From the Guidelines
Angelman syndrome is a rare genetic disorder caused by the lack of expression of the UBE3A gene on chromosome 15, typically due to the absence of the maternally inherited contribution of this region. This condition affects the nervous system, leading to developmental delays, intellectual disability, speech impairment, and movement problems 1. The UBE3A gene is silenced by methylation on the paternally inherited allele, and its absence leads to the characteristic symptoms of Angelman syndrome.
Key Characteristics
- Developmental delays and intellectual disability
- Speech impairment, with most individuals using fewer than 10 words
- Movement problems, including jerky movements and balance issues
- Seizures, typically beginning between ages 2 and 3
- Sleep disturbances and fascination with water
- Characteristic facial appearance with a wide mouth and widely spaced teeth
Management and Treatment
Treatment for Angelman syndrome focuses on managing symptoms, as there is no cure 1. This includes:
- Anticonvulsant medications to control seizures
- Physical therapy to improve mobility and balance
- Occupational therapy to enhance daily living skills
- Speech therapy or communication devices to improve communication abilities
- Early intervention is crucial for maximizing developmental potential, and a multidisciplinary approach is essential for providing comprehensive care.
From the Research
Definition and Characteristics of Angelman Syndrome
- Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, deficits in speech, motor abnormalities, altered electroencephalography (EEG) activity, spontaneous epileptic seizures, sleep disturbances, and a happy demeanor with frequent laughter 2, 3, 4, 5.
- The disorder is typically caused by deletion or a loss-of-function mutation of the maternal copy of the ubiquitin ligase E3A (UBE3A) gene 2, 3, 5.
Prevalence and Genetic Factors
- Angelman syndrome is a rare disorder, affecting approximately 1 in 15,000 people 3.
- The UBE3A gene is located on chromosome 15q11-13 and is biallelically expressed throughout the body but only maternally expressed in the brain due to an RNA antisense transcript that silences the paternal copy 3.
Symptoms and Associated Challenges
- Individuals with Angelman syndrome often experience severe developmental delay, impaired communication skills, and a high prevalence of seizures, sleep disturbances, ataxia, motor deficits, and microcephaly 3, 4, 5.
- The disorder is also associated with behavioral concerns such as hyperactivity, aggression, self-injury, repetitive behavior, and sleep disorders 5.
Treatment Options and Emerging Therapies
- There is currently no cure for Angelman syndrome, but advancements in small molecule drugs and gene therapies offer a promising approach for the treatment of the disorder 3, 6, 5.
- Various pharmacologic approaches have been used to treat behavioral aspects of AS, including neuropsychiatric phenomena and sleep disturbances, as well as seizures in the context of the disorder 2.
- Emerging gene therapies and small molecule drugs are being developed to target the underlying genetic causes of the disorder and associated symptoms 3, 6, 5.