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....
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).
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.