Illness-associated muscle weakness in dystroglycanopathies

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Dystroglycanopathy (DG) is a group of rare genetic muscular dystrophies.
• Acute illness-associated weakness (AIAW) is a poorly understood phenomenon in DG patients.
• Duchenne-Becker muscular dystrophy (DBMD) serves as a comparison for membrane-related muscular dystrophies.

Purpose of the Study:

• To describe the characteristics of AIAW in DG patients.
• To determine the frequency of AIAW in DG.
• To compare the frequency of AIAW in DG to DBMD patients.

Main Methods:

• Patients in a DG natural history study provided medical history and underwent annual follow-ups.
• A survey tool was used to collect data on episodes of sudden weakness and preceding illnesses.
• Demographic and clinical data were collected from DG and DBMD cohorts.

Main Results:

• AIAW was reported in 23% of DG patients versus 4% of DBMD patients (OR 7.35, p=0.005).
• Twenty-one DG patients with mutations in various genes (FKRP, FKTN, POMT1, POMT2, POMGNT1) reported AIAW.
• AIAW typically occurred in children under 7 years old, often following respiratory infections, and preceded diagnosis in nearly half of affected DG patients.

Conclusions:

• DG patients, irrespective of genotype, can experience acute, transient weakness during febrile illnesses.
• This AIAW phenomenon is significantly less common in DBMD.
• The underlying physiological mechanism of AIAW in DG remains unknown.