CLINICAL/SCIENTIFIC NOTES OPEN ACCESS Galloping tongue syndrome in a PRRT2 mutation carrier Dolores Vilas, MD, PhD, Anna Marcé-Grau, PhD, Alfons Macaya, PhD, Josep Valls-Solé, MD, PhD, and Correspondence Dr. Tolosa Eduard Tolosa, MD, PhD etolosa@clinic.cat Neurol Genet 2019;5:e377. doi:10.1212/NXG.0000000000000377 Abnormal lingual movements are not uncommon. A rare lingual syndrome consisting of MORE ONLINE involuntary wave-like lingual movements has been labeled as “galloping tongue.”1 Herein, we Video report a patient with galloping tongue syndrome carrier of a mutation in the PRRT2 gene. Clinical findings A 17-year-old woman presented with involuntary tongue movements within the past years, appearing only with tongue protrusion. “Wavy” contractions of the tongue were evident during sustained tongue protrusion (video 1). The contractions developed immediately after sticking the tongue out, persisted during protrusion, and disappeared while at rest. The movements could not be disrupted, suppressed, or entrained with examiner-given rhythmic activities. Abrupt body movements, sleep deprivation, or coffee intake did not affect the abnormal movement. There was no history of exposure to neuroleptic medication or head trauma. The tongue contractions seemed to begin in the posterior midline region and progress in a wavy fashion to the anterior and lateral parts of the tongue. The results of routine hematologic and blood biochemistry including thyroid function tests, copper levels, and ceruloplasmin were normal. A urine toxicology screen did not reveal the presence of any drug of abuse. An electrophysiologic study with electrodes applied on the surface of the tongue showed no electrical activity while at rest. With tongue protrusion, the EMG activity was segmented in discharges of 200–300 ms duration and separated by brief periods of silence, with an ap- proximate frequency of 3 per second (figure 1). Her brain MRI was normal. Because the movement disorder did not affect the patient’s orolingual function, no treatment was started. The patient’s sister, a 14-year-old, presented with short episodes of choreo-dystonic move- ments of the left arm and neck that appeared when she started to run since the age of 10. These episodes usually last a few seconds and occur at least 10 times per day. Her consciousness level was normal during episodes. Her medical history included migraine. She was diagnosed as having paroxysmal kinesigenic dyskinesias (PKD). Treatment with carbamazepine led to a complete remission of the movements. There was no family history of epilepsy or infantile convulsions. The patient’s mother had severe recurrent migraine headaches. Her maternal cousin had been diagnosed with PKD. The patient, her 2 sisters (1 healthy and the other affected with PKD), and their mother were available for PRRT2 mutation screen (figure 2). Direct sequencing identified a heterozygous truncating mutation in the proband, her mother, and the symptomatic sister: GRC37/hg19: chr16:29825025 GA/A, NM_145239: c.650delG, producing the amino acid change NP_660282.2: p.R217Qfs*12. This variant is not listed in public genomic databases, in- cluding ExAC (exac.broadinstitute.org/). From the Parkinson’s Disease and Movement Disorders Unit (D.V., E.T.), Neurology Service, ICN, Hospital Clı́nic, University of Barcelona, Spain; Pediatric Neurology Research Group (A.M.-G., A.M.), Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Spain; Electrophysiology Unit (J.V.-S.), Neurology Service, ICN, Hospital Clinic, University of Barcelona, Spain; Institut August Pi I Sunyer Biomedical Research Institute (IDIBAPS) (J.V.-S., E.T.). Go to Neurology.org/NG for full disclosures. Funding information is provided at the end of the article. The Article Processing Charge was funded by the authors. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. 