Angelman syndrome is a rare genetic disorder that primarily affects the nervous system, leading to developmental delays and neurological issues. This condition impacts approximately 1 in 12,000 to 20,000 people globally. While infants with Angelman syndrome typically appear normal at birth, developmental delays usually become noticeable between 6 and 12 months of age.
Genetic Causes of Angelman Syndrome
Angelman syndrome arises from a problem with the UBE3A gene, located on chromosome 15. Humans inherit two copies of most genes, one from each parent. For the UBE3A gene, only the copy inherited from the mother is active in brain nerve cells; the paternal copy is typically “switched off” due to genomic imprinting. If the maternal copy of the UBE3A gene is missing or not functioning correctly, the syndrome’s characteristics emerge.
The most common cause, accounting for about 70% of cases, is a deletion of a segment of the maternal chromosome 15 that includes the UBE3A gene. Other less common causes include a mutation within the maternal UBE3A gene, inheriting two copies of chromosome 15 from the father (paternal uniparental disomy), or a defect in the imprinting center that controls the UBE3A gene’s activation.
Early Signs and Symptoms in Infants
Developmental delays become apparent between 6 and 12 months of age. These early signs can guide caregivers to seek further evaluation.
Feeding Difficulties
Infants with Angelman syndrome often experience feeding problems during their first few months of life. These difficulties stem from an inability to coordinate sucking and swallowing. Issues like gastroesophageal reflux disease (GERD), where stomach contents leak back into the esophagus, are also common.
Significant Developmental Delays
One of the earliest and most noticeable signs is a delay in reaching motor milestones. Infants may not be able to sit unsupported, crawl, or babble between 6 and 12 months. They may also exhibit low muscle tone, known as hypotonia, which can contribute to delayed motor skill development.
Characteristic Movements
Specific movement patterns may emerge. These include jerky limb movements, tremors in the arms and legs, an unsteady, uncoordinated gait when they eventually begin to walk, and hand-flapping movements.
Specific Behaviors
Infants with Angelman syndrome often exhibit a distinct and generally happy demeanor. This can manifest as frequent smiling and laughter, sometimes appearing unprovoked or unrelated to the situation. They may also be easily excitable, restless, and have a short attention span.
Sleep Disturbances
Sleep problems commonly begin in infancy. These disturbances can include abnormal nighttime sleep duration, frequent waking, and a reduced need for sleep compared to other children. While sleep issues may improve with age, they can persist into adulthood.
The Diagnostic Process
The diagnostic journey for Angelman syndrome typically begins when an infant’s developmental delays and characteristic symptoms prompt concern from parents or healthcare professionals. Early signs often overlap with other developmental conditions like cerebral palsy or autism, leading to an initial misdiagnosis in about half of all cases.
A pediatrician or neurologist will conduct a clinical evaluation, observing the infant’s motor skills, language development, and overall behavior. If Angelman syndrome is suspected based on these observations, definitive confirmation requires specific genetic blood tests. These tests look for alterations in the UBE3A gene or chromosome 15.
Genetic testing methods include DNA methylation analysis, which can identify about 80% of cases by detecting abnormal patterns on chromosome 15. If this test is normal, a UBE3A gene sequencing test may be performed to look for smaller mutations within the gene. Additionally, a chromosomal microarray (CMA) can identify missing segments of chromosomes, and a fluorescent in situ hybridization (FISH) test can detect specific chromosome deletions. An electroencephalogram (EEG), which measures brain electrical activity, may also be performed due to the association between Angelman syndrome and seizures, which typically begin between 2 and 3 years of age.
Early Intervention and Management
While there is currently no cure for Angelman syndrome, early intervention is highly recommended to help maximize an infant’s potential and improve their quality of life. A multidisciplinary team of healthcare professionals typically collaborates to address the varied needs of individuals with this condition.
Physical therapy is often initiated early to help with motor skill development, balance, and overall mobility. Therapists guide exercises to strengthen muscles and promote milestones such as sitting, crawling, and eventually walking, which can also help prevent joint stiffness as the child grows. Occupational therapy focuses on improving daily living skills and fine motor coordination, assisting with tasks like feeding, dressing, and manipulating objects. This therapy can also address sensory processing challenges common in Angelman syndrome.
Communication therapy is also a significant component, aiming to build foundational skills for future non-verbal communication. Given that many individuals with Angelman syndrome have limited or no spoken language, therapists may introduce methods such as sign language, picture exchange communication systems (PECS), or augmentative and alternative communication (AAC) devices. Medical management for associated issues like seizures, which affect a majority of individuals, often involves anti-seizure medications. Sleep problems can be managed through behavioral strategies and, if needed, medication. Additionally, feeding difficulties and gastrointestinal issues like constipation or reflux may require dietary adjustments, specialized feeding techniques, or medication.