Background: Mutations in the voltage-gated Na(V)1.7 Na+ channel alpha 1 gene SCN9A have been linked to pain disorders, such as inherited primary erythromelalgia and paroxysmal extreme pain disorder... Show moreBackground: Mutations in the voltage-gated Na(V)1.7 Na+ channel alpha 1 gene SCN9A have been linked to pain disorders, such as inherited primary erythromelalgia and paroxysmal extreme pain disorder. Both show clinical overlap with complex regional pain syndrome (CRPS), a condition that is characterized by pain in association with combinations of vasomotor, sudomotor, sensory, and motor disturbances. Therefore, we here investigated the involvement of the SCN9A gene in familial CRPS. Methods: We performed a mutation analysis of the SCN9A gene in four index cases of families with CRPS. All 26 coding exons and adjacent sequences of the SCN9A gene were analyzed for mutations using direct sequencing analysis. Results: No causal gene mutations were identified in the SCN9A gene in any of the patients. Conclusions: Despite the fact that the SCN9A gene is an excellent candidate, we did not find evidence that it plays a major role in familial CRPS. Show less
Rooij, A.M. de; Perez, R.S.G.M.; Huygen, F.J.; Eijs, F. van; Kleef, M. van; Bauer, M.C.R.; ... ; Marinus, J. 2010
Complex Regional Pain Syndrome (CRPS) usually develops after a noxious event, but spontaneous onsets have been described in 3-11% of the cases. The existence of spontaneous-onset CRPS is highly... Show moreComplex Regional Pain Syndrome (CRPS) usually develops after a noxious event, but spontaneous onsets have been described in 3-11% of the cases. The existence of spontaneous-onset CRPS is highly debated and the aim of the present study was therefore to compare the phenotypic characteristics of CRPS patients with a spontaneous onset, with those of patients with a trauma-induced onset. Data of 537 CRPS patients followed up at four departments of anesthesiology were analyzed and comprised 498 (93%) patients with and 39 (7%) patients without a known eliciting event. There where no significant differences between the two groups in gender, or in onset in upper or lower limb or left or right side of the body. Compared to CRPS patients with a trauma-induced onset, spontaneous-onset cases were on average 9 years younger at disease onset and had a 1.4 years longer median disease duration. No significant differences in frequency were found for any of the 34 compared signs and symptoms when the effect of multiple testing was controlled. In conclusion, CRPS may develop both with and without a precipitating noxious event, with both groups exhibiting a largely similar clinical presentation. Spontaneous-onset CRPS patients generally develop the syndrome at a younger age, possibly indicating a susceptibility to develop the condition. The longer disease duration in spontaneous-onset cases may reflect a more gradual disease onset, poorer prognosis, or a delay in diagnosis, possibly as a result of reluctance to make this diagnosis in the absence of a clear initiating event. (C) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved. Show less
Gosso, M.F.; Rooij, A.M. de; Alsina-Sanchis, E.; Kamphorst, J.T.; Marinus, J.; Hilten, J.J. van; Maagdenberg, A.M.J.M. van den 2010
Complex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain... Show moreComplex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain poorly understood. Several genes (so-called DYT genes) identified in other causes of dystonia play a role in mechanisms that have been implicated in CRPS. Because different mutations in the same gene can result in diverse phenotypes, we sequenced all coding exons of the DYT1, DYT5a, DYT5b, DYT6, DYT11, DYT12, and DYT16 genes in 44 CRPS patients with fixed dystonia to investigate whether high-penetrant causal mutations play a role in CRPS. No such mutations were identified, indicating that these genes do not seem to play a major role in CRPS. Show less
Complex Regional Pain Syndrome (CRPS) is a painful disorder affecting one or more extremities. CRPS is characterized by various combinations of sensory, autonomic and motor disturbances. Genetic... Show moreComplex Regional Pain Syndrome (CRPS) is a painful disorder affecting one or more extremities. CRPS is characterized by various combinations of sensory, autonomic and motor disturbances. Genetic factors are suggested to play a role in CRPS, but this has not been extensively studied. Therefore the aims of this thesis were to study the contribution and the size of the contribution of genetic factors in CRPS and to identify possible susceptibility and causative genes for CRPS. In our studies we have shown that CRPS may develop without a noxious event and it has been suggested that such patients have a larger genetic predisposition. Furthermore we have found that CRPS may occur in a familial form, but did not observe a clear inheritance pattern. We calculated a measure of familial aggregation. This study yielded no indications for a large overall increased risk of developing CRPS for siblings of CRPS patients. Significant associations were found with CRPS and dystonia and two HLA-B62 and HLA-DQ8. We also evaluated the presence of causative mutations in known primary dystonia genes and causative mutations in the SCN9A gene. No such mutations were identified, indicating that these genes do not seem to play a major role in CRPS. Show less
