Angelman Syndrome

Description

Diagnosis Coding

ICD-10

Q93.5, Other deletions of part of a chromosome

Q93.51, Angelman syndrome (usable after October 1, 2018)

See ICD-10 Other Deletions of Part of a Chromosome for further coding details.

Description

Child with Angelman Syndrome
Angelman syndrome (AS) 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 AS are typically social, delays in language and other features, such as decreased eye contact, are reminiscent of autism. Seizures, acquired microcephaly, gait ataxia, tremor, scoliosis, sleep and eating problems, and speech impairment are common. Children with AS appear normal at birth, then show progressive developmental delays. It is not until 2 years of age or later that the typical syndrome phenotype becomes obvious, yet it is often apparent by 6 months of age. The diagnosis of AS is based on clinical features and genetic testing, which confirms the diagnosis in approximately 90% of individuals with the typical phenotype.

Photo, left: Courtesy of Freyja Robison

Prevalence

Angelman syndrome affects an estimated 1:12,000 to 1:20,000 people. [Genetic: 2018]

Genetics

AS and Prader-Willi syndrome 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 AS are missing a functional copy of the UBE3A gene from their mother.

Genetic abnormalities leading to AS 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]

Prognosis

Most children with AS will have seizures and will need antiepileptic therapy. Children with AS 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 chronic and restrictive lung diseases.

Roles Of The Medical Home

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.

Practice Guidelines

There are no published practice guidelines for the management of AS, but expert recommendations are available from [Dagli: 2017].

Helpful Articles

PubMed search for Angelman syndrome in children, last 5 years.

Bird LM.
Angelman syndrome: review of clinical and molecular aspects.
Appl Clin Genet. 2014;7:93-104. PubMed abstract / Full Text

Larson AM, Shinnick JE, Shaaya EA, Thiele EA, Thibert RL.
Angelman syndrome in adulthood.
Am J Med Genet A. 2015;167A(2):331-44. PubMed abstract / Full Text

Kyllerman M.
Angelman syndrome.
Handb Clin Neurol. 2013;111:287-90. PubMed abstract

Tan WH, Bird LM, Thibert RL, Williams CA.
If not Angelman, what is it? A review of Angelman-like syndromes.
Am J Med Genet A. 2014;164A(4):975-92. PubMed abstract

Williams CA, Dagli A.
Management of Genetic Syndromes (Chapter 6-Angelman Syndrome).
3rd ed. Wiley-Blackwell; 2010. 978-0-470-19141-5 http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Textbook with information about the medical management of common genetic syndromes; chapter 6 has information about Angelman syndrome.

Clinical Assessment

Pearls & Alerts

Pain may be the cause of prolonged irritability

The happy affect seen in children with AS 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.

Response to negative genetic testing

If genetic testing comes back negative for AS, differential diagnoses should be considered.

Considerations when diagnosing seizures

The majority of children with AS will require treatment for seizures; however, diagnosis can be challenging since movement abnormalities can be mistaken for seizures and EEG abnormalities can exist despite absence of seizures.

Screening

Of Family Members

No specific screening is indicated for family members of the child with AS.

For Complications

Because scoliosis occurs in about 50% of individuals with AS and is diagnosed at a mean age of 12 years, early and routine scoliosis screening may be useful. [Larson: 2015]

Diagnostic Criteria

Initial diagnosis is based on clinical features and confirmatory molecular genetic testing or UBE3A sequence analysis. Approximately 10% of children with AS have negative genetic testing and are diagnosed based on clinical features alone. Few children with AS are diagnosed before their 2nd birthday due to non-specific presentation in infancy. Consensus criteria for the clinical diagnosis of AS, 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. 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 can 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.

Differential Diagnosis

Cerebral palsy, static encephalopathy, idiopathic seizures and other non-specific entities may be diagnosed during the time when infants with AS present with non-specific developmental delay 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 AS is not seen in girls with Rett syndrome. Diagnosis can be made by MECP2 gene testing in Rett syndrome and UBE3A gene testing in AS. See the Portal's Rett Syndrome for diagnosis and management information.

