• Users Online: 213
  • Print this page
  • Email this page


 
 
Table of Contents
CASE REPORTS
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 96-98

Jerky dystonic tremor: a less-recognized feature of DYT-THAP1


Sterling Hospital, Ahmedabad, Gujarat 380052, India

Date of Submission18-Sep-2020
Date of Decision21-Mar-2021
Date of Acceptance10-May-2021
Date of Web Publication30-Aug-2021

Correspondence Address:
Dr. Narendrakumar H Barad
Sterling Hospital, Ahmedabad, Gujarat.
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AOMD.AOMD_45_20

Rights and Permissions
  Abstract 

Dystonia is a very complex movement disorder. Recently, the classification of dystonia has been updated by a group of experts to simplify the clinical approach to dystonia. As per this new classification, clinically we can divide dystonia into either isolated or combined dystonia. In the isolated group, dystonia is the only feature with or without tremor. In the isolated dystonia (DYT) group, DYT-TOR1A and DYT-THAP1 are the commoner entities worldwide. In DYT-THAP1 cases, apart from classic generalized dystonia phenotype, appendicular tremor has also been described. However, in some cases, it could be jerky and may create confusion with myoclonus. To prevent this confusion and subsequent investigations in the line of myoclonic dystonic syndromes, identification of this jerky tremor assumes great clinical significance. Hereby, we are describing a genetically confirmed DYT-THAP1 patient with a jerky dystonic tremor of upper limbs.

Keywords: Botulinum injection, DYT-THAP1, erky dystonic tremor, thap1, torticollis


How to cite this article:
Barad NH. Jerky dystonic tremor: a less-recognized feature of DYT-THAP1. Ann Mov Disord 2021;4:96-8

How to cite this URL:
Barad NH. Jerky dystonic tremor: a less-recognized feature of DYT-THAP1. Ann Mov Disord [serial online] 2021 [cited 2021 Dec 1];4:96-8. Available from: https://www.aomd.in/text.asp?2021/4/2/96/324804




  Key Messages: Top


We are describing the jerky nature of dystonic tremor in a genetically confirmed case of DYT-THAP1. We want to highlight this feature in DYT-THAP1 cases to avoid its interpretation as myoclonic in nature and subsequent investigations in the line of myoclonus-dystonia syndromes. This will help in keeping such cases in the isolated dystonia group and make further workup and management of such cases easier, especially in resource-limited set-ups.


  Introduction Top


Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. These dystonic movements are typically patterned and twisting and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. As per recent literature, clinically we can divide dystonia as isolated (± tremor) or combined dystonia. Among the isolated dystonia cases, DYT-TOR1A and DYT-THAP1 are the commoner entities described worldwide.[1] DYT-THAP1 is early-onset autosomal dominant dystonia caused by a mutation in the THAP1 (Thanatos‐associated domain‐containing apoptosis‐associated protein 1) gene.[2] Appendicular symptoms in the form of tremor have been described in the literature in DYT-THAP1 cases.[3] However, description of the jerky nature of dystonic tremor is not highlighted. Such a description is important to avoid confusion of this entity with myoclonus-dystonia syndromes.


  Case Report Top


We hereby describe a patient from India with genetically confirmed DYT-THAP1, who presented with many unusual features and a very benign disease course. The patient is a 54-year-old male, right-handed person with education level up to grade 10 of the Indian education system. He presented to us with history of involuntary movements of left upper limb followed by left lower limb since last 30 yrs (insidious onset and very slowly progressive, had some difficulty in walking though he was able to do business and household activities independently). Now since last 1 year, he also noticed involvement of the right side of the body along with prominent involvement of the cranio-cervical region in the form of difficulty in speaking and neck tilt to the right side [Video 1]. In past history, he had some febrile illness few days prior to the onset of symptoms on the left side. There was no sleep benefit or diurnal variation. He did not have any cognitive or psychiatric symptoms, and there was no relevant past medical or family history. He has normal appetite, sleep, and sphincter functions; no history of any drugs, toxic metal, or tobacco exposure. His general examination and examination of other systems were normal. No organomegaly or eye signs were present. Neurological examination in the sitting position showed facial grimacing and hypophonia, right laterocollis with prominent platysma, some laryngeal dystonia, dystonic posturing of all four limbs (left » right, upper limbs » lower limbs), and dystonic jerky tremors of upper limbs (left » right) [Video 1]. Clinically, tongue or oropharyngeal region was not involved. He was walking with some compensatory tilt to one side along with evident left upper limb tremor. Examination of higher mental functions, cranial nerves, motor system, sensory system, and cerebellum was normal. His relevant blood investigations, cerebrospinal fluid routine and microbiology, and imaging of brain and spine were normal. No giant wave was seen in cortical somatosensory evoked potential (SSEP). Detailed neurophysiological study of jerky movement was not done due to lack of availability. His clinical exome sequencing revealed a pathogenic heterozygous missense variation in exon 2 of the THAP1 gene (chr8:g.42694511G>C; p.Arg29Gly;ENST00000254250.3) [Figure 1]. In addition, to phenotype–genotype correlation, the observed variation lies in the THAP domain of the THAP1 protein, and a different amino acid substitution affecting the same codon (p.Arg29Gly) has been reported in patients affected with dystonia.[4],[5] In treatment, he was given trihexyphenidyl and botulinum injection for right laterocollis. He responded very well to botulinum injection.
Figure 1: Chromatograph figure

