From the Guidelines
Angelman syndrome is a genetic disorder that affects the nervous system, causing developmental delays, intellectual disability, speech problems, and movement issues, and the most effective management approach is a multidisciplinary one, including anticonvulsant medications, physical therapy, occupational therapy, speech therapy, and behavioral therapy, as supported by the most recent study 1. The condition is caused by a missing or defective gene on chromosome 15, specifically the UBE3A gene, which is typically inherited from the mother. Symptoms usually appear in early childhood and include:
- Delayed development
- Minimal or absent speech
- Seizures
- A happy demeanor with frequent smiling and laughter
- Distinctive physical features such as a small head size and wide mouth There is no cure for Angelman syndrome, but treatment focuses on managing symptoms to improve quality of life. Key management strategies include:
- Anticonvulsant medications like valproic acid or clonazepam for seizures
- Physical therapy to improve mobility
- Occupational therapy for daily living skills
- Speech therapy using alternative communication methods
- Behavioral therapy Sleep disturbances, common in this condition, may be managed with melatonin. Early intervention is crucial for maximizing developmental potential, as highlighted in the study 1. While individuals with Angelman syndrome have significant challenges, they typically have a normal lifespan and can achieve various developmental milestones with appropriate support and therapies tailored to their specific needs, as noted in the guidelines 1 and the recent review 1.
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