An Overview of Angelman Syndrome

Angelman syndrome is a rare genetic disorder characterized by significant developmental and intellectual disability, movement problems, seizures, sleep irregularities, and an atypically happy demeanor. Once referred to as "happy puppet syndrome" (a term now considered a pejorative), the condition affects one of every 15,000 births, according to the non-profit Angelman Syndrome Foundation.

Young cerebral palsy patient with caregiver
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While children with Angelman syndrome will have distinctive features and symptoms, the condition is usually only recognized when the child is six to 12 months old. Because the condition is so rare, Angelman syndrome is frequently misdiagnosed as autism or cerebral palsy.

While there is no cure for Angelman syndrome, anticonvulsant drugs, physical therapy, occupational therapy, and speech and language therapy can significantly improve the quality of life. Those affected can live normal lifespans but will invariably require lifelong care.


Angelman syndrome was named after a British pediatrician, Harry Angelman, who in 1965 described the condition based on its characteristic symptoms. Those characteristics can be broadly classified as physical, developmental, behavioral, and neurological.

Physical Characteristics

In the same that Down syndrome can be recognized by specific head and facial abnormalities, Angelman syndrome is characterized by a head circumference that is disproportionately small.The symptom is not usually seen at the time of birth but only as the baby develops, during which time the head fails to grow in tandem with the rest of the body.

This results in microcephaly, a condition in which the brain is abnormally small. Unlike some forms of microcephaly which are apparent at birth (such as newborns congenitally infected with Zika virus), those caused by Angelman syndrome are only recognized between the ages of one and two.

In addition to head size, other characteristic symptoms may include:

  • Brachycephaly (flat back of the head)
  • Telecanthus (wide-set eyes)
  • Bilateral epicanthic folds (prominent skin folds on the upper and lower eyelids)
  • Strabismus (crossed eyes)
  • Macrostomia (wide mouth)
  • Widely spaced teeth
  • Tapered fingers with broad thumbs
  • Smooth palms with abnormal creases
  • Skin, hair, or eye hypopigmentation (absence of color)

Angelman syndrome is neither associated with an abnormal stature, limb size, nor sexual development. Puberty and fertility in both males and females are not affected. Menstruation and spermatogenesis (the development of sperm during puberty) occur at more or less the same time as other children.

As children with Angelman syndrome get older, the progressive lateral curvature of the spine (scoliosis) may become apparent. Some adults will also develop macrognathia (the abnormal enlargement of the jaw) and keratoconus (the bulging of the cornea).

Obesity is also common, most especially in adult women.

Developmental Characteristics

Angelman syndrome is characterized by severe developmental and intellectual disability.As with the physical symptoms of the disorder, the developmental signs may not be noticed until the baby is between six and 12 months and certain milestones, such as crawling, babbling, or cooing, fail to appear.

As the child gets older, the impairment will become more apparent. While the scope of impairment can vary, children and adults with Angelman syndrome will almost invariably have severe to profound intellectual disability.

While the diagnostic values for this remain contentious, the IQ of adults with Angelman syndrome is usually well below 70 for cognitive ability (meaning the capacity to comprehend and reason). Generally speaking, scores below 70 represent some degree of learning or developmental disability.

Further compounding these limitations is the almost total absence of speech and words. In fact, most people with Angelman syndrome will develop more than five to 10 words in their vocabulary (although, paradoxically, they will remain extremely receptive to non-verbal forms of communication).

Other developmental and intellectual deficits include:

  • Severe learning disability due, in part, to poor memory retention and short attention spans
  • Impaired fine and gross motor skills due largely to the neurological symptoms of the disease

Despite these limitations, Angelman syndrome is not a progressive disease. Therefore, with ongoing physical, occupational, and communication therapy, individuals with the disorder may be able to learn to dress, eat with a knife and fork, respond to basic instructions, and perform household chores.

