 10.1352/0895-8017(2000)105<0025:PBAWQA>2.0.CO;2
   PubMedGoogle Scholar
• Buntinx IM, Hennekam RCM, Brouwer OF, et al. Clinical profile of Angelman syndrome at different ages. Am J Med Genet. 1995;56(2):176–183. doi: 10.1002/ajmg.1320560213
   PubMed Web of Science ®Google Scholar
• Sadhwani A, Willen JM, LaVallee N, et al. Maladaptive behaviors in individuals with Angelman syndrome. Am J Med Genet A. 2019;179(6):983–992. doi: 10.1002/ajmg.a.61140
   PubMed Web of Science ®Google Scholar
• Zori RT, Hendrickson J, Woolven S, et al. Angelman syndrome: clinical profile. J Child Neurol. 1992;7(3):270–280. doi: 10.1177/088307389200700307
   PubMed Web of Science ®Google Scholar
• Barry RJ, Leitner RP, Clarke AR, et al. Behavioral aspects of Angelman syndrome: a case control study. Am J Med Genet. 2005;132(1):8–12. doi: 10.1002/ajmg.a.30154
   Google Scholar
• Wheeler AC, Sacco P, Cabo R. Unmet clinical needs and burden in Angelman syndrome: a review of the literature. Orphanet J Rare Dis. 2017;12(1):164. doi: 10.1186/s13023-017-0716-z
   PubMedGoogle Scholar
• Wolraich ML, Hagan JF Jr, Allan C, et al. Clinical practice guidelines for the diagnosis, evaluation and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2019;144(4):e20192528. doi: 10.1542/peds.2019-2528
   PubMed Web of Science ®Google Scholar
• Keary CJ, Thom RP, McDougle CJ. Stimulant intolerance in children with Angelman syndrome with hyperactivity: a case series. Psychiatr Genet. 2022;32(2):80–86. doi: 10.1097/YPG.0000000000000307
   PubMed Web of Science ®Google Scholar
• Research Units on Pediatric Psychopharmacology Autism Network. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry. 2005;62(11):1266–1274. doi: 10.1001/archpsyc.62.11.1266
   PubMed Web of Science ®Google Scholar
• Scahill L, McCracken JT, King BH, et al. Extended-release guanfacine for hyperactivity in children with autism spectrum disorder. Am J Psychiatry. 2015;172(12):1197–1206. doi: 10.1176/appi.ajp.2015.15010055
   PubMed Web of Science ®Google Scholar
• Harfterkamp M, Loo-Neus G, Minderaa RB, et al. A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012;51(7):733–741. doi: 10.1016/j.jaac.2012.04.011
   PubMed Web of Science ®Google Scholar
• Fankhauser MP, Karumanchi VC, German ML, et al. A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in autism. J Clin Psychiatry. 1992;53(3):77–82.
   PubMed Web of Science ®Google Scholar
• Arron K, Oliver C, Moss J, et al. The prevalence and phenomenology of self-injurious and aggressive behavior in genetic syndromes. J Intellectual Disability Res. 2011;55(2):109–120. doi: 10.1111/j.1365-2788.2010.01337.x
   PubMedGoogle Scholar
• Strachan R, Shaw R, Burrow C, et al. Experimental functional analysis of aggression in children with Angelman syndrome. Res Dev Disab. 2009;30(5):1095–1106. doi: 10.1016/j.ridd.2009.03.005
   PubMed Web of Science ®Google Scholar
• Wheeler AC, Okoniewski KC, Wylie A, et al. Anxiety-associated and separation distress-associated behaviours in Angelman syndrome. J Intellect Disabil Res. 2019;63(10):1234–1247. doi: 10.1111/jir.12635
   PubMed Web of Science ®Google Scholar
• Keary CJ, Mullett JE, Nowinski L, et al. Parent description of anxiety in Angelman syndrome. J Autism Dev Disord. 2021;52(8):3612–3625. doi: 10.1007/s10803-021-05238-8
   PubMed Web of Science ®Google Scholar
• Balaj K, Nowinski L, Walsh B, et al. Buspirone for the treatment of anxiety-related symptoms in Angelman syndrome: a case series. Psychiatr Genet. 2019;29(2):51–56. doi: 10.1097/YPG.0000000000000218
   PubMed Web of Science ®Google Scholar
• Riddle MA, Bernstein GA, Cook EH, et al. Anxiolytics, adrenergic agents, and naltrexone. J Am Acad Child Adolesc Psychiatry. 1999;38(5):546–556. doi: 10.1097/00004583-199905000-00016
   PubMed Web of Science ®Google Scholar
