Objective: We present a case of a patient with a history of recurrent stroke-like lesions, epilepsy, and progressive generalized dystonia with dystonic tremor secondary to a pathogenic POLG mutation. This case highlights both the diagnostic and therapeutic challenges associated with POLG-related disorders, with a focus on dystonia as a rare clinical feature.

Background: POLG-related disorders include a broad spectrum of neurologic phenotypes including ataxia, parkinsonism, neuropathy, stroke-like episodes, and epilepsy. While dystonia has been previously observed in patients with pathogenic POLG mutations, it is rare and remains poorly described in the literature [1].

Method: Case report

Results: A 28-year-old woman with a history of recurrent stroke-like lesions and epilepsy presented for evaluation of worsening tremor of her hands and head, as well as vocal changes. Eight years ago she developed new onset seizures accompanied by stroke-like lesions on MRI. This was previously attributed to PRES, despite a lack of hypertension. Five years later, she developed a tremor in her hands. On physical examination, an irregular postural and kinetic tremor was noted with intermittent dystonic posturing in both hands, described as wrist flexion and adduction. Lateral torticollis with associated head tremor as well as spasmodic dysphonia were also present. Vitamin E and copper levels were within normal limits. Paraneoplastic testing was negative. CSF protein was mildly elevated at 55 mg/dL. Muscle biopsy was performed and was unremarkable. The GeneDx dystonia genetic panel was negative. The GeneDx mitochondria genetic panel showed two variants in the POLG gene, one pathogenic variant (c.2734+1G>T) and a variant of unknown significance (c.3614 G>T). Carbidopa/levodopa was trialed with minimal improvement. Eventually, DBS with bilateral GPi targeting was placed and led to significant improvement in both pain and hand mobility. With the pathogenic variant, her symptoms were most likely associated with a POLG-related disorder.

Conclusion: POLG-related disorders are a group of mitochondrial diseases caused by mutations in the POLG gene, which encodes the mitochondrial DNA polymerase gamma. While dystonia is not commonly recognized in POLG-related disorders, this case highlights its potential as a disabling feature that warrants prompt consideration and treatment.

References: 1. Synofzik, M., SchüLe, R., Schulte, C., KrüGer, R., Lindig, T., SchöLs, L. and Asmus, F. (2010), Complex hyperkinetic movement disorders associated with POLG mutations†. Mov. Disord., 25: 2472-2475.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dystonia-as-a-rare-manifestation-of-polg-related-disease-a-case-report/