Progressive Myoclonus Epilepsy Caused by SACS Mutations (P5.158)
Bibliographic record
Abstract
OBJECTIVE and BACKGROUND: Mutations in SACS are classically known to cause autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Recently, two patients clinically diagnosed with progressive myoclonus epilepsy (PME) were found to have probably pathogenic SACS mutations. In this report, we provide a detailed description of one of these cases of PME due to mutations in SACS. METHODS: Case report. RESULTS: The patient is a 25-year-old female who was born to healthy, non-consanguineous parents. Psychomotor development and cognition were normal, except for a mild learning difficulty. At the age of 13 years, she began to experience spontaneous and stimulus-induced myoclonic jerks. Two years later she had her first secondarily generalized convulsive seizure. Over the years, she also presented absence, dyscognitive, atonic, and tonic seizures, as well as photosensitivity. Seizures then became pharmacoresistant, and cognitive function significantly deteriorated. Additionally, she developed exotropia, bilateral dysmetria, dysarthria, and cerebellar ataxia. The latter, in association with her severe action myoclonus, resulted in this patient being wheelchair bound. Further, she had hypertonia and hyperactive reflexes in her lower extremities, bilateral extensor plantar reflex. EEG studies showed bihemispheric slow wave background activity with multifocal interictal epileptiform discharges. Brain MRI revealed diffuse cerebral, cerebellar, and corpus callosum atrophy. Based on the aforementioned evidence, she was clinically diagnosed with PME. Genetic testing as well and skin and muscle biopsies were undertaken to investigate the most frequent causes of PME, including mitochondrial diseases, and these investigations were all normal. She finally underwent whole-exome sequencing, which revealed two rare compound heterozygous missense variants in SACS: c.1373C>T (p.Thr458Ile) and c.8393C>A (p.Pro2798Gln). Both variants were felt to be probably pathogenic and responsible for the patient’s phenotype. Notably, the variants had been previously reported in patients with ARSACS. CONCLUSIONS: In conclusion, we describe a patient with PME caused by alterations in the SACS gene.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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 teacher head, 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".