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Angelman Syndrome

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Guidance for primary care clinicians diagnosing and managing children with Angelman syndrome

Angelman syndrome is a genetic disorder that causes severe developmental delay, intellectual disability, and a distinctive and recognizable pattern of behaviors, including frequent smiling, laughing, and hyperactivity. Although children with Angelman syndrome are typically social, delays in language and other features, such as decreased eye contact, are reminiscent of autism. Seizures, acquired microcephaly, gait ataxia, tremors, scoliosis, sleep and eating problems, and speech impairment are common. Children with Angelman syndrome appear normal at birth and then show progressive developmental delays. It is not until 2 years of age or later that the typical syndrome phenotype becomes obvious. Although feeding problems and hypotonia may be present at birth, developmental delay is often apparent by 6 months of age. Eighty percent of children with Angelman syndrome have seizures, usually presenting before 3 years of age. The diagnosis of Angelman syndrome is based on clinical features and genetic testing, which confirms the diagnosis of individuals with the typical phenotype.

In addition to well-child and acute-care visits, the medical home may want to schedule periodic chronic-care visits to help with ongoing issues, including behavior and educational progress. Needs will change over the life of the child; an infant may require only early intervention, whereas an adolescent with seizures, difficulty sleeping, hyperactivity, and self-injurious behavior may need many more interventions.

Other Names

AS

Key Points

Testing for suspected Angelman syndrome
Consider beginning with methylation studies (detects approximately 85% of individuals with Angelman syndrome, including those with a deletion, uniparental disomy (UPD), or an imprinting defect). If methylation studies are normal, proceed with UBE3A sequence analysis (detects an additional 11% of individuals with Angelman syndrome).

Screening for Angelman syndrome
Screen for feeding difficulties, constipation, gastroesophageal reflux, strabismus, scoliosis, seizures, and sleep dysregulation. Refer to GI, neurology, ortho, or sleep if needed.

Therapies
Physical therapy, occupational therapy, and speech therapy with an emphasis on nonverbal methods of communication, including augmentative communication aids (e.g., picture cards or communication boards) and signing, are beneficial.

Detecting pain
The happy affect seen in children with Angelman syndrome is so persistent that medical causes for pain, such as severe gastroesophageal reflux, should be considered when patients appear irritable or “miserable” for prolonged periods. See Pediatric Pain Assessment & Rating Scales.

Diagnosing seizures
Most children with Angelman syndrome will require treatment for seizures; however, diagnosis can be challenging since movement abnormalities can be mistaken for seizures, and EEG abnormalities can exist despite the absence of seizures.

Seizure medications may worsen seizures
The use of vigabatrin, carbamazepine, and tiagabine in children with Angelman syndrome may lead to an increase in absence and myoclonic seizures.

Consult a specialist
When facing the complexities of Angelman syndrome, seeking guidance from specialists becomes paramount. Their expertise in various domains, such as gastroenterology, neurology, orthopedics, and sleep medicine, can provide insights and tailored recommendations for managing the unique challenges posed by Angelman syndrome. Angelman Syndrome Foundation (ASF) clinics offer access to a range of professionals who specialize in treating Angelman syndrome. By utilizing its global network of patient-powered data, the clinics are working towards improving the quality of life, empowering families, and transforming the future of Angelman syndrome care. All individuals with Angelman syndrome are eligible and welcome to visit an ASF Clinic, and each clinic accepts a variety of insurance plans and policies. See Find a Clinic (ASF).

Roles of the primary care pediatrician
The medical home plays a central role in coordinating various aspects of care. This includes orchestrating referrals to subspecialists, overseeing therapeutic interventions, monitoring pain management strategies, aiding in accurate seizure diagnosis, and collaborating closely with specialists to ensure comprehensive and holistic care for the affected individuals.

