Investigating Phenotypic, Epigenetic, and NeuroGenetic Traits in Rare and Ultra-rare Neurodevelopmental Disorders (Project PENGUIN)

NCT07329257 | Recruiting DMC

• 2 other identifiers: 2130290SYT-1
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Rare genetic neurodevelopmental disorders, such as Syt-1 or Baker Gordon Syndrome (BAGOS) arise from mutations in genes essential for brain development and function, often disrupting neurotransmission and neuronal connectivity. These conditions present with a wide range of symptoms including developmental delays, seizures, motor and behavioral challenges, and vary widely in severity. These disorders are complex, and they remain poorly understood and lack effective treatments. Natural history and clinical genetic studies are crucial for mapping how these disorders progress, improving diagnostic accuracy, and guiding therapy development. A major focus is identifying reliable biomarkers (genetic, imaging, and physiological) to track disease severity and support clinical trials. This study will securely collect and analyze data to better understand disease impact, develop patient-derived model systems, and build resources to support future treatments.

Conditions

Baker Gordon Syndrome; Rare Neurodevelopmental Conditions; Rare Neurogenetic Conditions; Syt-1 Disorder; Epilepsy; Seizure; Genetic Mutations; Autism in Children; Developmental Delay (Disorder)

Keywords

Baker Gordon Syndrome; BAGOS; Rare Conditions; Rare; Neurogenetic; Neurodevelopmental; Ultra-rare; Genetic mutation; Autism

Outcome Measures

Primary Outcomes (3)

• Disease onset patterns, symptom evolution, and progression severity in rare neurodevelopmental disorders

  3 years

• Identify and validate biomarkers (genetic, imaging, and physiological) that correlate with disease severity and progression

  3 years

• Establish patient-derived and control cell lines (e.g., fibroblasts, induced pluripotent stem cells) to generate model systems for mechanistic studies and pre-clinical evaluation of potential therapies

  3 years

Secondary Outcomes (3)

• Develop a deep phenotypic profile (cognitive, motor, behavioral, and neurological)

  3 years

• Distribution of clinical presentation features, including age at onset, core symptoms, severity scores, and disease progression measures, within and across genetic subtypes

  3 years

• Build a repository to support future interventional clinical trials

  3 years

Interventions

No Intervention: Observational Cohort OTHER

There is no intervention for this Natural History Study

Eligibility Criteria

• Age: Up to 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with a diagnosed or suspected rare genetic neurodevelopmental disorder. Parents and caregivers over 18 years of age can participate in the study as healthy controls.

You may qualify if:

• Diagnosed or suspected neurogenetic disorder
• Individuals 0-99

You may not qualify if:

• Individuals unwilling or unable to complete visits with the study team.
• For control parents/caregivers of those with a rare condition:
• No history of a neurological disorder.
• \>18 years.
• Legal caregiver of the patient diagnosed with a rare neurodevelopmental disorder.
• Individuals unwilling or unable to complete the visit with the study team.
• Individuals who have a history of neurological disorders.
• \< 18 years old
• For all individuals who participate in the skin biopsy:
• Individuals with disease that is known to be associated with poor wound healing.
• Individuals with a history of allergic reaction to lidocaine.
• Medical History of cellulitis, diabetes mellitus, poor extremity circulation, deep vein thrombosis, or a history of non-traumatic amputation.
• Currently taking anticoagulation or have taken with last 6 months

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

University of Missouri - Columbia

Columbia, Missouri, 65201, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Participants in this study have the option to provide a one-time skin biopsy and/or blood draw.

MeSH Terms

Conditions

Epilepsy; Seizures; Autistic Disorder; Developmental Disabilities

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• W. David Arnold, MD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sophia R Marchetti

CONTACT

573-882-6720; sophiamarchetti@health.missouri.edu

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Director, UM System NextGen Precision Health Initiative. Professor, Physical Medicine and Rehabilitation

Study Record Dates

• First Submitted: December 10, 2025
• First Posted: January 9, 2026
• Study Start: December 4, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 9, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)