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PRRT2 mutations: exploring the phenotypical boundaries
  1. Tania Djémié1,2,
  2. Sarah Weckhuysen1,2,3,
  3. Philip Holmgren1,2,
  4. Katia Hardies1,2,
  5. Tine Van Dyck1,2,
  6. Rik Hendrickx1,2,
  7. An-Sofie Schoonjans4,
  8. Wim Van Paesschen5,
  9. Anna C Jansen6,7,
  10. Linda De Meirleir6,
  11. Laila Abdel Moteleb Selim8,
  12. Marian Y Girgis8,
  13. Gunnar Buyse9,
  14. Lieven Lagae9,
  15. Katrien Smets1,2,10,
  16. Iris Smouts1,2,10,
  17. Kristl G Claeys11,
  18. Vic Van den Bergh12,
  19. Thierry Grisar13,
  20. Ilan Blatt14,
  21. Zamir Shorer15,
  22. Filip Roelens16,
  23. Zaid Afawi17,
  24. Ingo Helbig18,
  25. Berten Ceulemans4,19,
  26. Peter De Jonghe1,2,10,
  27. Arvid Suls1,2
  1. 1Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
  2. 2Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
  3. 3Epilepsy Centre Kempenhaeghe, Oosterhout, the Netherlands
  4. 4Pediatric Neurology, Division of Neurology, Antwerp University Hospital, Antwerp, Belgium
  5. 5Department of Neurology, University Hospital Gasthuisberg, Leuven, Belgium
  6. 6Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel, Brussels, Belgium
  7. 7Department of Public Health, Vrije Universiteit Brussel, Brussels, Belgium
  8. 8Pediatric Neurology and Neurometabolic Unit, Cairo University Children Hospital, Cairo, Egypt
  9. 9Department of Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium
  10. 10Department of Neurology, Antwerp University Hospital, Antwerp, Belgium
  11. 11Department of Neurology and Institute of Neuropathology, RWTH Aachen University, Aachen, Germany
  12. 12General Hospital of Turnhout, Turnhout, Belgium
  13. 13University of Liège, GIGA Neurosciences Centre, Liège, Belgium
  14. 14Department of Neurology, Sheba Medical Center, Tel-Hashomer, Israel
  15. 15Division of Pediatric, Ben Gurion University of the Negev, Beer Sheva, Israel
  16. 16Department of Pediatrics, Heilig Hart Ziekenhuis, Roeselare, Belgium
  17. 17Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
  18. 18Department of Neuropediatrics, University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
  19. 19Epilepsy Center for Children and Youth, Pulderbos, Belgium
  1. Correspondence to Dr Arvid Suls, Neurogenetics Group, VIB-Department of Molecular Genetics, University of Antwerp, Campus CDE, Parking P4, Building V1.33, Universiteitsplein 1, Antwerp 2610, Belgium; arvid.suls{at}


Background Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene have been identified in patients with benign (familial) infantile convulsions (B(F)IC), infantile convulsions with choreoathetosis (ICCA) and paroxysmal dyskinesias (PDs). However it remains unknown whether PRRT2 mutations are causal in other epilepsy syndromes. After we discovered a PRRT2 mutation in a large family with ICCA containing one individual with febrile seizures (FS) and one individual with West syndrome, we analysed PRRT2 in a heterogeneous cohort of patients with different types of infantile epilepsy.

Methods We screened a cohort of 460 patients with B(F)IC or ICCA, fever related seizures or infantile epileptic encephalopathies. All patients were tested for point mutations using direct sequencing.

Results We identified heterozygous mutations in 16 individuals: 10 familial and 6 sporadic cases. All patients were diagnosed with B(F)IC, ICCA or PD. We were not able to detect mutations in any of the other epilepsy syndromes. Several mutation carriers had learning disabilities and/or impaired fine motor skills later in life.

Conclusions PRRT2 mutations do not seem to be involved in the aetiology of FS or infantile epileptic encephalopathies. Therefore B(F)IC, ICCA and PD remain the core phenotypes associated with PRRT2 mutations. The presence of learning disabilities or neuropsychiatric problems in several mutation carriers calls for additional clinical studies addressing this developmental aspect in more detail.


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