Genetic DiseaseCAGS NHSNCT05528744
Delineating the Molecular Spectrum and the Clinical, Imaging and Neuronal Phenotype of Chopra-Amiel-Gordon Syndrome
An observational study of Genetic Disease and Chopra-Amiel-Gordon Syndrome, run by Boston Children's Hospital at 1 site in United States.
Trial summary
The purpose of this study is to establish the longitudinal natural history of individuals with confirmed or suspected Chopra-Amiel-Gordon Syndrome (CAGS) to learn more about the range of symptoms, changes in the structure of the brain seen on imaging, and learning difficulties that individuals with this disorder may… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Genetic Disease, Chopra-Amiel-Gordon Syndrome, CAGS
- What is being tested?
- Observational Study and Sample collection only
- How many people
- 125 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Aug 2022to Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population consists of patients of all ages and genders with a variant in ANKRD17 confirmed by pre-existing clinical genetic testing
Who may be able to join
- Participants must have a variant in ANKRD17 with a classification of VUS, likely pathogenic, or pathogenic
- Participants with a known diagnosis or CAGS have a disease-causing (likely pathogenic or pathogenic) variant in ANKRD17 evidenced by a pre-existing clinical genetic report.
- Participants with a suspected diagnosis of CAGS must have a variant of uncertain significance in ANKRD17 evidenced by a pre-existing clinical genetic report and clinical features of CAGS
- Participants with a VUS in ANKRD17 must have a variant of uncertain significance in ANKRD17
Who cannot join
- No evidence of a disease-causing or potentially disease-causing variant ANRKD17 variant on a pre-existing clinical genetic report.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jillian O'Toole, MS, CGC contact
United States1 site, 1 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Maya Chopra, MBBS, FRACP, 6179196258, maya.chopra@childrens.harvard.edu
Abigail Sveden, MS, CGC, 617-919-5214, Abigail.sveden@childrens.harvard.edu
About this study
The purpose of this study is to establish the longitudinal natural history of individuals with confirmed or suspected Chopra-Amiel-Gordon Syndrome (CAGS) to learn more about the range of symptoms, changes in the structure of the brain seen on imaging, and learning difficulties that individuals with this disorder may experience. The investigators will obtain medical history, family history, MRI records, patient photographs, genetic test results, neurobehavioral and quality of life questionnaires from individuals with confirmed or suspected CAGS at annual research visits. Participants may also complete standardized research neurobehavioral assessments, research EEGs, and sample collections at each visit. This data will be maintained on a secure research database. Samples collected will be used for functional testing and the generation of iPSC cell lines, for neuronal reprogramming and phenotyping.
Read the detailed description
Heterozygous loss of function variants in ANKRD17 were recently implicated in a newly-identified rare intellectual disability syndrome. In an international collaborative effort spanning 4 years, the mutational and phenotypic spectrum of 34 patients were described (Chopra et al AJHG 2021). The core phenotypic features of this syndrome were shown to be intellectual disability, particularly affecting speech, and shared dysmorphic features. Variably present neurodevelopmental features were epilepsy /abnormal EEG, autism spectrum disorder, gait / balance difficulties and neuroimaging abnormalities. Extra-neurological features include growth delay, renal anomalies, hypermobility, pigmentary lesions and feeding problems. All variants were identified on whole exome or whole genome sequencing, and most were shown to be de novo and truncating, although some patients harbored missense variants particularly in highly conserved ankyrin repeat domains. While this initial project presented compelling evidence for a novel gene-disease relationship and established the key phenotypic features of this new disorder, there were limitations to this work. The neurodevelopmental profile and MRI findings were ascertained through physician report only rather than independent standardized assessment. Intriguingly, while it was observed that expressive language delay was more markedly affected than other developmental parameters, this observation was not validated with standardized patient evaluation. Currently, the impact of ANKRD17 haploinsufficiency on human neuronal morphology / excitability, and in turn, the correlation of this neuronal phenotype to the clinical neurodevelopmental profile is unknown. With this study, the investigators plan to deeply characterize the longitudinal spectrum of clinical, neuroimaging and neuronal cellular features of this disorder, pairing preclinical with clinical science. The robust annual systematic evaluation of patients who are known or suspected to have this condition will lead to a better understanding of the true phenotypic spectrum and correlations to genotype. The inclusion of patients with ANKRD17 VUS and/or suspected to have CAGS, in particular, may expand the phenotypic and genotypic spectrum of the condition, and clarify diagnoses for these participants. The generation of patient-specific iPSC lines and isogenic controls will allow for future projects to generate neuronal populations from clinically characterized patients, which will bridge the knowledge gap on the biological underpinnings of the disorder and potentially lead to biomarkers that reflect specific disrupted neurodevelopmental pathways.
