Congenital myopathies: The current status

Area of Science:

• Neuromuscular Diseases
• Molecular Genetics
• Muscle Pathology

Background:

• Congenital myopathies (CM) were initially classified based on muscle biopsy findings using enzyme histochemistry and electron microscopy.
• The advent of the molecular era and techniques like immunohistochemistry significantly expanded the understanding and classification of CM.
• Historically, CM classification relied on distinct myopathological hallmarks identified in muscle biopsies.

Purpose of the Study:

• To trace the historical evolution of congenital myopathy classification.
• To examine the impact of molecular genetics on the nosography and classification of CM.
• To address the challenges in classifying CM lacking traditional myopathological features.

Main Methods:

• Review of historical literature on neuromuscular diseases and congenital myopathies.
• Analysis of diagnostic criteria evolution from myopathology to molecular genetics.
• Examination of how molecular discoveries have reshaped CM nosography and classification.

Main Results:

• Initial CM classification relied on distinct myopathological features (central core, nemaline, centronuclear myopathies).
• Molecular genetics revealed allelism between CM and other neuromuscular diseases, and expanded the spectrum of mutations within genes.
• Recent CM identification is increasingly based on molecular defects, sometimes lacking clear myopathological hallmarks, creating classification ambiguity.

Conclusions:

• The classification and nomenclature of congenital myopathies are increasingly complex due to molecular discoveries.
• Molecular insights have blurred traditional diagnostic boundaries, necessitating revised classification frameworks.
• Further research is needed to clarify the classification of molecularly defined CM lacking distinct myopathological features.