Early-Onset Hypotonia & Motor Dysfunction

Early hypotonia and motor dysfunction are hallmark features of CHKB-associated congenital megaconial muscular dystrophy. Symptoms typically manifest in infancy, with newborns exhibiting poor head control, reduced muscle tone, weak antigravity movements, and delayed gross motor milestones.

The earliest pathology often arises in posterior muscle compartments, followed by progressive involvement of anterior and medial groups. Children may experience difficulty sitting, standing, walking, climbing, or maintaining endurance. Gait abnormalities, fatigue, and frequent falls become more pronounced over time.

As the disease advances, muscle fibres undergo structural degeneration and fatty infiltration, contributing to increasing weakness and reduced mobility. Many individuals eventually require orthopaedic evaluation, physical therapy, mobility aids, and ongoing rehabilitation support.

Although symptomatic therapies can improve function and quality of life, the absence of disease-modifying treatment underscores the need for gene therapy approaches that target the underlying biochemical defect and preserve neuromuscular integrity.