- Conditions
- Genetic Disease, Chopra-Amiel-Gordon Syndrome, CAGS, ANKRD17
- Being tested
- Observational Study, Sample collection only
- Keywords
- Syndrome, Neurodevelopmental, ANKRD17 Loss of function, ANKRD17, Rare Disease, CAGS, Chopra-Amiel-Gordon
- Medical subject headings
- Genetic Diseases, Inborn, Syndrome, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational StudyOther
No intervention. This is an observational study
Sample collection onlyOther
Collection of blood and/or skin samples.
| Study group | Role | What they receive |
|---|---|---|
| Proband | Study participants who have suspected or confirmed CAGS based on having a variant of uncertain significance, likely pathogenic variant, or pathogenic variant in ANKRD17 and clinical features of the condition. Receives: Other: Observational Study | |
| Unaffected family members | Family members of the proband who do not have an ANKRD17 variant. Receives: Other: Sample collection only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Research registry of molecular and phenotypic information related to CAGS
The primary endpoint of this cross-sectional natural history study will be the creation and implementation of a research registry of molecular and phenotypic information for CAGS.
Measured: 4-5 years
Generation of patient-derived iPSC cell lines
An additional objective of this cross-sectional natural history study will be the generation of patient-derived iPSC cell lines. iPSC cell lines will be created from blood and skin samples of individuals with ANKRD17 variants, using samples from unaffected family members as controls.
Measured: 4-5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2022
- Study start27 Aug 2022
- Primary completionDec 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Genetic DiseaseStudies 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
- Other
- Time perspective
- Prospective
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maya Chopra, Boston Children's Hospital
- Investigators
- Maya Chopra, MBBS, FRACP, Study chair, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05528744
- Sponsor's protocol ID
- P00041124
- Acronym
- CAGS NHS
- Status last verified
- Feb 2026
- First submitted
- 3 May 2022
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sveden A, Gordon CT, Amiel J, Chopra M. ANKRD17-Related Neurodevelopmental Syndrome. 2022 Dec 22. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK588029/
PubMed 36548456Chopra M, McEntagart M, Clayton-Smith J, Platzer K, Shukla A, Girisha KM, Kaur A, Kaur P, Pfundt R, Veenstra-Knol H, Mancini GMS, Cappuccio G, Brunetti-Pierri N, Kortum F, Hempel M, Denecke J, Lehman A; CAUSES Study; Kleefstra T, Stuurman KE, Wilke M, Thompson ML, Bebin EM, Bijlsma EK, Hoffer MJV, Peeters-Scholte C, Slavotinek A, Weiss WA, Yip T, Hodoglugil U, Whittle A, diMonda J, Neira J, Yang S, Kirby A, Pinz H, Lechner R, Sleutels F, Helbig I, McKeown S, Helbig K, Willaert R, Juusola J, Semotok J, Hadonou M, Short J; Genomics England Research Consortium; Yachelevich N, Lala S, Fernandez-Jaen A, Pelayo JP, Klockner C, Kamphausen SB, Abou Jamra R, Arelin M, Innes AM, Niskakoski A, Amin S, Williams M, Evans J, Smithson S, Smedley D, de Burca A, Kini U, Delatycki MB, Gallacher L, Yeung A, Pais L, Field M, Martin E, Charles P, Courtin T, Keren B, Iascone M, Cereda A, Poke G, Abadie V, Chalouhi C, Parthasarathy P, Halliday BJ, Robertson SP, Lyonnet S, Amiel J, Gordon CT. Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism. Am J Hum Genet. 2021 Jun 3;108(6):1138-1150. doi: 10.1016/j.ajhg.2021.04.007. Epub 2021 Apr 27.