Practice Guidelines

Duis J,Nespeca M,Summers J,Bird L,Bindels-de Heus KGCB,Valstar MJ,de Wit MY,Navis C,Ten Hooven-Radstaake M,van Iperen-Kolk BM,Ernst S,Dendrinos M,Katz T,Diaz-Medina G,Katyayan A,Nangia S,Thibert R,Glaze D,Keary C,Pelc K,Simon N,Sadhwani A,Heussler H,Wheeler A,Woeber C,DeRamus M,Thomas A,Kertcher E,DeValk L,Kalemeris K,Arps K,Baym C,Harris N,Gorham JP,Bohnsack BL,Chambers RC,Harris S,Chambers HG,Okoniewski K,Jalazo ER,Berent A, Bacino CA,Williams C,Anderson A.
A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome.
Mol Genet Genomic Med. 2022;10(3):e1843. PubMed abstract / Full Text

Diagnosis

Presentations

The original patients reported as having Angelman all had severe learning disability, epileptic seizures, ataxia, absent speech, and dysmorphic facial features with a prominent chin, deep-set eyes, wide mouth with protruding tongue, and microcephaly with a flat occiput. They were also hypopigmented with fair hair and blue eyes. Although many patients with Angelman syndrome have these characteristics, it is now clear that the clinical spectrum is much broader than was originally thought, and presentations vary considerably.
Early signs of Angelman syndrome, such as developmental delay, microcephaly, hypotonia, and failure to thrive, are nonspecific. Thus, patients can be misdiagnosed with similar pathologies. The most consistent clinical features are the behavioral features with a happy, smiling demeanor, frequent laughing, decreased eye contact, and mostly nonverbal. It is necessary, therefore, to have a high index of clinical suspicion in a child with the behavioral phenotype of the condition. [Clayton-Smith: 2003] [Dang: 2023] See Photographs of Individuals with AS (Angelman Syndrome Foundation).

Diagnostic Criteria & Classifications

Initial diagnosis is based on clinical features and confirmatory molecular genetic testing or UBE3A sequence analysis. Approximately 10% of children who clinically appear to have Angelman syndrome have negative genetic testing and are diagnosed based on clinical features alone. For those with negative testing, an alternative diagnosis should be sought since many conditions have overlapping features. Few children with Angelman syndrome are diagnosed before their second birthday due to non-specific presentation in infancy. Consensus criteria for the clinical diagnosis, published in 2006, are summarized below. [Williams: 2006]
A. Consistent features (found in 100% of children with AS):
  • Developmental delay, functionally severe
  • Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs. Movement disorder can be mild. It may not appear as frank ataxia but can be forward lurching, unsteadiness, clumsiness, or quick, jerky motion.
  • Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with uplifted hand-flapping or waving movements; hyper-motoric behavior
  • Speech impairment, none or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
B. Frequent features (found in 80% of children with AS):
  • Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (≤2 S.D. of normal OFC) by age 2 years. Microcephaly is more pronounced in those with 15q11.2-q13 deletions.
  • Seizures, onset usually <3 years of age. Seizure severity usually decreases with age, but the seizure disorder lasts throughout adulthood.
  • Abnormal EEG, with a characteristic pattern. The EEG abnormalities can occur in the first 2 years of life and precede clinical features; they are often not correlated with clinical seizure events.
C. Associated features (found in 20-80% of children with AS):
  • Flat occiput
  • Occipital groove
  • Protruding tongue
  • Tongue thrusting; suck/swallowing disorders
  • Feeding problems and/or truncal hypotonia during infancy
  • Prognathia
  • Wide mouth, wide-spaced teeth
  • Frequent drooling
  • Excessive chewing/mouthing behaviors
  • Strabismus
  • Hypopigmented skin, light hair, and eye color (compared to family), seen only in deletion cases
  • Hyperactive lower extremity deep tendon reflexes
  • Uplifted, flexed arm position, especially during ambulation
  • Wide-based gait with pronated or valgus-positioned ankles
  • Increased sensitivity to heat
  • Abnormal sleep-wake cycles and diminished need for sleep
  • Attraction to/fascination with water; fascination with crinkly items such as certain papers and plastics
  • Abnormal food-related behaviors
  • Obesity (in the older child)
  • Scoliosis
  • Constipation
If characteristic features are found, consider genetic testing. Genetic testing approaches are described below in the Genetic Testing section.

