Counseling At-Risk Parkinson’s Disease Cohorts: Integrating Emerging Evidence
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Purpose of Review
This article evaluates the current state of testing and counseling viewpoints for Parkinson’s disease (PD) risk gene carriers and their families.
Recent discoveries of mutations in genes associated with increased risk for PD not only portend novel possibilities for targeted clinical research but also present salient challenges for genetic counseling.
A patient-centered and transparent approach to counseling that assesses preferences and communication styles is described to aid in facilitating the use of evolving evidence regarding strategies to attenuate PD phenoconversion in non-manifesting carriers.
KeywordsParkinson’s disease LRRK2 Genetic counseling Genetic testing Genetic screening Phenoconversion Ashkenazi Jews North African Berbers
Leonard L. Sokol extends his gratitude toward Chad Serels and Michael Star for their discussions related to the manuscript.
All authors read and approved of the final manuscript. Leonard L. Sokol and Michael J. Young conceived, organized, and wrote the first draft. Joseph Jankvoic organized, reviewed, critiqued, added intellectual content, and mentored efforts.
Compliance with Ethical Standards
Conflict of Interest
Leonard L. Sokol and Michael J. Young have nothing to disclose.
Joseph Jankovic has received research grants from Adamas Pharmaceuticals, Inc.; Allergan, Inc.; Auspex Pharmaceuticals, Inc.; CHDI Foundation; Civitas/Acorda Therapeutics; Huntington Study Group; Ipsen Limited; Kyowa Haako Kirin Pharma, Inc.; Lundbeck, Inc.; Medtronic; Merz Pharmaceuticals; Michael J. Fox Foundation for Parkinson Research; National Institutes of Health; National Parkinson Foundation; Omeros Corporation; Parkinson Study Group; Pfizer; Prothena Biosciences, Inc.; Psyadon Pharmaceuticals, Inc.; St. Jude Medical; and Teva Pharmaceutical Industries Ltd. He has served as a consultant or as an advisory committee member for the following: Adamas Pharmaceuticals, Inc.; Allergan, Inc.; Auspex Pharmaceuticals, Inc.; and Teva Pharmaceutical Industries Ltd. He has received royalties from Cambridge, Elsevier, Future Science Group, Hodder Arnold, Lippincott Williams and Wilkins, and Wiley-Blackwell. In addition, he serves on the editorial boards of Medlink, Neurology, Expert Review of Neurotherapeutics, Neurology in Clinical Practice, The Botulinum Journal, PeerJ, Therapeutic Advances in Neurological Disorders, Neurotherapeutics, Tremor and Other Hyperkinetic Movements, Journal of Parkinson’s Disease, and UpToDate.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance
- 3.Deng H-X, Shi Y, Yang Y, Ahmeti KB, Miller N, Huang C, et al. Identification of TMEM230 mutations in familial Parkinson’s disease. Nat Genet [Internet]. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2016;advance on. Available from: http://dx.doi.org/10.1038/ng.3589
- 4.Lill CM. Genetics of Parkinson’s disease. Mol. Cell. Probes [Internet]. Elsevier Ltd; 2016;6:1687–91. Available from: http://dx.doi.org/10.1016/j.mcp.2016.11.001
- 6.Giladi N, Mirelman A, Thaler A, Bar-Shira A, Gurevich T, Orr-Urtreger A. Fighting the risk of developing Parkinson’s disease; Clinical counseling for first degree relatives of patients with Parkinson’s disease. J. Neurol. Sci. [Internet]. Elsevier B.V.; 2011;310:17–20. Available from: http://dx.doi.org/10.1016/j.jns.2011.06.005
