An observational study in Genetic Disease, Chopra-Amiel-Gordon Syndrome and CAGS, sponsored by Boston Children's Hospital. Recruiting at 1 site in United States. Per ClinicalTrials.gov, last updated 2026-02-17.
Sponsored by Boston Children's Hospital · Observational
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.
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.
583 studies on the registry are indexed under Genetic Diseases, Inborn; 157 are open to participants now.
This study's planned enrollment of 125 is below the median of 151 across 239 observational studies indexed under Genetic Diseases, Inborn.
Browse Genetic Diseases, Inborn studies →Boston Children's Hospital is the lead sponsor of 608 studies on the registry; 147 are open to participants now.
Of its 32 completed or terminated interventional studies of FDA-regulated products, 19 (59%) have results posted.
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The study population consists of patients of all ages and genders with a variant in ANKRD17 confirmed by pre-existing clinical genetic testing
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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.
Other: Observational Study
Family members of the proband who do not have an ANKRD17 variant.
Other: Sample collection only
No intervention. This is an observational study
Collection of blood and/or skin samples.
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.
Time frame: 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.
Time frame: 4-5 years
Plan to share: No
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