Mowat/Mowat-Wilson syndrome can also be associated with a happy affect, microcephaly, seizures, constipation, and developmental delay. Mowat syndrome is caused by mutations in the ZEB2 gene. AS and Mowat syndrome can be differentiated by genetic testing. See Mowat-Wilson Syndrome (Genetics Home Reference) for more information.

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 AS 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 AS include:
  • Seizures
  • Sleep disturbance
  • Strabismus
  • Aspiration pneumonia
  • Chronic lung disease
  • 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 AS. [Larson: 2015]

History & Examination

Family History

Ask about a family history of AS, autistic features, intellectual disability, and neurologic problems.

Pregnancy Or Perinatal History

Pregnancy and birth history is usually normal. Newborns may have difficulty learning to drink by breast and/or bottle. There may be a history of mild hypotonia.

Current And Past Medical History

Complete a full medical history; ask about sleep and behavior.

Developmental And Educational Progress

Evaluate for achievement of developmental milestones. Gross motor and language delay are common. Ask about hyper-motoric activity, frequent mouthing of objects, and short attention span. Language delay and impairment are usually severe. Receptive language may be better than expressive language, but still quite delayed for age. [Dan: 2003]

Social And Family Functioning

Ask about family coping strategies and available resources.

Physical Exam

General

Look for a happy, smiling demeanor with frequent laughing and decreased eye contact. See Photographs of Individuals with AS (Angelman Syndrome Foundation).

Growth Parameters

Ht | Wt | OFC - 50% of children with AS will have acquired microcephaly with head circumferences below the 2nd percentile by 1 year of age. Monitor for weight loss due to eating difficulties.

HEENT

Evaluate for strabismus. Sometimes children with AS will have hypopigmented irises, skin, and hair due to deletion of a contiguous gene that is associated with albinism, OCA2.

Mouth/Teeth

Dental hygiene may be challenging. Check teeth for orthodontic issues and caries.

Extremities/Musculoskeletal

Look for hypotonia and tremulousness. Check deep tendon reflexes that may be hyperreflexic. Walking typically occurs after the age of 2 years and the gait of children with AS is often stilted, with a robot-like character. Arms are often held up, bent at the elbows, palms facing outward. Scoliosis is common in adolescents. Tight ankles and knees may also be noted, particularly in adolescents and adults.

Testing

Laboratory Testing

Monitor anti-epileptic medication levels and associated labs if necessary.

Genetic Testing

DNA methylation analysis identifies approximately 80% of individuals with AS, including microdeletions of the AS/Prader-Willi syndrome critical region in 68%, UBE3A mutations in 11%, paternal uniparental disomy of chromosome 15 in 7%, imprinting defects in 3%, unbalanced chromosome translocation in <1%, and unknown (11%). If this test is negative, yet AS is still highly suspected, UBE3A sequence analysis may be ordered by genetics.

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

Other Testing

Recommended baseline assessments for diagnosis and preventive care: [Dagli: 2017]
  • Brain MRI - baseline. Does not usually need to be repeated unless clinical picture changes. May show atrophy and delayed myelination, but no structural lesions.
  • EEG - Baseline and as clinically indicated for management of seizures. Many seizure types are associated with AS, 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.
  • Orthopedic assessment if scoliosis, gait impairment, tight Achilles tendons, and/or moderate to severe hypotonia are present. Children with AS tend to walk late, between 2 1/2 and 6 years of age. The gait may appear jerky and stiff. Scoliosis tends to appear later in childhood or in adolescence.
  • Ophthalmology examination to look for strabismus, ocular albinism (seen in a subgroup of children with AS), and to evaluate visual acuity
  • Speech/language evaluation as needed, though verbal expression is rare in this disorder
  • Physical therapy evaluation as needed
  • Assess for Gastroesophageal Reflux Disease in infants and toddlers; maximize diet and avoid under/over nutrition in children of all ages.

