Delineating the Molecular Spectrum and the Clinical, Imaging and Neuronal Phenotype of Chopra-Amiel-Gordon Syndrome
Boston Children's Hospital
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 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.
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.…
Eligibility
- Age range
- Not specified
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 Exclusion C…
Interventions
- OtherObservational Study
No intervention. This is an observational study
- OtherSample collection only
Collection of blood and/or skin samples.
Location
- Boston Children's HospitalBoston, Massachusetts