Angelman Syndrome: Everything you need to know

Have you heard of Angelman syndrome? Chances are, you haven’t. Most of the general population is unaware of this rare congenital disorder which impacts the nervous system. From seizures to developmental delays, it presents with a vast array of symptoms. Those with Angelman syndrome are truly angels as they display a joyful, happy demeanor in the midst of pain.

Angelman Syndrome
Angelman Syndrome

What is Angelman Syndrome?

Angelman syndrome is a rare genetic disorder of the nervous system. The disorder was previously named “Happy Puppet Syndrome” because the happy demeanor and jerky muscle movements in all of the original patients. The condition was later renamed after Dr. Harry Angelman who first founded Angelman syndrome in 1965.

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The frequency in which Angelman syndrome occurs is estimated to be 1 in every 10,000 to 20,000 people. Male and females are equally affected. Considering Angelman syndrome is so rare, and many go undiagnosed, it is difficult to determine its prevalence in the population.

Causes of Angelman Syndrome

Genetic changes in the UBE3A gene located on Chromosome 15 cause the unique symptoms of Angelman syndrome. In normal development, a healthy child will inherit one copy of the gene from each parent. Both copies direct bodily functions. Only one copy of the gene inherited from the mother is active in certain areas of the brain.

When a section of the gene is missing, mutated, or the child has a chromosomal deletion preventing the gene’s expression, there are no active copies to provide the nervous system with the vital UBE3A protein. Thus, Angelman syndrome is the result. Inheriting two copies of Chromosome 15 from the father cause a small percentage of Angelman syndrome cases.

Physical Characteristics of Angelman Syndrome 

Distinctive physical characteristics, especially facial features, are hallmark signs of Angelman syndrome. These unique features are not displayed at birth. Instead, they develop around age 2 or 3 and vary in severity. The late presentation is why Angelman syndrome often goes misdiagnosed or undiagnosed.

  • Prominent chin—A prominent chin sticks out from the jaw.
  • Deep-set eyes—The eyes are set deeper into the skull.
  • Macrostomia—Macrostomia is the medical term defining widening of the mouth.
  • Protruding tongue—Angelman syndrome comes with numerous oral symptoms including a protruding tongue. A protruding tongue is the result of a muscular imbalance where the tongue pokes through the anterior incisors and canine teeth.  
  • Widely spaced teeth—The teeth of someone with Angelman syndrome have large gaps precipitating excessive drooling.
  • Brachycephaly—Defined as flattening of the entire back of the head, brachycephaly occurs when the skull is soft enough to alter the head shape.
  • Tapered fingers—When fingers are tapered, the ends of the fingers are obviously smaller than the base and middle. Tapered fingers are indicative of certain genetic conditions.
  • Scoliosis—Adolescents with Angelman syndrome are prone to a progressive abnormal curvature of the spine.
  • Hypopigmentation—Skin, hair, and eyes have a lack of color. Angelman syndrome patients might have blonde hair and blue eyes without a family history of those traits.

Angelman Syndrome Symptoms: Neurological 

Neurological symptoms are the main manifestations of Angelman syndrome because the syndrome impedes the normal functioning of vital brain processes. Especially with motor delays, the neurological symptoms are less evident until the toddler stage when it is obvious the child has missed major motor milestones.

  • Microcephaly—Microcephaly, a reduced head and brain size in comparison to age, develops in patients with Angelman syndrome during the first 18 months of life. The brain and head do not develop properly causing each to be smaller.
  • Epileptic seizures—Seizures originate around 1 and 5 years of age and tend to improve in adolescence before flaring again in adulthood.
  • AtaxiaJerky muscle movements, tremors, an unsteady gait, and balance issues are due to the lack of voluntary coordination of muscle movement.
  •  Motor delays—Motor milestones like sitting up, turning over, crawling, and walking are delayed. Children with Angelman syndrome typically do not learn to walk until they are between the ages of 2 and 10. Walking is slow and jerky when it does occur.
  • Truncal hypotonia—Unlike other disorders, decreased muscle tone (hypotonia) is not widespread in Angelman syndrome. Hypotonia is confined to the trunk muscles.
  • Hypertonia—Aside from the trunk, the limbs demonstrate an increase in muscle tone (hypertonia).
  • Hyperreflexia—Hyperreflexia is an exaggerated reflex response. It contributes to motor abnormalities and is secondary to changes in muscle tone.
  • Strabismus—Strabismus, the misalignment of the eyes, is also known as being cross eyed. In Angelman syndrome, strabismus is a symptom caused by decreased muscle control in the eyes.
  • Feeding difficulties—Poor feeding is common in infants, as uncoordinated muscle movements prevent swallowing and sucking efficiently. Feeding difficulties can provoke gastroesophageal reflux disease (GERD) if the esophagus is effected and stomach contents reflux into the throat.
  • Delayed gastrointestinal motility—Uncoordinated muscle movements can impact the muscles of the stomach and intestines. Food takes longer to leave the gastrointestinal tract causing reflux, vomiting, and constipation.

