Lippincott Williams & Wilkins



Table e-1. Clinical characteristics of patients in the validation cohort Patient 1Patient 2Patient 3Patient 4Patient 5Patient 6SexFFFFHFAge (yrs)213421666518First sign, age (yrs)Exercise intolerance, 9Unexplained falls, 8Subacute proximal weakness, 13Asymptomatic hyperCKemia, 65Asymptomatic hyperCKemia, 59Exercise intolerance+myalgia, 15Duration (yrs)12.5268163Pattern of weaknessShoulder and hip girdleShoulder and hip girdle, axialShoulder and hip girdleNormal strength initially then slight shoulder and hip girdle weakness (4/5)Slight hip girdle weakness (4/5)Normal strengthScapular wingingAbsentPresentAbsentAbsentPresentAbsentAmbulation StatusIndependentWheelchairIndependentIndependentIndependentIndependentCK (IU/L)9,83212,00017,0001,8666,0001,200EMG/NCSMyopathicMyopathicMyopathicMyopathicMyopathicMyopathicMuscle Pathology FindingsAtrophy and chronic myopathic changes (fibrosis, fiber size variability), myofiber regeneration, inflammatory infiltrate, MHC-1 sarcolemmal stainingChronic myopathic changes (fibrosis, fiber size variability), myofiber necrosis and regeneration, no inflammatory infiltrate, no MHC-1 stainingChronic myopathic changes (fibrosis), myofiber necrosis and regeneration, small perivascular inflammatory infiltrates, no MHC-1 staining, no C5b-9 depositionNo chronic myopathic changes, myofiber necrosis and regeneration, small perivascular inflammatory infiltrates, no MHC-1 staining, sarcolemmal C5b-9 depositionChronic myopathic changes (fiber size variability, internalized nuclei), no myofiber necrosis and regeneration, no inflammatory infiltrate, slight MHC-1 staining, no C5b-9 depositionNo chronic myopathic changes, myofiber necrosis and regeneration, no inflammatory infiltrate, no MHC-1 staining, no C5b-9 depositionGenetic and molecular testingLGMD panel (IHC+WB), FKRP, anoctamin 5LGMD panel (IHC+WB), acid maltaseLGMD panel (IHC+WB), calpain/anoctamin 5 mutationsLGMD panel (IHC+WB), DM1, DM2, anoctamin 5 mutationLGMD panel (IHC), acid maltaseLGMD panel (IHC+WB), anoctamin 5 mutationAnti-SRPNegativeNegativeNegativeNegativeNegativeNegativeHLA-DRB1unknownunknownunknownunknownunknownunknownEchocardiogramNormalNormalNormalNormalSlight concentric ventricular hypertrophyNormalPFTFVC 3.4 L (66%)FVC 71%unknownFVC 3.05 L (118%)FVC 3.73 L (102%)FVC 3.40 L (99%)Other commentsHeterozygote factor V Leiden mutation and protein S deficiency (no thrombotic event)Hashimoto thyroiditisDyslipidemia, statin exposureCoronary artery disease with statin exposureHeterozygote factor V Leiden mutation (no thrombotic event)Patient 7Patient 8Patient 9Patient 10Patient 11Patient 12GenderFHFFHFAge (yrs)521744316330First sign, age (yrs)Asymptomatic hyperCKemia, 47HyperCKemia +myalgia, 14Proximal weakness, 21Exercise intolerance, 14Elevated LFTs, 47Difficulty rising from a chair+myalgia, 15Duration (yrs)5323161615Pattern of weaknessShoulder and hip girdleShoulder and hip girdleShoulder and hip girdleShoulder and hip girdleShoulder and hip girdleShoulder and hip girdleScapular wingingAbsentPresentPresentPresentAbsentAbsentAmbulation StatusIndependentIndependentWheelchairIndependentIndependentIndependent for short distance with caneCK (IU/L)4,00010,8587,0005,9851,8515,890EMG/NCSMyopathicMyopathicMyopathicMyopathicMyopathicMyopathicMuscle Pathology FindingsChronic myopathic changes (fibrosis, fiber size variability, internalized nuclei), myofiber regeneration, no inflammatory infiltrate, slight MHC-1 staining, sarcolemmal C5b-9 depositionAtrophy and chronic myopathic changes (fibrosis, fiber size variability, internalized nuclei), myofiber regeneration, inflammatory infiltrate, positive MHC-1 staining, no C5b-9 depositionChronic myopathic changes (fibrosis), myofiber necrosis and regeneration, small perivascular inflammatory infiltrates, no MHC-1 