Angelman SyndromeNCT00296764
Characterization of Angelman Syndrome
An observational study of Angelman Syndrome, run by Boston Children's Hospital at 6 sites in United States.
Trial summary
Angelman Syndrome (AS) is a developmental disorder that is caused by a deficiency of a maternally transmitted gene. It is inherited at birth, and affects movement, speech, and social demeanor. Read more about this study
- Who is it for?
- Ages 1 day to 60 years
- Conditions the study is for
- Angelman Syndrome
- How many people
- 302 participants
- Where
- 6 sitesUnited States
- Study dates
- Feb 2006to Aug 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patients with Angelman syndrome (molecular or clinical diagnosis) between the ages of 1 day and 60 years.
Who may be able to join
- Molecular diagnosis of Angelman syndrome OR
- Meets all major diagnostic criteria for Angelman Syndrome and 3 of the 6 minor criteria:
- Major Criteria:
- Functionally severe developmental delay
- Speech impairment; none or minimal words used
- Movement or balance disorder
Show all 14Show fewer
- Behavioral uniqueness, frequent laughs/smiling, excitable personality, hand flapping, short attention span
- Minor Criteria:
- Deceleration in head circumference growth (post-natal)
- Seizures (myoclonic, absence, drop, tonic-clonic)
- Abnormal EEG (with patterns suggestive of AS, or hypsarrhythmia)
- Sleep disturbance
- Attraction to or fascination with water
- Drooling
Who cannot join
- Does not meet diagnostic criteria for Angelman Syndrome
- Other medical or genetic disorders (except autism)
- Born extremely premature
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital and Medical Center
Cincinnati, Ohio, 45229
Greenwood Genetic Center
Greenwood, South Carolina, 29646
Baylor College of Medicine
Houston, Texas, 77030
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Rady Children's Hospital San Diego
San Diego, California, 92123
About this study
Official title: Angelman Syndrome Natural History Study
Angelman Syndrome (AS) is a developmental disorder that is caused by a deficiency of a maternally transmitted gene. It is inherited at birth, and affects movement, speech, and social demeanor. This study will gain a better understanding of the disease progression and clinical features of AS by observing children with AS over an extended period of time.
Read the detailed description
AS is a developmental disorder that affects movement, speech, and social demeanor. The disorder is caused by a deficiency of a maternally transmitted gene and is inherited at birth. Children with AS, however, are often not diagnosed until they are between 3 and 7 years old. Symptoms of AS may include, but are not limited to, functionally severe developmental delay; speech impairments; movement or balance problems; and behavioral uniqueness, including any combination of frequent laughter or smiling, apparent happy demeanor, easily excitable personality, hand flapping movements, and short attention span. There are four molecular variations of AS, but past clinical studies have been inconsistent in highlighting the phenotypic differences between them. This study will gain a better understanding of the disease progression and clinical features of AS by observing children with AS over a period of 5 to 10 years. The study will also attempt to establish genotype-phenotype correlations, which might aid in future clinical care of AS patients.
Participation in this observational study will be limited to current or future patients at one of the five study sites. A clinical evaluation will be performed at baseline, including a general patient history, physical and neurological examinations, a nutritional assessment, neuro-imaging, electroencephalography, laboratory testing, and neurodevelopmental testing. A blood sample or mucosal sample will also be taken at baseline to acquire DNA for potential genetic testing. All assessments except the neuro-imaging, electroencephalography, and blood sampling will be repeated at yearly study visits for as long as funding can be secured. In addition, participants will be photographed and perhaps videotaped on a yearly basis in order to document clinical phenotypes and any neurologic abnormalities. Participants may be followed-up for a total of 10 years.