Behavioral Characteristics

Perhaps the most striking characteristic of Angelman syndrome is happiness. It is a unique behavioral feature in which the affected adult or child will laugh and smile frequently while maintaining a heightened state of cheer and excitability (often typified by hand-flapping or waving movements).

Children with Angelman syndrome will often be hyperactive and have extremely short attention spans. The laughter or smiling will often be prolonged, unprovoked, and, at times, inappropriate. Despite their physical and intellectual limitations, affected children tend to have boundless curiosity and may appear to be in a constant state of motion.

Irregular sleep is also common, generally resulting in no more than four to five hours of sleep at a time. The chronic lack of sleep may further enhance the underlying hyperactivity.

Other behavioral signs include:

  • Tongue thrusting or a protruding tongue
  • Drooling
  • Excessive chewing or mouth motions
  • An abnormal fascination with water

As the child gets older, some of these behaviors will begin to moderate. As adulthood approaches, hyperactivity and poor sleep patterns can often subside or disappear entirely.

Neurological Characteristics

Angelman syndrome is classified as a neuro-genetic disorder, meaning that the underlying genetic cause triggers the impairment of the central and peripheral nervous system functions. This can lead to an array of symptoms that directly and indirectly impact movement and other physiological functions.

Early signs of Angelman syndrome typically include balance and motor problems associated with ataxia (the inability to coordinate muscle movements). As a result, movements are often jerky and accompanied by fine tremors in the arms and legs. Children will often have a stiff gait and walk with their elbows raised and wrists bent. In around 10 percent of cases, a child will not be able to walk unaided.

Over time, increased muscle tone in the arms and legs coupled with decreased muscle tone in the trunk will lead to hyperreflexia (exaggerated or repeating reflex responses).

Another characteristic neurological symptom is seizures. These tend to first appear when the child is two to three years of age. Unlike other forms of epilepsy, the types of seizures can vary enormously in an affected individual and may include tonic-clonic, myoclonic, and absence seizures.

Children with Angelman-associated seizures will invariably have abnormal readings on an electroencephalogram (EEG), a device which measures electrical brain activity.

Among the indirect symptoms of Angelman syndrome, poor feeding is common in infants due to their inability to coordinate the muscles needed to swallow or suck. The problem can persist well into adulthood, leading to symptoms of gastroesophageal reflux disorder (GERD) as food and acids backflow (reflux) from the stomach into the esophagus.


Angelman syndrome is caused by an error in a gene located on chromosome 15 known as the ubiquitin protein ligase E3A (UBE3A) gene.

Chromosomes, which are present in the nucleus of every human cell, carry the genetic information for each individual. Human cells normally have 46 chromosomes, including 22 pairs (numbered from 1 through 22) and two additional sex chromosomes (designated X and Y). When a child is conceived, each parent will contribute half (or 23) of the chromosomes, the combination of which will determine the unique characteristics of the child.

With Angelman syndrome, the UBE3A gene is unique in that only the mother's contribution is active in the brain; the fathers are not. As such, if the maternal gene is missing or damaged, there will be no working copy of the UBE3A gene in the brain. If this happens, Angelman syndrome will invariably occur.

In around 70 percent of cases, a chromosomal error will cause the complete deletion of chromosome 15, including the UBE3A gene. This error appears random and can affect any pregnancy, whether there is a history of Angelman syndrome or not.

The remainder of cases would involve either a mutation of the UBE3A gene, the translocation (switching of position) of UBE3A and another gene, or the inheritance of two paternal UBE3A. In cases of UBE3A mutation, mothers with Angelman syndrome have a 50 percent chance of passing the mutation to her baby.

With that being said, as many as 10 percent of cases have no known cause.


