A Prospective Natural History and Outcome Measure Validation Study of Congenital Myasthenic Syndromes

NCT06630650 | Recruiting

• 2 other identifiers: 10002093002093-N
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders that affect how the nerves communicate with muscles. These can cause many problems that affect how people can move and use their bodies. Objective: This is a natural history study to learn more about how CMSs affect the body and cause changes over time. Eligibility: People aged 6 months or older with a CMS. The study will focus on DOK7- and COLQ-related CMSs, as well as other forms. Design: Participants will have up to 7 visits in 5 years. At each visit, participants will undergo many tests, including: Physical exam with blood and urine tests. Tests of their heart and lung function. Exams of the eyes, lungs, muscles, and nerves. These will be done with different specialists. Exams of the arms and hands and of body use and movements. These will also be done with specialists. Photos and videos may be taken. Muscle ultrasound. Participants will lie still as a wand is rubbed over their skin. Magnetic resonance imaging (MRI) scans. Participants will lie still on a bed that slides partway into a large tube. A parent or other person may remain in the room, too. The scan will take 60 minutes. Electromyography (EMG). Participants will lie still or may be asked to move around. A machine will measure the electrical activity in their muscles. An activity monitor may be placed on the participant s wrist, ankle, or hip for up to 2 weeks. The monitor is about the size of a wristwatch. A sample of skin may be removed....

Conditions

Myasthenic Syndromes, Congenital

Keywords

Congenital Myasthenic Syndrome; Collagen Q; Downstream of tyrosine kinase 7; DOK7; COLQ

Outcome Measures

Primary Outcomes (2)

• Characterize baseline clinical manifestations and CMS disease

  One year

• Assess the validity and interrater reliability of outcome measures in CMS

  5 Years

Secondary Outcomes (1)

• Characterize the extended disease course of CMS

  Years 2-5

Study Arms (1)

COLQ-related CMS

Genetically confirmed COLQ-related CMS

Eligibility Criteria

• Age: 6 Months - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with congenital myasthenic syndromes with a focus on DOK7 and COLQ subtypes.

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged \>= 6 months of age
• Clinically stable as evidenced by medical record review and remote screening questionnaire
• Genetically confirmed congenital myasthenic syndrome (pathogenic or likely pathogenic variants identified by CLIA testing in an established CMS-related gene including but not limited to DOK7, COLQ, CHRNE, RAPSN, CHAT, GFPT1, DPAGT1 OR pathogenic/likely pathogenic variant in combination with a variant of uncertain significance (VUS) AND additional clinical supporting evidence of CMS).
• Agreement to adhere to Lifestyle Considerations throughout study duration
• Ability of subject to understand and the willingness to provide informed consent (\>=18 years of age) and assent (\>=7 years of age).

You may not qualify if:

• Received gene transfer therapy
• Pregnant women (prior to enrollment)
• Ongoing medical condition or medication use that is deemed by the Principal Investigator to interfere with the conduct or assessments of the study or safety of the subject.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

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Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Myasthenic Syndromes, Congenital

Condition Hierarchy (Ancestors)

Neuromuscular Junction Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Christopher Grunseich, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christopher J Mendoza

CONTACT

(301) 402-9080; christopher.mendoza2@nih.gov

Christopher Grunseich, M.D.

CONTACT

(301) 402-5423; grunseichc@mail.nih.gov

Study Design

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

Study Record Dates

• First Submitted: October 6, 2024
• First Posted: October 8, 2024
• Study Start: May 12, 2025
• Primary Completion (Estimated): December 2, 2042
• Study Completion (Estimated): December 2, 2044
• Last Updated: June 26, 2026

Record last verified: 2026-06-24

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)