- 7.Pont-Sunyer C, Bressman S, Raymond D, Glickman A, Tolosa E, Saunders-Pullman R. Disclosure of research results in genetic studies of Parkinson’s disease caused by LRRK2 mutations. Mov. Disord. [Internet]. 2015;0:n/a-n/a. Available from: http://doi.wiley.com/10.1002/mds.26250
- 9.•• Marder K, Wang Y, Alcalay RN, Mejia-santana H, Lee A, Raymond D, et al. Age-specific penetrance of LRRK2 G2019S in the Michael J. Fox Ashkenazi Jewish LRRK2 Consortium. 2015;1–8. This study suggests a relatively low PD penetrance of Ashkenazi-Jewish, LRRK2-carriers.Google Scholar
- 10.Alcalay RN, Mirelman A, Saunders-pullman R, Tang M, Santana HM, Raymond D, et al. Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. 2013;28:1966–71.Google Scholar
- 11.Saunders-Pullman R, Alcalay RN, Mirelman A, Wang C, Luciano MS, Ortega RA, et al. REM sleep behavior disorder, as assessed by questionnaire, in G2019S LRRK2 mutation PD and carriers. Mov. Disord. 2015;0:n/a-n/a.Google Scholar
- 13.Kalia LV, Lang AE, Hazrati LN, Fujioka S, Wszolek ZK, Dickson DW, et al. Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol. [Internet]. 2015;72:100–5. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4399368&tool=pmcentrez&rendertype=abstract CrossRefGoogle Scholar
- 14.Alcalay RN, Caccappolo E, Mejia-Santana H, Tang MX, Rosado L, Ross BM, et al. Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the consortium on risk for early onset Parkinson disease study. Arch Neurol [Internet]. 2010;67:1116–22. Available from: http://archpsyc.jamanetwork.com/pdfaccess.ashx?ResourceID=1412925&PDFSource=13 Google Scholar
- 15.Shkedi-Rafid S, Ofer-Bialer G, Meiner V, Calderon-Margalit R. Clinicians’ attitudes toward general screening of the Ashkenazi-Jewish population for prevalent founder BRCA1/2 and LRRK2 mutations. Public Health Genomics [Internet]. Karger Publishers; 2013 [cited 2015 Nov 30];16:174–83. Available from: http://www.karger.com/Article/FullText/351592.
- 16.Gupte M, Alcalay RN, Mejia-Santana H, Raymond D, Saunders-Pullman R, Roos E, et al. Interest in genetic testing in Ashkenazi Jewish Parkinson’s disease patients and their unaffected relatives. J Genet Couns [Internet]. 2015;24:238–46. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4331260&tool=pmcentrez&rendertype=abstract CrossRefGoogle Scholar
- 17.Pahwa R, Lyons KE. Early diagnosis of Parkinson’s disease: recommendations from diagnostic clinical guidelines. Am J Manag. 2010;16:S94–9.Google Scholar
- 18.Buhat DML, Tan E-K. Genetic testing of LRRK2 in Parkinson’s disease: is there a clinical role? Parkinsonism Relat. Disord. [Internet]. Elsevier Ltd; 2014; 20 Suppl 1:S54–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24262189.
- 22.Sanderson SC, Wardle J. Associations between anticipated reactions to genetic test results and interest in genetic testing: will self-selection reduce the potential for harm? Genet. Test. [Internet]. United States: MARY ANN LIEBERT INC; 2008;12:59–66. Available from: http://uc.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw3V1La9tAEF4MJaVQSps-oiSFPbS9GFG9tVsIwS0updAcYoXSk9A-FAKpHSoZmj_S39sZzUq2nBx67s1Ig63d-Tw7M5r5hjEe18hSpiW4ojW4C3ENLgRONK-z3MSiqsajfCb9XMHNtf9By1u72ww1V7BZVCptsTWFOhc6Igf4GuxZnIJ72cKdZn3dNo5-CbYXL14t.
- 27.Johnson R, Harkins K, Cary M, Sankar P, Karlawish J. The relative contributions of disease label and disease prognosis to Alzheimer’s stigma: a vignette-based experiment. Soc. Sci. Med. [Internet]. Elsevier Ltd; 2015;143:117–27. Available from: http://dx.doi.org/10.1016/j.socscimed.2015.08.031.
