Predictive Genetic Testing: The Huntington Disease Model

Abstract

Predictive or presymptomatic genetic testing enables individuals at risk for a hereditary late‐onset disease to learn about their genetic status before symptoms have appeared. The predictive testing protocol for Huntington disease (HD) safeguards the interests of test candidates and has served as a model for other diseases. Most people seen for genetic counselling regarding HD are the asymptomatic children of an affected parent. Predictive testing provides the opportunity to get relief from the anguish of being at risk, to have prenatal tests or preimplantation genetic testing in order to have children free of the disorder, and to make informed plans for the future regarding marriage, education, professional career and finances. The common experience has been that tested individuals found relief from their prior psychological distress and that they benefited psychologically. Having children proved to be an additional stress factor for partners.

Key Concepts

  • Predictive testing provides the opportunity to get relief from uncertainty and prepare better for the future.
  • Preimplantation genetic testing enables couples to have a pregnancy without the burden of termination after an unfavourable prenatal test result.
  • At 55 years of age and being not symptomatic, there is still a 25% empirical chance of being a carrier of the Huntington's gene.
  • The Huntington disease CAG repeat length accounts for roughly 50–77% of the variation in the age of onset.
  • Predictive testing requires informed consent by the individual at risk and the provision of psychological support.
  • Predictive testing for adult‐onset disorders without treatment options should not be offered to children and adolescents.
  • Counselling test candidates at 25% risk to get Huntington disease requires a family system approach.
  • The predictive test candidate's beliefs about causation and emotional, social and cultural issues may affect the perception of the information that is given in genetic counselling.

Keywords: predictive; presymptomatic; prenatal; Huntington disease; risk estimation; exclusion testing; 25% risk; preimplantation genetic testing

Figure 1. Exclusion testing in Huntington disease (HD). In this family, the HD gene is associated with marker genotype H. Thus, if a person (or pregnancy) at 25% risk has also inherited genotype H (a), he/she will be at high risk of developing HD (50%, the same as for the intervening parent), whereas if a person has inherited genotype A (b), derived from the unaffected grandparent, the risk will be low.
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Further Reading

Almqvist EW, Bloch M, Brinkman R, Craufurd D and Hayden MR (1999) A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease. American Journal of Human Genetics 64 (5): 1293–1304.

Folstein SE (1991) Huntington Disease: A Disorder of Families. Baltimore, MD: The Johns Hopkins University Press.

Kay C, Fisher E and Hayden AR (2014) Epidemiology. In: Bates GP, Tabrizi SJ and Jones L (eds) Huntington's Disease, 4th edn, pp. 131–162. Oxford: Oxford University Press.

MacLeod R and Tibben A (2014) Genetic counseling and testing. In: Bates GP, Tabrizi SJ and Jones L (eds) Huntington's Disease, 4th edn, pp. 165–181. Oxford: Oxford University Press.

Marteau T and Richards M (eds) (1996) The Troubled Helix: Social and Psychological Implications of the New Human Genetics. Cambridge, UK: Cambridge University Press.

Web Links

Huntingtin (HTT); LocusID: 3064. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3064

Huntingtin (HTT); OMIM number: 143100. http://omim.org/entry/143100

http://en.hdyo.org/you

http://en.hdbuzz.net/

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How to Cite close
Tibben, Aad, and Bijlsma, Emilia(Aug 2016) Predictive Genetic Testing: The Huntington Disease Model. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005617.pub3]