Christine Klein, Rosalind Chuang, and Connie Marras contributed equally to this work.
Article first published online: 6 JUL 2011
Copyright © 2011 Movement Disorder Society
Volume 26, Issue 10, pages 1793–1802, 15 August 2011
How to Cite
Klein, C., Chuang, R., Marras, C. and Lang, A. E. (2011), The curious case of phenocopies in families with genetic Parkinson's disease. Mov. Disord., 26: 1793–1802. doi: 10.1002/mds.23853
Funding agencies: C.K. is the recipient of a career development award from the Volkswagen Foundation and from the Hermann and Lilly Schilling Foundation. C.M. is a recipient of a new investigator award from the Canadian Institutes of Health Research. A.E.L. is supported, in part, from the Jack Clark Chair for Parkinson's Disease Research at the University of Toronto and the Edmond J. Safra Program in Parkinson's Disease at the University of Toronto and University Health Network.
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 26 AUG 2011
- Article first published online: 6 JUL 2011
- Manuscript Accepted: 26 MAY 2011
- Manuscript Revised: 11 MAY 2011
- Manuscript Received: 21 MAR 2011
- Parkinson's disease;
- genetic testing;
- linkage analysis
Monogenic forms of Parkinson's disease account for ∼3% of all “idiopathic” Parkinson's disease. With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with α-synuclein, leucine-rich repeat kinase 2, Parkin, or PTEN-induced kinase 1 mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age-specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, “sporadic Parkinson's disease” was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting. © 2011 Movement Disorder Society