Article Text

other Versions

Diagnostic genetic testing for Huntington's disease
  1. David Craufurd1,2,
  2. Rhona MacLeod1,2,
  3. Marina Frontali3,
  4. Oliver Quarrell4,
  5. Emilia K Bijlsma5,
  6. Mary Davis6,
  7. Lena Elisabeth Hjermind7,8,
  8. Nayana Lahiri9,
  9. Paola Mandich10,11,
  10. Asunción Martinez12,
  11. Aad Tibben5,
  12. Raymund A Roos13
  13. on behalf of the Working Group on Genetic Counselling and Testing of the European Huntington's Disease Network (EHDN)
  1. 1Faculty of Medicine and Human Sciences, Institute of Human Development, University of Manchester and Manchester Academic Health Science Centre, Manchester, UK
  2. 2Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  3. 3Instituto di Farmacologia Traslazionale del CNR, Rome, Italy
  4. 4Department of Clinical Genetics, Sheffield Children's Hospital, Sheffield, UK
  5. 5Centre for Human and Clinical Genetics, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
  6. 6Neurogenetics Unit, Institute of Neurology, London, UK
  7. 7Memory Disorders Research Group, Section of Neurogenetics, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen
  8. 8Department of Cellular and Molecular Medicine, Section of Neurogenetics, Panum Institute, University of Copenhagen, Copenhagen, Denmark
  9. 9NE Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK
  10. 10Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), University of Genoa, Genoa, Italy
  11. 11UO of Medical Genetics, IRCCS AOU San Martino of Genova, Genoa, Italy
  12. 12Neurological Department, Fundación Jiménez Díaz, Madrid, Spain
  13. 13Department of Neurology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
  1. Correspondence to Dr D Craufurd, Manchester Centre for Genomic Medicine, St. Mary's Hospital, Oxford Road, Manchester M13 9WL, UK; david.craufurd{at}

Statistics from


Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by a combination of motor abnormalities (chorea, dystonia, hypokinesia), cognitive impairment and neuropsychiatric symptoms, including depression, irritability and apathy. The age at onset is typically 35–45 years but it can present in juveniles and the elderly.1 The disease slowly progresses over 15–20 years.1 It is inherited as an autosomal dominant trait, with each child of an affected parent having a 50% risk of carrying the gene mutation and therefore of developing HD themselves. The cause is a CAG trinucleotide expansion mutation in the HTT gene that encodes the ubiquitously expressed huntingtin protein. Genetic testing by direct mutation analysis has been available clinically since the mutation was identified in 1993.2 Measurement of the CAG repeat length acts as a trait marker rather than a state marker; that is, the genetic test can be used either to confirm a clinical diagnosis of HD in symptomatic people or to predict whether or not an at-risk person will go on to develop HD. An abnormal result indicates that the person will one day develop HD, but gives no indication of his or her clinical state at the time of testing.

The pretest counselling requirements differ for diagnostic and presymptomatic (predictive) testing. The variety and complexity of clinical situations where diagnostic genetic testing for HD may be indicated make it impractical to construct guidelines such as those governing predictive testing.3 ,4 The purpose of this article is to draw the attention of neurologists and psychiatrists to the challenges and pitfalls encountered in diagnostic testing for HD. We make the following recommendations to guide practice and help ensure the best possible outcome for individuals and their family.

A diagnostic genetic test is carried out where an individual is already symptomatic. According to current convention, …

View Full Text

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Editors' commentary
    Phil Smith Geraint Fuller