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Published on: January 11, 2014
A Cross-Sectional Study of Nemaline Myopathy
Kimberly Amburgey1, Meryl Acker1, Samia Saeed1
1From the Division of Neurology (K.A.), Genetics and Genome Biology (K.A., M.A., J.J.D., M.B., N.S.), Division of Respiratory Medicine (R.A., F.S., T.T.), Centre for Computational Medicine (M.B., N.S.), Division of Emergency Medicine (M.D.), and Division of Clinical and Metabolic Genetics (S.H.), Hospital for Sick Children; Princess Margaret Hospital (S.S.), Department of Medical Oncology and Hematology; University of Toronto (R.A.), Ontario, Canada; The Manton Center for Orphan Disease Research (A.H.B., C.A.G.), Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, MA; National Institute of Neurological Disorders and Stroke (C.G.B.), Neuromuscular and Neurogenetic Disorders of Childhood Section, and Clinical Research Center (M.S.J.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Department of Computer Science (M.B., M.G., N.S.), University of Toronto, Ontario, Canada; Columbia University Irving Medical Center (A.C.), Division of Pediatric Pulmonology, New York, NY; Goryeb Children's Hospital (J.D.), Department of Pediatric Neurology, Morristown, NJ; Mount Sinai Hospital (C.H.), Prenatal Diagnosis and Medical Genetics, Toronto, Ontario, Canada; Medical College of Wisconsin (M.W.L.), Department of Pathology and Laboratory Medicine, Milwaukee; Children's Hospital of Philadelphia (O.H.M.), Division of Pulmonology, PA; UT Southwestern Medical Center (L.N.), Department of Physical Therapy, Dallas, TX; and Driscoll Children's Hospital (C.H.W.), Division of Neurology, Texas A&M University, Corpus Christi.
Nemaline myopathy (NM) is a rare neuromuscular disorder with significant disability. This study highlights a stable disease course and identifies key outcome measures for future clinical trials in NM patients.
Area of Science:
- Neurology
- Genetics
- Clinical Research
Background:
- Nemaline myopathy (NM) is a rare neuromuscular disorder characterized by genetic and clinical variability.
- Understanding the natural history and identifying reliable outcome measures are crucial for effective management and therapeutic development.
Purpose of the Study:
- To establish the disease natural history of Nemaline myopathy through a cross-sectional study.
- To explore and validate pilot outcome measures for assessing disease progression and severity in NM.
- To investigate the clinical phenotype associated with different genetic mutations in NM.
Main Methods:
- A cross-sectional study involving 57 individuals with NM, with a subset undergoing longitudinal assessment.
- Utilized clinical evaluations, including history and physical examination.
- Employed functional outcome measures such as Motor Function Measure (MFM), pulmonary function tests (PFTs), myometry, goniometry, and bulbar assessments.
Main Results:
- The majority of NM patients (54%) presented with typical congenital NM, while 42% had severe forms requiring significant support (mechanical ventilation, wheelchair, feeding tubes).
- Abnormalities were common across functional assessments: reduced MFM scores, abnormal PFTs in 65%, and bulbar dysfunction in all assessed patients.
- Genetic analysis identified mutations in ACTA1, NEB, and TPM2, with a significant portion (17 individuals) remaining genetically unresolved, exhibiting more severe disease phenotypes.
Conclusions:
- NM is associated with substantial disability and a generally stable disease course.
- The study identified MFM, PFTs, and a novel bulbar assessment (slurp test) as promising outcome measures for future NM clinical trials.
- Further diagnostic investigation is warranted for the genetically unresolved NM patient cohort to better understand their disease.
