Clinical and electrophysiological evaluation of myasthenic features in an alpha-dystroglycanopathy cohort (FKRP-predominant)

• Published in: Neuromuscular disorders : NMD 2020-03, Vol.30 (3), p.213-218
• Main Authors: Gonzalez-Perez, Paloma, Smith, Cheryl, Sebetka, Wendy L., Gedlinske, Amber, Perlman, Seth, Mathews, Katherine D
• Format: Article
• Language: English
• Subjects: Adult; Cohort Studies; Dystroglycans - metabolism; Electrophysiological Phenomena; Fatigue; Fatigue - diagnosis; Fatigue - etiology; Fatigue - physiopathology; Fukutin-related protein (FKRP); Humans; Muscle Weakness - diagnosis; Muscle Weakness - etiology; Muscle Weakness - physiopathology; Muscular Dystrophies - complications; Muscular Dystrophies - diagnosis; Muscular Dystrophies - metabolism; Muscular Dystrophies - physiopathology; Myasthenia; Neuromuscular junction; Neuromuscular Junction - physiopathology; Pentosyltransferases - genetics; Phenotype
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2020.01.002

•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.