- Conditions
- Angelman Syndrome
- Keywords
- Developmental Disorders
- Medical subject headings
- Angelman Syndrome, Developmental Disabilities
What is being measured
The primary outcome is the main question the study is designed to answer.
medical morbidity
to characterize the medical problems associated with Angelman syndrome, and to determine the relative prevalence of those problems in the different molecular subclasses of Angelman syndrome
Measured: annually
developmental progress
Assess with a variety of neuropsychological instruments, including Bayley Scales of Infant Development, Vineland Adaptive Behavior Scales, Preschool Language Scale
Measured: annually
Secondary outcomes (1)
autism
Evaluate for autism spectrum disorder using Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised
Measured: annually
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2006 (estimated)
- Study startFeb 2006
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Rady Children's Hospital, San Diego, Baylor College of Medicine, Greenwood Genetic Center, Children's Hospital Medical Center, Cincinnati, Vanderbilt University Medical Center, National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, Wen-Hann Tan, Boston Children's Hospital
- Investigators
- Carlos A. Bacino, MD, Principal investigator, Baylor College of Medicine, Department of Molecular and Human GeneticsLynne Bird, MD, Study chair, Rady Childrens Hospital San Diego, UCSD Dept of PediatricsSteven A. Skinner, MD, Principal investigator, Greenwood Genetic CenterWen-Hann Tan, BMBS, Principal investigator, Boston Children's HospitalLogan K Wink, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiSarika Peters, PhD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00296764
- Sponsor's protocol ID
- RDCRN 5203
- Other IDs
- U54RR019478
- Status last verified
- Feb 2021
- First submitted
- 24 Feb 2006
- Last updated
- 2 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Varela MC, Kok F, Otto PA, Koiffmann CP. Phenotypic variability in Angelman syndrome: comparison among different deletion classes and between deletion and UPD subjects. Eur J Hum Genet. 2004 Dec;12(12):987-92. doi: 10.1038/sj.ejhg.5201264.
PubMed 15470370Peters SU, Beaudet AL, Madduri N, Bacino CA. Autism in Angelman syndrome: implications for autism research. Clin Genet. 2004 Dec;66(6):530-6. doi: 10.1111/j.1399-0004.2004.00362.x.
PubMed 15521981Locke DP, Segraves R, Nicholls RD, Schwartz S, Pinkel D, Albertson DG, Eichler EE. BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications. J Med Genet. 2004 Mar;41(3):175-82. doi: 10.1136/jmg.2003.013813.
PubMed 14985376Smith JC. Angelman syndrome: evolution of the phenotype in adolescents and adults. Dev Med Child Neurol. 2001 Jul;43(7):476-80. doi: 10.1017/s0012162201000871.
PubMed 11463179Williams CA, Lossie A, Driscoll D; R.C. Phillips Unit. Angelman syndrome: mimicking conditions and phenotypes. Am J Med Genet. 2001 Jun 1;101(1):59-64. doi: 10.1002/ajmg.1316.
PubMed 11343340Sadhwani A, Powers S, Wheeler A, Miller H, Potter SN, Peters SU, Bacino CA, Skinner SA, Wink LK, Erickson CA, Bird LM, Tan WH. Developmental milestones and daily living skills in individuals with Angelman syndrome. J Neurodev Disord. 2024 Jun 15;16(1):32. doi: 10.1186/s11689-024-09548-7.
PubMed 38879552Frohlich J, Chiang JN, Mediano PAM, Nespeca M, Saravanapandian V, Toker D, Dell'Italia J, Hipp JF, Jeste SS, Chu CJ, Bird LM, Monti MM. Neural complexity is a common denominator of human consciousness across diverse regimes of cortical dynamics. Commun Biol. 2022 Dec 15;5(1):1374. doi: 10.1038/s42003-022-04331-7.
PubMed 36522453Keute M, Miller MT, Krishnan ML, Sadhwani A, Chamberlain S, Thibert RL, Tan WH, Bird LM, Hipp JF. Angelman syndrome genotypes manifest varying degrees of clinical severity and developmental impairment. Mol Psychiatry. 2021 Jul;26(7):3625-3633. doi: 10.1038/s41380-020-0858-6. Epub 2020 Aug 13.
PubMed 32792659Frohlich J, Miller MT, Bird LM, Garces P, Purtell H, Hoener MC, Philpot BD, Sidorov MS, Tan WH, Hernandez MC, Rotenberg A, Jeste SS, Krishnan M, Khwaja O, Hipp JF. Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes. Biol Psychiatry. 2019 May 1;85(9):752-759. doi: 10.1016/j.biopsych.2019.01.008. Epub 2019 Jan 19.
