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Research paper
Phenotypes and genetic architecture of focal primary torsion dystonia
  1. Justus L Groen1,2,
  2. Marlot C Kallen1,
  3. Bart P C van de Warrenburg3,
  4. J D Speelman1,
  5. Jacobus J van Hilten4,
  6. Majid Aramideh5,
  7. Agnita J W Boon6,
  8. Christine Klein7,
  9. Johannes H T M Koelman1,
  10. Ton P Langeveld8,
  11. Frank Baas2,
  12. Marina A J Tijssen1,9
  1. 1Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Genome Analysis, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  3. 3Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  4. 4Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
  5. 5Department of Neurology, Medical Centre Alkmaar, Alkmaar, The Netherlands
  6. 6Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
  7. 7Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany
  8. 8Department of Otolaryngeal, Leiden University Medical Centre, Leiden, The Netherlands
  9. 9Department of Neurology, Groningen University Medical Centre, Groningen, The Netherlands
  1. Correspondence to Professor M A J de Koning-Tijssen, Department of Neurology AB 51, University Medical Centre Groningen, PO BOX 30001, 9700 RB Groningen, The Netherlands;{at}


Background The focal primary torsion dystonias (FPTDs) form a group of clinical heterogeneous syndromes and can be considered a genetic complex disease; it is thought to be primed by genetic variants with variable impact and triggered by non-genetic factors. Thorough clinical description of FPTDs cohorts is sparse but essential for further progress in genetic research.

Objective To establish suggested relations between age at onset (AaO), site and family history in a large focal dystonias cohort and gain more insight into familial clustering for genetic research.

Patients and methods A prospective cohort study between March 2008 and March 2011, including 676 FPTD patients attending the botulinum toxin outpatient clinics of six Dutch movement disorder centres.

Results and conclusions Of all of the FPTD patients, 25% had a familial predisposition; in 2.4% a Mendelian inheritance pattern was noted. With a stronger family history, a significantly lower AaO was seen in all focal dystonias. In both the sporadic and familial focal dystonia groups, AaO had an effect on the distribution of dystonia, with a caudal to cranial tendency. In all focal dystonia forms, women were more frequently affected, except for writer's cramp. Careful clinical characterisation will allow the formation of phenotype subgroups. We suggest that genetic research into FPTDs will benefit from this approach and discuss genetic research strategies to decipher the complex background of focal dystonias.

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  • Funding JLG is supported by AMC Graduate School Scholarship and Prinses Beatrix Fund. BPCvdW received research grants from the Princess Beatrix Fund; the Brain Foundation; the European Union (6th Framework program, EuroSCA/LSHM-CT-2004-503304, Brussels); and Ipsen Pharmaceuticals. JJvH is supported by a Dutch government grant (BSIK03016). CK is supported by a career development award from the Hermann and Lilly Schilling Foundation. MAJdK-T received research support from the Prinses Beatrix Fund and a grant from The Netherlands Organisation for Health Research and Development (VIDI research grant #016.056.333). This work was supported by Prinses Beatrix Fund grant No WAR 2008-55.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the medical ethical committees of AMC, MCAlkmaar, Erasmus MC, UMCN and LUMC.

  • Provenance and peer review Not commissioned; externally peer reviewed.