Subspecialist Collaborations & Other Resources

Developmental - Behavioral Pediatrics (see Services below for relevant providers)

Refer for developmental evaluation, which can help guide care and planning.

Pediatric Physical Medicine & Rehabilitation (see Services below for relevant providers)

Refer for developmental evaluation and care planning.

Pediatric Gastroenterology (see Services below for relevant providers)

Gastroesophageal reflux and constipation are common; referral may help with evaluation and management.

Pediatric Orthopedics (see Services below for relevant providers)

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 Services below for relevant providers)

Refer for problems with eye muscle coordination, acuity, and evaluation of ocular albinism.

Speech - Language Pathologists (see Services below for relevant providers)

Evaluation and treatment are helpful for enhancing verbal and nonverbal communication skills.

Electroencephalography (EEG) (see Services below for relevant providers)

Recommend to establish baseline and if there is a significant change in seizure pattern.

Pediatric Genetics (see Services below for relevant providers)

Periodic visits can help establish an appropriate referral base and can help explore differential diagnoses.

Pediatric Neurology (see Services below for relevant providers)

Seizures may be difficult to control and periodic evaluations or concurrent care with a pediatric neurologist may be helpful.

Sleep Studies/Polysomnography (see Services below for relevant providers)

Polysomnography can help diagnose sleep difficulties.

Pediatric Dentistry (see Services below for relevant providers)

Refer for management of orthodontic issues, caries, and basic care, which can be challenging to manage in children with AS.

Treatment & Management

Pearls & Alerts

Seizure medications may make seizures worse

Use of vigabatrin, carbamazepine, and tiagabine in children with AS may lead to an increase in absence and myoclonic seizures. This paradoxical seizure development is not limited to individuals with AS.

Communication

Speech therapy should focus on nonverbal methods of communication. Augmentative communication aids such as picture cards or communication boards should be used at the earliest appropriate time. Attempts to teach signing should begin as soon as the child is sufficiently attentive.

How should common problems be managed differently in children with Angelman Syndrome?

Common Complaints

Constipation is a common problem for individuals with AS and may be difficult to manage. See the Portal’s Constipation for assistance in managing and minimizing constipation.

Systems

Development (general)

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. 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.

Language: Speech therapy should be initiated as soon as the diagnosis is confirmed. Most children will use only nonverbal methods of communication; begin early with signing, picture cards, and communication boards. See Augmentative Communication (general).

Subspecialist Collaborations & Other Resources

Developmental - Behavioral Pediatrics (see Services below for relevant providers)

May be helpful for an evaluation of strengths and weaknesses and the development of a specific plan for developmental services.

Early Intervention for Children with Disabilities/Delays (see Services below for relevant providers)

Free or low cost for most families; provides developmental assessment and interventions, generally in the home.

Physical Therapy (see Services below for relevant providers)

Often helpful, particularly for non-ambulatory patients

Occupational Therapy, Pediatric (see Services below for relevant providers)

Helpful for those with feeding and fine motor problems

Speech - Language Pathologists (see Services below for relevant providers)

May be effective for enhancing communication

Neurology

Seizures may be difficult to control and multiple medications may be needed. A pediatric neurologist who has experience with AS may help avoid over-treatment. The more commonly prescribed medications include valproic acid, clonazepam, topiramate, lamotrigine, and ethosuximide. Corticosteroids [Forrest: 2009], ketogenic diets, low glycemic index diets [Thibert: 2012], and vagus nerve stimulators may also be helpful. There is no standard medication to use, though vigabatrin and tigabine (anticonvulsants that increase brain GABA levels) are contraindicated in individuals with AS. For a subset of individuals (<5%), carbamazepine may be the most effective medication for the prevention of seizures; however, use caution since carbamazepine has been shown to exacerbate seizures in almost 60% of patients.

