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Angelman syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Delayed ability to walk, Global developmental delay, and Secondary microcephaly; and very common findings: Cerebral cortical atrophy, Seizure, Ataxia, and Motor delay and others. 89 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	30	Cerebral cortical atrophy, Seizure, Ataxia
Digestive system	9	Feeding difficulties in infancy, Constipation, Gastroesophageal reflux
Eyes	7	Strabismus, Nystagmus, Ptosis
Head and neck	5	Secondary microcephaly, Hypoplasia of the maxilla, Mandibular prognathia
Muscles	4	Cerebral cortical atrophy, Low muscle tone (hypotonia), Generalized hypotonia
Arms and legs	2	Limb tremor, Recurrent hand flapping
Skin	1	Hypopigmentation of the skin
Bones and joints	1	Sideways curvature of the spine (scoliosis)
Hormones	1	Precocious puberty in females

GeneReviews

Clinical Guidance

Angelman syndrome (AS) is characterized by severe developmental delay and intellectual disability, severe speech impairment, gait ataxia and/or tremulousness of the limbs, and a unique behavior with an apparent happy demeanor that includes frequent laughing, smiling, and excitability. Microcephaly and seizures are also common. Developmental delays are first noted at around age six months; however, the unique clinical features of AS do not become manifest until after age one year. Table 2. Angelman Syndrome: Frequency of Select Features

Feature	% of Persons with Feature	Comment
Seizures	90%	Many seizure types; nonconvulsive status epilepticus in 20%
Nonepileptic myoclonus	20%

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Consensus criteria for the clinical diagnosis of Angelman syndrome (AS) have been developed in conjunction with the Scientific Advisory Committee of the US Angelman Syndrome Foundation . Several reviews are available .

Suggestive Findings

AS should be suspected in individuals with the following clinical, laboratory, and radiographic findings.

Clinical

Source: GeneReviews — "Angelman Syndrome"

GeneReviews

Differential Diagnosis

Infants with Angelman syndrome (AS) commonly present with nonspecific psychomotor delay and/or seizures; therefore, the differential diagnosis is broad and nonspecific, encompassing such entities as cerebral palsy, static encephalopathy, or mitochondrial encephalomyopathy. The tremulousness and jerky limb movements seen in most infants with AS may help distinguish AS from these conditions. AS-mimicking conditions have been reviewed and many of these, as well as additional disorders to consider in the differential diagnosis, are listed in . Table 3. Genes of Interest in the Differential Diagnosis of Angelman Syndrome

Gene	Disorder	MOI	Characteristic Features	Distinguishing Features
ADSL	Adenylosuccinate lyase deficiency (ADSLD, OMIM 103050)

Genetic testing for UBE3A is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for Angelman syndrome has been reported in the published literature.

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for Angelman syndrome. An additional 13 compounds hold orphan drug designation.

Foundational Care

Standard-of-care therapies for Angelman syndrome include treatments and supportive measures that are widely used in clinical practice, even when they are not FDA-approved specifically for this condition. These represent first-line care and are curated from clinical guidelines.

- Seizure management (often requires multiple antiepileptic medications; valproate and benzodiazepines often used)

- Physical therapy for motor development and gait

- Speech therapy and augmentative/alternative communication (AAC)

- Behavioral interventions for sleep disturbances

- Occupational therapy for daily living skills

Orphan Drug Designations

While no drugs are FDA-approved specifically for Angelman syndrome, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for Angelman syndrome. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor	Designated	Exclusivity End	Designation Status
non-replicating recombinant adeno-associated virus serotype hu68 (AAVhu68) vector, which expresses a variant of the UBE3A gene	non-replicating recombinant adeno-associated virus serotype hu68 (AAVhu68) vector, which expresses a variant of the UBE3A gene	MavriX Bio, LLC	2025	—	Designated
insulin like growth factor 2 receptor ligand	insulin like growth factor 2 receptor ligand	New York University	2024	—	Designated

GeneReviews

Management Guidelines

No clinical practice guidelines for Angelman syndrome (AS) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with AS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Angelman Syndrome

System/Concern	Evaluation	Comment
Neurologic	Neurologic eval	To incl brain MR, EEG Development
behavior	Developmental behavioral assessment	To incl:; Motor, adaptive, cognitive, nonverbal language ability; Language ability need for special communication devices; Eval for early intervention / special education; Screening for behavior concerns incl sleep disturbances Gastrointestinal/

GeneReviews

Clinical Guidance

Overtreatment

Children with AS are at risk for medication overtreatment because their movement abnormalities can be mistaken for seizures and because EEG abnormalities can persist even when seizures are controlled.
The behavioral phenotype of AS includes hyperexcitability, hypermotoric behaviors, and deficits in social communication. These limitations place affected individuals at risk for social disruptions. On occasion, the use of risperidone (Risperdal®) or other atypical antipsychotic drugs provides some but often limited benefit. When such drugs are needed, care must be taken to avoid oversedation and other side effects.