Click here to view






  Discussion Top


The features of upper limb onset with very slowly progressive generalization are well described in DYT-THAP1 cases.[6] Speech involvement and cervical involvement are also described in DYT-THAP1 cases. Asymmetric appendicular dystonic tremor of variable amplitude is described in DYT-THAP1 cases by LeDoux[3]; however, whether it could be “jerky” in some is not highlighted. Clot et al.[7] described myoclonus in DYT-THAP1 cases; however, there was no electrophysiological confirmation of myoclonus and it may be just a jerky dystonic tremor. We have considered DYT-ANO3, DYT-SCGE, and DYT-KMT2B in differentials; however, detailed clinical history, isolated phenomenology, and clinical course of our patient favor DYT-THAP1 as the most likely etiology over all above-mentioned dystonia syndromes. Although positive family history can be seen up to 60% of the cases, however, it was negative in our case. This may be due to de novo mutation, incomplete penetrance, or milder phenotype in his parents. The present case had appendicular dystonic tremor with a jerky component which may create confusion with myoclonic dystonia syndromes. Besides, a very good response to botulinum injection for cervical dystonia, despite generalized phenotype, is also an important point to keep in mind while treating such patients to provide possible affordable help in this otherwise very much distressing entity.

In conclusion, appendicular dystonic tremor may have jerky nature in DYT-THAP1 cases. It may have a sporadic presentation due to many reasons despite being an autosomal dominant inheritance. A trial of botulinum toxin for disabling craniocervical dystonia despite having a generalized dystonic phenotype is well justified in some DYT-THAP1 cases to reduce morbidity.

Acknowledgements

I want to acknowledge my patient for his full cooperation and consent for this publication.

Ethical compliance statement

Ethical committee approval is not required for this case report. Written informed consent of the patient was obtained for the video recording and for online publication and dissemination.

Conflicts of interest

There are no conflicts of interest.

Financial support and sponsorship

Nil.



 
  References Top

1.
Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, et al. Phenomenology and classification of dystonia: A consensus update. Mov Disord 2013;28:863-73.  Back to cited text no. 1
    
2.
Fuchs T, Gavarini S, Saunders-Pullman R, Raymond D, Ehrlich ME, Bressman SB, et al. Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia. Nat Genet 2009;41:286-8.  Back to cited text no. 2
    
3.
LeDoux MS. Dystonia: Phenomenology. Parkinsonism Relat Disord 2012;18(Suppl 1):S162-4.  Back to cited text no. 3
    
4.
Paisán-Ruiz C, Ruiz-Martinez J, Ruibal M, Mok KY, Indakoetxea B, Gorostidi A, et al. Identification of a novel THAP1 mutation at R29 amino-acid residue in sporadic patients with early-onset dystonia. Mov Disord 2009;24:2428-9.  Back to cited text no. 4
    
5.
Pfam: Home Page. Available from: http://pfam.xfam.org/ (accessed March 16, 2021).  Back to cited text no. 5
    
6.
Blanchard A, Ea V, Roubertie A, Martin M, Coquart C, Claustres M, et al. DYT6 dystonia: Review of the literature and creation of the UMD locus-specific database (LSDB) for mutations in the THAP1 gene. Hum Mutat 2011;32:1213-24.  Back to cited text no. 6
    
7.
Clot F, Grabli D, Burbaud P, Aya M, Derkinderen P, Defebvre L, et al. Screening of the THAP1 gene in patients with early-onset dystonia: Myoclonic jerks are part of the dystonia 6 phenotype. Neurogenetics 2011;12:87-9.  Back to cited text no. 7
    


    Figures

  [Figure 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Key Messages:
Introduction
Case Report
Discussion
References
Article Figures

 Article Access Statistics
    Viewed240    
    Printed10    
    Emailed0    
    PDF Downloaded31    
    Comments [Add]    

Recommend this journal