A case of late-onset proximal and distal muscle weakness

At initial presentation, our patient was a 49-year-old woman with 3 years of progressive weakness. She noted difficulty standing up straight and climbing stairs. Over the next 2 years, she had “winging” of her shoulder blades and difficulty lifting her arms over her head. She denied fatigue, fasciculations, myalgias, cramps or stiffness, ptosis, double vision, difficulty chewing or swallowing, dysarthria, dyspnea, sensory symptoms, incontinence, rash, arthralgias, and bone pain. The patient’s mother developed difficulty walking in her late 50s, with “flapping of her feet,” winging of the scapulae, dysphagia, and dysarthria. A maternal uncle also used a wheelchair in mid-adult life, and the patient’s maternal grandmother was diagnosed with Roussy-Levy syndrome. The patient has one 48-year-old brother and 6 adult children without medical problems. Her family history and medical history were otherwise unremarkable. She was taking no medications. General examination was unremarkable. Mental status was normal. Cranial nerves were intact. Motor examination revealed bilateral scapular winging and paraspinal muscle atrophy. No fasciculations, myotonia, or paramyotonia were appreciated. Manual muscle testing demonstrated Medical Research Council (MRC) grades of 4 proximally and 4+ distally in the arms and legs. Sensation and muscle stretch reflexes were intact. Plantar responses were flexor. The patient had a hyperlordotic, wide-based, and waddling gait. The patient’s weakness progressed over the next several years. At the age of 54 years, she had the following MRC scores: neck flexion 5−, neck extension 5−, shoulder abduction 3−, elbow flexion 4 on the right and 2 on the left, elbow extension 5, wrist extension 4+ on the right and 4 on the left, wrist flexion 5, finger extension 4+, and finger flexors 5. In the lower extremities, she had hip flexion, abduction, and extension 2, knee extension 3−, ankle dorsiflexion and plantar flexion 1 on right and 4− on left. Workup …

[1]  Steven A Greenberg,et al.  Sarcoplasmic redistribution of nuclear TDP‐43 in inclusion body myositis , 2009, Muscle & nerve.

[2]  B. Udd.  165th ENMC International Workshop: Distal myopathies 6–8th February 2009 Naarden, The Netherlands , 2009, Neuromuscular Disorders.

[3]  A. Pestronk,et al.  Valosin-containing protein disease: Inclusion body myopathy with Paget’s disease of the bone and fronto-temporal dementia , 2009, Neuromuscular Disorders.

[4]  K. Claeys,et al.  Clinical outcome in 19 French and Spanish patients with valosin-containing protein myopathy associated with Paget’s disease of bone and frontotemporal dementia , 2009, Neuromuscular Disorders.

[5]  V. Kimonis,et al.  VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder. , 2008, Biochimica et biophysica acta.

[6]  A. Pestronk,et al.  TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[7]  Charles D. Smith,et al.  Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia , 2008, American journal of medical genetics. Part A.

[8]  S. Greenberg,et al.  Nuclear localization of valosin‐containing protein in normal muscle and muscle affected by inclusion‐body myositis , 2007, Muscle & nerve.

[9]  R. Griggs,et al.  Zaspopathy in a large classic late-onset distal myopathy family. , 2007, Brain : a journal of neurology.

[10]  N. Cairns,et al.  TDP‐43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations , 2007, Journal of neuropathology and experimental neurology.

[11]  Andrew G Engel,et al.  Mutations in ZASP define a novel form of muscular dystrophy in humans , 2005, Annals of neurology.

[12]  Andrew G Engel,et al.  Mutations in myotilin cause myofibrillar myopathy , 2004, Neurology.

[13]  K. Ohno,et al.  Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. , 2004, Brain : a journal of neurology.

[14]  M. Ferrante,et al.  The wide spectrum of myofibrillar myopathy suggests a multifactorial etiology and pathogenesis , 1998, Neurology.