- Angelman syndrome (AS) is a complex neurodevelopmental disorder characterized by severe developmental delays, speech impairment, movement and balance problems, and a distinctive behavioral pattern. The condition typically becomes apparent in early childhood, usually between 6 and 12 months of age, as developmental milestones are missed.
- The genetic basis of Angelman syndrome primarily involves the loss of function of the maternal copy of the UBE3A gene located on chromosome 15q11-q13. This can occur through several genetic mechanisms: deletion of the maternal 15q11-q13 region (approximately 70% of cases), paternal uniparental disomy (3-7%), imprinting defects (2-3%), or UBE3A mutations (5-10%). The remaining cases may involve unidentified mechanisms.
- The characteristic clinical features of Angelman syndrome include severe intellectual disability, minimal or absent speech (with receptive language skills typically higher than expressive ones), ataxic movements, and unique behavioral characteristics. Perhaps the most distinctive behavioral feature is a happy demeanor with frequent smiling, laughter, and excitability, often described as a “happy puppet” appearance.
- Neurological manifestations are prominent in Angelman syndrome. These include seizures (occurring in 80-95% of individuals), typically beginning before age 3. The EEG pattern in AS is characteristic and can be helpful in diagnosis, showing distinctive large-amplitude slow-spike waves. Movement disorders include ataxic gait, tremulous limb movements, and hypermotoric behavior.
- Sleep disturbances are common in individuals with Angelman syndrome, with reduced need for sleep, difficulty falling asleep, and frequent night waking. Many individuals sleep only 5-6 hours per night and can remain alert during much of the day despite minimal sleep.
- Physical features may include microcephaly (small head size), which typically develops by age 2. Other common features include deep-set eyes, protruding tongue, wide mouth, widely spaced teeth, and fair skin and hair (particularly in deletion cases). Most individuals also develop scoliosis, especially during adolescence.
- Communication challenges are significant in Angelman syndrome. While most individuals do not develop verbal language, many can learn to communicate through alternative methods such as augmentative and alternative communication (AAC) devices, sign language, or picture-based systems. Their receptive language abilities often exceed their expressive abilities.
- Medical management of Angelman syndrome requires a multidisciplinary approach. This includes treatment for seizures, physical therapy for movement disorders, occupational therapy for daily living skills, and speech therapy for communication. Gastrointestinal issues, feeding difficulties, and dental problems also require regular monitoring and management.
- The prognosis for individuals with Angelman syndrome varies. While intellectual disability is severe, many individuals can achieve some degree of independence in daily living activities. Life expectancy is generally normal, though individuals require lifelong care and support. The happy disposition and social nature of individuals with AS often aid in their interactions and relationships with others.
- Research into Angelman syndrome is active and promising. Current therapeutic approaches under investigation include attempts to activate the silenced paternal UBE3A copy, protein replacement strategies, and gene therapy. Understanding of the condition’s molecular basis has led to several clinical trials exploring potential treatments.
- Early intervention is crucial in Angelman syndrome. This includes physical therapy, occupational therapy, and speech therapy, which should begin as soon as possible after diagnosis. Educational approaches need to be tailored to each individual’s abilities and challenges, with a focus on functional skills and communication.
- Genetic counseling is important for families affected by Angelman syndrome. The recurrence risk varies depending on the genetic mechanism causing the condition, and this information is crucial for family planning decisions.
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