Overview

Angelman Syndrome is a rare neurogenetic disorder that primarily affects the nervous system and development. It is characterized by severe developmental delays, speech impairment, movement and balance problems, and frequent, happy behavior including laughter and smiling. The condition typically becomes noticeable within the first year of life. While Angelman Syndrome can cause significant disabilities, individuals often have a long life expectancy and can live healthy lives with appropriate care and support.

Causes

Angelman Syndrome is most commonly caused by a genetic abnormality involving the UBE3A gene located on chromosome 15. The UBE3A gene plays an essential role in normal brain function. In most people, the UBE3A gene is inherited from both parents, but only the mother’s copy is active in certain parts of the brain. Angelman Syndrome occurs when the maternal copy of the UBE3A gene is missing or not functioning properly.

The main causes include:

• Deletion: The most common cause, where a portion of chromosome 15 is missing (maternal deletion).
• UBE3A mutation: A mutation within the gene itself rendering it inactive.
• Paternal uniparental disomy (UPD): The child inherits two copies of chromosome 15 from the father and none from the mother.
• Imprinting defects: The maternal gene is present but incorrectly silenced.
• Unknown causes: In a small percentage of cases, the exact cause remains unidentified despite testing.

Symptoms

Angelman Syndrome presents with a distinctive set of symptoms that can vary in severity. Common symptoms include:

• Severe developmental delay: Delays in reaching milestones like sitting, walking, or talking.
• Minimal or absent speech: Very limited verbal communication, though non-verbal communication is often well-developed.
• Frequent laughter and smiling: A happy demeanor with an excitable personality.
• Movement and balance issues: Ataxia (unsteady walking), jerky movements, and poor motor coordination.
• Seizures: Typically begin before the age of 3 years and can vary in type and severity.
• Sleep problems: Difficulty falling asleep or frequent nighttime waking.
• Distinct facial features: Wide mouth, protruding tongue, light-colored hair and skin (in some cases), and a prominent chin.
• Hyperactivity: Short attention span and quick, restless movements.
• Feeding difficulties in infancy: Trouble feeding and poor weight gain during early infancy.

Diagnosis

Diagnosis of Angelman Syndrome involves several steps, including clinical evaluation and genetic testing:

• Clinical observation: Pediatricians may suspect Angelman Syndrome based on developmental delays, lack of speech, and characteristic behaviors.
• Genetic testing:
  • Methylation studies: Detects approximately 80% of cases by identifying problems in the imprinting center.
  • UBE3A sequencing: Used to identify mutations within the UBE3A gene.
  • Microarray analysis: Detects larger deletions or duplications in chromosome 15.
• EEG (electroencephalogram): Often shows distinctive brain activity patterns associated with Angelman Syndrome.

Treatment

There is no cure for Angelman Syndrome, but treatment focuses on managing symptoms and improving quality of life through supportive care:

• Therapies:
  • Physical therapy: Improves mobility, balance, and strength.
  • Speech therapy: Focuses on non-verbal communication techniques and augmentative communication devices.
  • Occupational therapy: Helps with fine motor skills and daily living activities.
• Seizure management: Antiepileptic medications to control seizures.
• Sleep management: Behavioral techniques and, in some cases, medications to help with sleep problems.
• Behavioral therapy: Strategies to manage hyperactivity and improve focus.
• Special education: Individualized educational programs to meet the child’s developmental needs.

Prognosis

Despite developmental challenges, most individuals with Angelman Syndrome have a normal life expectancy. With early intervention and supportive care, children can make progress in communication, mobility, and daily skills. Many individuals remain cheerful and sociable, bringing joy to their families and caregivers.

While speech limitations and motor difficulties often persist, many people with Angelman Syndrome can learn to communicate effectively through alternative methods and live fulfilling lives with proper support. Ongoing medical care, therapy, and educational interventions are crucial to maximizing independence and well-being.