title: Clinical findings and diagnosis in genetic prion diseases in Germany.
abstract: 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.
authors.affiliation: Department of Neurology, National Reference Center for TSE Surveillance, University Medical School, Georg-August University Göttingen, Robert-Koch Str. 40, 37075, Göttingen, Germany.|Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Krasnianski
authors.affiliation: Department of Neurology, National Reference Center for TSE Surveillance, University Medical School, Georg-August University Göttingen, Robert-Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Heinemann
authors.affiliation: Department of Neurology, National Reference Center for TSE Surveillance, University Medical School, Georg-August University Göttingen, Robert-Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ponto
authors.affiliation: Department of Neurology, National Reference Center for TSE Surveillance, University Medical School, Georg-August University Göttingen, Robert-Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Kortt
authors.affiliation: Department of Neuroradiology, University Medical School, Georg-August University Göttingen, Göttingen, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Kallenberg
authors.affiliation: Department of Neurology, National Reference Center for TSE Surveillance, University Medical School, Georg-August University Göttingen, Robert-Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Varges
authors.affiliation: Department of Neuropathology, University Medical School, Georg-August University Göttingen, Göttingen, Germany.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Schulz-Schaeffer
authors.affiliation: Department of Neuropathology, Ludwig-Maximillian University Munich, Munich, Germany.
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.affiliation: Department of Neurology, National Reference Center for TSE Surveillance, University Medical School, Georg-August University Göttingen, Robert-Koch Str. 40, 37075, Göttingen, Germany. epicjd@med.uni-goettingen.de.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000328:Adult; D003062:Codon / Q000235:genetics*; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D017096:Prion Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions
keywords: Familial CJD; M129V polymorphism; PRNP mutation; Prion disease