PubMed 33909992
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Delineating the Molecular Spectrum and the Clinical, Imaging and Neuronal Phenotype of Chopra-Amiel-Gordon Syndrome
- ClinicalTrials.gov ID
- NCT05528744
- Acronym / sponsor ID
- CAGS NHS / P00041124
- Conditions
- Genetic Disease, Chopra-Amiel-Gordon Syndrome, CAGS, ANKRD17
- Keywords
- Syndrome, Neurodevelopmental, ANKRD17 Loss of function, ANKRD17, Rare Disease, CAGS, Chopra-Amiel-Gordon
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 27 Aug 2022 (actual)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 6 Sep 2022 (actual)
- 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.
The purpose of this study is to establish the longitudinal natural history of individuals with confirmed or suspected Chopra-Amiel-Gordon Syndrome (CAGS) to learn more about the range of symptoms, changes in the structure of the brain seen on imaging, and learning difficulties that individuals with this disorder may experience. The investigators will obtain medical history, family history, MRI records, patient photographs, genetic test results, neurobehavioral and quality of life questionnaires from individuals with confirmed or suspected CAGS at annual research visits. Participants may also complete standardized research neurobehavioral assessments, research EEGs, and sample collections at each visit. This data will be maintained on a secure research database. Samples collected will be used for functional testing and the generation of iPSC cell lines, for neuronal reprogramming and phenotyping.
Detailed description
Heterozygous loss of function variants in ANKRD17 were recently implicated in a newly-identified rare intellectual disability syndrome. In an international collaborative effort spanning 4 years, the mutational and phenotypic spectrum of 34 patients were described (Chopra et al AJHG 2021). The core phenotypic features of this syndrome were shown to be intellectual disability, particularly affecting speech, and shared dysmorphic features. Variably present neurodevelopmental features were epilepsy /abnormal EEG, autism spectrum disorder, gait / balance difficulties and neuroimaging abnormalities. Extra-neurological features include growth delay, renal anomalies, hypermobility, pigmentary lesions and feeding problems. All variants were identified on whole exome or whole genome sequencing, and most were shown to be de novo and truncating, although some patients harbored missense variants particularly in highly conserved ankyrin repeat domains. While this initial project presented compelling evidence for a novel gene-disease relationship and established the key phenotypic features of this new disorder, there were limitations to this work. The neurodevelopmental profile and MRI findings were ascertained through physician report only rather than independent standardized assessment. Intriguingly, while it was observed that expressive language delay was more markedly affected than other developmental parameters, this observation was not validated with standardized patient evaluation. Currently, the impact of ANKRD17 haploinsufficiency on human neuronal morphology / excitability, and in turn, the correlation of this neuronal phenotype to the clinical neurodevelopmental profile is unknown. With this study, the investigators plan to deeply characterize the longitudinal spectrum of clinical, neuroimaging and neuronal cellular features of this disorder, pairing preclinical with clinical science. The robust annual systematic evaluation of patients who are known or suspected to have this condition will lead to a better understanding of the true phenotypic spectrum and correlations to genotype. The inclusion of patients with ANKRD17 VUS and/or suspected to have CAGS, in particular, may expand the phenotypic and genotypic spectrum of the condition, and clarify diagnoses for these participants. The generation of patient-specific iPSC lines and isogenic controls will allow for future projects to generate neuronal populations from clinically characterized patients, which will bridge the knowledge gap on the biological underpinnings of the disorder and potentially lead to biomarkers that reflect specific disrupted neurodevelopmental pathways.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Proband | – | Other: Observational StudyStudy participants who have suspected or confirmed CAGS based on having a variant of uncertain significance, likely pathogenic variant, or pathogenic variant in ANKRD17 and clinical features of the condition. |
| Unaffected family members | – | Other: Sample collection onlyFamily members of the proband who do not have an ANKRD17 variant. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population consists of patients of all ages and genders with a variant in ANKRD17 confirmed by pre-existing clinical genetic testing
Key inclusion criteria (4 listed)
- Participants must have a variant in ANKRD17 with a classification of VUS, likely pathogenic, or pathogenic
- Participants with a known diagnosis or CAGS have a disease-causing (likely pathogenic or pathogenic) variant in ANKRD17 evidenced by a pre-existing clinical genetic report.
