Functional results and quality of life after joint preserving or sacrificing surgery in Charcot-Marie-Tooth foot deformities

Tejero, Sergio; Chans-Veres, Juan; Carranza-Bencano, Andrés; Galhoum, Ahmed E; Poggio, Daniel; Valderrábano, Víctor; Herrera-Pérez, Mario

doi:10.1007/s00264-021-04978-7

Cited by 6 publications

(1 citation statement)

References 26 publications

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“…How surgical procedures on the feet of CMT patients affect outcomes is complicated. While some experts argue that surgery has an effect on the MRC scale for foot dorsiflexion strength, specifically in cases of ankle arthrodesis, studies have shown that foot surgery does not have an effect on the CMTES and CMTPedS foot dorsiflexion 51–54 . Because we wish to enrich the differences in mild and severe phenotypes from genetic modifiers, not environmentally acquired changes, we chose to exclude patients who had prior foot surgery.…”

Section: Discussionmentioning

confidence: 99%

A study concept of expeditious clinical enrollment for genetic modifier studies in Charcot–Marie–Tooth neuropathy 1A

Xu,

Danzi,

Ruiz

et al. 2024

J Peripheral Nervous Sys

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BackgroundCaused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot–Marie–Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets. In this study, we present a comprehensive analysis of clinical examination results from 1564 CMT1A patients sourced from a prospective natural history study conducted by the RDCRN‐INC (Inherited Neuropathy Consortium). Our primary objective is to delineate extreme phenotype profiles (mild and severe) within this patient cohort, thereby enhancing our ability to detect genetic modifiers with large effects.MethodsWe have conducted large‐scale statistical analyses of the RDCRN‐INC database to characterize CMT1A severity across multiple metrics.ResultsWe defined patients below the 10th (mild) and above the 90th (severe) percentiles of age‐normalized disease severity based on the CMT Examination Score V2 and foot dorsiflexion strength (MRC scale). Based on extreme phenotype categories, we defined a statistically justified recruitment strategy, which we propose to use in future modifier studies.InterpretationLeveraging whole genome sequencing with base pair resolution, a future genetic modifier evaluation will include single nucleotide association, gene burden tests, and structural variant analysis. The present work not only provides insight into the severity and course of CMT1A, but also elucidates the statistical foundation and practical considerations for a cost‐efficient and straightforward patient enrollment strategy that we intend to conduct on additional patients recruited globally.

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Section: Discussionmentioning

confidence: 99%