Stimulus-Induced Drop Episodes in Coffin-Lowry Syndrome□V

Objective. Coffin-Lowry syndrome (CLS) is a rare disorder characterized by moderate to severe mental retardation, facial dysmorphism, tapering digits, and skeletal deformity. Paroxysmal drop attacks occur in patients with CLS, characterized by sudden loss of muscle tone induced by unexpected tactile or auditory stimuli. Our objective is to characterize these attacks better using neurophysiologic studies. Methods. We report 2 teenage boys with CLS and stimulus-induced drop episodes (SIDEs). Simultaneous surface electromyogram (EMG) and video electroencephalogram were performed during SIDEs on our 2 patients. Results. Both patients had SIDEs stimulated by a loud noise, unexpected light touch stimulation, or visual threat that were characterized by abrupt episodes of complete or partial loss of lower extremity tone. These events were not associated with impairment of consciousness, and immediate recovery was noted. Simultaneous surface EMG and video electroencephalogram revealed no epileptiform discharges in either patient. In the first patient, after unexpected tactile or auditory stimulation, tonic EMG activity in paraspinal muscles was lost briefly, similar to that seen in cataplexy. In the second patient, at 6 years of age, sudden nonepileptic drop episodes were induced by an unexpected tactile, auditory, or visual stimulation. At 11 years of age, his episodes had changed to brief myoclonic jerk and tonic spasm that were triggered by unexpected tactile and auditory stimuli. An increase in tonic EMG activity occurred during the attacks, consistent with hyperekplexia. Conclusions. Our data suggest that SIDEs in CLS are a heterogeneous group of nonepileptic events that may manifest features of both cataplexy and hyperekplexia, even in the same patient. Pediatrics 2003;111:e197–e202. URL: http://www.pediatrics.org/cgi/content/full/111/3/ e197; Coffin-Lowry syndrome, drop episodes, nonepileptic events, hyperekplexia, cataplexy. ABBREVIATIONS. CLS, Coffin-Lowry syndrome; SIDE, stimulusinduced drop episode; sEMG, surface electromyogram; VEEG, video electroencephalogram. Coffin-Lowry syndrome (CLS) was independently reported by Coffin et al1 in 1966 and Lowry et al2 in 1971 as a phenotype characterized by moderate to severe mental retardation, facial dysmorphism, tapering digits, and skeletal deformity. The condition is transmitted by X-linked semidominant inheritance. The gene locus has been mapped to Xp22.2, and mutations have been identified in affected patients in the RSK-2 gene, a growth factor–regulated protein kinase.3 Stimulus-induced drop episodes (SIDEs) have been recently recognized in patients with CLS.4–7 These episodes are characterized by a sudden falling that is induced by unexpected tactile or auditory stimuli.4–7 These events have been labeled by various names, including cataplexy, nonepileptic collapses with atonia, exaggerated startle responses, hyperekplexia, and drop episodes. The pathophysiology of SIDEs is not well understood. It does not seem to be an epileptic phenomenon, as epileptiform activity was absent during the episodes in all previously reported cases.4,5,7 We report our experience in 2 patients with SIDEs in CLS. On the basis of our cases and review of the literature, we suggest that there are diverse mechanisms of SIDEs in CLS.