Screening & Diagnostic Testing

Genetic Testing

DNA methylation analysis identifies approximately 85% of individuals with Angelman syndrome, including microdeletions of the AS/Prader-Willi syndrome critical region in 68%, paternal uniparental disomy of chromosome 15 in 7%, and imprinting defects in 3%. If this test is negative, yet Angelman syndrome is still highly suspected, UBE3A sequence analysis should be ordered by genetics. If negative, it’s highly recommended to proceed with more comprehensive genetic testing, since there are AS-like conditions, which can be clinically similar, like Phelan-McDermid, Christianson syndrome, Pitt-Hopkins syndrome, Kleefstra, and others.

See Diagnostic Testing for Angelman Syndrome (Angelman.org) for a diagram with a suggested order for testing, Lab Testing for AS (Genetic Testing Registry) for testing sites, and Practice Guidelines for the Molecular Analysis of Prader-Willi and Angelman Syndrome [Ramsden: 2010]] for more details.

Laboratory Testing

No routine screening or diagnostic labs are recommended other than genetic testing.

Sensory

Obtain a baseline ophthalmology examination to look for strabismus and ocular albinism (seen in a subgroup of children with Angelman syndrome) and to evaluate visual acuity.

Imaging

Recommended baseline assessments for diagnosis and preventive care: [Dagli: 2017]

  • Brain MRI - baseline. Does not usually need to be repeated unless clinical picture changes. It may show atrophy and delayed myelination but no structural lesions.
  • EEG –
    • Baseline and as clinically indicated for the management of seizures. Many seizure types are associated with Angelman syndrome, including grand mal, absence, and others; infantile spasms are rare. The typical abnormalities involve generalized changes with areas of high-amplitude delta activity alternating with spike and slow-wave activity.
    • The electroencephalogram (EEG) waveforms in Angelman syndrome are usually quite abnormal and consist of variable frequency (mostly in Delta but can be in Theta range), high-amplitude, and rhythmic activity mixed with spikes regardless of the presence of epilepsy. When seen in an appropriate clinical context, EEG findings can help identify those with Angelman syndrome at an early age.

Screening Family Members

No specific screening is indicated for family members of the child with AS. However, because point mutations in UBE3A and some imprinting deletions can be inherited from the mother, maternal genetic testing should be performed when these are identified in the child.

Genetics & Inheritance

Angelman and Prader-Willi syndromes are examples of a genetic phenomenon called imprinting, where the clinical phenotype of a gene abnormality depends on the parent of origin of the gene defect. Individuals with Angelman syndrome are missing a functional copy of the UBE3A gene from their mother.
Genetic abnormalities leading to Angelman syndrome may result from:
  1. Deletions in the 15q11.2-q13 region of the maternally inherited chromosome 15
  2. Paternal uniparental disomy, where both copies of the gene derive from the father
  3. Mutations in the maternally inherited UBE3A gene
  4. An imprinting defect of the maternally inherited 15q11.2-q13 locus
The UBE3A gene produces a protein involved in targeting selected proteins for degradation in the ubiquitin pathway. It is unknown whether the clinical phenotype results from failure of degradation of these proteins, decreased new protein due to accumulation of old proteins, or other mechanisms. [Dagli: 2017]

Prevalence

The true prevalence is unknown. Studies have suggested prevalence rates in the 1:20,000 to 1:50,000 range. [Genetic: 2018] [Mertz: 2013] [Yakoreva: 2019]

