When myopathy breaks the rules: a late-onset distal presentation.

Area of Science:

• Neurology
• Genetics
• Pathology

Background:

• Myopathies often manifest as proximal or generalized muscle weakness.
• Recognizing diverse clinical presentations, including distal myopathies, is essential for accurate diagnosis.
• Myofibrillar myopathies (MFMs) are gaining attention due to recent genetic discoveries.

Observation:

• A case of distal myopathy with a purely distal lower limb phenotype is presented.
• The condition was genetically confirmed as ZASP (Z-band alternatively spliced PDZ motif-containing protein) myofibrillar myopathy (MFM).

Findings:

• ZASP MFM represents a newly characterized diagnosis within the spectrum of myofibrillar myopathies.
• The study elucidates the pathophysiology of ZASP and other MFMs.
• Differential diagnosis for late-onset distal symmetrical weakness is discussed, highlighting ZASP MFM's potential role.

Implications:

• ZASP MFM should be considered in the differential diagnosis of late-onset myopathies, particularly those with distal or autosomal dominant inheritance patterns.
• Cardiac evaluation is recommended for patients with ZASP MFM.
• The availability of genetic testing facilitates diagnosis and understanding of ZASP MFM.