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Presymptomatic genetic testing in CADASIL
1Department of Neurology and CERVCO, GH Saint-Louis-Lariboisière-Fernand Widal, APHP et Université Paris, 7 Denis Diderot, Paris, France.
Insights
Presymptomatic genetic testing for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is rarely sought and has a high dropout rate. A multidisciplinary approach minimizes negative impacts for those completing the genetic counseling process.
Area of Science:
- Neurology
- Genetics
- Rare Diseases
Background:
- Genetic counseling for cerebrovascular diseases remains under-researched.
- Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic cerebrovascular disorder.
- Understanding the characteristics and outcomes of presymptomatic testing (PT) for CADASIL is crucial.
Purpose of the Study:
- To investigate the characteristics, motivations, and long-term outcomes of presymptomatic genetic testing (PT) in individuals at risk for CADASIL.
- To evaluate the effectiveness of a multidisciplinary genetic counseling approach for CADASIL.
- To assess the psychological and quality of life impacts of PT in CADASIL carriers.
Main Methods:
- A 7-year prospective study at a national center for rare vascular diseases.
- Recruitment of subjects seeking PT for CADASIL, collecting sociodemographic, motivational, and psychological data.
- A 6-month multidisciplinary consultation process involving geneticists, neurologists, and psychologists.
- Assessment of cognitive performance, mood, autonomy, and quality of life for mutation carriers.
Main Results:
- Only 33 subjects applied for PT for CADASIL over 7 years, with a 63% dropout rate after the initial step.
- Subjects seeking PT were predominantly women, partnered, had children, and were of high sociocultural background.
- Six carriers of the NOTCH3 mutation were identified, remained asymptomatic with a high quality of life after a mean follow-up of 19 months.
- No significant negative events were reported by carriers, and two had children post-testing.
Conclusions:
- Presymptomatic genetic testing for CADASIL is infrequently requested and experiences a high dropout rate.
- A structured, multidisciplinary, and multistep genetic counseling process appears effective in mitigating adverse psychological consequences.
- The study provides initial insights into the utility and impact of genetic counseling for CADASIL, suggesting potential benefits for well-selected individuals.
Abstract:
Genetic counselling has been poorly investigated in cerebrovascular diseases. Characteristics, motivations and long-term outcome of presymptomatic tests (PT) in subjects at risk of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) were investigated at the National Centre for Rare Vascular Diseases of the Brain and/or Retina (CERVCO). Sociodemographic, motivational and psychological variables were collected between 2003 and 2010 for PT applicants. Multidisciplinary consultations (with a geneticist, neurologist and psychologist) were proposed over a 6 month period. When PT showed a deleterious mutation of the NOTCH3 gene, cognitive performances, mood, autonomy and quality of life were also assessed. Over 7 years, only 33 subjects asked for a PT of CADASIL. They were predominantly women, lived as a couple, had children and were of high sociocultural level. The dropout rate after the first step of the procedure was 63%. The characteristics of the 11 subjects who reached the end of the procedure did not differ from the 22 who dropped out. Six were carriers of the deleterious mutation and were still asymptomatic after a mean follow-up of 19 months. They did not experience any particular negative event and all of them indicated a high score of overall quality of life. Indeed, two carriers gave birth to their first child. These initial data in CADASIL show that PT is rarely requested and that there is a high dropout rate. Our study also highlights that a multidisciplinary and multistep procedure in genetic counselling testing appears useful to obtain minimal harmful consequences of genetic testing.
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