Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-22T17:32:33.208Z Has data issue: false hasContentIssue false
  • English
  • Français

Familial Parkinson’s Disease: A Clinical Genetic Analysis

Published online by Cambridge University Press:  18 September 2015

Vincenzo Bonifati ,
Edito Fabrizio ,
Nicola Vanacore ,
Michele De Mari  and
Giuseppe Meco
Vincenzo Bonifati*
Affiliation:
Department of Neurosciences, “La Sapienza” University, Rome
Edito Fabrizio
Affiliation:
Department of Neurosciences, “La Sapienza” University, Rome
Nicola Vanacore
Affiliation:
Department of Neurosciences, “La Sapienza” University, Rome
Michele De Mari
Affiliation:
Institute of Neurology, University of Bari, Italy
Giuseppe Meco
Affiliation:
Department of Neurosciences, “La Sapienza” University, Rome
*
Department of Neurosciences, Viale dell’Università30, 00185 Roma, Italy
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective

To study the frequency, clinical features and clinical genetics of familial Parkinson’s disease (PD).

Methods

Family history for PD and tremors was studied in 100 consecutive PD cases. Spouses served as controls. Clinical features were compared between personally verified familial and sporadic PD cases, from the same consecutive clinical series. Clinical genetic analysis was performed in a larger group of non-consecutive multicase PD families.

Results

Family history for PD was positive in 24% of consecutive PD cases and in 6% of spouse controls (p < 0.001). When family history for isolated tremor is also considered, the number of positive cases rises to 43% compared with 9% in controls (p < 0.001). Nine of the consecutive cases had at least one living affected relative, for a total of 20 familial PD cases. These familial cases showed an earlier onset age when compared with sporadic ones from the same consecutive series. Within 22 non-consecutive PD families with at least two living and personally examined PD cases (total 52 PD cases), the crude segregation ratios were similar for parents and siblings and the lifetime cumulative risks approached 0.4 in siblings and tended to be comparable, but at later ages, in parents. Ancestral relatives were all unilaterally distributed. In some families, anticipation of onset age in new generations was observed.

Conclusions

The frequency of positive family history for PD and for PD and tremor is higher among PD cases than controls. Familial and sporadic PD only differ in onset age. The clinical genetic analyses support autosomal dominant inheritance with strongly age-related penetrance as most likely in familial PD.

Résumé

Résumé<span class='italic'><span class='bold'>Objectif</span></span>

Étudier la fréquence, les manifestations cliniques et la génétique clinique de la maladie de Parkinson familiale (MP).

<span class='italic'><span class='bold'>Méthodes</span></span>

Nous avons étudié l’histoire familiale quant à la MP et au tremblement chez 100 cas consécutifs de MP. Les conjoints ont servi de contrôles. Nous avons comparé les manifestations cliniques entre les cas familiaux et sporadiques de MP confirmés personnellement, dans cette même série de cas. Nous avons procédé à une analyse génétique clinique chez un groupe plus considérable de familles comprenant plusieurs cas de MP non consécutifs.

<span class='italic'><span class='bold'>Résultats</span></span>

L’histoire familiale était positive chez 24% des cas consécutifs de MP et chez 6% des conjoints servant de contrôles (p < 0.001). Quand nous tenons également compte d’une histoire familiale de tremblement, le nombre de cas positifs s’élève à 43% comparé à 9% chez les contrôles (p < 0.001). Neuf des cas consécutifs avaient au moins un membre vivant de sa famille qui était atteint, pour un total de 20 cas de MP familiale. Ces cas familiaux présentaient un âge de début plus précoce comparé aux cas sporadiques de la même série de cas consécutifs. Dans 22 familles de MP non consécutives comprenant au moins deux cas de MP vivants et examinés personnellement (pour un total de 52 cas de MP), le ratio de ségrégation brut était le même pour les parents et la fratrie, et le risque cumulatif à vie, qui était de près de 0.4 dans la fratrie, avait tendance à être comparable chez les parents, mais à un âge plus tardif. Les cas dans la parenté plus éloignée étaient toujours dans la même lignée, soit paternelle ou maternelle. Dans certaines familles, nous avons observé un phénomène d’anticipation quant à l’âge de début de la maladie dans les générations subséquentes.

