STXBP1 and SYNGAP1 Related Disorders Natural History Study

NCT06555965 | Recruiting DMC

• 1 other identifier: 23-021140
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to find out more about STXBP1 and SYNGAP1 related disorders. The information gathered by this study will be used to prepare for clinical treatment trials. The primary objective of the study is to better define and outline the clinical spectrum of STXBP1 and SYNGAP1 through detailed developmental, seizure, and quality of life assessments as an extension of routine clinical care.

Conditions

Genetic Disease; STXBP1 Encephalopathy With Epilepsy; SYNGAP1-Related Intellectual Disability

Keywords

STXBP1; Natural History; Clinical Research; SYNGAP1

Outcome Measures

Primary Outcomes (1)

• Changes in percentiles recorded on clinical assessments over time

  The primary analysis will include all subjects meeting all inclusion and exclusion criteria and completing Visit 1. For each subject, the percentage of items performed correctly on the clinical assessments will be recorded. Changes in percentiles over time will be analyzed using a linear mixed effects model, to account for repeated measures for each patient.

  Every 6 months upto 5 years

Study Arms (2)

STXBP1 cohort

Other: Non-interventional study

SYNGAP1 cohort

Other: Non-interventional study

Interventions

Non-interventional study OTHER

There is no planned intervention in this study

STXBP1 cohort; SYNGAP1 cohort

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participating individuals must have a confirmed genetic diagnosis of STXBP1 or SYNGAP1 related disorders. Participants can be any age and present with any disease severity

You may qualify if:

• Male or female of any age.
• Presence of a STXBP1 or SYNGAP1 gene mutation. The variant in STXBP1 or SYNGAP1 must be classified as causative based on clinical and variant classification criteria. Historical documentation is sufficient to support eligibility for the study. Confirmatory testing will be obtained, if necessary, at baseline and performed by a CLIA certified laboratory.

You may not qualify if:

• The presence of a confirmed mutation in a gene other than STXBP1 or SYNGAP1 that is known to contribute to a neurodevelopmental disability. This includes full gene deletions of STXBP1 or SYNGAP1 that include other genes beyond STXBP1 or SYNGAP1.
• The presence of a significant non-STXBP1-RD or non-SYNGAP1-RD related central nervous impairment/behavioral disturbance that would confound the scientific rigor or interpretation of results of the study.
• History of intraventricular hemorrhage, structural brain deficit or congenital heart disease
• The presence of a clinical comorbidity deemed by the investigator to potentially confound the typical presentation of STXBP1-RD or SYNGAP1-RD.
• Pregnant women or females of age of menarche who are found to be pregnant upon urine pregnancy testing.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• STXBP1 Foundation: collaborator

Study Sites (5)

Stanford Medicine Children's Health

Palo Alto, California, 94304, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80011, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10065, United States

RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19403, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (4)

• Xian J, Parthasarathy S, Ruggiero SM, Balagura G, Fitch E, Helbig K, Gan J, Ganesan S, Kaufman MC, Ellis CA, Lewis-Smith D, Galer P, Cunningham K, O'Brien M, Cosico M, Baker K, Darling A, Veiga de Goes F, El Achkar CM, Doering JH, Furia F, Garcia-Cazorla A, Gardella E, Geertjens L, Klein C, Kolesnik-Taylor A, Lammertse H, Lee J, Mackie A, Misra-Isrie M, Olson H, Sexton E, Sheidley B, Smith L, Sotero L, Stamberger H, Syrbe S, Thalwitzer KM, van Berkel A, van Haelst M, Yuskaitis C, Weckhuysen S, Prosser B, Son Rigby C, Demarest S, Pierce S, Zhang Y, Moller RS, Bruining H, Poduri A, Zara F, Verhage M, Striano P, Helbig I. Assessing the landscape of STXBP1-related disorders in 534 individuals. Brain. 2022 Jun 3;145(5):1668-1683. doi: 10.1093/brain/awab327.

  PMID: 35190816 BACKGROUND

• Yang P, Broadbent R, Prasad C, Levin S, Goobie S, Knoll JH, Prasad AN. De novo STXBP1 Mutations in Two Patients With Developmental Delay With or Without Epileptic Seizures. Front Neurol. 2021 Dec 24;12:804078. doi: 10.3389/fneur.2021.804078. eCollection 2021.

  PMID: 35002943 BACKGROUND

• Wang HH, Liao HF, Hsieh CL. Reliability, sensitivity to change, and responsiveness of the peabody developmental motor scales-second edition for children with cerebral palsy. Phys Ther. 2006 Oct;86(10):1351-9. doi: 10.2522/ptj.20050259.

  PMID: 17012639 BACKGROUND

• Demarest S, Pestana-Knight EM, Olson HE, Downs J, Marsh ED, Kaufmann WE, Partridge CA, Leonard H, Gwadry-Sridhar F, Frame KE, Cross JH, Chin RFM, Parikh S, Panzer A, Weisenberg J, Utley K, Jaksha A, Amin S, Khwaja O, Devinsky O, Neul JL, Percy AK, Benke TA. Severity Assessment in CDKL5 Deficiency Disorder. Pediatr Neurol. 2019 Aug;97:38-42. doi: 10.1016/j.pediatrneurol.2019.03.017. Epub 2019 Mar 27.

  PMID: 31147226 BACKGROUND

MeSH Terms

Conditions

Genetic Diseases, Inborn; Epileptic Encephalopathy, Early Infantile, 4

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ingo Helbig, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joeylynn Nolan, RRT NPS AE-C

CONTACT

2674411813; COYNEJ@chop.edu

Victoria Chisari, BA, NS

CONTACT

ChisariV@chop.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2024
• First Posted: August 15, 2024
• Study Start: August 30, 2023
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: October 29, 2025

Record last verified: 2025-10

Locations

US (5)