staining, no C5b-9 depositionChronic myopathic changes (fibrosis, fiber size variability, internalized nuclei), myofiber necrosis and regeneration, no inflammatory infiltrates, slight MHC-1 staining, sarcolemmal C5b-9 depositionAtrophy and chronic myopathic changes (fiber size variability, internalized nuclei), myofiber necrosis and regeneration, no inflammatory infiltrates, no MHC-1 staining, no C5b-9 depositionAtrophy and chronic myopathic changes (fibrosis, fiber size variability, internalized nuclei), myofiber necrosis and regeneration, no inflammatory infiltrates, no MHC-1 staining, sarcolemmal C5b-9 depositionGenetic and molecular testingLGMD panel(IHC +WB), DM2, anoctamin 5, acid maltase, FKRPLGMD panel (IHC+WB), acid maltase, anoctamin 5LGMD panel (IHC+WB), calpain, FKRP and anoctamin 5LGMD panel (IHC+WB), FSHD, acid maltase, SMN1/2LGMD panel (IHC+WB), acid maltase, anoctamin 5LGMD panel (IHC+WB), anoctamin 5, DM1, FSHDAnti-SRPNegativeNegativeNegativeNegativeNegativeNegativeHLA-DRB1unknownunknownunknownunknownunknownunknownEchocardiogramNormalNormalNormalNormalNormalNormalPFTFVC 80%FVC 5.25 L (88%)FVC 2.67 L (86%)FVC 2.44 L (74%)FVC 3.84L (94%)FVC 3.29 L (85%)Other commentsStatin exposure at the age of 38, nine years before first elevated CK level testingRed yeast rice (lovastatin) exposureRaynaud phenomenonPatient 13Patient 14Patient 15Patient 16Patient 17GenderFFFFFAge (yrs)2565603047First sign, age (yrs)Unexplained falls, 14Difficulty rising from a chair, 55Myalgia+difficulty climbing stairs, 50Exercise intolerance, 26Proximal weakness, 30Duration (yrs)91010417Pattern of weaknessShoulder and hip girdleShoulder and hip girdleShoulder and hip girdleShoulder and hip girdleShoulder and hip girdleScapular wingingAbsentAbsentAbsentAbsentPresentAmbulation StatusWheelchairIndependentWheelchairIndependentIndependentCK (IU/L)4,0003,30010,0005,4735,600EMG/NCSMyopathicMyopathicMyopathicMyopathicMyopathicMuscle Pathology FindingsChronic myopathic changes (fibrosis, fiber size variability, internalized nuclei), myofiber necrosis and regeneration, no inflammatory infiltrates, slight MHC-1 staining, no C5b-9 depositionAtrophy and chronic myopathic changes (fiber size variability), myofiber necrosis and regeneration, no inflammatory infiltrate, slight MHC-1 stainingChronic myopathic changes (fibrosis, fiber size variability, internalized nuclei), myofiber necrosis and regenera tion, no inflammatory infiltratesChronic myopathic changes (fibrosis, fiber size variability, internalized nuclei), myofiber necrosis and regeneration, no inflammatory infiltrates, positive MHC-1 staining, no C5b-9 depositionAtrophy and chronic myopathic changes (fibrosis, internalized nuclei), myofiber necrosis and regeneration, inflammatory infiltrates and sarcolemmal C5b-9 depositionGenetic and molecular testingLGMD panel (IHC+WB), anoctamin 5LGMD panel (IHC+WB), acid maltase, mitochondrial DNALGMD panel (IHC+WB)LGMD panel (IHC+WB), DM2LGMD panel (IHC+WB)Anti-SRPNegativeNegativeNegativeNegativeNegativeHLA-DRB1UnknownUnknownUnknownUnknownUnknownEchocardiogramNormalConcentric ventricular hypertrophyNormalNormalNormalPFTUnknownFVC 2.81 L (95%)FVC 1.21 L (43%)UnknownFVC 4.04 L (143%)Other commentsStatin exposure 3 years after first symptoms, Hypertension, Cancer-associated myositis to an squamous-cell esophageal carcinomaNo statin exposure, Hashimoto thyroiditisCK= creatine kinase, LFT= Liver function tests, N.D.= Not done, MHC-1= major histocompatibility complex-1, LGMD= Limb-girdle muscular dystrophy, IHC=immunohistochemistry, WB=western blot, FSHD= Fascioscapulohumeral muscular dystrophy, DM1= myotonic dystrophy type 1, DM2= myotonic dystrophy type 2, FKRP=fukutin-related protein, PFT= Pulmonary function test, FVC= Forced vital capacity ................
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