Condition: Angelman Syndrome


Angelman syndrome is a complex genetic disorder that primarily affects the nervous system. Common indications of this condition include delayed development, intellectual disability, severe speech impairment and ataxia.  

Most affected children experience recurrent epileptic seizures and present with microcephaly.  

Delayed development is observed by the age of 6 to 12 months, while other signs and symptoms typically appear in early childhood. 

Signs and symptoms of Angelman syndrome include: 

  • Developmental delays, including no prone progression (i.e. crawling) or babbling by 6 to 12 months 
  • Intellectual disability 
  • No speech or minimal speech 
  • Difficulty walking and ataxia 
  • Frequent smiling and outbursts of laughter 
  • Happy, excitable personality 

People with Angelman syndrome might also shows signs including: 

  • Epileptic seizures, usually initiating between 2 and 3 years of age 
  • Suggestive electroencephalographic patterns 
  • Stiff or jerky movements 
  • Microcephaly, with flatness in the back of the head (microbrachycephaly) 
  • Macrostomia 
  • Wide-spaced teeth 
  • Prognathism 
  • Macrognathism 
  • Tongue thrusting 
  • Hypopigmented hair, skin and eyes 
  • Unusual behaviors, e.g., asterixis and arms uplifted while walking 

Children with Angelman syndrome are generally described as having a happy, excitable demeanor marked by frequent smiling, outbursts of laughter, and hand-flapping movements. Hyperactivity, an abbreviated attention span and a fascination with water are characteristic.  

Most affected children have difficulty sleeping, yet require less sleep than their non-affected peers. 

With age, people with Angelman syndrome often become less excitable and the sleeping difficulties tend to resolve. However, affected individuals do continue to have intellectual disability, severe speech impairment and seizures throughout their lifespan. Adults with Angelman syndrome typically have distinctive facial features. 

Other common features include unusually fair skin with light-colored hair and an abnormal side-to-side curvature of the spine (scoliosis). The life expectancy of people with this condition appears to be nearly normal. 

State of the Science

In a 2006 study out of Brazil, investigators studied 19 children with Angelman syndrome (1). A ketogenic diet was effective in all four cases of refractory epilepsy.  

A 2010 report describes the case of a 5-year-old girl with Angelman syndrome who was suffering with: over five episodes of refractory epileptic seizures per day; severe learning disabilities; poor sleep; hyperactivity and a poor attention span (2). 

She was given a ketogenic diet and, within the first weeks of initiation, she ceased experiencing absence seizures. In addition, a significant reduction in seizure frequency was observed. Within two months, she remained free of seizures. Improved sleep patterns were also noted within weeks of initiation. 

Hyperactivity was also gradually reduced, and improvements in attention and willingness to participate in group games was confirmed by her parents and teachers. Laughing outbursts and reaction to noise were reduced and interactions with others were improved. 

The authors note: “The impressive clinical improvement of our patient gives some hope that the ketogenic diet may have its own place in our reserve for the treatment of Angelman syndrome where epilepsy is very common and typically refractory to medication.” 

Also in 2010, an 18-month-old girl was admitted to the emergency department at Kaiser Permanente Hospital in Bellflower, California. She presented with sudden onset of approximately 12 prolonged atonic seizures and prominent dysautonomia. Six different anti-epileptic drugs (AEDs) were aggressively administered in an attempt to control the seizures, but they were in-effective. 

She was then placed on a ketogenic diet. Within two days of the initiation of a 2:1 ketogenic diet, the patient’s seizures were reduced to only intermittent and partial at night; the atonic-dysautonomic seizures were almost completely controlled. Subsequent outpatient clinic visits confirmed that she was well controlled on the KD diet. 

In 2012, a cohort of pediatric patients with Angelman syndrome and refractory epilepsy were treated with a low-glycemic-index treatment (LGIT) diet for four months. All subjects on the LGIT diet experienced a decrease in seizure frequency, with five of six patients initially experiencing over an 80% reduction in frequency. Developmental gains were also noted. 

Eight months after the study, at the 1-year mark, all five subjects who remained on the diet had an over 90% reduction in seizures. 

In 2016, researchers at the Byrd Alzheimer’s Institute at the University of South Florida, in Tampa, used a mouse model of Angelman syndrome (AS mice). 

As mice were supplemented with a specific ketone, a patented acetoacetate donor (KE), ad libitum for eight weeks. KE administration improved motor coordination, learning, memory and synaptic plasticity.  

The ketone was also anti-convulsant and beneficially altered brain amino acid metabolism in AS-treated animals. According to the authors, these findings “suggest that KE supplementation produces sustained ketosis.” 

In 2017, Massachusetts General scientists carried out a retrospective case medical record review of 23 subjects who received an LGIT diet for seizure control (6). 

Overall, the majority of subjects attained some level of seizure control with the LGIT diet. Specifically, 22% became completely seizure free, 43% were seizure free except for concomitant illness or non-convulsive status epilepticus and 30% achieved a decrease in seizure frequency. 

Ongoing Angelman Research  

Vanderbilt University is conducting a study on Angelman syndrome, entitled “Evaluation of the Safety and Tolerability of a Nutritional Formulation in Angelman Syndrome.” 

The 16-week randomized, double-blind, controlled crossover study, due to be completed at the end of 2019, will be studying the effects of a nutritional formulation containing MCT + BHB, comparing a ketogenic, low-glycemic and standard American diet in children aged 4-11 years (Clin Trials ID: NCT03644693). 

The study is being expanded into Australia in conjunction with a grant from the Foundation for Angelman Syndrome Therapeutics Australia. 


  1. Centers for Disease Control and Prevention. (November 1, 2016). It’s Your Life. Treat Your Diabetes Well. Retrieved October 28, 2017 from
  2. Ishii, Y., Ohta, T., Sasase, T., Morinaga, H., Hata, T., Miyajima, K., . . . Matsushita, M. (2010). A high-fat diet inhibits the progression of diabetes mellitus in type 2 diabetic rats. Nutr Res, 30(7), 483-491. doi: 10.1016/j.nutres.2010.06.013
  3. Mobbs, C. V., Mastaitis, J., Isoda, F., & Poplawski, M. (2013). Treatment of diabetes and diabetic complications with a ketogenic diet. Journal of Child Neurology, 28(8), 1009-1014. doi: 10.1177/0883073813487596
  4. Paoli, A., Rubini, A., Volek, J. S., & Grimaldi, K. A. (2013). Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition, 67(8), 789-796. doi: 10.1038/ejcn.2013.116
  5. Shifflett, T. (September 26, 2017). Diabetes & Ketogenic Diet: Can You Manage Your Diabetes On A Ketogenic Diet? Retrieved October 29, 2017 from
  6. Zhang, X., Qin, J., Zhao, Y., Shi, J., Lan, R., Gan, Y., . . . Du, B. (2016). Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice. Nutr Res, 36(4), 349-358. doi: 10.1016/j.nutres.2015.12.002

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