From the Guidelines
Angelman syndrome is a genetic disorder that requires a multidisciplinary approach to manage its symptoms, with no cure available, and treatment should focus on improving quality of life through physical, speech, and occupational therapy, as well as managing seizures and sleep disturbances. The disorder is characterized by developmental delays, intellectual disability, speech impairment, movement and balance problems, and a happy, excitable demeanor with frequent smiling and laughter, caused by the loss of function of the UBE3A gene on chromosome 15, typically due to deletion or mutation of the maternal copy of this gene 1. Some key aspects of managing Angelman syndrome include:
- Physical therapy to improve mobility and coordination
- Speech therapy to develop communication skills
- Occupational therapy for daily living skills
- Behavioral therapy to address any behavioral challenges
- Seizure management with anticonvulsant medications such as valproic acid, clonazepam, or levetiracetam, with dosing individualized based on age, weight, and seizure type
- Sleep disturbance management with melatonin, typically 1-6 mg at bedtime Genetic counseling is also important for families, as Angelman syndrome has a recurrence risk of up to 50% in some cases, depending on the genetic mechanism, such as imprinting errors or balanced translocations involving chromosome 15 1. Early intervention is crucial to maximize developmental potential, and most individuals with Angelman syndrome will require lifelong support and supervision, with a focus on improving their quality of life and reducing morbidity and mortality.
From the Research
Definition and Prevalence of Angelman Syndrome
- Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals 2
- It is estimated that AS accounts for up to 6% of all children presenting with severe mental retardation and epilepsy 3
Clinical Features of Angelman Syndrome
- The main clinical features of AS include developmental delay, severely impaired expressive language, ataxic gait, tremulousness of limbs, and a typical behavioral profile 3
- Seizures, abnormal electroencephalography, microcephaly, and scoliosis are observed in >80% of patients 3
- Individuals with AS often have a happy demeanor, hypermotoric behavior, and low attention span 3
Genetic Causes of Angelman Syndrome
- Approximately 70% of patients show a deletion involving the maternally inherited chromosome 15q11-q13 3
- 3% show chromosome 15 paternal uniparental disomy (UPD), 1% harbor a mutation in the imprinting center, and 6% harbor intragenic mutations of the ubiquitin-protein ligase E3A (UBE3A) gene 3
- 20% of patients have no detectable genetic abnormality 3
Diagnosis and Management of Angelman Syndrome
- Approximately 75% of cases are detected through the methylation test, which allows the detection of AS due to deletions, UPD and IC mutations 3
- Mutation analysis of the UBE3A gene should be performed when the methylation test is negative 3
- A multidisciplinary approach and consensus statement have been proposed to establish standards of care for AS 2
- Rehabilitation interventions, including physiotherapy, applied behavioral analysis, and augmentative and alternative communication, can help improve patients' autonomy and quality of life 4
Quality of Life and Sleep Problems in Angelman Syndrome
- Sleep problems, seizures, and inability to walk are significant factors affecting quality of life in individuals with AS 5
- Interventions to improve sleep, such as pharmacological and behavioral treatments, have shown provisional evidence but weak evidence for effectiveness 6
- Further high-quality research is needed to evaluate interventions for the treatment of sleep problems in AS 6