Differential Diagnosis

Cerebral Palsey, static encephalopathy, idiopathic seizures, and other non-specific entities may be diagnosed when infants with Angelman syndrome present with non-specific developmental delays and then develop seizures and more typical facial features. More specific diagnoses of inborn errors of metabolism or mitochondrial disorders, which will be ruled out based on negative testing for these disorders, may also be considered.
Rett Syndrome (in girls) and other MECP2-associated persistent developmental delays can be difficult to distinguish from AS, particularly in girls who do not demonstrate the typical regressive development and hand-wringing noted in Rett syndrome. [Jedele: 2007] The smiling, happy effect of children with Angelman syndrome is not seen in girls with Rett syndrome. Diagnosis can be made by MECP2 gene testing in Rett syndrome and UBE3A gene testing in Angelman syndrome.
Mowat-Wilson Syndrome (MedlinePlus) can also be associated with a happy affect, microcephaly, seizures, constipation, and developmental delay. Mowat syndrome is caused by mutations in the ZEB2 gene. Angelman syndrome and Mowat syndrome can be differentiated by genetic testing.
Phelan-McDermid syndrome (deletion 22q13) may also have some clinical overlap with AS. Other non-specific chromosome imbalances are also possible.
Christianson syndrome presents only in males and has been attributed to mutations of SLC9A6. This is very rare and does not account for the 10% of individuals with negative genetic testing.
Pitt-Hopkins Syndrome (GeneReviews) is characterized by intellectual disability, wide mouth and distinctive facial features, and intermittent hyperventilation followed by apnea. Features that may overlap with Angelman syndrome include microcephaly, seizures, ataxic gait, and happy personality.
Other chromosome anomalies, some inborn errors of metabolism, and brain anomalies that result in speech and balance impairments should also be considered. [Tan: 2014]]

Comorbid Conditions

Conditions or problems commonly found in children with Angelman syndrome include:

  • Seizures
  • Sleep disturbance
  • Strabismus
  • Aspiration pneumonia
  • Scoliosis
  • Gastroesophageal reflux
  • Constipation
  • Contractures

Larson et al. reviewed the frequency of secondary conditions and their impact based on phone interviews of caregivers of 110 adolescents and young adults with Angelman syndrome. [Larson: 2015]

Prognosis

Most children with Angelman syndrome will have seizures, need antiepileptic therapy, and communicate non-verbally. Children with Angelman syndrome do not show developmental regression and, with good proactive care, should have normal life expectancies. They are, however, at risk for early death due to seizures, aspiration pneumonia, and accidents.

Treatment & Management

No treatments are available for the underlying cause of Angelman syndrome. However, researchers are currently exploring gene therapy as well as strategies (such as antisense oligonucleotides) to “reactivate the expression” of the paternal UBE3A gene to allow it to express, mitigating the impact of the defective maternal gene. [Beaudet: 2016] [Meng: 2015]

Development

Developmental therapy should begin at the time of diagnosis. This may be accessed through Early Intervention programs for children under 3. After age 3, developmental services may be available through the child's school district or in private settings, depending on resources.
Most children with Angelman syndrome will use only nonverbal methods of communication. Attempts to teach signing should begin as soon as the child is sufficiently attentive. Speech therapy should be initiated promptly, focusing on nonverbal methods of communication such as signing, picture cards, and communication boards. See Augmentative Communication (AAC).
Many children will require long-term physical therapy if they are non-ambulatory or unstable in their gait. Children may also require positioning chairs and/or wheelchairs. Occupational therapy for fine motor problems and feeding difficulties may also be helpful.

Neurology

Many seizure types are associated with Angelman syndrome, including grand mal, absence, and others; infantile spasms are rare. The majority of children will require treatment for seizures; however, diagnosis can be challenging since movement abnormalities can be mistaken for seizures, and EEG abnormalities can exist despite the absence of seizures. The typical abnormalities involve generalized changes with areas of high-amplitude delta activity alternating with spike and slow-wave activity.
  • Strongly consider referral to Pediatric Neurology to discuss seizure types and prescribe rescue medication in the event an initial seizure is prolonged. At a minimum, obtain a baseline EEG if there is clinical suspicion of seizures or if looking for the EEG “signature” to help determine if UBE3A sequencing is needed for a child whose methylation studies are negative.
  • Monitor antiepileptic medication levels and associated labs if necessary. Use of vigabatrin, carbamazepine, and tiagabine in children with Angelman syndrome and other individuals may lead to an increase in absence and myoclonic seizures.