Source: GeneReviews — "Angelman Syndrome"

GeneReviews

Therapies Under Investigation

Clinical trials involving oral administration of folate, vitamin B12, creatine, and betaine have been undertaken in an attempt to augment DNA methylation pathways and possibly increase expression of the paternal UBE3A allele in the central nervous system; however, the initial trial did not demonstrate significant clinical benefit . An ongoing study using oral gaboxadol, a highly selective GABA receptor agonist, has not yet shown clear benefit . A study of oral levodopa/carbidopa did not show significant benefit in AS . Two clinical trials are currently evaluating antisense oligonucleotide-mediated enhancement of UBE3A expression: one trial is sponsored by HoffmannLa Roche (molecule RO7248824; NCT04428281) and the other is sponsored by GeneTX Biotherapeutics (molecule GTX-102; NCT04259281).

Source: GeneReviews — "Angelman Syndrome"

Clinical Trials

20 trials found

Explore Trials

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

20 clinical trials registered, 3 recruiting. Interventions under study include other interventions, drug therapy, procedural interventions, and gene therapy. Pipeline includes 5 PHASE3, 1 PHASE2, 2 PHASE1. Research is sponsored by a mix of industry and academic institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT06353620](https://clinicaltrials.gov/study/NCT06353620)	Structural-functional Connectome in Drug-resistant Epilepsies and Neurodevelopmental Syndromes With Epilepsy	—	IRCCS Eugenio Medea	RECRUITING
[NCT04507997](https://clinicaltrials.gov/study/NCT04507997)	Angelman Syndrome Natural History Study	—	Boston Children's Hospital	RECRUITING
[NCT05945576](https://clinicaltrials.gov/study/NCT05945576)	IDMet (RaDiCo Cohort) (RaDiCo-IDMet)	—	Institut National de la Santé Et de la Recherche Médicale, France	RECRUITING

287 publications have been identified in PubMed for Angelman syndrome. Research spans Basic Science / Preclinical (32%), Review / Meta-Analysis (21%), and Epidemiology / Natural History (15%).

Research Type	Count	% of Total
Laboratory research	93	32%
Research summaries	61	21%
Disease patterns and progression	43	15%
Testing and diagnosis research	29	10%
Patient case studies	28	10%
New treatment approaches	15

Recent Publications

Shim Y (2026). [PMID: 41630268](https://pubmed.ncbi.nlm.nih.gov/41630268/). *Medicine (Baltimore)*. [Epidemiology / Natural History]
Krzeski JC (2026). [PMID: 41652151](https://pubmed.ncbi.nlm.nih.gov/41652151/). *Mol Psychiatry*. [Basic Science / Preclinical]
Smeenk H (2026). [PMID: 41764319](https://pubmed.ncbi.nlm.nih.gov/41764319/). *Sci Rep*. [Gene Therapy / Novel Therapeutics]
Pombo DSD (2026). [PMID: 42531823](https://pubmed.ncbi.nlm.nih.gov/42531823/). *J Chromatogr A*. [Basic Science / Preclinical]
Alberti S (2026). [PMID: 42768751](https://pubmed.ncbi.nlm.nih.gov/42768751/). *Mol Ther*. [Review / Meta-Analysis]
Geier B (2026). [PMID: 41545316](https://pubmed.ncbi.nlm.nih.gov/41545316/). *Fly (Austin)*. [Basic Science / Preclinical]
Shen Y (2026). [PMID: 40944492](https://pubmed.ncbi.nlm.nih.gov/40944492/). *Ann Neurol*. [Basic Science / Preclinical]
Khalid A (2026). [PMID: 42292720](https://pubmed.ncbi.nlm.nih.gov/42292720/). *Cureus*. [Case Report / Case Series]
Chin HL (2026). [PMID: 42434914](https://pubmed.ncbi.nlm.nih.gov/42434914/). *Epileptic Disord*. [Diagnostic / Biomarker]
Vihma H (2026). [PMID: 41632831](https://pubmed.ncbi.nlm.nih.gov/41632831/). *JCI Insight*. [Basic Science / Preclinical]

Latest News & Developments

5 recent

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AI-curated news mentioning Angelman syndrome

Updated Oct 14, 2026

Gene & Cell Therapy•

Pipeline & Approvals

•20 days ago(Oct 14)

Ultragenyx Rare Disease Voucher Sales Secure $413M for More Potential Pipeline Building - MedCity News

