Introduction 

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited muscular dystrophy. The condition affects approximately 1 in 20,000 people in Europe, and clinical variability ranges from mild weakness to severe.¹ Physicians often rely on functional and structural investigations to confirm diagnosis and assess the disease’s severity, as sometimes clinical features can be misleading. Among these, electromyography(EMG) and muscle biopsy are among the most informative modalities.¹

FSHD typically affects the facial, scapular, and humeral muscles, often asymmetrically. However, the progression and severity of the disease can vary among patients. EMG and muscle biopsy provide insights into both the functional activity and structural integrity of the muscle, helping to differentiate FSHD from other muscular dystrophies and, in some cases, from neuropathic conditions.¹ This article reviews the findings of EMG and muscle biopsy in FSHD, highlighting their diagnostic value, limitations, and clinical implications.

Electromyography in FSHD

Electromyography is a cornerstone for evaluating neuromuscular disorders. It provides a real-time assessment of motor unit function. In FSHD, EMG typically shows myopathic patterns, but the degree and distribution of abnormalities vary between individuals.

EMG findings in genetically confirmed patients

In a study of 37 patients with genetically confirmed FSHD, EMG consistently demonstrated myopathic abnormalities across all participants.² The most severe changes were noted in the tibialis anterior and deltoid muscles, with milder abnormalities in the biceps brachii and vastus lateralis.² This distribution shows the typical pattern of weakness in FSHD, which usually starts in the shoulders and progresses to the trunk and legs.

Interestingly, EMG abnormalities did not correlate directly with clinical symptom severity. Some patients with minimal weakness showed marked EMG changes, while others with obvious weakness showed only mild EMG changes.² This suggests that EMG can act as a sensitive tool for detecting subclinical disease, especially in muscles not yet weakened.

Quantitative EMG and the size index

Quantitative EMG techniques improve diagnostic accuracy. The size index of motor unit potentials has been identified as the most reliable parameter for detecting myopathic processes in FSHD.² This approach enhances sensitivity and can help track disease activity over time. Compared with classical dystrophies, however, EMG changes in FSHD tend to be less severe, reflecting its patchy and asymmetric pathology.²

Atypical EMG patterns and overlapping disorders

Although EMG typically indicates a myopathic process, atypical patterns sometimes occur. In one case involving a patient with both FSHD and Charcot-Marie-Tooth neuropathy type 1A (CMT1A), the findings included mild myopathic changes in proximal muscles, along with neurogenic abnormalities in distal muscles, such as the tibialis anterior.³ This underscores EMG’s ability to detect overlapping neuromuscular syndromes and highlights the importance of considering dual diagnoses when findings do not fit the classic FSHD profile.

Muscle biopsy in FSHD

Muscle biopsy offers structural confirmation of muscle disease. However, its use has declined with the availability of genetic testing. In FSHD, the muscle biopsy results can vary significantly and may appear normal, yet they still provide valuable diagnostic insights.

Histopathological findings

In a genetically homogeneous cohort examined using EMG, about one-third of patients showed normal skeletal muscle histology despite having been diagnosed with FSHD.² Among those with abnormalities, findings included fibre size variability, connective tissue expansion, and mild myopathic changes.²

In the overlapping FSHD and CMT1A case, muscle biopsy of the tibialis anterior revealed fibre splitting, increased endomysial connective tissue, type I fibre predominance, and numerous hypertrophic type I fibres.³ While consistent with myopathy, the presence of small, neurogenic-like fibres indicated a dual pathological process, reflecting both dystrophic and neuropathic mechanisms.

Comparison to classical dystrophies

Compared to Duchenne or Becker muscular dystrophy, FSHD biopsies often demonstrate less severe necrosis, regeneration, and fibre loss.² Instead, FSHD pathology is typically more subtle and asymmetric, consistent with its variable clinical course. Nevertheless, connective tissue accumulation and fibre type imbalance confirm progressive muscle degeneration, even when biopsies appear relatively mild.

Integrating EMG and muscle biopsy findings

When combined, EMG and muscle biopsy offer a comprehensive view of muscle health:

• EMG detects functional changes early, sometimes before weakness is visible
• Muscle biopsy shows structural changes, though it may remain normal in a subset of patients
• In overlapping syndromes, these tools help differentiate myopathic from neurogenic processes

Together, EMG and muscle biopsy provide complementary insights that genetic testing alone cannot always offer.

Clinical and research implications

Understanding disease progression

EMG and muscle biopsy results support that FSHD causes patchy, muscle-specific degeneration, usually more severe in the tibialis anterior and deltoid muscles.² This targeted involvement explains the asymmetric weakness characteristic of the condition and helps clinicians select specific muscles for monitoring.

Relevance for overlapping syndromes

The coexistence of FSHD and CMT1A demonstrates the diagnostic utility of EMG and muscle biopsy beyond genetic confirmation. Mixed findings should prompt clinicians to investigate additional causes of muscle weakness to ensure accurate diagnosis and management.³

Future therapeutic monitoring

As clinical trials test new therapies for FSHD, EMG and muscle biopsy serve as valuable endpoints. EMG monitors functional improvements, while muscle biopsy reveals cellular-level therapeutic effects. Their combined use will remain essential for assessing how individuals respond to treatment.

Patient impact and diagnostic challenges

From a patient’s perspective, EMG and muscle biopsy procedures can be stressful. Yet they often provide critical answers in complex diagnostic journeys. Notably, the presence of normal muscle biopsies in about one-third of patients underscores the importance of careful communication: a normal muscle biopsy does not rule out FSHD.² Similarly, atypical EMG results should lead to further evaluation rather than dismissal.

For patients with overlapping conditions, accurate interpretation of EMG and muscle biopsy findings is vital for rehabilitation strategies, genetic counselling, and long-term planning.³ As new therapies emerge, accurate diagnoses are needed to enable early and effective treatment for patients with FSHD.

Summary

• FSHD is genetically defined but clinically variable, necessitating multimodal assessment
• EMG consistently shows myopathic changes, most pronounced in the tibialis anterior and deltoid, though findings may not match clinical severity²
• Quantitative EMG, particularly the size index, enhances sensitivity for detecting early or subtle disease²
• Muscle biopsy may be normal in one-third of cases, but when abnormal, it shows fiber size variability, connective tissue expansion, and mild myopathic features²
• In overlapping syndromes, such as FSHD with CMT1A, EMG and muscle biopsy reveal mixed myopathic and neurogenic patterns³
• Compared with classical dystrophies, FSHD produces less severe histopathological changes, reflecting its slower, asymmetric progression
• EMG and muscle biopsy remain critical complements to genetic testing, aiding in early detection, atypical presentations, and therapeutic evaluation

Ultimately, EMG and muscle biopsy remain invaluable for understanding the functional and structural realities of FSHD, guiding diagnosis, management, and future therapeutic monitoring.