Subspecialist Collaborations & Other Resources

Pediatric Neurology (see Services below for relevant providers)

Helpful for management of seizures

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.

If associated medical causes are ruled out and the child is still not sleeping well, medications may be helpful. The medical home may consider using short-term medications such as chloral hydrate or diphenhydramine for transient sleep problems, but often medications such as trazodone, clonidine, or amitryptiline may be necessary. Melatonin is sometimes successful. [Braam: 2008] Some families have had to confine the child to a safe bedroom so the family can get rest. See the Portal's Medications for Sleep (general) and Sleep Problems (general) for more information.

Subspecialist Collaborations & Other Resources

Pediatric Sleep Medicine (see Services below for relevant providers)

Consider referral for evaluation and/or help in management, especially when apnea, restless legs, or seizures are suspected.

Musculoskeletal

Individuals with AS may have subluxed or pronated ankles, tight Achilles tendons, and/or scoliosis. These problems may require bracing and sometimes surgery.

Subspecialist Collaborations & Other Resources

Pediatric Orthopedics (see Services below for relevant providers)

A baseline visit and periodic evaluations may be helpful.

Gastro-Intestinal & Bowel Function

Newborns with AS often have feeding problems requiring special nipples or tube feeding. Many children have gastroesophageal reflux and subsequent vomiting and poor weight gain. Positioning, medications, and occasionally, Nissen fundoplication may be required. See Gastroesophageal Reflux Disease, Feeding & Nutrition, and Power Packing (general) for more information.

Constipation is also a common problem; see the Portal's Constipation for more information.

Subspecialist Collaborations & Other Resources

Pediatric Gastroenterology (see Services below for relevant providers)

Consider referral for challenging feeding problems and poor weight gain, gastroesophageal reflux, and severe constipation.

Eyes/Vision

Children with AS may have decreased visual acuity and/or strabismus, which may require surgical correction.

Subspecialist Collaborations & Other Resources

Pediatric Ophthalmology (see Services below for relevant providers)

Initial and periodic evaluation may identify problems early and limit consequences of poor vision.

Mental Health/Behavior

Hyperactivity and other behavior issues can be difficult to manage in older children and adolescents. The treatment plan often includes behavior management and/or medications since behavioral management alone often is 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 AS, 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 AS. [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. [Summers: 1995] [Pelc: 2008] See Autism Spectrum Disorder for more information regarding use of these medications.

Subspecialist Collaborations & Other Resources

Psychologist, Child-18 (PhD, PsyD) (see Services below for relevant providers)

Behavior evaluation and management may be helpful for families

Psychiatrist, Child-18 (MD) (see Services below for relevant providers)

If medications are necessary, consider a consult with a child psychiatrist.

CSHCN Clinics (see Services below for relevant providers)

A clinic or program that focuses on AS or individuals with dual diagnosis may be very helpful.

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. See Sexuality and People with Disabilities (PDF Document 257 KB) for more information.

Females with AS may have difficulty with personal hygiene and families may benefit from help with menstrual management of individuals with disabilities.

Subspecialist Collaborations & Other Resources

Developmental - Behavioral Pediatrics (see Services below for relevant providers)

May be helpful in issues of sexuality and menstruation management

Gynecology (Ped/Adol, Special Needs) (see Services below for relevant providers)

Consider referral for problems associated with menses and concern about fertility

Transitions

Transition planning is very important, especially in the following areas: [Larson: 2015]
  • Medical care - Families should discuss 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 and supplemental security income. (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 AS until they turn 22. Transition planning, covering topics such as where the individual will live and how they will support themselves, should begin in the early teens so that appropriate skills can be taught in school.

Questions from Clinicians

If I suspect Angelman syndrome, what testing should I send?

Consider beginning with methylation studies (detects approximately 78% of individuals with AS, 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 AS).

What type of screening studies and/or subspecialty care does this patient need?