Angelman Syndrome Symptoms: Behavioral

An excitable, happy demeanor is an intriguing, yet well-known behavioral characteristic of Angelman syndrome. Still, the behavioral characteristics are multi-faceted. They adopt motor, social, and psychological components.  

  • HyperactivityHyperactivity in Angelman syndrome is described as hypermotoric because there is an increase in motor activity. More so than similarly aged peers without the condition, infants and toddlers are “hyper”—continuously roaming the room and putting hands and toys in their mouths. In older children, hyperactivity leads to unwanted aggressive behaviors (i.e. pinching, biting, hitting).
  • AggressionAlthough the syndrome causes an overall happy demeanor, 7 out of 10 patients show aggressive behavior. Examples of aggressive behavior are hair pulling, kicking, and biting. Aggression correlates with low levels of adult attention.
  • Self-injury—Next to aggression, self-injury includes behaviors performed to intentionally harm oneself (i.e. banging head against the wall, biting, scratching).
  • InattentionDistractibility and inattention are related to hyperactivity. While hyperactivity occurs more frequently in Angelman syndrome than in control subjects with mental retardation, experts claim inattention is comparable (Pelc et al., 2008). Seizures are partly responsible for distractibility and attention.
  • Frequent smiling and laughing—Early on, babies and children possess happy, excitable personalities. Frequent, unsuppressed laughter stems from abnormalities in the left hemisphere of the brain which regulate laughter.  
  • Attraction to objects—Water, crinkling paper, plastics, and shiny objects are fascinating to children with Angelman syndrome and engross their attention.
  • ObesityAngelman syndrome increases appetite. Supervision is crucial in late childhood and adolescence to avoid unhealthy eating behaviors (i.e. consuming non-food items, overeating).
  • Oral motor behaviors—Children exhibit excessive chewing, drooling, and tongue thrusting.

Angelman Syndrome Symptoms: Intellectual Characteristics

Intellectual disability is a symptom of Angelman syndrome. The term refers to difficulties with cognitive functioning, as well as practical and social skills. Although unnoticed at birth, intellectual deficits are apparent when the child fails to reach developmental milestones such as crawling, cooing, and speaking.

Speech impairments are extensive. People with Angelman syndrome use 2 to 10 words in their vocabulary. They suffer from receptive dysphasia—the inability to understand what is said to them—and expressive dysphasia in that they struggle to communicate their thoughts and feelings. Older adolescents and adults communicate through hand gestures and communication technology.  

Those with Angelman syndrome learn at a slower pace. This includes self-care, following directions, and sociability. Regardless, they show a desire to interact with others.

Angelman Syndrome Symptoms: Sleep Disorders

Studies of Angelman syndrome reflect the highest incidence of sleep disturbance (between 48-70%) compared with other rare genetic syndromes. Beginning as an infant shortly after birth, babies with Angelman syndrome show a decreased need for sleep. They have an erratic, disrupted sleep cycle. Sleeping during daylight hours and waking throughout the night is not uncommon. Factors such as obesity may contribute to sleep apnea in which breathing repeatedly stops and starts during sleep.

Adults with Angelman Syndrome

Most children born with Angelman syndrome do survive through adulthood. The prognosis of Angelman syndrome is a near normal life-span. With age, those with Angelman syndrome notice a reduction in sleep disturbances and behavioral characteristics (i.e. excitability). However, the physical facial features of an adult with Angelman syndrome are “coarse”—meaning their features are less defined and adopt a rounded appearance with thickened skin, subcutaneous and bony tissues.

While some symptoms improve, seizures, intellectual delays, and speech impairment remain profound well into adulthood. Researchers claim epilepsy is the leading cause of hospitalizations in the third and fourth decades (Larson et al., 2014). Despite the challenges, adults with Angelman syndrome lead productive lives. They are not able to live on their own without daily care, but they can work in supervised job positions.

Diagnosing Angelman Syndrome

Diagnosing Angelman syndrome relies primarily on clinical methods. Unique facial features, intellectual disability, delayed development, and behavioral characteristics are suggestive of the diagnosis. Providing the patient meets the criteria, a neurologist or a geneticist validates the diagnosis. No testing, like brain scans, lends evidence to the diagnosis because brain scans are normal in Angelman Syndrome.

If the clinical diagnosis is insufficient, DNA methylation tests can reveal the missing chromosomes or parenteral DNA pattern to confirm chromosomal defects. Genetic sequencing locates the mutation in the UBE3A gene. The majority of patients are diagnosed between the ages of 3 and 7, as it usually takes years to connect the constellation of behavioral and physical symptoms.