PubMed 30826071Killian JT, Lane JB, Cutter GR, Skinner SA, Kaufmann WE, Tarquinio DC, Glaze DG, Motil KJ, Neul JL, Percy AK. Pubertal development in Rett syndrome deviates from typical females. Pediatr Neurol. 2014 Dec;51(6):769-75. doi: 10.1016/j.pediatrneurol.2014.08.013. Epub 2014 Aug 29.
PubMed 25283752Neul JL, Lane JB, Lee HS, Geerts S, Barrish JO, Annese F, Baggett LM, Barnes K, Skinner SA, Motil KJ, Glaze DG, Kaufmann WE, Percy AK. Developmental delay in Rett syndrome: data from the natural history study. J Neurodev Disord. 2014;6(1):20. doi: 10.1186/1866-1955-6-20. Epub 2014 Jul 22.
PubMed 25071871
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angelman Syndrome Natural History Study
- ClinicalTrials.gov ID
- NCT00296764
- Acronym / sponsor ID
- RDCRN 5203
- Conditions
- Angelman Syndrome
- Keywords
- Developmental Disorders
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 302 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Rady Children's Hospital, San Diego, Baylor College of Medicine, Greenwood Genetic Center, Children's Hospital Medical Center, Cincinnati, Vanderbilt University Medical Center, National Center for Research Resources (NCRR)
- Study start
- Feb 2006 (actual)
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 27 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Angelman Syndrome (AS) is a developmental disorder that is caused by a deficiency of a maternally transmitted gene. It is inherited at birth, and affects movement, speech, and social demeanor. This study will gain a better understanding of the disease progression and clinical features of AS by observing children with AS over an extended period of time.
Detailed description
AS is a developmental disorder that affects movement, speech, and social demeanor. The disorder is caused by a deficiency of a maternally transmitted gene and is inherited at birth. Children with AS, however, are often not diagnosed until they are between 3 and 7 years old. Symptoms of AS may include, but are not limited to, functionally severe developmental delay; speech impairments; movement or balance problems; and behavioral uniqueness, including any combination of frequent laughter or smiling, apparent happy demeanor, easily excitable personality, hand flapping movements, and short attention span. There are four molecular variations of AS, but past clinical studies have been inconsistent in highlighting the phenotypic differences between them. This study will gain a better understanding of the disease progression and clinical features of AS by observing children with AS over a period of 5 to 10 years. The study will also attempt to establish genotype-phenotype correlations, which might aid in future clinical care of AS patients.
Participation in this observational study will be limited to current or future patients at one of the five study sites. A clinical evaluation will be performed at baseline, including a general patient history, physical and neurological examinations, a nutritional assessment, neuro-imaging, electroencephalography, laboratory testing, and neurodevelopmental testing. A blood sample or mucosal sample will also be taken at baseline to acquire DNA for potential genetic testing. All assessments except the neuro-imaging, electroencephalography, and blood sampling will be repeated at yearly study visits for as long as funding can be secured. In addition, participants will be photographed and perhaps videotaped on a yearly basis in order to document clinical phenotypes and any neurologic abnormalities. Participants may be followed-up for a total of 10 years.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 1 day to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patients with Angelman syndrome (molecular or clinical diagnosis) between the ages of 1 day and 60 years.
Key inclusion criteria (14 listed)
- Molecular diagnosis of Angelman syndrome OR
- Meets all major diagnostic criteria for Angelman Syndrome and 3 of the 6 minor criteria:
- Functionally severe developmental delay
- Speech impairment; none or minimal words used
- Movement or balance disorder
Key exclusion criteria (3 listed)
- Does not meet diagnostic criteria for Angelman Syndrome
- Other medical or genetic disorders (except autism)
- Born extremely premature
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
medical morbidity
Time frame: annually
to characterize the medical problems associated with Angelman syndrome, and to determine the relative prevalence of those problems in the different molecular subclasses of Angelman syndrome
developmental progress
Time frame: annually
Assess with a variety of neuropsychological instruments, including Bayley Scales of Infant Development, Vineland Adaptive Behavior Scales, Preschool Language Scale
1 secondary outcome
autism
Time frame: annually
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2021.
- Background: PubMed 15470370Varela MC, Kok F, Otto PA, Koiffmann CP. Phenotypic variability in Angelman syndrome: comparison among different deletion classes and between deletion and UPD subjects. Eur J Hum Genet. 2004 Dec;12(12):987-92. doi: 10.1038/sj.ejhg.5201264.
