domingo, 7 de septiembre de 2014

Diagnostic genetic testing for Huntington's disease -- Craufurd et al. -- Practical Neurology

Diagnostic genetic testing for Huntington's disease -- Craufurd et al. -- Practical Neurology

Pract Neurol doi:10.1136/practneurol-2013-000790
  • How to do it

Diagnostic genetic testing for Huntington's disease

  1. Raymund A Roos13 
  2. on behalf of the Working Group on Genetic Counselling and Testing of the European Huntington's Disease Network (EHDN)
+Author Affiliations
  1. 1Faculty of Medicine and Human SciencesInstitute of Human Development, University of Manchester and Manchester Academic Health Science CentreManchester, UK
  2. 2Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation TrustManchester, UK
  3. 3Instituto di Farmacologia Traslazionale del CNRRome, Italy
  4. 4Department of Clinical GeneticsSheffield Children's HospitalSheffield, UK
  5. 5Centre for Human and Clinical Genetics, Leiden University Medical Centre (LUMC)Leiden, The Netherlands
  6. 6Neurogenetics Unit, Institute of NeurologyLondon, UK
  7. 7Memory Disorders Research Group, Section of Neurogenetics, Department of NeurologyRigshospitaletCopenhagen University HospitalCopenhagen
  8. 8Department of Cellular and Molecular Medicine, Section of NeurogeneticsPanum Institute, University of CopenhagenCopenhagen, Denmark
  9. 9NE Thames Regional Genetics ServiceGreat Ormond Street HospitalLondon, UK
  10. 10Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI)University of GenoaGenoa, Italy
  11. 11UO of Medical Genetics, IRCCS AOU San Martino of GenovaGenoa, Italy
  12. 12Neurological DepartmentFundación Jiménez DíazMadrid, Spain
  13. 13Department of NeurologyLeiden University Medical Centre (LUMC)Leiden, The Netherlands
  1. Correspondence toDr D Craufurd, Manchester Centre for Genomic Medicine, St. Mary's Hospital, Oxford Road, Manchester M13 9WL, UK;
  • Accepted 2 August 2014
  • Published Online First 28 August 2014


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.

No hay comentarios:

Publicar un comentario