Objective: To redefine phenotypical characteristics for both chloride (ClCh) and sodium channelopathies (NaCh) in non-dystrophic myotonic syndromes (NDM).
Methods: In a cross-sectional, nationwide study, standardised interviews and clinical bedside tests were performed in 62 genetically confirmed NDM patients, 32 ClCh and 30 NaCh.
Results: Standardised interviews revealed that ClCh reported a higher frequency of muscle weakness (75 versus 36.7%; p<0.01), the warm-up phenomenon (100 versus 46.7%; p<0.001), and difficulties in standing up quickly (90.6 versus 50.0%; p<0.001), running (90.6% versus 66.7; p<0.05), and climbing stairs (90.6 versus 63.3%; p=0.01). Patients with NaCh reported an earlier onset (4.4 versus 9.6 years; p<0.001), and higher frequencies of paradoxical (50.0 versus 0%; p<0.001), and painful myotonia (56.7 versus 28.1%; p<0.05). Standardised clinical bedside tests showed a higher incidence and longer relaxation times of myotonia in the leg muscles for ClCh (100 vs. 60%; mean duration of chair tests 12.5 vs. 6.3 seconds; p<0.001), and in eyelid muscles for NaCh (96.7 vs. 46.9%; mean relaxation time of 19.2 vs. 4.3 seconds; p<0.001). Transient paresis was only observed in ClCh (62.5%) and paradoxical myotonia only in NaCh (30.0%). Multivariate logistic regression analyses allowed us to propose clinical guidelines for genetic testing.
Conclusion: This study redefined the phenotypical characteristics of NDM in both ClCh and NaCh. The clinical guidelines that we proposed may help clinicians working in outpatient clinics to perform focussed genetic analysis of either CLCN1 or SCN4A.