- Background: PubMed 15521981Peters SU, Beaudet AL, Madduri N, Bacino CA. Autism in Angelman syndrome: implications for autism research. Clin Genet. 2004 Dec;66(6):530-6. doi: 10.1111/j.1399-0004.2004.00362.x.
- Background: PubMed 14985376Locke DP, Segraves R, Nicholls RD, Schwartz S, Pinkel D, Albertson DG, Eichler EE. BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications. J Med Genet. 2004 Mar;41(3):175-82. doi: 10.1136/jmg.2003.013813.
- Background: PubMed 11463179Smith JC. Angelman syndrome: evolution of the phenotype in adolescents and adults. Dev Med Child Neurol. 2001 Jul;43(7):476-80. doi: 10.1017/s0012162201000871.
- Background: PubMed 11343340Williams CA, Lossie A, Driscoll D; R.C. Phillips Unit. Angelman syndrome: mimicking conditions and phenotypes. Am J Med Genet. 2001 Jun 1;101(1):59-64. doi: 10.1002/ajmg.1316.
- Derived from this study: PubMed 38879552Sadhwani A, Powers S, Wheeler A, Miller H, Potter SN, Peters SU, Bacino CA, Skinner SA, Wink LK, Erickson CA, Bird LM, Tan WH. Developmental milestones and daily living skills in individuals with Angelman syndrome. J Neurodev Disord. 2024 Jun 15;16(1):32. doi: 10.1186/s11689-024-09548-7.
- Derived from this study: PubMed 36522453Frohlich J, Chiang JN, Mediano PAM, Nespeca M, Saravanapandian V, Toker D, Dell'Italia J, Hipp JF, Jeste SS, Chu CJ, Bird LM, Monti MM. Neural complexity is a common denominator of human consciousness across diverse regimes of cortical dynamics. Commun Biol. 2022 Dec 15;5(1):1374. doi: 10.1038/s42003-022-04331-7.
- Derived from this study: PubMed 32792659Keute M, Miller MT, Krishnan ML, Sadhwani A, Chamberlain S, Thibert RL, Tan WH, Bird LM, Hipp JF. Angelman syndrome genotypes manifest varying degrees of clinical severity and developmental impairment. Mol Psychiatry. 2021 Jul;26(7):3625-3633. doi: 10.1038/s41380-020-0858-6. Epub 2020 Aug 13.
- Derived from this study: PubMed 30826071Frohlich J, Miller MT, Bird LM, Garces P, Purtell H, Hoener MC, Philpot BD, Sidorov MS, Tan WH, Hernandez MC, Rotenberg A, Jeste SS, Krishnan M, Khwaja O, Hipp JF. Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes. Biol Psychiatry. 2019 May 1;85(9):752-759. doi: 10.1016/j.biopsych.2019.01.008. Epub 2019 Jan 19.
- Derived from this study: PubMed 25283752Killian JT, Lane JB, Cutter GR, Skinner SA, Kaufmann WE, Tarquinio DC, Glaze DG, Motil KJ, Neul JL, Percy AK. Pubertal development in Rett syndrome deviates from typical females. Pediatr Neurol. 2014 Dec;51(6):769-75. doi: 10.1016/j.pediatrneurol.2014.08.013. Epub 2014 Aug 29.
- Derived from this study: PubMed 25071871Neul JL, Lane JB, Lee HS, Geerts S, Barrish JO, Annese F, Baggett LM, Barnes K, Skinner SA, Motil KJ, Glaze DG, Kaufmann WE, Percy AK. Developmental delay in Rett syndrome: data from the natural history study. J Neurodev Disord. 2014;6(1):20. doi: 10.1186/1866-1955-6-20. Epub 2014 Jul 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlos A. Bacino, MD principal investigator
Baylor College of Medicine, Department of Molecular and Human Genetics
Lynne Bird, MD study chair
Rady Childrens Hospital San Diego, UCSD Dept of Pediatrics
Steven A. Skinner, MD principal investigator
Greenwood Genetic Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Angelman Syndrome, run by Boston Children's Hospital at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
medical morbidity (time frame: annually). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00296764, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2021.