<span class='italic'><span class='bold'>Conclusions</span></span>

Une histoire familiale de MP et de MP et tremblement est plus fréquente parmi les cas de MP que parmi les contrôles. La seule différence entre les cas familiaux et sporadiques est l’âge de début de la maladie. Les analyses génétiques cliniques sont en faveur d’une hérédité autosomale dominante de la MP, avec une penetrance fortement reliée à l’âge.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 22 , Issue 4 , November 1995 , pp. 272 - 279
Copyright
Copyright © Canadian Neurological Sciences Federation 1995

References

REFERENCES

1. Golbe, LI. The genetics of Parkinson’s disease: a reconsideration. Neurology 1990; 40 (Suppl. 3): 7–14.Google ScholarPubMed
2. Duvoisin, RC, Johnson, WG. Hereditary Lewy-body parkinsonism and evidence for a genetic etiology of Parkinson’s disease. Brain Pathol 1992; 2: 309–320.Google Scholar
3. Johnson, WG, Hodge, SE, Duvoisin, R. Twin studies and the genetics of Parkinson’s disease – a reappraisal. Mov Disord 1990; 5: 187–194.CrossRefGoogle ScholarPubMed
4. Burn, DJ, Mark, MH, Playford, ED, et al. Parkinson’s disease in twins studied with 18F-dopa and positron emission tomography. Neurology 1992; 42: 1894–1900.Google Scholar
5. Sawle, GV, Wroe, SJ, Lees, AJ, Brooks, DJ, Frackowiak, RSJ. The identification of presymptomatic parkinsonism: clinical and [18F]dopa positron emission tomography studies in an Irish kindred. Ann Neurol 1992; 32: 609–617.CrossRefGoogle Scholar
6. Spellman, GG. Report of familial cases of parkinsonism. JAMA 1962; 179: 160–162.CrossRefGoogle ScholarPubMed
7. Golbe, LI, Di Iorio, G, Bonavita, V, Miller, DC, Duvoisin, RC. A large kindred with autosomal dominant Parkinson’s disease. Ann Neurol 1990; 27: 276–282.CrossRefGoogle ScholarPubMed
8. Golbe, LI, Lazzarini, AM, Schwarz, KO, et al. Autosomal dominant parkinsonism with benign course and typical Lewy-body pathology. Neurology 1993; 43: 2222–2227.Google Scholar
9. Waters, CH, Miller, CA. Autosomal dominant Lewy Body parkinsonism in a four-generation family. Ann Neurol 1994; 35: 59–64.Google Scholar
10. Barbeau, A, Roy, M. Familial subsets in idiopathic Parkinson’s disease. Can J Neurol Sci 1984; 11: 144–150.Google Scholar
11. Calne, S, Schoenberg, B, Martin, W, et al. Familial Parkinson’s disease: possible role of environmental factors. Can J Neurol Sci 1987; 14: 303–305.Google Scholar
12. Mjones, SH. Paralysis agitans: a clinical and genetic study. Acta Psychiatr Neurol 1949; 25 (Suppl. 54): 1–195.Google Scholar
13. Martin, WE, Young, WI, Anderson, VE. Parkinson’s disease. A genetic study. Brain 1973; 96: 495–506.Google Scholar
14. Kondo, K, Kurland, LT, Schull, WJ. Parkinson’s disease. Genetic analysis and evidence of a multifactorial etiology. Mayo Clin Proc 1973; 48:465–475.Google ScholarPubMed
15. Maraganore, DM, Harding, AE, Marsden, CD. A clinical and genetic study of familial Parkinson’s disease. Mov Disord 1991; 6: 205–211.CrossRefGoogle ScholarPubMed
16. Lazzarini, AM, Myers, RH, Zimmerman, TR, et al. A clinical genetic study of Parkinson’s disease: evidence for dominant transmission. Neurology 1994; 44: 499–506.Google Scholar
17. Butterfield, PG, Valanis, BG, Spencer, PS, Lindeman, CA, Nutt, JG. Environmental antecedents of young-onset Parkinson’s disease. Neurology 1993; 43: 1150–1158.Google Scholar
18. Hubble, JP, Cao, T, Hassanein, RES, Neuberger, JS, Koller, WC. Risk factors for Parkinson’s disease. Neurology 1993; 43: 1693–1697.Google Scholar
19. Semchuk, KM, Love, EJ, Lee, RG. Parkinson’s disease: a test of the multifactorial etiologic hypothesis. Neurology 1993; 43: 1173–1180.CrossRefGoogle ScholarPubMed
20. Vogel, F, Motulsky, AG. Human Genetics – Problems and Approaches. Berlin: Springer-Verlag, 1986.CrossRefGoogle Scholar
21. Kaplan, EL, Meier, P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.Google Scholar
22. Chase, GA, Folstein, MF, Breitner, JCS, Beaty, TH, Self, SG. The use of life tables and survival analysis in testing genetic hypotheses, with an application to Alzheimer’s disease. Am J Epidemiol 1983; 117:590–597.CrossRefGoogle ScholarPubMed