- 29.Botkin JR, Belmont JW, Berg JS, Berkman BE, Bombard Y, Holm IA, et al. Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. Am J Hum Genet [Internet] The American Society of Human Genetics. 2015;97:6–21. doi: 10.1016/j.ajhg.2015.05.022.CrossRefGoogle Scholar
- 30.Bondi MW, Ph D, Galasko D, Salmon DP. Effect of knowledge of APOE genotype on subjective and objective memory performance in healthy older adults. 2014;201–8.Google Scholar
- 31.Dahodwala N, Connolly J, Farmer J, Stern MB, Jennings D, Siderowf A. Interest in predictive testing for Parkinson’s disease: impact of neuroprotective therapy. Parkinsonism Relat Disord [Internet]. 2007;13:495–9. Available from: http://www.sciencedirect.com/science/article/pii/S1353802007000491 CrossRefGoogle Scholar
- 32.Text of H.R. 493 (110th): Genetic Information Nondiscrimination Act of 2008 (Passed Congress/Enrolled Bill version) - GovTrack.us [Internet]. [cited 2015 Dec 7]. Available from: https://www.govtrack.us/congress/bills/110/hr493/text
- 34.Wolf R, Young MJ, Stein MA, Bursztajn HJ. Genetic discrimination: transatlantic perspectives on the case for a European level legal response. In: Quinn G, de Paor A, Blanck P, editors. 2015.Google Scholar
- 35.•• Racette BA, Willis AW. Time to change the blind men and the elephant approach to Parkinson disease? Neurology [Internet]. 2015;85:190–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26070339. This commentary contends that the research focus should broaden away from “the cure” to prevention within Parkinson's disease CrossRefGoogle Scholar
- 36.•• Armstrong MJ, Shulman LM, Vandigo J, Mullins CD. Patient engagement and shared decision-making: what do they look like in neurology practice? Neurol. Clin. Pract. AAN Enterprises; 2016;10–1212. This review outlines several examples of shared decision-making in the course of conveying various treatment options to patients with Parkinson's disease.Google Scholar
- 37.Fischhoff B. Risk perception and communication. Oxford Textb. Public Heal. Fifth Ed. 2009. p. 940–52.Google Scholar
- 38.Chao S, Roberts JS, Marteau TM, Silliman R, Cupples LA, Green RC. Health behavior changes after genetic risk assessment for Alzheimer disease: the REVEAL study. Alzheimer Dis. Assoc. Disord. 2008. p. 94–7.Google Scholar
- 39.Christensen KD, Roberts JS, Whitehouse PJ, Royal CDM, Obisesan TO, Cupples LA, et al. Disclosing pleiotropic effects during genetic risk assessment for Alzheimer disease: a randomized trial disclosing pleiotropic effects during risk assessment for Alzheimer disease. Ann Intern Med [Internet]. 2016;164:155–63. doi: 10.7326/M15-0187.CrossRefGoogle Scholar
- 40.Young MJ. Bioenhancements and the telos of medicine. Med. Heal. Care Philos. [Internet]. Springer Netherlands; 2015;18:515–22. Available from: http://link.springer.com/10.1007/s11019-015-9634-9.
- 41.Wolf-Brom R., Stein M. BH. Genes. Identity and clinical ethics under conditions of uncertainty. In: Quinn G., Paor A. BP, editor. Genet. Discrim. Transatl. Perspect. Case a Eur. Lev. Leg. Response. Routledge, Taylor & Francis Group; 2016.Google Scholar
- 43.Bellou V, Belbasis L, Tzoulaki I, Evangelou E, Ioannidis JPA. Environmental risk factors and Parkinson’s disease: an umbrella review of meta-analyses. Parkinsonism Relat. Disord. [Internet]. Elsevier; 2016;23:1–9. Available from: http://dx.doi.org/10.1016/j.parkreldis.2015.12.008.
- 44.Feng Y, Jankovic J, Wu Y-C. Epigenetic mechanisms in Parkinson’s disease. J. Neurol. Sci. [Internet]. Elsevier B.V.; 2015;349:3–9. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0022510X14007825.
- 46.Kalia LV, Lang AE, Hazrati L-N, Fujioka S, Wszolek ZK, Dickson DW, et al. Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol. [Internet]. 2015;72:100–5. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4399368&tool=pmcentrez&rendertype=abstract CrossRefGoogle Scholar
- 47.Giladi N, Mirelman A, Thaler A, Orr-Urtreger A. A personalized approach to Parkinson’s disease patients based on founder mutation analysis. Front Neurol [Internet]. 2016;7:1–5. Available from: http://journal.frontiersin.org/Article/10.3389/fneur.2016.00071/abstract Google Scholar
- 48.• Sokol LL, Espay AJ. Runny nose sign: sequential rhinorreha and syncope in dementia with Lewy bodies. Neurol Clin Pract [Internet]. 2016;6:e14–6. doi: 10.1212/CPJ.0000000000000203. The first report of rhinorrhea concomitant with parasympathetic activation in an Ashkenazi-Jewish male with GBA-associated Lewy-body dementia CrossRefGoogle Scholar
- 49.Brin S. LRRK2 [Internet]. 2008 [cited 2015 Dec 22]. Available from: http://too.blogspot.com/2008/09/lrrk2.html.
- 50.Goetz T. Sergey Brin’s search for a Parkinson’s cure | WIRED [Internet]. 2010 [cited 2015 Nov 25]. Available from: http://www.wired.com/2010/06/ff_sergeys_search/.
- 51.•• Fraser KB, Moehle MS, Alcalay RN, West AB, Bressman S, Giladi N, et al. Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers. Neurology AAN Enterprises. 2016;86:994–9. This study detects a urinary biomarker within LRRK2-PD patients Google Scholar