Ultragenyx Pharmaceutical sold two priority review vouchers, each from an FDA approval of a gene therapy. Both therapies came from business deals and proceeds from the voucher sales put Ultragenyx in a better financial position to pursue yet another deal for a rare disease asset. Another voucher came from the mid-September FDA nod for Fayuvi, a gene therapy for a different rare inherited enzyme deficiency called Sanfilippo syndrome Type A. Each product is the first approved therapy for its respective ultra-rare indication. While the Ultragenyx gene therapies carry multi-million-dollar price tags, neither product is expected to become a big revenue driver. Much of the company’s future financial expectations had rested on apazunersen, which was in development for Angelman syndrome, a rare genetic neurological disorder with no FDA-approved therapies. Both therapies came from business deals and proceeds from the voucher sales put Ultragenyx in a better financial position to pursue yet another deal for a rare disease asset. ... Ultragenyx Pharmaceutical recently received two separate FDA approvals for gene therapies in the span of a month, each regulatory nod accompanied by a voucher the company could use to speed up the future review of another rare disease drug. Ultragenyx’s two gene therapies also came from business deals. The capital from the voucher sales could be applied toward another deal for a different rare disease therapeutic candidate. While the company made clear its intent to sell both vouchers, it has not said how it will use the proceeds. In a prepared statement, Chief Financial Officer Howard Horn noted that the Sanfilippo gene therapy benefited from capital generated by a previous voucher sale, “demonstrating the important role the [priority review voucher] program plays in helping companies develop transformative therapies for rare disease patients.”

Treatment & Clinical News•

Science & Discovery

•about 1 month ago(Oct 1)

MavriX Bio Announces FDA Rare Pediatric Disease Designation for Investigational MVX-220 for the Treatment of Angelman Syndrome

/PRNewswire/ -- AS2Bio: MavriX Bio, a clinical-stage biotechnology company focused on the development of transformative genetic therapies for Angelman syndrome... 1, 2026 /PRNewswire/ -- AS2Bio: MavriX Bio, a clinical-stage biotechnology company focused on the development of transformative genetic therapies for Angelman syndrome (AS), today announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD) to its investigational gene therapy, MVX-220, for the treatment of AS, a rare and debilitating neurogenetic disorder caused by the loss of function of the maternally inherited Ubiquitin Protein Ligase E3A (UBE3A) gene. GEMMABio is a clinical-stage therapeutics company focused on speeding the research of and global access to life-changing advanced therapies for those living with rare diseases. The company conducts research and product development functions to bring gene therapy discoveries from the bench to the bedside faster and affordably. There are no approved treatments for individuals living with AS. Rare Pediatric Disease Designation is granted by the FDA to therapies intended to treat serious or life-threatening diseases that primarily affect individuals from birth through 18 years of age and affect fewer than 200,000 people in the United States. "This designation represents an important milestone in our development program and reinforces our commitment to advancing innovative genetic treatments for individuals living with Angelman syndrome." Developed with funding from the Foundation for Angelman Syndrome Therapeutics (FAST), MVX-220 was advanced by MavriX Bio for clinical development following a research collaboration with Gemma Biotherapeutics.

BioSpace•

Pipeline & Approvals

•about 2 months ago(Sep 9)

Novo’s canned heart disease trials, Novartis’ clinical fails, first approval for Alexander disease

Ionis Pharmaceuticals secures the first targeted approval for Alexander disease, marking a significant milestone in rare disease treatment. Meanwhile, Novo Nordisk and Novartis face setbacks with late-stage trial cancellations and Phase 3 failures in cardiovascular and muscular dystrophy indications.

BioPharma Dive•

Funding & Deals

•2 months ago(Sep 3)

Ultragenyx to weigh ‘significant’ cost cuts as Angelman drug fails key study

Ultragenyx faces a significant setback as its Angelman syndrome therapy fails a key study, prompting the company to consider major cost cuts. This failure impacts the company's financial strategy and highlights the challenges in developing treatments for this rare disease.

BioSpace•

Pipeline & Approvals

•2 months ago(Sep 3)

Ultragenyx’s 'high-risk' Angelman bet fails, cratering stock and forcing strategic review

Ultragenyx's Phase 3 trial for apazunersen in Angelman syndrome has failed, significantly impacting the company's stock and prompting a strategic review. This setback removes a critical asset that was expected to drive future milestones for the biotech.

View all news for Angelman syndrome

Angelman syndrome

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Latest News & Developments

Ultragenyx Rare Disease Voucher Sales Secure $413M for More Potential Pipeline Building - MedCity News

MavriX Bio Announces FDA Rare Pediatric Disease Designation for Investigational MVX-220 for the Treatment of Angelman Syndrome

Novo’s canned heart disease trials, Novartis’ clinical fails, first approval for Alexander disease

Ultragenyx to weigh ‘significant’ cost cuts as Angelman drug fails key study

Ultragenyx’s 'high-risk' Angelman bet fails, cratering stock and forcing strategic review