Membrane dysfunction in Andersen-Tawil syndrome assessed by velocity recovery cycles.
BACKGROUND
Andersen-Tawil syndrome (ATS) due to Kir2.1mutations typically manifests as periodic paralysis, cardiac arrhythmias and developmental abnormalities but is often difficult to diagnose clinically. This study was undertaken to determine whether sarcolemmal dysfunction could be identified with muscle velocity recovery cycles (MVRCs).


METHODS
Eleven genetically confirmed ATS patients and 20 normal controls were studied. MVRCs were recorded with 1, 2, and 5 conditioning stimuli and with single conditioning stimuli during intermittent repetitive stimulation at 20 Hz, in addition to the long exercise test.


RESULTS
ATS patients had longer relative refractory periods (P < 0.0001) and less early supernormality, consistent with membrane depolarization. Patients had reduced enhancement of late supernormality with 5 conditioning stimuli (P < 0.0001), and less latency reduction during repetitive stimulation (P < 0.001). Patients were separated completely from controls by combining MVRC and repetitive stimulation.


CONCLUSIONS
MVRCs combined with repetitive stimulation differentiated ATS patients from controls more effectively than the conventional long-exercise test.
MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom.
S Veronica
SV
Tan
Werner J
WJ
Z'graggen
Delphine
D
Boërio
Dipa L Raja
DL
Rayan
Robin
R
Howard
Michael G
MG
Hanna
Hugh
H
Bostock
D000328:Adult; D050030:Andersen Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D053447:Channelopathies / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012508:Sarcolemma / Q000502:physiology*
C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying