A Case of De Novo DNM2-Related Centronuclear Myopathy with Electrical But Not Clinical Myotonia

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A Case of De Novo DNM2-Related Centronuclear Myopathy with Electrical But Not Clinical Myotonia

Rare muscle disorders often reveal unexpected insights into human biology—and a recent case of centronuclear myopathy (CNM) offers a new look at how genetic mutations can cause “hidden” electrical changes in muscles without obvious symptoms. Researchers from Peking University Third Hospital and affiliated institutions detailed this unique case in a 2020 study, shedding light on a little-understood presentation of dynamin 2 (DNM2)-related disease.

The Patient’s Story

The patient, a 39-year-old man, had a lifelong history of muscle challenges: he was born with generalized low muscle tone (hypotonia) and struggled to run during elementary school. By adulthood, he faced progressive muscle atrophy (wasting) and weakness. Neurological exams uncovered:

  • Facial muscle shrinkage,
  • Limited ability to move his left eye inward (adduction),
  • Uneven weakness—worse in the proximal (upper arm/shoulder) muscles of his arms and distal (lower leg/foot) muscles of his legs.

Crucially, he had no clinical myotonia—the classic muscle stiffness or “locking” that patients feel (and doctors observe) when muscles can’t relax after movement.

Tests Reveal a Hidden Sign: Electrical Myotonia

Blood work showed a mild rise in creatine kinase (CK), a marker of muscle damage (223 IU/L; normal <170 IU/L). But electromyography (EMG)—a test that records muscle electrical activity—told a surprising story:

  • Normal nerve conduction: Ruled out nerve damage (e.g., Charcot-Marie-Tooth disease).
  • Myotonic discharges: Waxing-and-waning electrical signals typical of muscle hyperexcitability—even though the patient had no stiffness.
  • Myogenic damage: Short, low-amplitude motor unit potentials (muscle fiber signals) that recruited early—signs of muscle, not nerve, disease.

A muscle biopsy of his left biceps brachii confirmed CNM: almost every muscle fiber had a central nucleus (nuclei normally sit at the fiber’s edge). Special stains—including nicotinamide dehydrogenase tetrazolium reductase (NADH-TR), desmin, and vimentin—revealed:

  • Increased activity around the central nucleus,
  • “Spoke-like” strands radiating from the nucleus—an iconic CNM feature.

The Genetic Clue: A De Novo DNM2 Mutation

Genetic testing uncovered the root cause: a de novo (new, non-inherited) heterozygous mutation in the DNM2 gene: c.1565G>A. This changes the amino acid at position 522 from arginine to histidine (R522H)—a mutation previously linked to CNM and Charcot-Marie-Tooth disease.

The patient’s parents had no such mutation, proving the change arose spontaneously in him.

Why This Case Matters

DNM2 mutations are rare, but they’re known to cause CNM—a group of muscle diseases defined by central nuclei in muscle fibers. Most CNM cases don’t involve myotonia, but this patient’s EMG findings highlight a key gap: how can muscles show electrical myotonia without clinical symptoms?

Myotonia is usually “visible”: think of the slow hand-grip release in myotonic dystrophy. But electrical myotonia (abnormal EMG signals) can occur alone, as seen in conditions like polymyositis or acid maltase deficiency. For CNM:

  • The first clinical myotonia case was reported in 1978 by Gil-Peralta et al.,
  • Stino and Iyadurai (2018) described a patient with the same R522H mutation and electrical (but no clinical) myotonia—but no muscle biopsy,
  • Two other CNM cohorts with the R522H mutation had no myotonia at all.

What This Means for Muscle Disease Research

This case confirms that DNM2-related CNM can cause electrical myotonia without clinical signs—a critical observation for doctors diagnosing rare muscle disorders. The team suspects the myotonia links to DNM2’s role in:

  • Maintaining the muscle cell skeleton (cytoskeleton),
  • Regulating cell membrane function.

More research is needed to unravel the exact mechanism—but this case adds a vital piece to the DNM2 puzzle.

Key Context & Ethics

DNM2 mutations are rare but linked to both CNM and Charcot-Marie-Tooth disease. The patient provided informed consent for his case (including images) to be published, with efforts to protect his anonymity.

References

The study was led by researchers from Peking University Third Hospital, Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, and Peking University’s School of Basic Medical Sciences. It builds on work by:

  • Stino & Iyadurai (2018, Muscle Nerve): First report of R522H mutation with electrical myotonia,
  • Chen et al. (2015, Neurol Sci): DNM2-related CNM in Chinese patients,
  • Gil-Peralta et al. (1978, J Neurol Neurosurg Psychiatry): First CNM case with clinical myotonia.

For full details, read the original study in the Chinese Medical Journal (2020):
doi.org/10.1097/CM9.0000000000000974

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