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Record W4315630594 · doi:10.21203/rs.3.rs-2431750/v1

Classic “PCH” genes are a rare cause of radiologic pontocerebellar hypoplasia

2023· preprint· en· W4315630594 on OpenAlexaff
Rohaya Binti Mohamad Zakaria, Maísa Malta, Félixe Pelletier, Nassima Addour-Boudrahem, Elana Pinchefsky, Christine Saint Martin, Myriam Sr

Bibliographic record

VenueResearch Square · 2023
Typepreprint
Languageen
FieldMedicine
TopicFetal and Pediatric Neurological Disorders
Canadian institutionsUniversité de MontréalMcGill University Health CentreMcGill University
Fundersnot available
KeywordsEtiologyHypoplasiaCohortMedicineLissencephalyNeuroimagingPonsCerebellumMicrocephalyCerebellar hypoplasia (non-human)PediatricsPathologyAnatomyGeneticsBiologyInternal medicineGene

Abstract

fetched live from OpenAlex

Abstract Background: The term Pontocerebellar Hypoplasia (PCH) was initially used to designate a heterogeneous group of fetal-onset genetic neurodegenerative disorders. As a descriptive term, PCH refers to pons and cerebellum of reduced volume. In addition to the classic PCH types, many other disorders can result in a similar imaging appearance. Objective: To review imaging, clinical and genetic features and underlying etiologies of a cohort of children with PCH on imaging. Methods: We systematically reviewed brain images and clinical charts of 38 patients with radiologic evidence of PCH. Results: Our cohort included 21 males and 17 females, with ages ranging between 8 days to 15 years. All individuals had pons and cerebellar vermis hypoplasia, and 63% had cerebellar hemisphere hypoplasia. Supratentorial anomalies were found in 71%. An underlying etiology was identified in 65% and included chromosomal (21%), monogenic (34%) and acquired (10%) causes. Only one patient had pathogenic variants in a “classic” PCH gene. Outcomes were poor regardless of etiology, though no one had regression. Approximately one third of patients deceased at a median age of 8 months. All individuals had global developmental delay, 50% were non-verbal, 64% were non-ambulatory and 45% required gastrostomy feeding. Conclusion: Radiologic PCH has heterogenous etiologies and the “classic” PCH genes underlie only a minority of cases. Broad genetic testing, including chromosomal microarray and exome or multigene panels, is recommended in individuals with PCH-like imaging appearance. Our results strongly suggest that the term PCH should be used to designate radiologic findings, and not to imply neurogenerative disorders.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.167
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.182
GPT teacher head0.401
Teacher spread0.219 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2023
Admission routes1
Has abstractyes

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