Misdiagnosing Angelman Syndrome 

Angelman syndrome is easily mistaken for various other conditions because of symptom overlap. But there are always contradictions that “just don’t add up” before Angelman syndrome is correctly diagnosed. For example, the syndrome is misdiagnosed as autism with hyperactivity, speech problems, and hand postures. Contrarily, those with this syndrome are very sociable unlike someone with true autism.

The following genetic and neurological conditions are misdiagnosed:  

  • Cerebral palsy—Uncoordinated muscle movements are mistaken for the jerky muscle movements in this syndrome.
  • Rett syndrome—A number of females with this syndrome are misdiagnosed with Rett syndrome, which is a neurological disorder with intellectual disability, speech problems, and seizures.
  • Prader-Willi syndromeCaused by a deletion on chromosome 15, Prader-Willi syndrome shares many symptoms with this syndrome like reduced muscle tone, feeding difficulties, and distinctive facial features.
  • Christianson syndrome—Happy demeanor, psychomotor delays, seizures, and ataxia occur in both conditions. The happy disposition is a major characteristic that makes medical professionals think Christianson syndrome rather than this syndrome.
  • Pitt-Hopkins syndrome—Intellectual disability, gait issues, ataxia, microcephaly, and a wide mouth are defining features. Diurnal hyperventilation sets Pitt-Hopkins syndrome apart.

Angelman Syndrome Treatment

A cure does not exist for this syndrome. Treatment consists of managing its symptoms. While there are favorable treatment options for secondary seizures and sleep disorders, treatments for the intellectual and behavioral characteristics are limited.


  • Anticonvulsants—Anticonvulsants or antiepileptic medications are typically prescribed in early childhood to control epileptic seizures.
  • Motility drugs—Motility medications increases the transit time for food to leave the gastrointestinal tract. These drugs treat the delayed emptying.
  • Laxatives—Laxatives stimulate the bowel to relieve constipation.
  • Proton-pump inhibitors (PPIs)—PPIs are a class of drugs that hinder gastric acid secretion. Patients with this syndrome benefit from PPIs to reduce episodes of acid reflux from gastroesophageal reflux disease.
  • Sedating medications—Since frequent waking is a symptom of Angelman syndrome, sedating medications are given to induce sleep. However, behavioral therapies are preferred.
  • Melatonin—Melatonin is a natural hormone produced by the body. It is released by the pineal gland to regulate the sleep-wake cycle. Studies on sleep disorders in Angelman syndrome report supplementing with melatonin promotes better sleep.
  • Risperidone—Hyperactive and disruptive behavior is occasionally treated with Risperdal (risperidone) for short durations.  


Early intervention is important to ensure children with Angelman syndrome grow physically, intellectually, and psychologically to meet their fullest potential. Support from family members and therapists are an asset to Angelman syndrome treatment.

  • Physical therapy—Ataxia and reduced muscle tone in Angelman syndrome makes physical therapy an essential part of treatment. Physical therapists assess which areas in the body are affected by jerking and tremor movements and then design an exercise plan. Physical therapy exercises increase the strength of muscle tone, steadies balance, and enhances motor skills.
  • Occupational therapy—Occupational therapy focuses on providing the patient with skills necessary for daily living. They give patients assistive devices to function independently. The therapy is tailored to the patient and ranges from braces for walking to bracing to reverse curvature of the spine. Ankle braces are particularly helpful.
  • Speech therapy—The goal of speech therapy is to overcome the lack of speech development. A speech therapist identifies barriers to communication while providing communication devices such as tablets and teaching the use of gestures, sign language, and picture cards. Professionals recommend speech therapy at an early age to aid in speech development.
  • Behavior modification—Those with Angelman syndrome display hyperactivity, a fascination with water, sleep disturbances and are prone to self-injurious behavior. Behavioral therapy pinpoints unwanted behaviors and gives strategies to cope.
  • Special eduction—Education is undoubtedly influenced by intellectual disability, but children with the disorder can succeed in special education programs. Special education educators work closely with physical and occupational therapists to correct physical barriers that hinder education in a classroom setting.
Special Education For Angelman Syndrome
Special Education For Angelman Syndrome
  • Surgical therapy—Severe cases of Angelman syndrome require surgery to correct scoliosis if traditional bracing fails and the curvature of the spine is interfering with organ function. Surgery of the gastrointestinal tract called a nissen fundoplication is also performed in severe cases to prevent reflux.


Larson, A. M., Shinnick, J. E., Shaaya, E. A., Thiele, E. A., & Thibert, R. L. (2014). Angelman syndrome in adulthood. American journal of medical genetics. Part A, 167A(2), 331-44.

Pelc, K., Cheron, G., & Dan, B. (2008). Behavior and neuropsychiatric manifestations in Angelman syndrome. Neuropsychiatric disease and treatment4(3), 577-84.

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