Parkin disease: a phenotypic study of a large case series

被引:277
作者
Khan, NL
Graham, E
Critchley, P
Schrag, AE
Wood, NW
Lees, AJ
Bhatia, KP
Quinn, N
机构
[1] Inst Neurol, Sobell Dept Neurosci & Movement Disorders, London WC1N 3BG, England
[2] Inst Neurol, Dept Mol Pathogenesis, London WC1N 3BG, England
[3] Royal Free Hosp, Reta Lila Weston Inst Neurol Studies, London NW3 2QG, England
[4] UCL, Sch Med, London W1N 8AA, England
[5] Leicester Royal Infirm, Dept Neurol, Leicester, Leics, England
关键词
parkin; PARK2; phenotype; mutation;
D O I
10.1093/brain/awg142
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Mutations in the parkin gene, PARK2, are a common cause of parkinsonism in familial as well as isolated cases with an age of onset <40 years and should be considered in the diagnostic work up of young-onset parkinsonism. We report a detailed clinical evaluation of a personal series of 24 patients with mutations in the parkin gene. The clinical presentation of most cases was broadly comparable to that of previous descriptions of autosomal recessive early-onset or juvenile parkinsonism and young-onset Parkinson's disease and also had similarities with phenotypes of dopa-responsive dystonia. However, our only case with consanguineous parents had an age of onset of 54 years. We report three new phenotypes at presentation: cervical dystonia; autonomic dysfunction and peripheral neuropathy; and pure exercise-induced dystonia. We emphasize a number of clinical features that can be seen in parkin disease: focal dystonia; early instability; freezing; festination or retropulsion; concurrent autonomic failure; dramatic response to anticholinergics; early or atypical l-dopa-induced dyskinesias; exquisite sensitivity to small doses of l-dopa; and recurrent psychosis, even taking l-dopa alone. We also report behavioural disorder prior to the onset of parkinsonism. Some relatives carrying a single parkin mutation without extrapyramidal symptoms or signs also had psychiatric symptoms that might be related to their carrier status.
引用
收藏
页码:1279 / 1292
页数:14
相关论文
共 41 条
[1]   Range of neuropsychiatric disturbances in patients with Parkinson's disease [J].
Aarsland, D ;
Larsen, JP ;
Lim, NG ;
Janvin, C ;
Karlsen, K ;
Tandberg, E ;
Cummings, JL .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1999, 67 (04) :492-496
[2]   A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe [J].
Abbas, N ;
Lücking, CB ;
Ricard, S ;
Dürr, A ;
Bonifati, V ;
De Michele, G ;
Bouley, S ;
Vaughan, JR ;
Gasser, T ;
Marconi, R ;
Broussolle, E ;
Brefel-Courbon, C ;
Harhangi, BS ;
Oostra, AB ;
Fabrizio, E ;
Böhme, GA ;
Pradier, L ;
Wood, NW ;
Filla, A ;
Meco, G ;
Denefle, P ;
Agid, Y ;
Brice, A .
HUMAN MOLECULAR GENETICS, 1999, 8 (04) :567-574
[3]   Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism [J].
Bonifati, V ;
Rizzu, P ;
van Baren, MJ ;
Schaap, O ;
Breedveld, GJ ;
Krieger, E ;
Dekker, MCJ ;
Squitieri, F ;
Ibanez, P ;
Joosse, M ;
van Dongen, JW ;
Vanacore, N ;
van Swieten, JC ;
Brice, A ;
Meco, G ;
van Duijn, CM ;
Oostra, BA ;
Heutink, P .
SCIENCE, 2003, 299 (5604) :256-259
[4]   [18F]-dopa PET study in patients with juvenile-onset PD and parkin gene mutations [J].
Broussolle, E ;
Lücking, CB ;
Ginovart, N ;
Pollak, P ;
Remy, P ;
Dürr, A .
NEUROLOGY, 2000, 55 (06) :877-879
[5]   Lewy bodies and parkinsonism in families with parkin mutations [J].
Farrer, M ;
Chan, P ;
Chen, R ;
Tan, L ;
Lincoln, S ;
Hernandez, D ;
Forno, L ;
Gwinn-Hardy, K ;
Petrucelli, L ;
Hussey, J ;
Singleton, A ;
Tanner, C ;
Hardy, J ;
Langston, JW .
ANNALS OF NEUROLOGY, 2001, 50 (03) :293-300
[6]   MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN [J].
FOLSTEIN, MF ;
FOLSTEIN, SE ;
MCHUGH, PR .
JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) :189-198
[7]   THE RELEVANCE OF THE LEWY BODY TO THE PATHOGENESIS OF IDIOPATHIC PARKINSONS-DISEASE [J].
GIBB, WRG ;
LEES, AJ .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1988, 51 (06) :745-752
[8]  
Hayashi S, 2000, MOVEMENT DISORD, V15, P884, DOI 10.1002/1531-8257(200009)15:5<884::AID-MDS1019>3.0.CO
[9]  
2-8
[10]   Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene [J].
Hilker, R ;
Klein, C ;
Ghaemi, M ;
Kis, B ;
Strotmann, T ;
Ozelius, LJ ;
Lenz, O ;
Vieregge, P ;
Herholz, K ;
Heiss, WD ;
Pramstaller, PP .
ANNALS OF NEUROLOGY, 2001, 49 (03) :367-376