Clinical Information

The limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of muscular dystrophies that show progressive weakness and muscle atrophy, predominantly affecting the hips, shoulders, and proximal extremity muscles. There is wide variability in age of onset, severity, and clinical presentation within the LGMD spectrum.

Congenital myasthenic syndromes occur as a result of compromised neuromuscular transmission. Clinical manifestations include fatigable weakness involving ocular, bulbar, and limb muscles. The severity and disease course are highly variable, but individuals usually present in infancy or early childhood. The clinical phenotype associated with a neonatal onset can include feeding difficulties, poor suck and cry, choking spells, eyelid ptosis, and muscle weakness. The clinical phenotype associated with a later childhood onset can include abnormal muscle fatigue, delayed motor milestones, ptosis, and extraocular muscle weakness.

The clinical overlap of limb-girdle muscular dystrophy and limb-girdle congenital myasthenic syndromes can make these conditions difficult to distinguish clinically. Misdiagnoses can lead to diagnostic delays of several decades, impacting prognostic predictions and appropriate management. This multigene panel can be an efficient and cost-effective way to establish a molecular diagnosis.