1 Figure 1 Electromyographic activity of the tongue recorded Figure 2 PRRT2 mutational analysis in a family with parox- with surface electrodes during tongue protrusion ysmal neurologic disorder Right, PRRT2 electropherograms: Top, wildtype sequence in the proband’s healthy sister; and bottom, guanine deletion at position 650 occurs at the end of a cytosine streak, a well-known hotspot in PKD. The variant results in a premature termination of transcription (p.R217Qfs*12). Left, family tree with various phenotypes indicated. torticollis have also been described.7 Seizures and migraine seem to be also part of the clinical spectrum.6 The cause of the lingual movements in our patient remains uncertain. A functional movement disorder seemed unlikely because the movement disorder could not be disrupted, suppressed, or entrained with examiner maneuvers, which had no impact in the patient’s life, and there was no obvious gain Discharges of 200–300 ms duration and separated by brief periods of si- for the patient. The study of similar cases and additional lence, with an approximate frequency of 3 per second were observed during tongue protrusion. Broken lines have been added to underline each EMG PRRT2 families will eventually clarify whether the “galloping discharge. tongue” syndrome is indeed a previously unrecognized manifestation of PRRT2 mutations. Discussion Author contributions D. Vilas and E. Tolosa: drafting/revising the manuscript and Herein, we describe a patient with “galloping tongue” syn- conceptualization of the study. A. Marcé-Grau and A. drome who was positive for the p.R217Q fs*12 mutation in Macaya: genetic analysis and revising the manuscript. J. the PRRT2 gene. Galloping tongue is an uncommon move- Vall-Solé: electrophysiologic study and revising the ment disorder.1–5 The characteristics of these lingual move- manuscript. ments have been variably described as transverse contractions, twisting, or undulating movements.2–5 Although these movements were present with the tongue at rest in most of Study funding the reported patients, in some cases the movements were also No targeted funding reported. observed during sustained action. Disclosure Our patient had a mutation in the PRRT2 gene known to be Disclosures available: Neurology.org/NG. associated with PKD.6 However, she did not have the typical paroxysmal dyskinesias seen in PKD. Her abnormal movements Publication history were triggered by action but were not paroxysmal because they Received by Neurology: Genetics May 28, 2019. Accepted in final form were present as long as the voluntary movement motion per- October 9, 2019. sisted, resembling an action dystonia. The topography of dys- kinesia, isolated to the tongue, was also uncharacteristic of PKD. References Still, we believe that the PRRT2 mutation could be linked to the 1. Keane JR. Galloping tongue: post-traumatic, episodic, rhythmic movements. Neu- rology 1984;34:251–252. patient’s movement disorder because it is action related and 2. Saddichha BA, Talukdar D. Serpentine tongue syndrome associated with ris- known causes of the disorder have been ruled out. Furthermore, peridone long-acting injection treatment. J Clin Psychopharmacol 2014;34: the phenotype of PRRT2 mutations is not limited to dystonia 3. 657–658. Nagappa M, Sinha S, Saini J, Bindu P, Taly A. Undulating tongue in Wilson’s disease. and chorea typical of PKD, but episodic ataxia and paroxysmal Ann Indian Acad Neurol 2014;17:225–226. 2 Neurology: Genetics | Volume 5, Number 6 | December 2019 Neurology.org/NG 4. Prashantha DK. Serpentingue tongue: a rare manifestation following initiation of 6. Méneret A, Grabli D, Depienne C, et al. PRRT2 mutations: a major cause of par- levodopa therapy in a patient with Parkinson’s disease. Parkinsonism Relat Disord oxysmal kinesigenic dyskinesia in the European population. Neurology 2012;79: 2009;15:718–719. 170–174. 5. Sheehy SHC, Lawrence T, Thevathasan AW. Serpentine tongue. A lingual dyskinesia. 7. Castelnovo G, Renard D, De Verdal M, Luc J, Thouvenot E, Riant F. Progressive Neurology 2008;70:e87. ataxia related to PRRT2 gene mutation. J Neurol Sci 2016;367:220–221. Neurology.org/NG Neurology: Genetics | Volume 5, Number 6 | December 2019 3