Baker Gordon Syndrome Natural History Study (BAGOS)

A Prospective, Longitudinal and Observational Natural History Study for Children and Adults With Baker Gordon Syndrome - Genetic Autism Alliance

The goal of this study is to conduct a prospective, longitudinal assessment of the natural clinical progression of children and adults with Synaptotagmin1-Associated Neurodevelopmental Disorder also known as Baker Gordon Syndrome (BAGOS). This will be performed by acquiring baseline measurements and developing effective outcome measures and diagnostic tools for the disorder, to prepare the healthcare system for future clinical trials.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy, Generalized; Sleep Disorder; Rare Diseases; Development Delay; Motor Delay; Autism or Autistic Traits; SYT-SSX Fusion Protein Expression
• Intervention / Treatment: Diagnostic test: Brain Magnetic Resonance Imaging (MRI); Genetic: Whole Genome Sequencing; Other: Induced Pluripotential Stem Cells

Detailed Description

The current natural history study is being conducted in anticipation of future treatments for patients with confirmed BAGOS. The study is an important avenue of investigation that will increase the understanding of the disorder and lead to important diagnostic and therapeutic advances. Its purpose is to identify demographic, genetic, environmental, and treatment modalities and concomitant medications that correlate with the disease's development and outcomes. This study will use standard scales and questionnaires for the assessment of global development, language, memory, and motor function, and by collecting sleep and seizure diaries. A small blood sample will be collected for whole genome sequencing and proteomic analysis. Brain imaging (MRI) and electroencephalography (EEG) recordings will be collected to identify disease biomarkers. The investigators will also be asking participants to provide a small skin sample for the development of patient specific stem cells which will be used to further understand the impact of Synaptotagmin1 mutations on neurodevelopment and as a potential screen for future therapies.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: W. David R Arnold, MD; Phone Number: 573-884-2924; Email: wdavidarnold@health.missouri.edu

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Recruiting
      • University of Missouri Columbia
      • Contact: W. David Arnold, MD; Phone Number: 573-884-2924; Email: wdavidarnold@health.missouri.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Study Population:

• Genetically confirmed BAGOS
• 0-99 years

This study will comprehensively evaluate the natural clinical progression of the disease using scales and questionnaires for the assessment of motor function and global development, and by collecting sleep and seizure diaries. In addition, genetic and proteomic analysis, EEG recordings and brain MRI will be collected to identify biomarkers that will indicate disease progression or improvements following treatment.

Description

Inclusion Criteria:

• Genetically confirmed diagnosis of Baker Gordon syndrome.
• 0-99 years
• Ability to send medical records and diagnostic test results.
• Ability to complete tests and questionnaires.

Exclusion Criteria:

• The presence of another condition or co-morbidity unrelated to Baker Gordon syndrome, that affects neurodevelopment.

In this study, the primary caregivers/LAR for each participant diagnosed Baker Gordon Syndrome will be also considered participants.

Caregivers/LAR will have to meet the following inclusion criteria:

• >18 years.
• Legal caregiver of the patient diagnosed with a Baker Gordon Syndrome.
• Willingness to follow study procedures, as assessed by the research team.
• Willingness to sign the consent form.
• Ability to understand all the information regarding the study, as assessed by the research team.

Caregivers/LAR Exclusion Criteria:

