Article Text

other Versions

PDF
Review
Genetic counselling in ALS: facts, uncertainties and clinical suggestions
  1. Adriano Chiò1,
  2. Stefania Battistini2,
  3. Andrea Calvo1,
  4. Claudia Caponnetto3,
  5. Francesca L Conforti4,
  6. Massimo Corbo5,
  7. Fabio Giannini2,
  8. Jessica Mandrioli6,
  9. Gabriele Mora7,
  10. Mario Sabatelli8,
  11. the ITALSGEN Consortium,,
  12. Clara Ajmone5,
  13. Enza Mastro1,
  14. Debora Pain7,
  15. Paola Mandich3,
  16. Silvana Penco9,
  17. Gabriella Restagno10,
  18. Marcella Zollino11,
  19. Antonella Surbone12
  1. 1Department of Neuroscience, ALS Center, ‘Rita Levi Montalcini’, University of Torino, Torino, and Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy
  2. 2Department of Neuroscience, Section of Neurology, University of Siena, Siena, Italy
  3. 3Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal-Pediatric Sciences (DINOGMI), University of Genova Italy, Genova, Italy
  4. 4Institute of Neurological Sciences, National Research Council, Cosenza, Italy
  5. 5Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milano, Italy
  6. 6Department of Neuroscience, Sant'Agostino-Estense Hospital, University of Modena, Modena, Italy
  7. 7ALS Center, Salvatore Maugeri Foundation IRCSS, Scientific Institute of Milan, Milan, Italy
  8. 8Neurological Institute, Catholic University and I.CO.M.M. Association for ALS Research, Rome, Italy
  9. 9Department of Laboratory Medicine, Medical Genetics, Niguarda Ca’ Granda Hospital, Milano, Italy
  10. 10Molecular Genetics Unit, Department of Clinical Pathology, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy
  11. 11Molecular Genetics Laboratory, Department of Laboratory Medicine, Catholic University of Rome, Rome, Italy
  12. 12Department of Medicine, New York University, New York, USA
  1. Correspondence to Professor Adriano Chiò, Department of Neuroscience, Turin ALS Expert Center, ‘Rita Levi Montalcini’ University of Turin, Via Cherasco 15, Torino I-10126, Italy; achio{at}usa.net

Abstract

The clinical approach to patients with amyotrophic lateral sclerosis (ALS) has been largely modified by the identification of novel genes, the detection of gene mutations in apparently sporadic patients, and the discovery of the strict genetic and clinical relation between ALS and frontotemporal dementia (FTD). As a consequence, clinicians are increasingly facing the dilemma on how to handle genetic counselling and testing both for ALS patients and their relatives. On the basis of existing literature on genetics of ALS and of other late-onset life-threatening disorders, we propose clinical suggestions to enable neurologists to provide optimal clinical and genetic counselling to patients and families. Genetic testing should be offered to ALS patients who have a first-degree or second-degree relative with ALS, FTD or both, and should be discussed with, but not offered to, all other ALS patients, with special emphasis on its major uncertainties. Presently, genetic testing should not be proposed to asymptomatic at-risk subjects, unless they request it or are enrolled in research programmes. Genetic counselling in ALS should take into account the uncertainties about the pathogenicity and penetrance of some genetic mutations; the possible presence of mutations of different genes in the same individual; the poor genotypic/phenotypic correlation in most ALS genes; and the phenotypic pleiotropy of some genes. Though psychological, social and ethical implications of genetic testing are still relatively unexplored in ALS, we recommend multidisciplinary counselling that addresses all relevant issues, including disclosure of tests results to family members and the risk for genetic discrimination.

  • ALS
  • Genetics

Statistics from Altmetric.com

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