92 To know or not to know: A case of CADASIL highlighting the ethical dilemmas of genetic testing among families carrying a highly heritable neurological condition
Bibliographic record
Abstract
Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of cerebral small vessel disease leading to early cerebrovascular changes. These changes result from mutations in the NOTCH3 gene that cause progressive accumulations of granular osmiophilic material (GOM) deposits, thickening arterial walls and reducing or restricting blood flow in the brain. The clinical presentation of CADASIL is characterized by migraines with aura, early and recurrent strokes, progressive cognitive impairment, and psychiatric disturbances. CADASIL is rare but frequently underrecognized or misdiagnosed. A genetic condition with a 50% risk of inheritance from an affected parent, the gold standard for diagnosis is genetic testing to determine the presence of mutations in the NOTCH3 gene. This presentation aims to familiarize neuropsychologists with the condition of CADASIL through a unique case study highlighting important psychological, social, and ethical considerations raised by genetic testing. Participants and Methods: This case study presents a 67-year-old, right-handed, married female diagnosed with CADASIL who was referred for neuropsychological evaluation of cognitive function and low mood concerns following multiple ischemic events. Results: Results revealed severe cognitive deficits in domains of attention, learning, and memory. Her superior verbal abilities and executive function remained largely intact. Assessment of mood revealed elevations in symptoms of depression and anxiety. The patient was aware of CADASIL in her father, paternal aunt, and younger brother, but elected to forego any genetic testing to confirm whether she had the condition until she experienced a stroke at age 61. She has two adult children who have also elected to forego testing and currently remain asymptomatic. Cognitive profile, mood disturbances, and patient perspectives on refraining from pre-symptomatic genetic testing for CADASIL diagnosis will be discussed. Conclusions: Aspects of this case are consistent with a small body of literature evidencing distinct psychological, emotional, and social challenges among families carrying genetic risk of CADASIL. While providing an example of an often underrecognized neurological disorder with which neuropsychologists should be familiar, this case uniquely raises ethical questions relevant to care providers and current treatment guidelines regarding genetic testing among families carrying highly heritable neurological conditions. In particular, personal ethical challenges around deciding to pursue or forego pre-symptomatic testing, and implications for family planning, highlight the importance of genetic counseling for affected families.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.005 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".