Orthopedics

Children with Angelman syndrome tend to walk late, between 2 1/2 and 6 years of age. The gait may appear jerky and stiff. Obtain an orthopedic assessment if gait impairment, subluxed or pronated ankles, tight Achilles tendons, and/or moderate to severe hypotonia are present. These problems may require bracing and sometimes surgery.

Scoliosis tends to appear later in childhood or in adolescence. Because scoliosis occurs in about 50% of individuals with Angelman syndrome and is diagnosed at a mean age of 12 years, early and routine scoliosis screening may be useful. [Larson: 2015] Refer to Orthopedics for management of scoliosis.

They might also have reduced bone density with immobility and prolonged anti-epileptic drug treatment. Hence, mobility is encouraged. Adequate Vitamin D intake is recommended. Consider checking the bone density of women using Depo-Provera every couple of years.

Ear, Nose, Throat

To address drooling, consider medications and/or refer to ENT for botox therapy.See Drooling in Children with Special Health Care Needs

Gastro-Intestinal & Bowel Function

Newborns with Angelman syndrome often have feeding problems requiring special nipples or tube feeding. Many children have gastroesophageal reflux with subsequent vomiting and poor weight gain. Positioning, medications, and occasionally, Nissen fundoplication may be required. Assess for Gastroesophageal Reflux Disease in infants and toddlers; maximize diet and avoid under/over nutrition in children of all ages. See Feeding & Nutrition and Boosting Calories for Babies, Toddlers, and Older Children.
Constipation is a common problem for individuals with Angelman syndrome and may be difficult to manage. See the Portal’s Constipation for assistance in managing and minimizing constipation.

Pulmonology

Pulmonary problems associated with Angelman syndrome include respiratory difficulties and a propensity for aspiration. Respiratory challenges can arise due to poor muscle tone, which affects the muscles responsible for breathing and coughing. Aspiration, the inhalation of food or liquids into the airways, is also a concern due to the impaired swallowing and coordination often seen in Angelman syndrome, which can lead to chronic inflammation and restrictive lung disease.
Treatment for the pulmonary issues associated with Angelman syndrome should involve a multidisciplinary approach. If clinically unwell or there are physical examination findings, regular monitoring of respiratory function and oxygen saturation levels is essential, especially during sleep, to identify any potential breathing abnormalities. Physical and occupational therapies can help improve muscle tone and coordination, indirectly aiding respiratory function. Nutritional interventions, including thickening feeds and dietician support, might be necessary if there is ongoing aspiration. In some cases, non-invasive ventilation (CPAP) or breathing assistance devices to support respiratory function might be necessary, although it may not be well tolerated.

Sleep

Sleep difficulties can be very challenging for families. Seizures [Conant: 2009], pain, or other health conditions, including Gastroesophageal Reflux Disease, should be considered in children who abruptly start having difficulty sleeping. Consider a sleep study to determine other causes of sleep problems, such as obstructive sleep apnea and/or restless leg syndrome.
Addressing sleep-related problems in Angelman syndrome involves establishing a consistent sleep-wake pattern and routine. Creating a pre-bedtime routine and minimizing stimulating elements in the bedroom can aid this process. Behavioral strategies form the core of treatment, where parents are empowered to shape a sleep-conducive environment, regulate sleep schedules, promote independent sleep initiation, and reinforce appropriate behavior. Research has shown lower nighttime melatonin levels in Angelman syndrome patients compared to controls. Limited studies on melatonin's use indicate potential benefits in enhancing sleep duration and onset. However, higher doses might be required in some cases. Managing parasomnias involves optimizing the sleep environment to prevent sleepwalking-related injuries while also addressing potential nocturnal seizures by adjusting anticonvulsant doses. [Dosier: 2017] Other pharmacological approaches include clonidine and trazodone. The sedative properties of antihistamines (diphenhydramine, promethazine) are sometimes employed as well.
See the Portal's Sleep Medications and Sleep Issues for more information.