• London EB, Yoo JH, Fethke ED, et al. The safety and effectiveness of high-dose propranolol as a treatment for challenging behaviors in individuals with autism spectrum disorders. J Clin Psychopharmacol. 2020;40(2):122–129. doi: 10.1097/JCP.0000000000001175
   PubMed Web of Science ®Google Scholar
• Moss J, Oliver C, Arron K, et al. The prevalence and phenomenology of repetitive behavior in genetic syndromes. J Autism Dev Disord. 2009;39(4):572–588. doi: 10.1007/s10803-008-0655-6
   PubMed Web of Science ®Google Scholar
• Heald M, Adams D, Oliver C. Profiles of atypical sensory processing in Angelman, Cornelia de Lange and fragile X syndromes. J Intellectual Disability Res. 2020;64(2):117–130. doi: 10.1111/jir.12702
   PubMed Web of Science ®Google Scholar
• Veatch OL, Malow BA, Lee HS, et al. Evaluating sleep disturbances in children with rare genetic neurodevelopmental syndromes. Pediatr Neurol. 2021;123:30–37. DOI:10.1016/j.pediatrneurol.2021.07.009
   PubMed Web of Science ®Google Scholar
• Clayton-Smith J. Angelman syndrome: evolution of the phenotype in adolescents and adults. Dev Med Child Neurol. 2001;43(7):476–480. doi: 10.1017/S0012162201000871
   PubMed Web of Science ®Google Scholar
• Sheldon SH, Ferber R, Kryger MH. Eds. Principles and practice of pediatric sleep medicine. London, (UK): Elsevier Health Sciences; 2005.
   Google Scholar
• Pelc K, Cheron G, Boyd SG, et al. Are there distinctive sleep problems in Angelman syndrome? Sleep Med. 2008;9(4):434–441. doi: 10.1016/j.sleep.2007.07.001
   PubMed Web of Science ®Google Scholar
• Bruni O, Ferri R, D’Agostino G, et al. Sleep disturbances in Angelman syndrome: a questionnaire study. Brain Dev. 2004;26(4):233–240. doi: 10.1016/S0387-7604(03)00160-8
   PubMed Web of Science ®Google Scholar
• Conant KD, Thibert RL, Thiele EA. Epilepsy and the sleep–wake patterns found in Angelman syndrome. Epilepsia. 2009;50(11):2497–2500. doi: 10.1111/j.1528-1167.2009.02109.x
   PubMed Web of Science ®Google Scholar
• Griffith GM, Hastings RP, Oliver C, et al. Psychological well‐being in parents of children with Angelman, Cornelia de Lange and cri du chat syndromes. J Intellectual Disability Res. 2011;55(4):397–410. doi: 10.1111/j.1365-2788.2011.01386.x
   PubMedGoogle Scholar
• Braam W, Didden R, Smits MG, et al. Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial. J Child Neurol. 2008;23(6):649–654. doi: 10.1177/0883073808314153
   PubMed Web of Science ®Google Scholar
• DeLorey TM, Handforth A, Anagnostaras SG, et al. Mice lacking the β3 subunit of the GABAA receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome. J Neurosci. 1998;18(20):8505–8514. doi: 10.1523/JNEUROSCI.18-20-08505.1998
   PubMed Web of Science ®Google Scholar
• Ryan CS, Edlund W, Mandrekar J, et al. Iron deficiency and its role in sleep disruption in patients with Angelman syndrome. J Child Neurol. 2020;35(14):963–969. doi: 10.1177/0883073820941755
   PubMed Web of Science ®Google Scholar
• Trickett J, Heald M, Oliver C. Sleep in children with Angelman syndrome: parental concerns and priorities. Res Dev Disabil. 2017;69:105–115. doi: 10.1016/j.ridd.2017.07.017
   PubMed Web of Science ®Google Scholar
• Allen KD, Kuhn BR, DeHaai KA, et al. Evaluation of a behavioral treatment package to reduce sleep problems in children with Angelman syndrome. Res Dev Disabil. 2013;34(1):676–686. doi: 10.1016/j.ridd.2012.10.001
   PubMed Web of Science ®Google Scholar
• Didden R, Korzilius H, Smits MG, et al. Sleep problems in individuals with Angelman syndrome. Am J Ment Retard. 2004;109(4):275–284. doi: 10.1352/0895-8017(2004)109<275:SPIIWS>2.0.CO;2
   PubMedGoogle Scholar
• Bindels-de Heus KG, Hooven-Radstaake MT, Legerstee JS, et al. Sleep problems in children with Angelman syndrome: the effect of a behavioral intervention program. Res Dev Disabil. 2023;135:104444.
