Presentation (CTI)

OBJECTIVES: CMS (Congenital Myasthenic Syndromes) are a group of rare genetic neuromuscular disorders. A frequent cause of CMS are mutations in the DOK7 gene. DOK7-CMS typically presents in early childhood as a limb-girdle pattern of muscle weakness and fatigability. The patient experience of DOK7-CMS remains poorly characterized and limited work has been conducted to evaluate whether existing Clinical Outcome Assessments (COAs) are fit for purpose in this context of use. This study aimed to identify the meaningful aspects of health in DOK7-CMS and examine the content validity of two COAs, originally developed for use in Myasthenia Gravis, through qualitative interviews with patients and clinicians.
METHODS: In-depth qualitative interviews were conducted with DOK7-CMS patients and experienced clinicians in the US, Canada and UK. Interviews involved concept elicitation (CE) questioning and cognitive debriefing (CD) of the Myasthenia Gravis Activities of Daily Living (MG-ADL) and MG Impairment Index (MGII). Interviews were audio-recorded, transcribed verbatim and analyzed using thematic analysis.
RESULTS: Twenty adult patients and 5 clinicians participated. Patients most frequently reported leg weakness, arm and shoulder weakness, and droopy eyelids with substantial impacts on their Activities of Daily Living (ADLs) and physical functioning.
CONCLUSIONS: These findings provide an understanding of the core symptoms of DOK7-CMS and the substantial impact on patients’ daily lives and physical functioning. Though the MG-ADL and MGII capture relevant impact on daily life, revisions are required to ensure that the measures are fit-for-purpose in DOK7-CMS. Future work should focus on revision of existing COAs or development of novel COAs to support patient relevant outcome assessment in DOK7-CMS clinical trials.