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Reflex sympathetic dystrophy: Complex regional pain syndrome Type I in children with mitochondrial disease and maternal inheritance
  1. Tomoyasu Higashimoto (tomoyasu.higashimoto{at}
  1. Cincinnati Children's Hospital Medical Center, United States
    1. Erin E Baldwin (ebaldwin{at}
    1. Childrens Hospital Los Angeles, United States
      1. Jeffrey I Gold (jgold{at}
      1. Childrens Hospital Los Angeles, United States
        1. Richard G Boles (rboles{at}
        1. Childrens Hospital Los Angeles, United States


          Objective: Complex Regional Pain Syndrome Type I (CRPS-I), previously known as Reflex Sympathetic Dystrophy (RSD), is an idiopathic condition characterized by localized, abnormally intense and prolonged pain, allodynia and autonomic nervous system changes (i.e., swelling, skin color and temperature changes, altered perspiration) that usually appears following a "noxious" trigger such as trauma or surgery. The objective of this report is to demonstrate that children with CRPS-I can have additional dysautonomic conditions secondary to an underlying maternally inherited mitochondrial disease, an association not previously published.

          Methods: Medical records of about 500 clinic patients seen by one pediatric metabolic geneticist were reviewed to identify children meeting established CRPS diagnostic criteria.

          Results: CRPS-I was present in eight children in seven families, each of which also had additional functional/dysautonomic conditions, the most common (≥4 cases per condition) being: gastrointestinal dysmotility, migraine, cyclic vomiting and chronic fatigue. All seven probands studied met Nijmegen (2002) diagnostic criteria for definite mitochondrial disease based upon the clinical signs and symptoms and biochemical analyses. Six of the seven families met our pedigree-based criteria for probable maternal inheritance.

          Conclusion: In one tertiary-care pediatric genetics practice, children meeting the CRPS-I diagnostic criteria frequently have additional autonomic-related conditions secondary to maternally-inherited mitochondrial disease, suggesting that mitochondrial DNA sequence variants can predispose towards the development of CRPS-I and other dysautonomias. CRPS-I should be considered in patients with mitochondrial disease who complain of idiopathic pain. Maternally inherited mitochondrial disease may not be a rare cause of CRPS-I, especially in children who present with other manifestations of dysautonomia.

          • Complex Regional Pain Syndrome Type I
          • Maternal Inheritance
          • Mitochondrial Disease
          • Quantitative Pedigree Analysis
          • Reflex Sympathetic Dystrophy

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