Journal article
Clinical and electrophysiological evaluation of myasthenic features in an alpha-dystroglycanopathy cohort (FKRP-predominant)
Neuromuscular disorders : NMD, Vol.30(3), pp.213-218
03/2020
DOI: 10.1016/j.nmd.2020.01.002
PMID: 32115343
Abstract
•Fatigue is a common symptom in α-dystroglycanopathy muscular dystrophies.•Fatigue did not predict abnormal NMJ transmission on electrodiagnostic studies.•NMJ defect was not found outside of the GMPPB α-dystroglycanopathy subgroup.•NMJ defect associates with mild GMPPB phenotypes and treatment response is variable.
A postsynaptic dysfunction of the neuromuscular junction has been reported in patients with alpha-dystroglycanopathy associated with mutations in guanosine diphosphate (GDP)-mannose pyrophosphorylase B gene (GMPPB), some of whom benefit from symptomatic treatment. In this study, we determine the frequency of myasthenic and fatigue symptoms and neuromuscular junction transmission defects in a fukutin-related protein (FKRP)-predominant alpha-dystroglycanopathy cohort. Thirty-one patients with alpha-dystroglycanopathies due to mutations in FKRP (n = 25), GMPPB (n = 4), POMGNT1 (n = 1), and POMT2 (n = 1) completed a six-question modified questionnaire for myasthenic symptoms and the PROMIS Short Form v1.0-Fatigue 8a survey, and they underwent 3 Hz repetitive nerve stimulation of spinal accessory nerve-trapezius and radial nerve-anconeus pairs. Results showed that fatigue with activity was common; 63% of the cohort reported fatigue with chewing. A defective postsynaptic neuromuscular junction transmission was not identified in any of the patients carrying FKRP mutations but only in one mildly affected patient with GMPPB mutations (c.79 G>C, p.D27H and c.402+1G>A, splice site variant). We conclude that symptoms of fatigue with activity did not predict abnormal neuromuscular junction transmission on electrodiagnostic studies in this cohort and that, unlike GMPPB subgroup, a defective neuromuscular junction transmission does not appear to be present in patients with FKRP-associated muscular dystrophies.
Details
- Title: Subtitle
- Clinical and electrophysiological evaluation of myasthenic features in an alpha-dystroglycanopathy cohort (FKRP-predominant)
- Creators
- Paloma Gonzalez-Perez - Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, United StatesCheryl Smith - Department of Neurology, West Virginia University Hospitals, Morgantown, WV 26506, United StatesWendy L Sebetka - Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United StatesAmber Gedlinske - Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United StatesSeth Perlman - Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United StatesKatherine D Mathews - Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Neuromuscular disorders : NMD, Vol.30(3), pp.213-218
- DOI
- 10.1016/j.nmd.2020.01.002
- PMID
- 32115343
- NLM abbreviation
- Neuromuscul Disord
- ISSN
- 0960-8966
- eISSN
- 1873-2364
- Publisher
- Elsevier B.V
- Grant note
- name: Wellstone Muscular Dystrophy Cooperative Research Center, award: U54 NS053672; DOI: 10.13039/100008893, name: University of Iowa, award: NIH U54TR001356; DOI: 10.13039/100000002, name: National Institutes of Health, award: 5R25NS079173
- Language
- English
- Date published
- 03/2020
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics); Internal Medicine
- Record Identifier
- 9984070421202771
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