23. Cupples, LA, Terrin, NC, Myers, RH, D’Agostino, RB. Using survival methods to estimate age-at-onset distributions for genetic diseases with an application to Huntington disease. Genet Epidemiol 1989; 6:361–371.Google Scholar
24. Cox, DR, Oakes, D. Analysis of survival data. London: Chapman & Hall, 1984.Google Scholar
25. Slater, E, Maxwell, J, Price, JS. Distribution of ancestral secondary cases in bipolar affective disorders. Br J Psychiat 1971: 118: 215–218.Google Scholar
26. Bonifati, V, Vanacore, N, Meco, G. Anticipation of onset age in familial Parkinson’s disease. Neurology 1994; 44: 1978–1979.Google Scholar
27. Marttila, RJ. Epidemiology. In: Koller, WC, ed. Handbook of Parkinson’s disease, 2nd Edition. New York: Marcel Dekker, 1992: 35–57.Google Scholar
28. Brooks, DJ, Playford, ED, Ibanez, V, et al. Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study. Neurology 1992; 42: 1554–1560.CrossRefGoogle ScholarPubMed
29. Gibb, WRG, Esiri, MM, Lees, AJ. Clinical and pathological features of diffuse cortical Lewy body disease (Lewy body dementia). Brain 1987; 110: 1131–1153.Google Scholar
30. Sage, JI, Miller, DC, Golbe, LI, Walters, A, Duvoisin, RC. Clinically atypical expression of pathologically typical Lewy-body parkinsonism. Clin Neuropharmacol 1990; 13: 36–47.Google Scholar
31. Mark, MH, Sage, JI, Dickson, DW, Schwarz, KO, Duvoisin, RC. Levodopa-nonresponsive Lewy body parkinsonism: clinicopathologic study of two cases. Neurology 1992; 42: 1323–1327.Google Scholar
32. Rajput, AH, Rozdilsky, B, Rajput, A. Accuracy of clinical diagnosis in parkinsonism – a prospective study. Can J Neurol Sci 1991; 18:275–278.Google Scholar
33. Payami, H, Larsen, K, Bernard, S, Nutt, J. Increased risk of Parkinson’s disease in parents and siblings of patients. Ann Neurol 1994; 36:659–661.Google Scholar
34. Bird, TD. Clinical genetics of familial Alzheimer disease. In: Terry, RD, Katzman, R, Bick, KL, eds. Alzheimer Disease. New York: Raven Press, 1994:65–74.Google Scholar
35. Campanella, G, Idone, M, de Michele, G, Filla, A. Paternal preponderance in familial Parkinson’s disease. Neurology 1984; 34: 1398–1399.Google Scholar
36. Zweig, RM, Singh, A, Cardillo, JE, Langston, JW. The familial occurrence of Parkinson’s disease. Lack of evidence for maternal inheritance. Arch Neurol 1992; 49: 1205–1207.Google Scholar
37. Young, WI, Martin, WE, Anderson, VE. The distribution of ancestral secondary cases in Parkinson’s disease. Clin Genet 1977; 11: 189–192.Google Scholar
38. Kahler, SG, Riley, E. Letter to the editors. Clin Genet 1979; 15: 110–111.Google Scholar
39. Haldane, JBS. The relative importance of principal and modifying genes in determining some human diseases. J Genet 1941; 41: 149–157.CrossRefGoogle Scholar
40. Golbe, LI, Di Iorio, G, Lazzarini, AM, Bonavita, V, Duvoisin, RC. A large kindred with Parkinson’s disease: onset age, segregation ratios, and anticipation [Abstract]. Mov Disord 1993: 8: 406.Google Scholar
41. Gusella, JF, MacDonald, ME, Ambrose, CM, Duyao, MP. Molecular genetics of Huntington’s disease. Arch Neurol 1993; 50: 1157–1163.Google Scholar
42. Wieringa, B. Commentary. Myotonic dystrophy reviewed: back to the future? Hum Mol Genet 1994; 3: 1–7.Google Scholar
43. La Spada, AR, Wilson, EM, Lubahn, DB, Harding, AE, Fischbeck, KH. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991; 352: 77–79.Google Scholar
44. Fu, Y-H, Kuhl, DPA, Pizzuti, A, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 1991; 67: 1047–1058.Google Scholar
45. Knight, SJL, Flannery, AV, Hirst, MC, et al. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell 1993; 74: 127–134.Google Scholar
46. Orr, HT, Chung, M, Banfi, S, et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nature Genet 1993; 4:221–226.Google Scholar
47. Koide, R, Ikeuchi, T, Onodera, O, et al. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nature Genet 1994; 6: 9–13.Google Scholar
48. Kawaguchi, Y, Okamoto, T, Taniwaki, M, et al. CAG expansion in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nature Genet 1994; 8: 221–228.Google Scholar