Redefining the clinical phenotypes of non-dystrophic myotonic syndromes.
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 vs 36.7%; p<0.01), the warm-up phenomenon (100 vs 46.7%; p<0.001), and difficulties in standing up quickly (90.6 vs 50.0%; p<0.001), running (90.6% vs 66.7; p<0.05) and climbing stairs (90.6 vs 63.3%; p = 0.01). Patients with NaCh reported an earlier onset (4.4 vs 9.6 years; p<0.001), and higher frequencies of paradoxical (50.0 vs 0%; p<0.001) and painful myotonia (56.7 vs 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 s; p<0.001), and in eyelid muscles for NaCh (96.7 vs 46.9%; mean relaxation time of 19.2 vs 4.3 s; 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 clinical guidelines to be proposed for genetic testing.


CONCLUSIONS
This study redefined the phenotypical characteristics of NDM in both ClCh and NaCh. The clinical guidelines proposed may help clinicians working in outpatient clinics to perform a focused genetic analysis of either CLCN1 or SCN4A.
Trip
J
J
Maastricht University Medical Centre, Department of Neurology, PO Box 5800, 6202 AZ Maastricht, The Netherlands. jeroen.trip@online.nl
Drost
G
G
Ginjaar
H B
HB
Nieman
F H M
FH
van der Kooi
A J
AJ
de Visser
M
M
van Engelen
B G M
BG
Faber
C G
CG
D000328:Adult; D000368:Aged; D053447:Channelopathies / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics*; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D004576:Electromyography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020967:Myotonic Disorders / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D062553:NAV1.4 Voltage-Gated Sodium Channel; D009426:Netherlands; D009460:Neurologic Examination; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult
C086321:CLC-1 channel; D018118:Chloride Channels; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels