Longitudinal changes in clinical outcome measures in COL6-related dystrophies and LAMA2-related dystrophies

Minal S Jain; Katherine Meilleur; Eunhee Kim; Gina Norato; Melissa Waite; Leslie Nelson; Michelle McGuire; Tina Duong; Katherine Keller; Donovan J Lott; Allan Glanzman; Kristy Rose; Marion Main; Courtney Fiorini; Irene Chrismer; Melody Linton; Monal Punjabi; Jeffrey Elliott; Fatoumata Tounkara; Ruhi Vasavada; Ranjani Logaraj; Jocelyn Winkert; Sandra Donkervoort; Meganne Leach; Jahannaz Dastgir; Linda Hynan; Carmel Nichols; Elizabeth Hartnett; Gilberto M Averion; James C Collins; Eunice S Kim; Angela Kokkinis; Alice Schindler; Kristen Zukosky; Robert Fee; Veronica Hinton; Payam Mohassel; Diana Bharucha-Goebel; Carole Vuillerot; Peter McGraw; Mark Barton; Joseph Fontana; Anne Rutkowski; A Reghan Foley; Carsten G Bönnemann

doi:10.1212/WNL.0000000000008517

Longitudinal changes in clinical outcome measures in COL6-related dystrophies and LAMA2-related dystrophies

Neurology. 2019 Nov 19;93(21):e1932-e1943. doi: 10.1212/WNL.0000000000008517. Epub 2019 Oct 25.

Authors

Minal S Jain¹, Katherine Meilleur², Eunhee Kim², Gina Norato², Melissa Waite², Leslie Nelson², Michelle McGuire², Tina Duong², Katherine Keller², Donovan J Lott², Allan Glanzman², Kristy Rose², Marion Main², Courtney Fiorini², Irene Chrismer², Melody Linton², Monal Punjabi², Jeffrey Elliott², Fatoumata Tounkara², Ruhi Vasavada², Ranjani Logaraj², Jocelyn Winkert², Sandra Donkervoort², Meganne Leach², Jahannaz Dastgir², Linda Hynan², Carmel Nichols², Elizabeth Hartnett², Gilberto M Averion², James C Collins², Eunice S Kim², Angela Kokkinis², Alice Schindler², Kristen Zukosky², Robert Fee², Veronica Hinton², Payam Mohassel², Diana Bharucha-Goebel², Carole Vuillerot², Peter McGraw², Mark Barton², Joseph Fontana², Anne Rutkowski², A Reghan Foley², Carsten G Bönnemann¹

