European Journal of Epidemiology

, Volume 31, Issue 2, pp 187–196 | Cite as

Clinical findings and diagnosis in genetic prion diseases in Germany

  • Anna Krasnianski
  • Uta Heinemann
  • Claudia Ponto
  • Jasmine Kortt
  • Kai Kallenberg
  • Daniela Varges
  • Walter J. Schulz-Schaeffer
  • Hans A. Kretzschmar
  • Inga Zerr


To describe the clinical syndrome and diagnostic tests in patients with genetic prion diseases (gPD) in Germany. Clinical features, MRI, EEG, and CSF markers were studied in 91 patients (28 D178N, 20 E200K, 17 inserts, 13 V210I, 8 P102L, 5 E196K). Dementia (35 %) and ataxia (29 %) were the most common initial symptoms and signs. A wide variety and high frequency of neurological/psychiatric symptoms and signs was found during disease course in all patients independently of the type of the mutation. Psychiatric manifestations were frequent (87 %). Neuropsychological abnormalities were observed in 67 %, and aphasia was the most common disturbance (45 %). In E200K, V210I and D178N patients, visual/oculomotor deficits were followed by ataxia early in the disease. Dementia followed by ataxia at onset was common in patients with insert and E196K mutation. P102L patients had isolated ataxia over a longer time period followed by pyramidal signs. Dementia was present only late in the disease course. All clinical routine tests such as MRI, EEG and CSF tests were less sensitive than in sporadic CJD. We provide the first detailed analysis of clinical signs and symptoms in a large group of patients with gPD. Frequency of clinical symptoms and signs was similar in different mutations in a later disease course, but the sequence of occurrence may be of great diagnostic importance. CSF markers were shown to be more sensitive than MRI and EEG.


Prion disease Familial CJD M129V polymorphism PRNP mutation 



First of all, we thank the patients and their families. The authors thank neurologists and psychiatrists throughout Germany for providing clinical and neuropathological data on patients and for sending CSF and blood samples. We thank Mrs. Henn, Staniszewski, Bodemer and Ciesielczyk for the excellent technical assistance. The assistance of Mrs. Ehrlich and Schneider-Dominco is gratefully acknowledged. This study was funded by the Robert Koch-Institute through funds of the Federal Ministry of Health (Grant Number 1369-341) and the European Commission (FP6-2005-SSP-5-A, 044438).


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Anna Krasnianski
    • 1
    • 5
  • Uta Heinemann
    • 1
  • Claudia Ponto
    • 1
  • Jasmine Kortt
    • 1
  • Kai Kallenberg
    • 2
  • Daniela Varges
    • 1
  • Walter J. Schulz-Schaeffer
    • 3
  • Hans A. Kretzschmar
    • 4
  • Inga Zerr
    • 1
  1. 1.Department of Neurology, National Reference Center for TSE Surveillance, University Medical SchoolGeorg-August University GöttingenGöttingenGermany
  2. 2.Department of Neuroradiology, University Medical SchoolGeorg-August University GöttingenGöttingenGermany
  3. 3.Department of Neuropathology, University Medical SchoolGeorg-August University GöttingenGöttingenGermany
  4. 4.Department of NeuropathologyLudwig-Maximillian University MunichMunichGermany
  5. 5.Department of Psychiatry, Psychosomatic Medicine and PsychotherapyGoethe UniversityFrankfurtGermany

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