Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers: An International Questionnaire Study

Stacha F.I. Reumers; Frederik Braun; Jennifer E. Spillane; Johann Böhm; Maartje Pennings; Meyke Schouten; Anneke J. van der Kooi; A. Reghan Foley; Carsten G. Bönnemann; Erik Jan Kamsteeg; Corrie E. Erasmus; Ulrike Schara-Schmidt; Heinz Jungbluth; Nicol C. Voermans

doi:10.1212/WNL.0000000000012236

Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers: An International Questionnaire Study

Stacha F.I. Reumers, Frederik Braun, Jennifer E. Spillane, Johann Böhm, Maartje Pennings, Meyke Schouten, Anneke J. van der Kooi, A. Reghan Foley, Carsten G. Bönnemann, Erik Jan Kamsteeg, Corrie E. Erasmus, Ulrike Schara-Schmidt, Heinz Jungbluth, Nicol C. Voermans

Randall Centre of Cell & Molecular Biophysics

Donders Institute for Brain, Cognition and Behaviour

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

OBJECTIVE: To characterize the spectrum of clinical features in a cohort of X-linked myotubular myopathy (XL-MTM) carriers, including prevalence, genetic features, clinical symptoms, and signs, as well as associated disease burden. METHODS: We performed a cross-sectional online questionnaire study among XL-MTM carriers. Participants were recruited from patient associations, medical centers, and registries in the United Kingdom, Germany, and the Netherlands. We used a custom-made questionnaire, the Checklist Individual Strength (CIS), the Frenchay Activities Index (FAI), the Short Form 12 (SF-12) health survey, and the McGill Pain Questionnaire. Carriers were classified as manifesting or nonmanifesting on the basis of self-reported ambulation and muscle weakness. RESULTS: The prevalence of manifesting carriers in this study population (n = 76) was 51%, subdivided into mild (independent ambulation, 39%), moderate (assisted ambulation, 9%), and severe (wheelchair dependent, 3%) phenotypes. In addition to muscle weakness, manifesting carriers frequently reported fatigue (70%) and exercise intolerance (49%). Manifesting carriers scored higher on the overall CIS (p = 0.001), the fatigue subscale (p < 0.001), and least severe pain subscale (p = 0.005) than nonmanifesting carriers. They scored lower on the FAI (p = 0.005) and the physical component of the SF-12 health survey (p < 0.001). CONCLUSIONS: The prevalence of manifesting XL-MTM carriers may be higher than currently assumed, most having a mild phenotype and a wide variety of symptoms. Manifesting carriers are particularly affected by fatigue, limitations of daily activities, pain, and reduced quality of life. Our findings should increase awareness and provide useful information for health care providers and future clinical trials.

Original language	English
Pages (from-to)	e501-e512
Journal	Neurology
Volume	97
Issue number	5
DOIs	https://doi.org/10.1212/WNL.0000000000012236
Publication status	Published - 3 Aug 2021

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Reumers, S. F. I., Braun, F., Spillane, J. E., Böhm, J., Pennings, M., Schouten, M., van der Kooi, A. J., Foley, A. R., Bönnemann, C. G., Kamsteeg, E. J., Erasmus, C. E., Schara-Schmidt, U., Jungbluth, H., & Voermans, N. C. (2021). Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers: An International Questionnaire Study. Neurology, 97(5), e501-e512. https://doi.org/10.1212/WNL.0000000000012236

@article{4e22aadacb494c12b4e3a5c8475365fe,

title = "Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers: An International Questionnaire Study",

abstract = "OBJECTIVE: To characterize the spectrum of clinical features in a cohort of X-linked myotubular myopathy (XL-MTM) carriers, including prevalence, genetic features, clinical symptoms, and signs, as well as associated disease burden. METHODS: We performed a cross-sectional online questionnaire study among XL-MTM carriers. Participants were recruited from patient associations, medical centers, and registries in the United Kingdom, Germany, and the Netherlands. We used a custom-made questionnaire, the Checklist Individual Strength (CIS), the Frenchay Activities Index (FAI), the Short Form 12 (SF-12) health survey, and the McGill Pain Questionnaire. Carriers were classified as manifesting or nonmanifesting on the basis of self-reported ambulation and muscle weakness. RESULTS: The prevalence of manifesting carriers in this study population (n = 76) was 51%, subdivided into mild (independent ambulation, 39%), moderate (assisted ambulation, 9%), and severe (wheelchair dependent, 3%) phenotypes. In addition to muscle weakness, manifesting carriers frequently reported fatigue (70%) and exercise intolerance (49%). Manifesting carriers scored higher on the overall CIS (p = 0.001), the fatigue subscale (p < 0.001), and least severe pain subscale (p = 0.005) than nonmanifesting carriers. They scored lower on the FAI (p = 0.005) and the physical component of the SF-12 health survey (p < 0.001). CONCLUSIONS: The prevalence of manifesting XL-MTM carriers may be higher than currently assumed, most having a mild phenotype and a wide variety of symptoms. Manifesting carriers are particularly affected by fatigue, limitations of daily activities, pain, and reduced quality of life. Our findings should increase awareness and provide useful information for health care providers and future clinical trials.",

