Childhood muscular dystrophies

Infancy- and childhood-onset muscular dystrophies are associated with a characteristic distribution and progression of motor dysfunction. The underlying causes of progressive childhood muscular dystrophies are heterogeneous involving diverse genetic pathways and genes that encode proteins of the plasma membrane, extracellular matrix, sarcomere, and nuclear membrane components. The prototypical clinicopathological features in an affected child may be adequate to fully distinguish it from other likely diagnoses based on four common features: (1) weakness and wasting of pelvic-femoral and scapular muscles with involvement of heart muscle; (2) elevation of serum muscle enzymes in particular serum creatine kinase; (3) necrosis and regeneration of myofibers; and (4) molecular neurogenetic assessment particularly utilizing next-generation sequencing of the genome of the likeliest candidates genes in an index case or family proband. A number of different animal models of therapeutic strategies have been developed for gene transfer therapy, but so far these techniques have not yet entered clinical practice. Treatment remains for the most part symptomatic with the goal of ameliorating locomotor and cardiorespiratory manifestations of the disease.