Drooling

Drooling in Angelman syndrome is not fully understood, but it's likely related to difficulties in controlling saliva rather than producing too much. Patients often have mouth features that make closing their mouth challenging, such as tongue thrusting and jaw protrusion. They may also have impaired sensation in their mouth and throat, affecting their ability to swallow and notice saliva escape. Factors like poor posture, frequent object mouthing, and specific medications can exacerbate drooling issues. Management strategies may include medications to reduce saliva production or referral to an ENT specialist for botox injections to address excessive drooling effectively.

Eyes/Vision

Children with Angelman syndrome may have decreased visual acuity and/or strabismus, which may require surgical correction. A limited subset of children with Angelman syndrome will have ocular albinism. Refer to Pediatric Ophthalmology to identify problems early and limit consequences of poor vision.

Mental Health/Behavior

Hyperactivity and other behavior issues can be difficult to address in older children and adolescents. The treatment plan often includes behavior management and/or medications since behavioral management alone is often ineffective. Stimulants such as methylphenidate can help with hyperactivity. For self-injurious or aggressive behaviors, or hyperactivity not helped by stimulant medication, atypical antipsychotics may be useful. [Pelc: 2008] Although use is not well studied in children with Angelman syndrome, risperidone (Risperdal) and aripiprazole (Abilify) are FDA-approved for the treatment of irritability in children ages 6-17 with autism and may be helpful for children with Angelman syndrome. [MedlinePlus: 2017] Risperidone is often associated with weight gain. SSRIs may also be helpful in some individuals. [Pelc: 2008] Failure to manage behavior problems may lead to a decreased quality of life for patients and families. [Pelc: 2008] Failure to manage behavior problems may lead to a decreased quality of life for patients and families. [Summers: 1995] [Pelc: 2008] See Autism Spectrum Disorder for more information regarding use of these medications. Supplementation with pyridoxine/ vitamins B6 is associated with improvement of neuropsychiatric adverse events in patients treated with Levetiracetam. [Besag: 2023] Also, occupational therapy focused on identifying calming sensory interventions is very helpful. Behavioral Therapy to help identify precipitants can also be very beneficial.

Pharmacy/Medications

There is currently no approved therapy specific to Angelman syndrome. One of the main therapeutic strategies currently being explored for Angelman syndrome involves reactivating the expression of the paternal UBE3A allele in the CNS (9, 10) using Antisense Oligonucleotides (ASO therapy). There are several ongoing clinical trials to test this strategy.

Maturation/Sexual/Reproductive

Although little information is available on the subject, families should assume that their child is fertile, and they should provide education about sexuality as appropriate. There is a significant risk to offspring if a parent has a deletion or UBE3A mutation. Hence, social and ethical issues of becoming pregnant/fathering children should be discussed fully. See Contraception & Menstrual Management and Sexuality and People with Disabilities (PDF Document 257 KB) for more information.
Females with Angelman syndrome may have difficulty with personal hygiene; families may benefit from help with menstrual management of individuals with disabilities. Multiple menstrual management options exist, catering to desired outcomes, ranging from regulating cycles to achieving complete amenorrhea. See Menstrual Management for Adolescents with Disabilities (AAP).
Both males and females with AS are fertile. There is a significant risk to offspring if a parent has a deletion or UBE3A mutation. Hence, social and ethical issues of becoming pregnant/fathering children should be discussed fully. Please refer to [Quint: 2016].

