Inherited neuropathies with predominant upper limb involvement: genetic heterogeneity and overlapping pathologies
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: In a subset of patients with inherited peripheral neuropathies the first symptom is atrophy and weakness of the intrinsic muscles of the hands, without involvement of lower limbs until later in the disease course. The exact pathomechanisms of this phenotype are currently unknown. The aim of this study was to characterize the clinical, neurophysiological and genetic features of a group of patients with a clinical diagnosis of upper limb predominant Charcot-Marie-Tooth disease (CMT). METHODS: The clinical, electrophysiology and genetic data of 11 patients with upper limb predominant peripheral neuropathy selected from a single-centre cohort of 461 patients diagnosed with inherited neuropathy were analysed and the clinical, electrophysiological and genetic characteristics of these patients reported. RESULTS: An overlapping phenotype of neuropathy and myopathy was detected in two patients. Four patients carry autosomal dominant mutations in GARS and a single patient had a homozygous mutation in SH3TC2. However, the underlying genetic diagnosis could not be confirmed in six patients by gene panel sequencing. CONCLUSIONS: Upper limb-onset inherited neuropathies are genetically heterogeneous and, in some cases, there is an overlapping myopathy. Autosomal dominant GARS mutations are the most common genetic cause; however, mutations in other CMT genes may also result in this phenotype in individual patients. The majority of these patients cannot be genetically diagnosed by gene panel testing of known CMT and myopathy genes, suggesting further genetic heterogeneity and highlighting the importance of further genetic investigations in these patients and families.
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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 | 0.002 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".