A Cross-Sectional Study of Nemaline Myopathy. Neurology 2021 Mar 09;96(10):e1425-e1436
Date
01/06/2021Pubmed ID
33397769Pubmed Central ID
PMC8055318DOI
10.1212/WNL.0000000000011458Scopus ID
2-s2.0-85102721587 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
OBJECTIVE: Nemaline myopathy (NM) is a rare neuromuscular condition with clinical and genetic heterogeneity. To establish disease natural history, we performed a cross-sectional study of NM, complemented by longitudinal assessment and exploration of pilot outcome measures.
METHODS: Fifty-seven individuals with NM were recruited at 2 family workshops, including 16 examined at both time points. Participants were evaluated by clinical history and physical examination. Functional outcome measures included the Motor Function Measure (MFM), pulmonary function tests (PFTs), myometry, goniometry, and bulbar assessments.
RESULTS: The most common clinical classification was typical congenital (54%), whereas 42% had more severe presentations. Fifty-eight percent of individuals needed mechanical support, with 26% requiring wheelchair, tracheostomy, and feeding tube. The MFM scale was performed in 44 of 57 participants and showed reduced scores in most with little floor/ceiling effect. Of the 27 individuals completing PFTs, abnormal values were observed in 65%. Last, bulbar function was abnormal in all patients examined, as determined with a novel outcome measure. Genotypes included mutations in ACTA1 (18), NEB (20), and TPM2 (2). Seventeen individuals were genetically unresolved. Patients with pathogenic ACTA1 and NEB variants were largely similar in clinical phenotype. Patients without genetic resolution had more severe disease.
CONCLUSION: We present a comprehensive cross-sectional study of NM. Our data identify significant disabilities and support a relatively stable disease course. We identify a need for further diagnostic investigation for the genetically unresolved group. MFM, PFTs, and the slurp test were identified as promising outcome measures for future clinical trials.
Author List
Amburgey K, Acker M, Saeed S, Amin R, Beggs AH, Bönnemann CG, Brudno M, Constantinescu A, Dastgir J, Diallo M, Genetti CA, Glueck M, Hewson S, Hum C, Jain MS, Lawlor MW, Meyer OH, Nelson L, Sultanum N, Syed F, Tran T, Wang CH, Dowling JJAuthor
Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ActinsAdolescent
Adult
Child
Child, Preschool
Cohort Studies
Cross-Sectional Studies
Disability Evaluation
Disease Progression
Enteral Nutrition
Female
Genotype
Humans
Infant
Longitudinal Studies
Male
Middle Aged
Muscle Proteins
Myopathies, Nemaline
Pilot Projects
Psychomotor Performance
Respiratory Function Tests
Sialorrhea
Tracheostomy
Treatment Outcome
Wheelchairs
Young Adult