From the Guidelines
Angelman syndrome is a rare genetic disorder that requires comprehensive management to improve quality of life, and treatment should focus on managing symptoms through anticonvulsant medications, physical therapy, occupational therapy, and speech therapy or alternative communication methods. Angelman syndrome is typically caused by the loss of function of the UBE3A gene on chromosome 15, which is normally inherited from the mother 1. Individuals with Angelman syndrome often have a happy, excitable demeanor with frequent smiling and laughter, which is why it was once called "happy puppet syndrome." Physical characteristics include seizures (in about 80% of cases), sleep disturbances, and distinctive facial features.
Some key aspects of Angelman syndrome management include:
- Anticonvulsant medications for seizures, such as valproic acid, levetiracetam, or clonazepam
- Physical therapy to improve mobility
- Occupational therapy for daily living skills
- Speech therapy or alternative communication methods Early intervention is crucial for maximizing developmental potential, and genetic counseling is recommended for families, as the recurrence risk varies depending on the specific genetic mechanism causing the syndrome 1. Despite significant challenges, with appropriate support, individuals with Angelman syndrome can learn and develop throughout their lives, though they typically require lifelong care and supervision. A recent review highlighted the importance of comprehensive and high-quality guidelines for rare genetic neurodevelopmental disorders, including Angelman syndrome, to ensure optimal care and management 1.
From the Research
Definition and Characteristics of Angelman Syndrome
- Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals 2
- Characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background 2
- Caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system 2
Treatment and Management
- There is no disease-modifying treatment available, but the therapeutic pipeline of Angelman syndrome includes at least 15 different approaches at preclinical or clinical development 3
- Therapies aim to restore the missing or nonfunctional UBE3A protein in the neurons via gene replacement or enzyme replacement therapies 3
- Compounds that target molecular pathways and effector proteins known to be involved in Angelman syndrome pathophysiology are also being developed 3
- Pharmacotherapeutic management of seizures is a critical priority to improve health-related quality of life in children with AS 4
- Levetiracetam and clobazam are the most commonly used antiseizure medications (ASMs) 4
Rehabilitation Interventions
- A comprehensive approach to rehabilitation interventions in patients with Angelman syndrome includes physiotherapy, applied behavioral analysis, toilet training, microswitch-cluster technology, and augmentative and alternative communication 5
- Individualized and multidisciplinary rehabilitation interventions help to improve patients' autonomy and quality of life 5
- The caregivers' role is fundamental to identify preferences and long-term improvements 5
Emerging Treatment Options
- Gene-based therapies are entering into clinical development 6
- Emerging gene therapies mean that increasing efforts should be directed toward the early identification of AS implemented equitably 6
- Behavioral therapy plays an important role in addressing mental health concerns such as aggression and disordered sleep 6