Angelman syndrome is diagnosed first and foremost by the clinical appearance of symptoms consistent with the disorder. Among the features a clinician will look for:

  • Characteristic head or facial abnormalities
  • A happy disposition with frequent laughing or smiling
  • Missed or delayed developmental milestones, especially the absence of speech
  • Motor dysfunction, including ataxia, fine tremors, hand-flapping, and a stiff gait
  • A history of seizures and abnormal EEG readings

While a genetic test can be used to confirm a UBE3A mutation and/or the deletion or inactivity of chromosome 15, as many as 20 percent of cases will have no evidence of a genetic cause.

Additional investigations may be needed to differentiate Angelman syndrome from disorders with similar characteristics. This includes autism, cerebral palsy, or Prader-Willi syndrome (a genetic disorder in which the chromosome 15 deletion is inherited from the father).

Without exception, early diagnosis allows you to pursue therapeutic options which may improve your child's life and long-term development if started immediately.


There is no cure for Angelman syndrome and no way to reverse the genetic defect. Treatment is focused entirely on the management of symptoms and supporting the health and well-being of the affected child or adult.

Anticonvulsant drugs can be helpful in controlling seizures, although the condition may be difficult to treat due to the wide variety of seizures a person can experience. No single anticonvulsant has proven effective in treating all seizure types. Improvements in sleep patterns, often with the use of the sleep hormone melatonin, may also contribute to a reduction in seizures.

Physical therapy, along with supportive ankle braces, can help a child achieve functional mobility. It also aids in maintaining joint flexibility and preventing stiffness. Occupational therapy may be used to teach self-care, such as dressing oneself (usually with clothes without zippers, buttons, or laces), brushing one’s teeth, or going to the bathroom on one’s own.

Verbal communication can remain a significant, long-term challenge even into adulthood. Speech and language therapy may help insofar as it stresses word recognition and may enhance the quality of verbal and non-verbal interactions.

GERD can often be controlled with diet, antacids, and proton pump inhibitors (PPIs). Severe cases may require a surgery, known as fundoplication, which tightens the esophageal sphincter through which food and acid can reflux.

Investigational research is underway to see if certain pharmaceutical agents can activate nerve receptors believed to behind Angelman syndrome and other forms of genetically induced intellectual disabilities. One such drug, known as OV101 (gaboxadol), was fast-tracked for research by the U.S. Food and Drug Administration in December 2017.

A Word From Verywell

Learning that your child has Angelman syndrome can be a traumatic event, particularly since children with the disorder will invariably need lifelong care. With that being said, there is no definite course to the disorder. Some people may experience profound impairment, while others will be able to develop functional social and communication skills.

What is characteristic of all children with Angelman syndrome is a general state of happiness and contentment. They enjoy play and human contact and exhibit a profound desire for personal interaction and affection.

While some of the more severe symptoms can be overwhelming, many of these will subside over time or may disappear altogether. To this end, it is important to find support from parents like you who have raised or raising a child with Angelman syndrome. Doing so can offer you greater insights into your current and future needs than any book could.

Perhaps the best way to start is to contact the Family Resource Team at the Angelman Syndrome Foundation who can provide you with referrals for support, financial assistance, insurance, and education. The Illinois-based charity also organizes family conferences every other year to support for families and caregivers living with the disease.

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Van buggenhout G, Fryns JP. Angelman syndrome . Eur J Hum Genet. 2009;17(11):1367-73. doi:10.1038/ejhg.2009.67

  3. Buiting K, Williams C, Horsthemke B. Angelman syndrome - insights into a rare neurogenetic disorder. Nat Rev Neurol. 2016;12(10):584-93. doi: 10.1038/nrneurol.2016.133

  4. Bird LM. Angelman syndrome: review of clinical and molecular aspects. Appl Clin Genet. 2014;7:93-104. doi:10.2147/TACG.S57386

  5. Tan, W. and Bird, L. Angelman syndrome: Current and emerging therapies in 2016.Am J Med Gen. 2016;172(4):384-401. DOI: 10.1002/ajmg.c.31536

Additional Reading

By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.