Surgery

Patients need rigorous pre-operative assessments and careful choice of anesthetic agents. Also, they need to be monitored closely due to the risk of bradycardia. The risk of reflux needs to be kept in mind. Also, there needs to be increased vigilance post-operatively of delayed recovery if there is a baseline reduction of mobility or muscle wasting.

Transitions

Transition planning is very important, especially in the following areas: [Larson: 2015]
  • Medical care - Families should discuss the transition of medical care from their pediatric medical home to an adult care provider. All necessary screening evaluations, e.g., scoliosis evaluation, should be performed before transition.
  • Financial considerations - If appropriate, once the individual turns 18 years of age, caregivers can apply for guardianship. (See Guardianship/Estate Planning for more information for families.) In many states, supplemental security income will automatically qualify the individual for Medicaid benefits.
  • Life planning - The public education system covers individuals with Angelman syndrome until they turn 22. Transition planning, covering topics such as where the individual will live and what support will be needed, should begin early. Individuals with Angelman syndrome generally need livelong supervision and have limited independence due to intellectual disability.

Services & Referrals

Find a Clinic (ASF)
A multidisciplinary approach for care of children with Angelman syndrome with DMD is preferred.

Pediatric Physical Medicine & Rehabilitation (see UT providers [11])
Refer for developmental evaluation and care planning.

Pediatric Gastroenterology (see UT providers [2])
Gastroesophageal reflux and constipation are common; referral may help with evaluation and management.

Pediatric Orthopedics (see UT providers [10])
Consider baseline referral and periodic follow-up for gross motor delay, hypotonia, tight Achilles tendons, and/or scoliosis. Frequency of evaluations will depend on degree of scoliosis.

Pediatric Ophthalmology (see UT providers [4])
Refer for problems with eye muscle coordination, acuity, and evaluation of ocular albinism.

Speech - Language Pathologists (see UT providers [65])
Evaluation and treatment are helpful for enhancing verbal and nonverbal communication skills.

Medical Genetics (see UT providers [7])
Periodic visits can help establish an appropriate referral base and can help explore differential diagnoses.

Pediatric Neurology (see UT providers [8])
Seizures may be difficult to control, and periodic evaluations or concurrent care with a pediatric neurologist may be helpful. Recommend to establish baseline and if there is a significant change in seizure pattern.

Gynecology: Pediatric/Adolescent; Special Needs (see UT providers [9])
Consider referral for problems associated with menses and concern about pregnancy prevention.

ICD-10 Coding

Q93.51, Angelman syndrome

ICD-10 Other Deletions of Part of a Chromosome (icd10data.com) provides further coding details.

Resources

Information & Support

For Professionals

Angelman Syndrome (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

Angelman Syndrome (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

Management of Angelman Syndrome (PDF Document 274 KB)
Evidence-based recommendations from the UK (2010) for the management of patients with Angelman Syndrome.

Facts About Angelman Syndrome (ASF)
Detailed information about genetics, medical issues, behavior, and education; Angelman Syndrome Foundation

For Parents and Patients

Angelman Syndrome Foundation (ASF)
Information, resources, and discussion forums for individuals with AS and their families. This organization also raises money for research on AS.

Angelman Syndrome (Orphanet)
Information and links about AS.

American Epilepsy Society
Information and resources to understand epilepsy, especially for those who are not familiar with the condition.

Tools

Sample Letter of Medical Necessity, Angelman/Rett (GeneDx.com) (Word Document 24 KB)
A customizable letter in Word format to provide support for testing for Angelman and Rett syndromes; from GeneDx, a commercial company that provides genomic testing and related services.

Services for Patients & Families in Utah (UT)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Studies

Angelman Syndrome Studies (clinicaltrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Angelman Syndrome Foundation Contact Registry
Sponsored by the Angelman Syndrome Foundation, the registry asks for contact and demographic data for individuals with Angelman syndrome and their families so they can: notify potential participants about Angelman research trials and alert families about recent events and research findings.

