Stacha F I Reumers1, Frederik Braun1, Jennifer E Spillane1, Johann Böhm1, Maartje Pennings1, Meyke Schouten1, Anneke J van der Kooi1, A Reghan Foley1, Carsten G Bönnemann1, Erik-Jan Kamsteeg1, Corrie E Erasmus1, Ulrike Schara-Schmidt1, Heinz Jungbluth1, Nicol C Voermans2. 1. From the Department of Neurology (S.F.I.R., N.C.V.), Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics (M.P., E.-j.K.), and Department of Clinical Genetics (M.S.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Pediatric Neurology and Neuromuscular Centre (F.B., U.S.-S.), University Hospital Essen, Germany; Department of Neurology (J.E.S.), St. Thomas Hospital, and Department of Paediatric Neurology (H.J.), Neuromuscular Service, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK; Department of Neurobiology and Genetics (J.B.), Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France; Department of Neurology (A.J.v.d.K.), Amsterdam University Medical Center, Neuroscience Institute, the Netherlands; Neuromuscular and Neurogenetic Disorders of Childhood Section (A.R.F., C.G.B.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Pediatric Neurology (C.E.E.), Radboud University Medical Center Amalia Children's Hospital, Nijmegen, the Netherlands; and Muscle Signalling Section (H.J.), Randall Division for Cell and Molecular Biophysics, King's College, London, UK. 2. From the Department of Neurology (S.F.I.R., N.C.V.), Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics (M.P., E.-j.K.), and Department of Clinical Genetics (M.S.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Pediatric Neurology and Neuromuscular Centre (F.B., U.S.-S.), University Hospital Essen, Germany; Department of Neurology (J.E.S.), St. Thomas Hospital, and Department of Paediatric Neurology (H.J.), Neuromuscular Service, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK; Department of Neurobiology and Genetics (J.B.), Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France; Department of Neurology (A.J.v.d.K.), Amsterdam University Medical Center, Neuroscience Institute, the Netherlands; Neuromuscular and Neurogenetic Disorders of Childhood Section (A.R.F., C.G.B.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Pediatric Neurology (C.E.E.), Radboud University Medical Center Amalia Children's Hospital, Nijmegen, the Netherlands; and Muscle Signalling Section (H.J.), Randall Division for Cell and Molecular Biophysics, King's College, London, UK. nicol.voermans@radboudumc.nl.
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.
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.
Authors: E M Hoogerwaard; E Bakker; P F Ippel; J C Oosterwijk; D F Majoor-Krakauer; N J Leschot; A J Van Essen; H G Brunner; P A van der Wouw; A A Wilde; M de Visser Journal: Lancet Date: 1999-06-19 Impact factor: 79.321
Authors: J Laporte; V Biancalana; S M Tanner; W Kress; V Schneider; C Wallgren-Pettersson; F Herger; A Buj-Bello; F Blondeau; S Liechti-Gallati; J L Mandel Journal: Hum Mutat Date: 2000 Impact factor: 4.878
Authors: J Laporte; L J Hu; C Kretz; J L Mandel; P Kioschis; J F Coy; S M Klauck; A Poustka; N Dahl Journal: Nat Genet Date: 1996-06 Impact factor: 38.330
Authors: Alan H Beggs; Barry J Byrne; Sabine De Chastonay; Tmirah Haselkorn; Imelda Hughes; Emma S James; Nancy L Kuntz; Jennifer Simon; Lindsay C Swanson; Michele L Yang; Zi-Fan Yu; Sabrina W Yum; Suyash Prasad Journal: Muscle Nerve Date: 2017-12-22 Impact factor: 3.217