What Is Angelman Syndrome?
Angelman syndrome is a rare genetic disorder caused by a mutation in a specific gene. It leads to developmental delay, with significant effects on speech and balance, as well as intellectual disability and epilepsy. Individuals with Angelman syndrome often smile frequently and appear unusually cheerful. Signs of developmental delay typically become noticeable between six and twelve months of age and are often the earliest manifestation of the condition. Seizures usually emerge later, most commonly between two and three years of age. Although Angelman syndrome cannot be cured, affected individuals generally have a life expectancy similar to that of the general population.
Why Is It Called “Angelman” Syndrome?
Angelman syndrome is named after Dr. Harry Angelman, a British pediatrician (Figure 1). He was the first to recognize a distinctive pattern of features in three children, including intellectual impairment, severe language difficulties, and an unusually happy demeanor. At the time, these characteristics were described as resembling “happy, angelic puppets” (Figure 2). This historical description later gave rise to the name Angelman syndrome.
Figure 1. Harry Angelman
Figure 2. “Like a happy angelic puppet”
Why Do Individuals with Angelman Syndrome Smile So Frequently?
Individuals with Angelman syndrome often display frequent smiling and cheerful behavior. This is not because they experience greater happiness, but because emotional regulation is impaired. Angelman syndrome is caused by a mutation in the UBE3A gene, which plays a critical role in neuronal synaptic function, emotional inhibition and regulation, and behavioral control. When the UBE3A gene is disrupted, inhibitory pathways in the nervous system become weaker. As a result, laughter, heightened excitement, and repetitive movements such as hand flapping are more easily triggered and less effectively regulated.
What Are the Other Typical Features of Angelman Syndrome?
Beyond the characteristic happy demeanor, Angelman syndrome is marked by significant developmental delay. Many children fail to reach early developmental milestones, such as crawling or babbling, between six and twelve months of age. Speech is often absent or extremely limited. Difficulties with walking, motor coordination, and balance are common, and individuals frequently appear easily excitable. Feeding challenges, including difficulty sucking or eating, may occur, and sleep disturbances—such as trouble falling asleep or staying asleep—are also frequently reported.
Why Is Angelman Syndrome Often Misdiagnosed?
The earliest signs of Angelman syndrome, particularly developmental delay, are nonspecific and can resemble a range of other conditions. Clinicians may initially attribute these symptoms to global developmental delay, prematurity-related delay, or benign hypotonia. Because these early features lack clear disease-specific markers, Angelman syndrome is difficult to identify in its initial stages. In addition, several characteristics of Angelman syndrome, including absent speech and repetitive behaviors, overlap with more common neurodevelopmental disorders such as autism spectrum disorder. Given the rarity of Angelman syndrome, early misdiagnosis is common. A correct diagnosis often occurs only later, when more distinctive features become apparent, such as pronounced balance impairment, frequent laughter, and severe language deficits.