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

What is the risk of seizure in Angelman syndrome?

Eighty percent of children with Angelman syndrome have seizures, usually presenting prior to 3 years of age.

What therapies are most beneficial for patients with Angelman syndrome?

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.

Issues Related to Angelman Syndrome

Development (general)

Augmentative Communication

Nutrition/Growth/Bone

Power Packing

Resources

Information for Clinicians

Angelman Syndrome (GeneReviews)
Information about diagnosis, clinical course, prognosis, and genetics; sponsored by the National Institutes of Health and the National Library of Medicine.

Angelman Syndrome (OMIM)
Extensive review of literature providing technical information for providers on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Helpful Articles

PubMed search for Angelman syndrome in children, last 5 years.

Bird LM.
Angelman syndrome: review of clinical and molecular aspects.
Appl Clin Genet. 2014;7:93-104. PubMed abstract / Full Text

Kyllerman M.
Angelman syndrome.
Handb Clin Neurol. 2013;111:287-90. PubMed abstract

Larson AM, Shinnick JE, Shaaya EA, Thiele EA, Thibert RL.
Angelman syndrome in adulthood.
Am J Med Genet A. 2015;167A(2):331-44. PubMed abstract / Full Text

Tan WH, Bird LM, Thibert RL, Williams CA.
If not Angelman, what is it? A review of Angelman-like syndromes.
Am J Med Genet A. 2014;164A(4):975-92. PubMed abstract

Williams CA, Dagli A.
Management of Genetic Syndromes (Chapter 6-Angelman Syndrome).
3rd ed. Wiley-Blackwell; 2010. 978-0-470-19141-5 http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Textbook with information about the medical management of common genetic syndromes; chapter 6 has information about Angelman syndrome.

Clinical Tools

Letters of Medical Necessity

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.

Information & Support for Families

Family Diagnosis Page

Information on the Web

The Portal's pages about Guardianship/Estate Planning, Financing Your Child's Healthcare, and Health Insurance/Financial Aids may be helpful for families.

Angelman Syndrome Foundation
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.

Angelman Syndrome (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.

Angelman Syndrome (Mayo Clinic)
Information about symptoms, causes, risk factors, complications, tests, treatment, and coping strategies.

American Epilepsy Society
Information and resources regarding epilepsy for professionals and families.

Prescription Assistance Programs (American Epilepsy Society)
Information and links to various prescription assistance programs.

National & Local Support

Foundation for Angelman Syndrome Therapeutics (FAST)
Established in 2008, FAST aims to assist individuals living with Angelman syndrome to realize their full potential and quality of life and to bring practical treatment into current medical practice as quickly as possible. The website offers educational material, ways to connect with the founder (a parent of a child with Angelman syndrome) and with other parents, and other resources.

Epilepsy Foundation
A national organization that provides information about epilepsy; programs to improve epilepsy treatment; materials to assist in helping people with epilepsy find jobs; activities in schools to educate the public; activities to educate policymakers; funds for research; and news about conferences and other items of interest.

Support Resources (Angelman Syndrome Foundation)
Educational and community resources for those caring for children with Angelman syndrome.

Services for Patients & Families in Utah

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CSHCN Clinics

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Developmental - Behavioral Pediatrics

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Early Childhood Education/Preschool

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Early Intervention for Children with Disabilities/Delays

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Electroencephalography (EEG)

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Gynecology (Ped/Adol, Special Needs)

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Occupational Therapy, Pediatric

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Pediatric Dentistry

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Pediatric Gastroenterology

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Pediatric Genetics

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Pediatric Neurology

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Pediatric Ophthalmology

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Pediatric Orthopedics

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Pediatric Physical Medicine & Rehabilitation

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Pediatric Sleep Medicine

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Physical Therapy

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Psychiatrist, Child-18 (MD)

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Psychologist, Child-18 (PhD, PsyD)

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School Districts

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Sleep Studies/Polysomnography

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Speech - Language Pathologists

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For other services related to this condition, browse our Services categories or search our database.

