POLG mutation presenting with late-onset jerky torticollis

Abstract

POLG is a nuclear gene and its gene product, polymerase gamma, is involved in the maintenance of mitochondrial DNA (mtDNA) and mutations thus lead to depletion of mtDNA [1]. The corresponding phenotype is markedly variable, and includes (among others) Alpers’ syndrome, mitochondrial spinocerebellar ataxia and epilepsy (MSCAE), chronic progressive external ophthalmoplegia, neuropathy, epilepsy, as well as myoclonus, cerebellar ataxia, and parkinsonism [2]. Herein we report a case of patient with compound heterozygous POLG mutation with unusual clinical presentation. A 43-year-old woman was referred to us for unexplained progressive shaking of the head, which had begun rather abruptly several months earlier. She also mentioned a feeling of imbalance on walking. Family history was negative. On examination, we saw a mild torticollis to the left with a side-to-side, jerky head tremor (see video). Eye movements were normal. Her gait was clearly abnormal, being broad-based and with deviations from the straight line, but was also rather atypical and effortful, and she could very suddenly lurch to the side. During walking, the head rotation and tremor could be observed. There was no appendicular ataxia. Tendon reflexes were all normal, as was the sensory examination. Our provisional diagnosis was cervical dystonia with either jerky tremor or myoclonic jerks, and we suspected some aggravation, particularly in her gait disturbance, related to psychosocial factors. Mutation analysis for the SGCE gene was negative and brain imaging was normal. She was given clonazepam in combination with botulinum toxin injections, which had a moderate effect. Her head tremor and gait difficulty continued to progress and she gradually developed jerks of her left arm and sensory disturbances in both arms. She was admitted at age 45 years because of a generalized tonic– clonic seizure. During admission, several short-lasting— possibly epileptic—myoclonic jerks were observed alternatingly in the left and right arm. At that time, the neurological examination showed incomplete external ophthalmoplegia; mild torticollis with a severe mainly side-to-side head tremor; myoclonic jerks of the left arm; ataxic finger chase and heel-shin slide; gait ataxia; and absent tendon reflexes. Brain MRI (Fig. 1) now revealed mild cerebellar atrophy, as well as small symmetric signal changes in the cerebellar white matter that were hyperintense on T2, fluid attenuated inversion recovery (FLAIR), and slightly hypointense on T1 images. Electroencephalography showed mild diffuse slowing without epileptic activity and electromyography indicated a sensory neuronopathy. As the clinical constellation was now very suggestive of a mitochondrial disorder, POLG mutation analysis was performed, which revealed a compound heterozygous mutation (c.1399G ? A and c.2243G ? C). Levetiracetam was Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6776-z) contains supplementary material, which is available to authorized users.