Helpful Articles

Articles about Angelman syndrome published within the last 5 years

Samanta D.
Epilepsy in Angelman syndrome: A scoping review.
Brain Dev. 2021;43(1):32-44. PubMed abstract / Full Text

Cassater D, Bustamante M, Sach-Peltason L, Rotenberg A, Nespeca M, Tan WH, Bird LM, Hipp JF.
Clinical Characterization of Epilepsy in Children With Angelman Syndrome.
Pediatr Neurol. 2021;124:42-50. PubMed abstract / Full Text

Bindels-de Heus KGCB, Hooven-Radstaake MT, Legerstee JS, Hoopen LWT, Dieleman GC, Moll HA, Mous SE, de Wit MY.
Sleep problems in children with Angelman Syndrome: The effect of a behavioral intervention program.
Res Dev Disabil. 2023;135:104444. PubMed abstract

Khan N, Cabo R, Burdine RD, Tan WH, Keary CJ, Ochoa-Lubinoff C, Bird LM.
Health-related quality of life and medication use among individuals with Angelman syndrome.
Qual Life Res. 2023;32(7):2059-2067. PubMed abstract

Carson RP, Herber DL, Pan Z, Phibbs F, Key AP, Gouelle A, Ergish P, Armour EA, Patel S, Duis J.
Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of Exogenous Ketones.
J Nutr. 2021;151(12):3628-3636. PubMed abstract / Full Text

Shaffer RC, Reisinger DL, Schmitt LM, Lamy M, Dominick KC, Smith EG, Coffman MC, Esbensen AJ.
Systematic Review: Emotion Dysregulation in Syndromic Causes of Intellectual and Developmental Disabilities.
J Am Acad Child Adolesc Psychiatry. 2023;62(5):518-557. PubMed abstract

Authors & Reviewers

Initial publication: January 2011; last update/revision: May 2024
Current Authors and Reviewers:
Author: Kirti Sivakoti, MD
Reviewers: Lynne M. Bird, MD
Adriana Gomes, MD
Authoring history
2019: update: Alan F. Rope, MDA
2019: revision: Arthur Beaudet, MDR
2018: update: Alan F. Rope, MDA
2015: update: Alan F. Rope, MDA
2011: first version: Alan F. Rope, MDA; Lynne M. Kerr, MD, PhDA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Beaudet AL, Meng L.
Gene-targeting pharmaceuticals for single-gene disorders.
Hum Mol Genet. 2016;25(R1):R18-26. PubMed abstract / Full Text

Besag FMC, Vasey MJ, Sen A.
Current evidence for adjunct pyridoxine (vitamin B6) for the treatment of behavioral adverse effects associated with levetiracetam: A systematic review.
Epilepsy Behav. 2023;140:109065. PubMed abstract

Bindels-de Heus KGCB, Hooven-Radstaake MT, Legerstee JS, Hoopen LWT, Dieleman GC, Moll HA, Mous SE, de Wit MY.
Sleep problems in children with Angelman Syndrome: The effect of a behavioral intervention program.
Res Dev Disabil. 2023;135:104444. PubMed abstract

Carson RP, Herber DL, Pan Z, Phibbs F, Key AP, Gouelle A, Ergish P, Armour EA, Patel S, Duis J.
Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of Exogenous Ketones.
J Nutr. 2021;151(12):3628-3636. PubMed abstract / Full Text

Cassater D, Bustamante M, Sach-Peltason L, Rotenberg A, Nespeca M, Tan WH, Bird LM, Hipp JF.
Clinical Characterization of Epilepsy in Children With Angelman Syndrome.
Pediatr Neurol. 2021;124:42-50. PubMed abstract / Full Text

Clayton-Smith J, Laan L.
Angelman syndrome: a review of the clinical and genetic aspects.
J Med Genet. 2003;40(2):87-95. PubMed abstract / Full Text

Conant KD, Thibert RL, Thiele EA.
Epilepsy and the sleep-wake patterns found in Angelman syndrome.
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