Authors & Reviewers

Initial Publication: August 2014; Last Update: August 2018
Current Authors and Reviewers (click on name for bio):
Authors: Alan F. Rope, MD
Lynne M. Kerr, MD, PhD
Authoring history
(Limited detail is available on authoring dates before 2014.)
2011: first version: Alan F. Rope, MDA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Bibliography

Bird LM.
Angelman syndrome: review of clinical and molecular aspects.
Appl Clin Genet. 2014;7:93-104. PubMed abstract / Full Text

Braam W, Didden R, Smits MG, Curfs LM.
Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial.
J Child Neurol. 2008;23(6):649-54. / Full Text

Conant KD, Thibert RL, Thiele EA.
Epilepsy and the sleep-wake patterns found in Angelman syndrome.
Epilepsia. 2009;50(11):2497-500. PubMed abstract

Dagli AI, Williams CA.
Angelman Syndrome.
GeneReviews. 2017. PubMed abstract / Full Text

Dan B, Boyd SG.
Angelman syndrome reviewed from a neurophysiological perspective. The UBE3A-GABRB3 hypothesis.
Neuropediatrics. 2003;34(4):169-76. PubMed abstract

Forrest KM, Young H, Dale RC, Gill DS.
Benefit of corticosteroid therapy in Angelman syndrome.
J Child Neurol. 2009;24(8):952-8. PubMed abstract

Genetic Home Reference.
Angelman syndrome.
U.S. Library of Medicine; (2018) http://ghr.nlm.nih.gov/condition/angelman-syndrome. Accessed on 8/2018.

Jedele KB.
The overlapping spectrum of rett and angelman syndromes: a clinical review.
Semin Pediatr Neurol. 2007;14(3):108-17. PubMed abstract

Kyllerman M.
Angelman syndrome.
Handb Clin Neurol. 2013;111:287-90. PubMed abstract

Larson AM, Shinnick JE, Shaaya EA, Thiele EA, Thibert RL.
Angelman syndrome in adulthood.
Am J Med Genet A. 2015;167A(2):331-44. PubMed abstract / Full Text

MedlinePlus.
Aripiprazole.
U.S. National Library of Medicine; (2017) http://www.nlm.nih.gov/medlineplus/druginfo/meds/a603012.html. Accessed on 8/2018.

Pelc K, Cheron G, Dan B.
Behavior and neuropsychiatric manifestations in Angelman syndrome.
Neuropsychiatr Dis Treat. 2008;4(3):577-84. PubMed abstract / Full Text

Ramsden SC, Clayton-Smith J, Birch R, Buiting K.
Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes.
BMC Med Genet. 2010;11:70. PubMed abstract / Full Text

Summers JA, Allison DB, Lynch PS, Sandler L.
Behaviour problems in Angelman syndrome.
J Intellect Disabil Res. 1995;39 ( Pt 2):97-106. PubMed abstract

Tan WH, Bird LM, Thibert RL, Williams CA.
If not Angelman, what is it? A review of Angelman-like syndromes.
Am J Med Genet A. 2014;164A(4):975-92. PubMed abstract

Thibert RL, Pfeifer HH, Larson AM, Raby AR, Reynolds AA, Morgan AK, Thiele EA.
Low glycemic index treatment for seizures in Angelman syndrome.
Epilepsia. 2012;53(9):1498-502. PubMed abstract / Full Text

Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA, Wagstaff J.
Angelman syndrome 2005: updated consensus for diagnostic criteria.
Am J Med Genet. 2006;140(5):413-8. PubMed abstract

Williams CA, Dagli A.
Management of Genetic Syndromes (Chapter 6-Angelman Syndrome).
3rd ed. Wiley-Blackwell; 2010. 978-0-470-19141-5 http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Textbook with information about the medical management of common genetic syndromes; chapter 6 has information about Angelman syndrome.