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SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness

BACKGROUND: SELENON(SEPN1)-related myopathy (SELENON-RM) is a rare congenital neuromuscular disease characterized by proximal and axial muscle weakness, spinal rigidity, scoliosis and respiratory impairment. No curative treatment options exist, but promising preclinical studies are ongoing. Currentl...

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Autores principales: Bouman, Karlijn, Groothuis, Jan T., Doorduin, Jonne, van Alfen, Nens, Udink ten Cate, Floris E.A., van den Heuvel, Frederik M.A., Nijveldt, Robin, Kamsteeg, Erik-Jan, Dittrich, Anne T.M., Draaisma, Jos M.T., Janssen, Mirian C.H., van Engelen, Baziel G.M., Erasmus, Corrie E., Voermans, Nicol C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10657684/
https://www.ncbi.nlm.nih.gov/pubmed/37807786
http://dx.doi.org/10.3233/JND-221673
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author Bouman, Karlijn
Groothuis, Jan T.
Doorduin, Jonne
van Alfen, Nens
Udink ten Cate, Floris E.A.
van den Heuvel, Frederik M.A.
Nijveldt, Robin
Kamsteeg, Erik-Jan
Dittrich, Anne T.M.
Draaisma, Jos M.T.
Janssen, Mirian C.H.
van Engelen, Baziel G.M.
Erasmus, Corrie E.
Voermans, Nicol C.
author_facet Bouman, Karlijn
Groothuis, Jan T.
Doorduin, Jonne
van Alfen, Nens
Udink ten Cate, Floris E.A.
van den Heuvel, Frederik M.A.
Nijveldt, Robin
Kamsteeg, Erik-Jan
Dittrich, Anne T.M.
Draaisma, Jos M.T.
Janssen, Mirian C.H.
van Engelen, Baziel G.M.
Erasmus, Corrie E.
Voermans, Nicol C.
author_sort Bouman, Karlijn
collection PubMed
description BACKGROUND: SELENON(SEPN1)-related myopathy (SELENON-RM) is a rare congenital neuromuscular disease characterized by proximal and axial muscle weakness, spinal rigidity, scoliosis and respiratory impairment. No curative treatment options exist, but promising preclinical studies are ongoing. Currently, natural history data are lacking, while selection of appropriate clinical and functional outcome measures is needed to reach trial readiness. OBJECTIVE: We aim to identify all Dutch and Dutch-speaking Belgian SELENON-RM patients, deep clinical phenotyping, trial readiness and optimization of clinical care. METHODS: This cross-sectional, single-center, observational study comprised neurological examination, functional measurements including Motor Function Measurement 20/32 (MFM-20/32) and accelerometry, questionnaires, muscle ultrasound, respiratory function tests, electro- and echocardiography, and dual-energy X-ray absorptiometry. RESULTS: Eleven patients with genetically confirmed SELENON-RM were included (20±13 (3–42) years, 73% male). Axial and proximal muscle weakness were most pronounced. The mean MFM-20/32 score was 71.2±15.1%, with domain 1 (standing and transfers) being most severely affected. Accelerometry showed a strong correlation with MFM-20/32. Questionnaires revealed impaired quality of life, pain and problematic fatigue. Muscle ultrasound showed symmetrically increased echogenicity in all muscles. Respiratory function, and particularly diaphragm function, was impaired in all patients, irrespective of the age. Cardiac assessment showed normal left ventricular systolic function in all patients but abnormal left ventricular global longitudinal strain in 43% of patients and QRS fragmentation in 80%. Further, 80% of patients showed decreased bone mineral density on dual-energy X-ray absorptiometry scan and 55% of patients retrospectively experienced fragility long bone fractures. CONCLUSIONS: We recommend cardiorespiratory follow-up as a part of routine clinical care in all patients. Furthermore, we advise vitamin D supplementation and optimization of calcium intake to improve bone quality. We recommend management interventions to reduce pain and fatigue. For future clinical trials, we propose MFM-20/32, accelerometry and muscle ultrasound to capture disease severity and possibly disease progression.
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spelling pubmed-106576842023-11-19 SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness Bouman, Karlijn Groothuis, Jan T. Doorduin, Jonne van Alfen, Nens Udink ten Cate, Floris E.A. van den Heuvel, Frederik M.A. Nijveldt, Robin Kamsteeg, Erik-Jan Dittrich, Anne T.M. Draaisma, Jos M.T. Janssen, Mirian C.H. van Engelen, Baziel G.M. Erasmus, Corrie E. Voermans, Nicol C. J Neuromuscul Dis Research Report BACKGROUND: SELENON(SEPN1)-related myopathy (SELENON-RM) is a rare congenital neuromuscular disease characterized by proximal and axial muscle weakness, spinal rigidity, scoliosis and respiratory impairment. No curative treatment options exist, but promising preclinical studies are ongoing. Currently, natural history data are lacking, while selection of appropriate clinical and functional outcome measures is needed to reach trial readiness. OBJECTIVE: We aim to identify all Dutch and Dutch-speaking Belgian SELENON-RM patients, deep clinical phenotyping, trial readiness and optimization of clinical care. METHODS: This cross-sectional, single-center, observational study comprised neurological examination, functional measurements including Motor Function Measurement 20/32 (MFM-20/32) and accelerometry, questionnaires, muscle ultrasound, respiratory function tests, electro- and echocardiography, and dual-energy X-ray absorptiometry. RESULTS: Eleven patients with genetically confirmed SELENON-RM were included (20±13 (3–42) years, 73% male). Axial and proximal muscle weakness were most pronounced. The mean MFM-20/32 score was 71.2±15.1%, with domain 1 (standing and transfers) being most severely affected. Accelerometry showed a strong correlation with MFM-20/32. Questionnaires revealed impaired quality of life, pain and problematic fatigue. Muscle ultrasound showed symmetrically increased echogenicity in all muscles. Respiratory function, and particularly diaphragm function, was impaired in all patients, irrespective of the age. Cardiac assessment showed normal left ventricular systolic function in all patients but abnormal left ventricular global longitudinal strain in 43% of patients and QRS fragmentation in 80%. Further, 80% of patients showed decreased bone mineral density on dual-energy X-ray absorptiometry scan and 55% of patients retrospectively experienced fragility long bone fractures. CONCLUSIONS: We recommend cardiorespiratory follow-up as a part of routine clinical care in all patients. Furthermore, we advise vitamin D supplementation and optimization of calcium intake to improve bone quality. We recommend management interventions to reduce pain and fatigue. For future clinical trials, we propose MFM-20/32, accelerometry and muscle ultrasound to capture disease severity and possibly disease progression. IOS Press 2023-11-07 /pmc/articles/PMC10657684/ /pubmed/37807786 http://dx.doi.org/10.3233/JND-221673 Text en © 2023 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Report
Bouman, Karlijn
Groothuis, Jan T.
Doorduin, Jonne
van Alfen, Nens
Udink ten Cate, Floris E.A.
van den Heuvel, Frederik M.A.
Nijveldt, Robin
Kamsteeg, Erik-Jan
Dittrich, Anne T.M.
Draaisma, Jos M.T.
Janssen, Mirian C.H.
van Engelen, Baziel G.M.
Erasmus, Corrie E.
Voermans, Nicol C.
SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness
title SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness
title_full SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness
title_fullStr SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness
title_full_unstemmed SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness
title_short SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness
title_sort selenon-related myopathy across the life span, a cross-sectional study for preparing trial readiness
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10657684/
https://www.ncbi.nlm.nih.gov/pubmed/37807786
http://dx.doi.org/10.3233/JND-221673
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