Increased Risk of Complex Regional Pain Syndrome in Siblings of Patients?

de Rooij, Annetje M.; de Mos, Marissa; van Hilten, Jacobus J.; Sturkenboom, Miriam C.J.M.; Gosso, M. Florencia; van den Maagdenberg, Arn M.J.M.; Marinus, Johan

doi:10.1016/j.jpain.2009.05.006

« PreviousThe Journal of Pain
Volume 10, Issue 12 , Pages 1250-1255, December 2009

Increased Risk of Complex Regional Pain Syndrome in Siblings of Patients?

Annetje M. de Rooij
- Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
Marissa de Mos
- Departments of Medical Informatics and Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
Jacobus J. van Hilten
- Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
Miriam C.J.M. Sturkenboom
- Departments of Medical Informatics and Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
M. Florencia Gosso
- Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Arn M.J.M. van den Maagdenberg
- Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Johan Marinus
- Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
- Address reprint requests to Dr J. Marinus, Leiden University Medical Centre, Department of Neurology (K5Q), PO Box 9600, 2300 RC Leiden, The Netherlands.

Received 28 January 2009; received in revised form 16 April 2009; accepted 28 May 2009. published online 23 October 2009.

Abstract

An increased risk among siblings of probands with complex regional pain syndrome (CRPS) may be indicative of a genetic contribution. We calculated the sibling recurrence risk ratio (λ_sibling), a measure of familial aggregation. We surveyed 405 CRPS patients to collect information on the occurrence of CRPS in their siblings and compared this risk with the population risk to develop the syndrome. Information on disease status was collected from 1242 siblings, of which 24 were possibly affected according to their siblings. The diagnosis was confirmed in 16 patients, rejected in 2, and could not be verified in the remaining 6. Age-specific risk ratios were calculated for younger (<50 years) and older (≥50 years) age groups. The strongest effects were seen in the younger age group, with a λ_sibling for possibly affected and confirmed cases of 5.6 (95% CI, 3.0 to 9.8) and 3.4 (95% CI, 1.5 to 6.8), respectively. We concluded that this study yielded no indications for an overall increased risk of developing CRPS for siblings of CRPS patients but that the risk was significantly increased in siblings younger than 50, which may indicate that genetic factors play a more pronounced role in this subgroup.

Perspective

We studied the risk of developing CRPS for siblings of patients with this syndrome. Although the overall risk for siblings was not increased compared with the population risk, the risk for younger siblings was elevated. To enhance chances of success, future genetic studies may consider restricting inclusion to younger-onset cases.

Key words: Complex regional pain syndrome, sibling recurrence risk ratio, genetic predisposition, heritability