• Less than 18 years old.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collection of relevant medical data (retrospective and prospective)	Collection of demographic data, BAGOS-related medical history, past medical and surgical history, current medication, history of immunizations and family medical history.	24 months
Neurological Assessment Scale	Hammersmith Infant Neurological Examination (HINE) (0-2 years ONLY). Maximum global score of 78. Higher scores indicate a higher degree of neurological performance.	24 months
Clinical Global Impressions Scale - Practitioner	Scales whereby practitioner rates from 1 to 7 the overall improvement/deterioration of the participant affected by BAGOS. One is improved and 7 denotes deterioration.	24 months
Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)	The PEDI-CAT is a computer adaptive caregiver report which measures Daily Activities, Mobility, Social/Cognitive, and Responsibility. It's designed for use with children and youth with a variety of physical and/or behavioral conditions.	24 months
Pediatric Evaluation of Disability Inventory	Pediatric Evaluation of Disability Inventory assesses key functional capabilities and performance in children ages 6 months to 7 years.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gross motor milestones	World Health Organization (WHO) Motor Milestones. Scale of 6 gross motor milestones. Lower scores denote worse motor function.	24 months
Global development assessment scale	Bayley Scales of Infant and Toddler Development - 4 (BSID-4) for Developmental delays. Scale is divided into five domains, which are further divided into subdomains. The first step is to calculate the starting point by beginning with the items that are age appropriate. The starting point is validated if three consecutive items are achieved. If the participant affected by Baker Gordon Syndrome does not achieve three consecutive items in a row at the age-appropriate starting point, the evaluator must go backwards to the lower age-starting point until the participant affected by Baker Gordon Syndrome achieves three items in a row. The assessment stops once five items in a row are not achieved.	24 months
Vineland Adaptive Behavior Scales Third Edition	Vineland Adaptive Behavior Scales Third Edition is the leading instrument for supporting the diagnosis of intellectual and developmental disabilities. Vineland-3 not only aids in diagnosis, but provides valuable information for developing educational and treatment plans	24 months
Aberrant behavior assessment (ABC)	Aberrant Behavior Checklist-Community (ABC-C). This scale comprises 58 items and is divided into five subdomains. The ABC-C is designed on a four-point scale with the lowest score representing less-affected patients while the highest score represents most-affected patients.	24 months
Conners 4th Edition	Conners 4th Edition (Conners 4™) provides a comprehensive assessment of symptoms and impairments associated with ADHD and common co-occurring problems and disorders in children and youth aged 6 to 18 years.	24 months
Test of Everyday Attention for Children 2nd Edition (TEA-Ch2)	Test of Everyday Attention for Children Second Edition (TEA-Ch2) uniquely measures separable aspects of attention.	24 months
NEPSY 2nd edition	NEPSY®-II results provide information relating to typical childhood disorders, enabling accurate diagnosis and intervention planning for success in school and at home.	24 months
The Infant/Toddler Sensory Profile	The Infant/Toddler Sensory Profile® was developed to evaluate sensory processing patterns in the very young. The results provide understanding of how sensory processing affects the child's daily functioning performance.	24 months
Mullen Scales of Early Learning	Mullen Scales of Early Learning is a developmentally integrated system that assesses language, motor, and perceptual abilities, measures cognitive ability and motor development quickly and reliability.	24 months
Behavior Assessment System for Children (BASC), 3rd Edition	Behavior Assessment System for Children (BASC), 3rd Edition. A comprehensive set of rating scales and forms, BASC-3 helps participants understand the behaviors and emotions of children and adolescents	24 months
Motor function assessment	Functional Mobility Scale (FMS). Scale which rates the walking ability in three different walking distances, and these distances will be rated on a 6-point scale. Higher scored denote less impairment.	24 months
Pediatric Sleep Questionnaire (PSQ)	A 22-point questionnaire that assesses the sleep patterns and potential abnormalities in children and their affected quality of life.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health economics	Interview with Caregivers	24 months
Laboratory tests	Genomic and proteomic analysis of plasma samples to determine biomarkers of disease progression	24 months
Brain magnetic resonance imaging (MRI)	Brain magnetic imaging (MRI) to measure the brain grey and white matter volume.	24 months
Clinical trial readiness	Demographic data collection	24 months
Clinical trial readiness	Facilities Preparation	24 months
Electroencephalogram activity recordings (EEG)	Electroencephalogram (EEG) to record brain activity of Baker Gordon Syndrome patients over a 2-hour period.	24 months

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Investigators: Principal Investigator: W. David Arnold, MD, University of Missouri-Columbia

Publications and helpful links

General Publications

• Riggs E, Shakkour Z, Anderson CL, Carney PR. SYT1-Associated Neurodevelopmental Disorder: A Narrative Review. Children (Basel). 2022 Sep 22;9(10):1439. doi: 10.3390/children9101439.

Helpful Links

• Baker Gordon Syndrome Foundation
• University of Missouri NextGen Precision Health
• Thompson Center for Autism and Neurodevelopment

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2024
• Primary Completion (Estimated): May 5, 2026
• Study Completion (Estimated): May 5, 2026

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 22, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Baker Gordon Syndrome; BAGOS; Synaptotagmin 1-Associated Neurodevelopmental Disorder
• Additional Relevant MeSH Terms: Autism Spectrum Disorder; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Disease Attributes; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Epilepsy; Communication Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Autistic Disorder; Rare Diseases; Sleep Wake Disorders; Learning Disabilities; Epilepsy, Generalized; Psychomotor Disorders; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cell Physiological Phenomena; Physiological Phenomena; Electrophysiological Phenomena; Diagnostic Techniques, Neurological; Genetic Techniques; Electrodiagnosis; Nervous System Physiological Phenomena; Sequence Analysis; Sequence Analysis, DNA; Synaptic Potentials; Membrane Potentials; Neural Inhibition; Synaptic Transmission; Electroencephalography; Whole Genome Sequencing; High-Throughput Nucleotide Sequencing; Inhibitory Postsynaptic Potentials
• Other Study ID Numbers: 2080722; SYT1 (Registry Identifier: Synaptotagmin 1-Associated Neurodevelopmental Disorder)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No