author = "Reumers, {Stacha F.I.} and Frederik Braun and Spillane, {Jennifer E.} and Johann B{\"o}hm and Maartje Pennings and Meyke Schouten and {van der Kooi}, {Anneke J.} and Foley, {A. Reghan} and B{\"o}nnemann, {Carsten G.} and Kamsteeg, {Erik Jan} and Erasmus, {Corrie E.} and Ulrike Schara-Schmidt and Heinz Jungbluth and Voermans, {Nicol C.}",

note = "Publisher Copyright: {\textcopyright} 2021 American Academy of Neurology. Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine",

year = "2021",

month = aug,

day = "3",

doi = "10.1212/WNL.0000000000012236",

language = "English",

volume = "97",

pages = "e501--e512",

journal = "Neurology",

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Reumers, SFI, Braun, F, Spillane, JE, Böhm, J, Pennings, M, Schouten, M, van der Kooi, AJ, Foley, AR, Bönnemann, CG, Kamsteeg, EJ, Erasmus, CE, Schara-Schmidt, U, Jungbluth, H & Voermans, NC 2021, 'Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers: An International Questionnaire Study', Neurology, vol. 97, no. 5, pp. e501-e512. https://doi.org/10.1212/WNL.0000000000012236

TY - JOUR

T1 - Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers

T2 - An International Questionnaire Study

AU - Reumers, Stacha F.I.

AU - Braun, Frederik

AU - Spillane, Jennifer E.

AU - Böhm, Johann

AU - Pennings, Maartje

AU - Schouten, Meyke

AU - van der Kooi, Anneke J.

AU - Foley, A. Reghan

AU - Bönnemann, Carsten G.

AU - Kamsteeg, Erik Jan

AU - Erasmus, Corrie E.

AU - Schara-Schmidt, Ulrike

AU - Jungbluth, Heinz

AU - Voermans, Nicol C.

PY - 2021/8/3

Y1 - 2021/8/3

N2 - OBJECTIVE: To characterize the spectrum of clinical features in a cohort of X-linked myotubular myopathy (XL-MTM) carriers, including prevalence, genetic features, clinical symptoms, and signs, as well as associated disease burden. METHODS: We performed a cross-sectional online questionnaire study among XL-MTM carriers. Participants were recruited from patient associations, medical centers, and registries in the United Kingdom, Germany, and the Netherlands. We used a custom-made questionnaire, the Checklist Individual Strength (CIS), the Frenchay Activities Index (FAI), the Short Form 12 (SF-12) health survey, and the McGill Pain Questionnaire. Carriers were classified as manifesting or nonmanifesting on the basis of self-reported ambulation and muscle weakness. RESULTS: The prevalence of manifesting carriers in this study population (n = 76) was 51%, subdivided into mild (independent ambulation, 39%), moderate (assisted ambulation, 9%), and severe (wheelchair dependent, 3%) phenotypes. In addition to muscle weakness, manifesting carriers frequently reported fatigue (70%) and exercise intolerance (49%). Manifesting carriers scored higher on the overall CIS (p = 0.001), the fatigue subscale (p < 0.001), and least severe pain subscale (p = 0.005) than nonmanifesting carriers. They scored lower on the FAI (p = 0.005) and the physical component of the SF-12 health survey (p < 0.001). CONCLUSIONS: The prevalence of manifesting XL-MTM carriers may be higher than currently assumed, most having a mild phenotype and a wide variety of symptoms. Manifesting carriers are particularly affected by fatigue, limitations of daily activities, pain, and reduced quality of life. Our findings should increase awareness and provide useful information for health care providers and future clinical trials.

AB - OBJECTIVE: To characterize the spectrum of clinical features in a cohort of X-linked myotubular myopathy (XL-MTM) carriers, including prevalence, genetic features, clinical symptoms, and signs, as well as associated disease burden. METHODS: We performed a cross-sectional online questionnaire study among XL-MTM carriers. Participants were recruited from patient associations, medical centers, and registries in the United Kingdom, Germany, and the Netherlands. We used a custom-made questionnaire, the Checklist Individual Strength (CIS), the Frenchay Activities Index (FAI), the Short Form 12 (SF-12) health survey, and the McGill Pain Questionnaire. Carriers were classified as manifesting or nonmanifesting on the basis of self-reported ambulation and muscle weakness. RESULTS: The prevalence of manifesting carriers in this study population (n = 76) was 51%, subdivided into mild (independent ambulation, 39%), moderate (assisted ambulation, 9%), and severe (wheelchair dependent, 3%) phenotypes. In addition to muscle weakness, manifesting carriers frequently reported fatigue (70%) and exercise intolerance (49%). Manifesting carriers scored higher on the overall CIS (p = 0.001), the fatigue subscale (p < 0.001), and least severe pain subscale (p = 0.005) than nonmanifesting carriers. They scored lower on the FAI (p = 0.005) and the physical component of the SF-12 health survey (p < 0.001). CONCLUSIONS: The prevalence of manifesting XL-MTM carriers may be higher than currently assumed, most having a mild phenotype and a wide variety of symptoms. Manifesting carriers are particularly affected by fatigue, limitations of daily activities, pain, and reduced quality of life. Our findings should increase awareness and provide useful information for health care providers and future clinical trials.

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U2 - 10.1212/WNL.0000000000012236

DO - 10.1212/WNL.0000000000012236

M3 - Article

C2 - 34011573

AN - SCOPUS:85113713216

SN - 0028-3878

VL - 97

SP - e501-e512

JO - Neurology

JF - Neurology

IS - 5

ER -

Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers: An International Questionnaire Study

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