- Participants with a suspected diagnosis of CAGS must have a variant of uncertain significance in ANKRD17 evidenced by a pre-existing clinical genetic report and clinical features of CAGS
- Participants with a VUS in ANKRD17 must have a variant of uncertain significance in ANKRD17
Key exclusion criteria (1 listed)
- No evidence of a disease-causing or potentially disease-causing variant ANRKD17 variant on a pre-existing clinical genetic report.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Observational StudyNo intervention. This is an observational study | Other | Proband |
| Sample collection onlyCollection of blood and/or skin samples. | Other | Unaffected family members |
Primary outcome
Research registry of molecular and phenotypic information related to CAGS
Time frame: 4-5 years
The primary endpoint of this cross-sectional natural history study will be the creation and implementation of a research registry of molecular and phenotypic information for CAGS.
Generation of patient-derived iPSC cell lines
Time frame: 4-5 years
An additional objective of this cross-sectional natural history study will be the generation of patient-derived iPSC cell lines. iPSC cell lines will be created from blood and skin samples of individuals with ANKRD17 variants, using samples from unaffected family members as controls.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Background: PubMed 36548456Sveden A, Gordon CT, Amiel J, Chopra M. ANKRD17-Related Neurodevelopmental Syndrome. 2022 Dec 22. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK588029/
- Background: PubMed 33909992Chopra M, McEntagart M, Clayton-Smith J, Platzer K, Shukla A, Girisha KM, Kaur A, Kaur P, Pfundt R, Veenstra-Knol H, Mancini GMS, Cappuccio G, Brunetti-Pierri N, Kortum F, Hempel M, Denecke J, Lehman A; CAUSES Study; Kleefstra T, Stuurman KE, Wilke M, Thompson ML, Bebin EM, Bijlsma EK, Hoffer MJV, Peeters-Scholte C, Slavotinek A, Weiss WA, Yip T, Hodoglugil U, Whittle A, diMonda J, Neira J, Yang S, Kirby A, Pinz H, Lechner R, Sleutels F, Helbig I, McKeown S, Helbig K, Willaert R, Juusola J, Semotok J, Hadonou M, Short J; Genomics England Research Consortium; Yachelevich N, Lala S, Fernandez-Jaen A, Pelayo JP, Klockner C, Kamphausen SB, Abou Jamra R, Arelin M, Innes AM, Niskakoski A, Amin S, Williams M, Evans J, Smithson S, Smedley D, de Burca A, Kini U, Delatycki MB, Gallacher L, Yeung A, Pais L, Field M, Martin E, Charles P, Courtin T, Keren B, Iascone M, Cereda A, Poke G, Abadie V, Chalouhi C, Parthasarathy P, Halliday BJ, Robertson SP, Lyonnet S, Amiel J, Gordon CT. Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism. Am J Hum Genet. 2021 Jun 3;108(6):1138-1150. doi: 10.1016/j.ajhg.2021.04.007. Epub 2021 Apr 27.
- 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.
Jillian O'Toole, MS, CGC contact
Maya Chopra, MBBS, FRACP study chair
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Genetic Disease and Chopra-Amiel-Gordon Syndrome, run by Boston Children's Hospital at 1 site 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 4 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Abigail Sveden, MS, CGC (617-919-5214, Abigail.sveden@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Research registry of molecular and phenotypic information related to CAGS (time frame: 4-5 years). 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 NCT05528744, which also lists 2 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 17 Feb 2026.