Full Access
Very early onset Huntington's disease: genetic mechanism and risk to siblings
David J. Clarke,
Sarah Bundey,
Corresponding Author
David J. Clarke
Department of Psychiatry, Queen Elizabeth Hospital, and Department of Clinical Genetics, Birmingham Maternity Hospital, Birmingham, UK
Dept. of Psychiatry Queen Elizabeth Hospital Birmingham B15 2TH U.K.Search for more papers by this authorSarah Bundey
Department of Psychiatry, Queen Elizabeth Hospital, and Department of Clinical Genetics, Birmingham Maternity Hospital, Birmingham, UK
Search for more papers by this authorDavid J. Clarke,
Sarah Bundey,
Corresponding Author
David J. Clarke
Department of Psychiatry, Queen Elizabeth Hospital, and Department of Clinical Genetics, Birmingham Maternity Hospital, Birmingham, UK
Dept. of Psychiatry Queen Elizabeth Hospital Birmingham B15 2TH U.K.Search for more papers by this authorSarah Bundey
Department of Psychiatry, Queen Elizabeth Hospital, and Department of Clinical Genetics, Birmingham Maternity Hospital, Birmingham, UK
Search for more papers by this authorAbstract
A study of very early onset Huntington's disease (VEOHD) has shown that at least 38% of gene-carrying sibs also develop symptoms before the age of 10, thus improving the genetic risk for those sibs who remain healthy. The prevalence of VEOHD among sibs shows that mutation during spermatogenesis is most unlikely to account for these uncommon cases. The data suggest that two mechanisms contribute to VEOHD: modification by many genes (individually of small effect), and an epigenetic mechanism occurring when transmission is through a series of males.
References
- Barrows, H. S. & W. C. Cooper (1963). Rigidity as a disease form of Huntington's disease. Bull. Los Angeles Neurol. Soc. 28, 144–147.
- Bolt, J. M. W. (1970). Huntington's chorea in the west of Scotland. Br. J. Psychiatry 116, 259–270.
- Brackenridge, C. J. (1972). Familial correlations for age at onset and age at death in Huntington's disease. J. Med. Genet. 9, 23–32.
- Brackenridge, C. J. (1973). The relation of sex of affected parent to the age at onset of Huntington's disease. J. Med. Genet. 10, 333–336.
- Bruyn, G. W. (1968). Huntington's chorea. Historical, clinical and laboratory synopsis. In Handbook of Clinical Neurology (Vol. 6). P. J. Vinken & G. W. Bruyn (eds.). Amsterdam , North Holland Publishing, pp. 298–378.
- Byers, R. K. & J. A. Dodge (1967). Huntington's chorea in children: report of four cases. Neurology 17, 587–596.
- Byers, R. K., F. H. Gilles & C. Fung (1973). Huntington's disease in children: neuropathologic study of four cases. Neurology 23, 561–569.
- Carlier, G., M. Reznik, G. Franck & H. Husquinet (1974). Etude anatomo-clinique d'une form infantile de la maladie de Huntington. Acta Neurol. Belg. 74, 36–63.
- Cotton, J. B., J. L. Grenier, J. P. Ladreyt, P. Guibaud & C. Cuche (1975). La maladie de Huntington chez l'enfant: a propos d'une observation anatomo-clinique. Pédiatrie 30, 609–619.
- Dralle, D., G. Schock & G. Neuhäuser (1985). Die Chorea Huntington im Kindesalter. Klin. Pädiatrie 197, 90–93.
- Emery, A. E. H. (1986). Methodology in Medical Genetics, 2nd Edit. Edinburgh . Churchill Livingstone, pp. 93–113.
- Farrer, L. A. & P. M. Conneally (1985). A genetic model for age at onset in Huntington disease. Am. J. Hum. Genet. 37, 350–357.
- Farrer, L. A., P. M. Conneally & P. I. Yu (1984). The natural history of Huntington disease: possible role of “aging genes. Am. J. Med. Genet. 18, 115–123.
- Farrer, L. A., R. H. Myers, L. A. Cupples & P. M. Conneally (1988). Considerations in using linkage analysis as a presymptomatic test for Huntington's disease. J. Med. Genet. 25, 577–588.
- Green, J. B., E. S. Dickinson & J. R. Gunderman (1973). Epilepsy in Huntington's chorea: clinical and neurophysiological studies. Adv. Neurol. 1, 105–113.
- Haldane, J. B. S. (1941). The relative importance of principal and modifying genes in determining some human diseases. J. Genet. 41, 149–157.
- Hayden, M. R., J. A. Soles & R. H. Ward (1985). Age of onset in siblings of persons with juvenile Huntington disease. Clin. Genet. 28, 100–105.
- Jervis, G. A. (1963). Huntington's chorea in childhood. Arch. Neurol. 9, 244–257.
- Jongen, P. J. H., W. O. Renier & F. J. M. Gabreëls (1980). Seven cases of Huntington's disease in childhood and levodopa induced improvement in the hypokinetic-rigid form. Clin. Neurol. Neurosurg. 82, 251–261.
- Katafuchi, Y., T. Fujimoto, E. Ono & N. Kuda (1984). A childhood form of Huntington's disease associated with marked pyramidal signs. Eur. Neurol. 23, 296–299.
- Markham, C. H. & J. W. Knox (1965). Observations on Huntington's chorea in childhood. J. Pediatr. 67, 46–57.
- Myers, R. H., D. Goldman, E. D. Bird, D. S. Sax, C. R. Merrill, M. Schoenfield & P. A. Wolf (1983). Maternal transmission in Huntington's disease. Lancet i, 208–210.
- Newcombe, R. G. (1981). A life table for onset of Huntington's chorea. Ann. Hum. Genet. 45, 375–385.
- Oliver, J. & K. Dewhurst (1969). Childhood and adolescent forms of Huntington's disease. J. Neurol. Neurosurg. Psychiatry 32, 455–459.
- Osborne, J. P., P. Munson & D. Burman (1982). Huntington's chorea: report of 3 cases and review of the literature. Arch. Dis. Child. 57, 99–103.
-
Owensby, N. M. (1925). Huntington's chorea in a twin child: case report.
J. Nerv. Ment. Dis.
61, 466–470.
10.1097/00005053-192505000-00002 Google Scholar
- Pleydell, M. J. (1955). Huntington's chorea in Northamptonshire. Br. Med. J. 2, 889.
- Reik, W. (1988). Genomic imprinting: a possible mechanism for the parental origin effect in Huntington's chorea. J. Med. Genet. 25, 805–808.
- Ridley, R. M., C. D. Frith, T. J. Crow & P. M. Conneally (1988). Anticipation in Huntington's disease is inherited through the male line but may originate in the female. J. Med. Genet. 25, 589–595.
- Tridon, P. & M. Brahic (1985). Á propos d'une famille de chorée de Huntington. J. Génét. Hum. 33, 119–122.
- Tridon, P., M. Laxenaire, M. Weber & F. Labourgade (1964). Forme infantile de chorée de Huntington. Rev. Neurol. 110, 531–535.
- Van Dijk, J. G., E. A. Van Der Velde, R. A. C. Roos & G. W. Bruyn (1986). Juvenile Huntington disease. Hum. Genet. 73, 235–239.
- Wallace, D. C. (1979). Distortion of Mendelian segregation in Huntington's disease. Adv. Neurol. 23, 73–81.
- Westall, J. (1979). Young people and Huntington's chorea. Concern 32, 17–24.
Citing Literature
