Angelman syndrome

Overview

Angelman syndrome is a rare neurogenetic disorder that affects the nervous system and causes severe developmental delays, speech impairments, movement and balance issues, and a characteristically happy demeanor. Children with Angelman syndrome typically have frequent laughter, smiling, and excitability. Despite significant developmental challenges, many individuals have a strong social personality and can live long lives with supportive care.

Angelman syndrome was first described by British pediatrician Dr. Harry Angelman in 1965, and it affects approximately 1 in 12,000 to 20,000 people worldwide.

Causes

Angelman syndrome is primarily caused by problems with the UBE3A gene located on chromosome 15q11.2-q13. In most people, only the maternal copy of this gene is active in certain areas of the brain. If this maternal copy is missing or not functioning correctly, the result is Angelman syndrome.

There are several genetic mechanisms that can lead to the condition:

• Deletion of the maternal 15q11.2-q13 region (most common, ~70% of cases)

• UBE3A gene mutation on the maternal allele (~10%)

• Paternal uniparental disomy (both chromosome 15s come from the father) (~7%)

• Imprinting defects affecting gene expression (~3%)

In rare cases, the cause is unknown but still suspected to involve the UBE3A gene.

Symptoms

Symptoms of Angelman syndrome typically appear in infancy and become more noticeable as developmental delays emerge. Common signs and symptoms include:

Developmental and Neurological Features:

• Severe speech impairment (minimal or no use of words)

• Delayed milestones such as sitting, walking, or talking

• Intellectual disability

• Ataxia (problems with movement and balance)

• Seizures, often beginning before age 3

• Characteristic EEG patterns

Behavioral Characteristics:

• Frequent laughter and smiling

• Happy, excitable personality

• Hyperactivity and short attention span

Physical Features:

• Small head size (microcephaly)

• Light skin and hair compared to family (in deletion cases)

• Tongue protrusion

• Sleep disturbances

Diagnosis

Diagnosis is usually made based on clinical features and confirmed with genetic testing. Key steps include:

• Developmental assessment: Identifying characteristic delays and behaviors

• Genetic testing: To detect deletions, mutations, uniparental disomy, or imprinting defects of the UBE3A gene

• Electroencephalogram (EEG): May reveal specific high-amplitude, slow-spike waves characteristic of the syndrome

• Brain MRI: Often normal but may help rule out other conditions

Treatment

There is no cure for Angelman syndrome, but supportive care and therapies can significantly improve quality of life and function. Treatment options include:

Therapies:

• Speech and language therapy: Focuses on nonverbal communication (e.g., sign language, AAC devices)

• Physical therapy: Improves mobility, balance, and posture

• Occupational therapy: Enhances daily living skills and hand function

• Behavioral therapy: Helps manage hyperactivity and improve social interactions

Medical Management:

• Anti-seizure medications: To control epilepsy

• Melatonin or other sleep aids: To improve sleep quality

Educational Support:

• Individualized education programs (IEPs)

• Special education and classroom accommodations

Prognosis

Angelman syndrome is a lifelong condition, but with proper care, individuals can lead long, happy lives. While intellectual and motor impairments are significant, many individuals learn to walk, communicate using alternative methods, and participate in social and recreational activities.

Seizures often become less severe with age, and sleep patterns may improve. Early diagnosis and intervention with therapy and education support are key to maximizing each individual’s developmental potential and quality of life.