Zhang et al. (2013) reported 2 unrelated large multigenerational Chinese families with a similar episodic pain syndrome with onset in early childhood. Intense pain was localized primarily to the distal lower extremities and occasionally in the upper body, ... Zhang et al. (2013) reported 2 unrelated large multigenerational Chinese families with a similar episodic pain syndrome with onset in early childhood. Intense pain was localized primarily to the distal lower extremities and occasionally in the upper body, especially in the joints of fingers and arms. Episodic pain appeared late in the day and occurred in cycles. The pain was exacerbated with fatigue, such as catching a cold or performing hard exercise, and was relieved by oral administration of antiinflammatory analgesic medicines. Episodes of pain were usually accompanied by sweating. The feeling of the pain region was extremely cold and the pain could be mitigated by a hot compress. All affected individuals reported that the sever pain episodes diminished with age. Neurologic examinations of 2 probands showed retained and intact sensitivities to joint position, light touch, and pinprick.
In 2 unrelated Chinese families with autosomal dominant familial episodic pain syndrome-3, Zhang et al. (2013) identified 2 different missense mutations in the SCN11A gene (R225C, 604385.0002; A808G, 604385.0003). The mutation in the first family was found by ... In 2 unrelated Chinese families with autosomal dominant familial episodic pain syndrome-3, Zhang et al. (2013) identified 2 different missense mutations in the SCN11A gene (R225C, 604385.0002; A808G, 604385.0003). The mutation in the first family was found by genomewide linkage analysis combined with whole-exome sequencing. Electrophysiologic studies in mouse dorsal root ganglia neurons showed that both mutations had higher peak current densities compared to wildtype, indicating higher electrical activity. Mutant channels also showed increased spontaneous firing compared to wildtype. However, voltage-dependence for activation and inactivation kinetics of mutant channels were similar to wildtype. Neurons expressing the A808G mutation fired more action potentials than those expressing the R225C mutation, which was consistent with the increased number of episodic pain episodes in the family carrying the A808G mutation. Zhang et al. (2013) noted that the SCN11A channel is not directly responsible for action potential generation, but suggested that higher electrical activities of the mutant channels may induce the opening of other sodium channels, such as SCN10A (604427), and thus cause dorsal root ganglion neurons to be hyperexcitable, which would contribute to the episodic pain syndrome.