Affiliations

¹ From the Rehabilitation Medicine Department (M.S.J., M.W., R.V., R.L., C.N.), Clinical Research Center, Neuromuscular Symptoms Unit (K.M., I.C., M.L., M.P., J.E., F.T., J.W.), Tissue Injury Branch, National Institute of Nursing Research, Clinical Trials Unit (E.K., G.N.) and Neuromuscular and Neurogenetic Disorders of Childhood Section (S.D., M.L., E.H., G.M.A., A.K., A.S., K.Z., P.M., D.B.-G., A.R.F., C.G.B.), Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, and Pulmonary Branch (M.B., J.F., P.M.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD; Departments of Physical Therapy (L.N.) and Clinical Sciences (L.H.), University of Texas Southwestern, Dallas; Occupational Therapy and Physical Therapy Department (M. McGuire, J.C.C.), Cincinnati Children's Hospital Medical Center, OH; Pediatric Rehabilitation Medicine Department (T.D.), Children's National Medical Center, Washington, DC; Physical Therapy Department (K.K.), Rady's Children Hospital, San Diego, CA; Department of Physical Therapy (D.J.L.), University of Florida, Gainesville; Physical Therapy Department (A.G.), Children's Hospital of Philadelphia, PA; Paediatric Gait Analysis Laboratory of New South Wales (K.R.), The Children's Hospital at Westmead, Sydney, Australia; Dubowitz Neuromuscular Centre (M. Main), Great Ormond Street Hospital for Children, London, UK; Department of Physical Therapy (C.F.), Kennedy Krieger Institute, Baltimore, MD; G.H. Sergievsky Center and Department of Neurology (R.F., V.H.), Columbia University, New York, NY; Goryeb Children's Hospital (J.D.), Morristown, NJ; CureCMD (E.S.K., A.R.), Torrance, CA; and L'Escale Service Central de MPR pédiatrique (C.V.), Hospices Civils de Lyon, France carsten.bonnemann@nih.gov mjain@cc.nih.gov.
² From the Rehabilitation Medicine Department (M.S.J., M.W., R.V., R.L., C.N.), Clinical Research Center, Neuromuscular Symptoms Unit (K.M., I.C., M.L., M.P., J.E., F.T., J.W.), Tissue Injury Branch, National Institute of Nursing Research, Clinical Trials Unit (E.K., G.N.) and Neuromuscular and Neurogenetic Disorders of Childhood Section (S.D., M.L., E.H., G.M.A., A.K., A.S., K.Z., P.M., D.B.-G., A.R.F., C.G.B.), Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, and Pulmonary Branch (M.B., J.F., P.M.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD; Departments of Physical Therapy (L.N.) and Clinical Sciences (L.H.), University of Texas Southwestern, Dallas; Occupational Therapy and Physical Therapy Department (M. McGuire, J.C.C.), Cincinnati Children's Hospital Medical Center, OH; Pediatric Rehabilitation Medicine Department (T.D.), Children's National Medical Center, Washington, DC; Physical Therapy Department (K.K.), Rady's Children Hospital, San Diego, CA; Department of Physical Therapy (D.J.L.), University of Florida, Gainesville; Physical Therapy Department (A.G.), Children's Hospital of Philadelphia, PA; Paediatric Gait Analysis Laboratory of New South Wales (K.R.), The Children's Hospital at Westmead, Sydney, Australia; Dubowitz Neuromuscular Centre (M. Main), Great Ormond Street Hospital for Children, London, UK; Department of Physical Therapy (C.F.), Kennedy Krieger Institute, Baltimore, MD; G.H. Sergievsky Center and Department of Neurology (R.F., V.H.), Columbia University, New York, NY; Goryeb Children's Hospital (J.D.), Morristown, NJ; CureCMD (E.S.K., A.R.), Torrance, CA; and L'Escale Service Central de MPR pédiatrique (C.V.), Hospices Civils de Lyon, France.

Abstract

Objective: To identify the rate of change of clinical outcome measures in children with 2 types of congenital muscular dystrophy (CMD), COL6-related dystrophies (COL6-RDs) and LAMA2-related dystrophies (LAMA2-RDs).

Methods: Over the course of 4 years, 47 individuals (23 with COL6-RD and 24 with LAMA2-RD) 4 to 22 years of age were evaluated. Assessments included the Motor Function Measure 32 (MFM32), myometry (knee flexors and extensors, elbow flexors and extensors), goniometry (knee and elbow extension), pulmonary function tests, and quality-of-life measures. Separate linear mixed-effects models were fitted for each outcome measurement, with subject-specific random intercepts.

Results: Total MFM32 scores for COL6-RDs and LAMA2-RDs decreased at a rate of 4.01 and 2.60 points, respectively, each year (p < 0.01). All muscle groups except elbow flexors for individuals with COL6-RDs decreased in strength between 1.70% (p < 0.05) and 2.55% (p < 0.01). Range-of-motion measurements decreased by 3.21° (p < 0.05) at the left elbow each year in individuals with LAMA2-RDs and 2.35° (p < 0.01) in right knee extension each year in individuals with COL6-RDs. Pulmonary function demonstrated a yearly decline in sitting forced vital capacity percent predicted of 3.03% (p < 0.01) in individuals with COL6-RDs. There was no significant change in quality-of-life measures analyzed.

Conclusion: Results of this study describe the rate of change of motor function as measured by the MFM32, muscle strength, range of motion, and pulmonary function in individuals with COL6-RDs and LAMA2-RDs.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Adolescent
Arthrometry, Articular
Child
Child, Preschool
Disease Progression
Enteral Nutrition
Female
Humans
Linear Models
Longitudinal Studies
Male
Mobility Limitation
Muscle Strength
Muscle Strength Dynamometer
Muscular Dystrophies / physiopathology*
Outcome Assessment, Health Care
Quality of Life
Respiratory Function Tests
Sclerosis / physiopathology*
Vital Capacity
Young Adult

Supplementary concepts

Muscular dystrophy congenital, merosin negative
Scleroatonic muscular dystrophy