   PubMed Web of Science ®Google Scholar
• Spruyt K, Curfs LM. Non-pharmacological management of problematic sleeping in children with developmental disabilities. Dev Med Child Neurol. 2015;57(2):120–136. doi: 10.1111/dmcn.12623
   PubMed Web of Science ®Google Scholar
• Summers JA, Allison DB, Lynch PS, et al. Behaviour problems in Angelman syndrome. J Intellect Disabil Res. 1995;39(2):97–106. doi: 10.1111/j.1365-2788.1995.tb00477.x
   PubMedGoogle Scholar
• Pereira JA, Ravichandran CT, Mullett J, et al. Characterization of sleep habits and medication outcomes for sleep disturbance in children and adults with Angelman syndrome. Am J Med Genet A. 2020;182(8):1913–1922. doi: 10.1002/ajmg.a.61642
   PubMed Web of Science ®Google Scholar
• Hanzlik E, Klinger SA, Carson R, et al. Mirtazapine for sleep disturbance in Angelman syndrome: a retrospective chart review of 8 pediatric cases. J Clin Sleep Med. 2020;16(4):591–595. doi: 10.5664/jcsm.8284
   PubMed Web of Science ®Google Scholar
• Meng L, Person RE, Huang W, Bartolomei MS, et al. Truncation of Ube3a-ATS unsilences paternal Ube3a and ameliorates behavioral defects in the Angelman syndrome mouse model. PLoS Genet. 2013;9(12):e1004039. doi: 10.1371/journal.pgen.1004039
   PubMed Web of Science ®Google Scholar
• Tan W-H, Bird LM. Angelman syndrome: Current and emerging therapies in 2016. Am J Med Genet Part C, Semin Med Genet. 2016;172C(4):384–401. doi: 10.1002/ajmg.c.31536
   Google Scholar
• Huang HS, Allen JA, Mabb AM, et al. Topoisomerase inhibitors unsilenced the dormant allele of Ube3a in neurons. Nature. 2012;481(7380):185–189. doi: 10.1038/nature10726
   Web of Science ®Google Scholar
• Plasschaert RN, Bartolomei MS. Autism: a long genetic explanation. Nature. 2013;501:36–37. doi: 10.1038/nature12553
   PubMed Web of Science ®Google Scholar
• Wolter JM, Mao H, Fragola G, et al. Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA. Nature. 2020;587(7833):281–284. doi: 10.1038/s41586-020-2835-2
   PubMed Web of Science ®Google Scholar
• Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378(7):625–635. doi: 10.1056/NEJMoa1710504
   PubMed Web of Science ®Google Scholar
• Meng L, Ward AJ, Chun S, et al. Towards a therapy for Angelman syndrome by targeting along non-coding RNA. Nature. 2015;518(7539):409–412. doi: 10.1038/nature13975
   PubMed Web of Science ®Google Scholar
• Daily JL, Nash K, Jinwal U, et al. Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome. PLoS One. 2011;6(12):e27221. doi: 10.1371/journal.pone.0027221
   PubMed Web of Science ®Google Scholar
• Silva-Santos S, vanWoerden GM, Bruinsma CF, et al. Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model. J Clin Invest. 2015;125(5):2069–2076. doi: 10.1172/JCI80554
   PubMed Web of Science ®Google Scholar
• Tan WH, Bird LM, Sadhwani A, et al. A randomized controlled trial of levodopa in patients with Angelman syndrome. Am J Med Genet A. 2018;176(5):1099–1107. doi: 10.1002/ajmg.a.38457
   PubMed Web of Science ®Google Scholar
• Wink LK, Fitzpatrick S, Shaffer R, et al. The neurobehavioral and molecular phenotype of Angelman syndrome. Am J Med Genet A. 2015;167A(11):2623–2628. doi: 10.1002/ajmg.a.37254
   PubMedGoogle Scholar
• Scahill L, Aman MG, McDougle CJ, et al. Trial design challenges when combining medication and parent training in children with pervasive developmental disorders. J Autism Dev Disord. 2009;39(5):720–729. doi: 10.1007/s10803-008-0675-2
   PubMed Web of Science ®Google Scholar