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Pure Progressive Ataxia and Palatal Tremor (PAPT) Associated with a New Polymerase Gamma (POLG) Mutation

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Abstract

Progressive ataxia with palatal tremor (PAPT) is a syndrome caused by cerebellar and brainstem lesions involving the dentato-rubro-olivary tract and associated with hypertrophic olivary degeneration. Etiologies include acquired posterior fossa lesions (e.g. tumors, superficial siderosis, and inflammatory diseases) and genetic disorders, such as glial fibrillary acidic protein (GFAP) and polymerase gamma (POLG) mutations. We describe the case of a 52-year-old man who developed pure progressive ataxia and palatal tremor. Genetic analysis has shown that he is compound heterozygote for a known pathogenic (W748S) and a novel POLG variant (I1185N). Patients with POLG recessive mutations usually manifest a more complex clinical picture, including polyneuropathy and epilepsy; our case emphasizes the need to consider a genetic origin in a seemingly sporadic and pure PAPT.

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Acknowledgments

We thank Pr Rita Horvath (Institute of Human Genetics, Newcastle University) and Pr Alexandra Durr (Department of Genetics, Hôpital La Pitié-Salpêtrière, Paris) for useful discussion.

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    Authors and Affiliations

    1. Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals, 4, Rue Gabrielle-Perret-Gentil, 1205, Geneva, Switzerland

      Nicolas Nicastro & Judit Horvath

    2. Division of Genetic Medicine, Geneva University Hospitals, Geneva, Switzerland

      Emmanuelle Ranza & Stylianos E. Antonarakis

    3. Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland

      Stylianos E. Antonarakis

    4. iGE3, Institute of Genetics and Genomics of Geneva, University of Geneva, Geneva, Switzerland

      Stylianos E. Antonarakis

    Authors
    1. Nicolas Nicastro
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    2. Emmanuelle Ranza
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    3. Stylianos E. Antonarakis
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    4. Judit Horvath
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    Corresponding author

    Correspondence to Judit Horvath.

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    Financial Disclosures

    Dr N. Nicastro reports no disclosure.

    Dr E. Ranza reports no disclosure.

    Prof. S.E. Antonarakis reports no disclosure relevant to the manuscript. He received funding from Geberit Foundation and the Synapsy NCCR of the Swiss National Science Foundation

    Dr J. Horvath reports no disclosure.

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    The authors declare that they have no competing interests.

    Additional information

    Nicolas Nicastro and Emmanuelle Ranza contributed equally to this work.

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    Video 1

    Neurological examination of the patient, showing pendular nystagmus, static and kinetic ataxia, and palatal tremor. (MPG 7560 kb)

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    Nicastro, N., Ranza, E., Antonarakis, S.E. et al. Pure Progressive Ataxia and Palatal Tremor (PAPT) Associated with a New Polymerase Gamma (POLG) Mutation. Cerebellum 15, 829–831 (2016). https://doi.org/10.1007/s12311-015-0749-6

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    • DOI: https://doi.org/10.1007/s12311-015-0749-6

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