Epilepsy in Angelman Syndrome and Response to Treatment

Abstract

Research Article| April 01 2010 Epilepsy in Angelman Syndrome and Response to Treatment AAP Grand Rounds (2010) 23 (4): 45. https://doi.org/10.1542/gr.23-4-45 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Epilepsy in Angelman Syndrome and Response to Treatment. AAP Grand Rounds April 2010; 23 (4): 45. https://doi.org/10.1542/gr.23-4-45 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: angelman syndrome, epilepsy Source: 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: https://doi.org/10.1111/j.1528-1167.2009.02108.xGoogle Scholar Using an electronic survey, investigators from the Massachusetts General Hospital in Boston; Angelman Syndrome Foundation in Aurora, IL; Texas Southwestern Medical Center, Dallas; and Rady Children’s Hospital, San Diego, studied the natural history and response to treatment of epilepsy in a large population of patients with Angelman syndrome (AS). Approximately 1,000 families of individuals with AS were asked to complete an online questionnaire made available for three months from February through May 2007. The survey included questions related to the nature of the child’s seizures, response to various medications, and medication side effects. Family members of 461 individuals (56% male) with AS completed the interview (46% response rate). The average age of patients at the time of the survey was 13.9 years (1.3–45 years) and their average age at diagnosis was 5.3 years (<1–35 years). Of the 461 subjects, 86% had experienced seizures with an average age of seizure onset of 2.9 years. The most frequently reported types of seizures were atonic (41%), generalized tonic-clonic (40%), atypical absence (37%), and complex partial (32%). Sixty percent of patients had at least two types of seizures. Convulsive status epilepticus occurred in 12%. Developmental regression occurred in 35%. Rates of epilepsy differed among genetic subtypes. Among study subjects, 65% had a maternal deletion, 18% an unknown subtype, 7% uniparental disomy, 7% ubiquitin-protein ligase E3 (UBE3A) mutations, and 2% imprinting defects. Patients with maternal deletions (89%) and unknown subtypes (90%) had the highest rates of epilepsy. Those with imprinting defects (55%) were least affected. At the time of the survey, 34% of patients were reported to be seizure-free for a median period of 3.2 years, beginning at an average age of 8.8 years. The most commonly prescribed antiepileptic medications (AED) were valproic acid (62%) and clonazepam (34%), but lamotrigine (24%) and levetiracetam (20%) had similar efficacy and tolerability. Only 15% responded to the initial AED. An additional 8% responded to a second agent but 77% had refractory seizures. Ketogenic diet was reported to be the most effective treatment in 11 of 31 subjects and vagus nerve stimulation in 8 of 16. The authors conclude that the newer AEDs are similarly effective to valproate and clonazepam but have similar or better side effect profiles and that further studies of nonpharmacologic therapies are needed. AS is a neurodevelopmental genetic disorder characterized by severe intellectual disability, severely impaired or absent speech, tongue protrusion, hypotonia from birth followed by hypertonia, ataxia, and frequent bouts of laughter. The behavior of children with AS is described as overactive, exuberant, sociable, and happy, and they have a wide-based gait, foot eversion, elbow flexion, and wrist supination. Epilepsy is a presenting symptom in >80% of patients, with onset between age 1 and 3 years.1 These children... You do not currently have access to this content.