ACTA1-Related Adult-Onset Scapuloperoneal Myopathy With Cores and Rods.

Area of Science:

• Neurology
• Genetics
• Muscle Diseases

Background:

• Actinopathies, caused by ACTA1 gene variants, typically present as severe congenital myopathies.
• However, significant clinical and myopathological variability exists, with recent reports including scapuloperoneal phenotypes.
• This highlights the need to broaden the understanding of actinopathy presentations.

Purpose of the Study:

• To present a case of a late-onset, slowly progressive scapuloperoneal actinopathy.
• To characterize the clinical, imaging, and pathological features associated with a novel ACTA1 variant.
• To investigate the potential role of cardiac alpha-actin in milder actinopathy phenotypes.

Main Methods:

• Clinical assessment of a 65-year-old woman with scapuloperoneal myopathy.
• Muscle imaging (MRI), muscle biopsy, and genetic analysis.
• Protein expression studies (immunofluorescence, western blot) for alpha-actin isoforms.

Main Results:

• The patient presented with late-onset (around 30 years) progressive weakness, initially proximal lower limbs, later involving distal upper and lower limbs.
• Muscle biopsy revealed cores and rods, and genetic analysis identified a novel heterozygous ACTA1 variant (c.1001C>T, p.(Pro334Leu)).
• Increased cardiac alpha-actin expression was observed, suggesting its involvement in milder actinopathy phenotypes.

Conclusions:

• This case expands the phenotypic spectrum of actinopathies to include milder, late-onset, slowly progressive scapuloperoneal myopathy.
• The presence of cores, rods, and cardiac alpha-actin overexpression is noted.
• The findings suggest cardiac alpha-actin may contribute to less severe forms of actinopathy.