Familial aggregation in fibromyalgia

Genetic and environmental factors may play a role in the etiopathology of fibromyalgia syndrome (FMS) and other related syndromes. There is a high aggregation of FMS in families of FMS patients. The mode of inheritance is unknown but it is most probably polygenic. There is evidence that polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems play a role in the etiology of FMS. These polymorphisms are not specific for FMS and are associated with other functional somatic disorders and depression. Future genetic studies in the field of FMS and related conditions should be conducted in larger cohorts of patients and ethnically matched control groups. Introduction Fibromyalgia is an idiopathic, chronic pain syndrome defined by widespread nonarticular musculoskeletal pain and generalized tender points [1]. Fibromyalgia syndrome (FMS) overlaps with several related syndromes, the functional somatic syndromes [2]. The pathogenesis of FMS and related conditions is not entirely understood, although the current concept views FMS as the result of central nervous system malfunction, resulting in amplification of pain transmission and interpretation [3,4]. Recent evidence suggests that FMS and related syndromes share heritable pathophysiological features [5,6]. Certain environmental factors may trigger the development of FMS and related conditions in genetically predisposed individuals [7]. The aim of this article is to review the current evidence that genetic and familial factors may play a role in the development of FMS. Familial aggregation in fibromyalgia The prevalence of FMS in the general population is estimated at 2% [8]. The prevalence of FMS and the observation of rheumatologists that this syndrome runs in families suggest that genetic and familial factors may play a role in its etiopathogenesis. Several studies have addressed the frequency of FMS in families of patients with FMS. Two studies [9,10] suggested that FMS segregates within families in an autosomal dominant mode of inheritance. One of them [9], based on clinical diagnostic criteria modified from Yunus, showed female preponderance and, in addition, postulated the existence of a latent or precursor stage of the disease characterized by abnormal palpable muscle consistency. If such a latent stage exists, this study actually showed that 70% of offspring of FMS patients are affected, a rate that considerably exceeds the one expected from autosomal dominant inheritance (50%) and suggests over-diagnosis in this study. In addition, this study rejected the polygenic mode of inheritance based on data on second degree relatives, which was not presented in the article. The second study by Stormorken and colleagues [10] was based on data retrieved from questionnaires regarding FMS symptoms in family members of index patients. According to this study, about two-thirds of the study population reported family clustering. However, the statement regarding a clear pattern of dominant inheritance was not corroborated by numerical data. A subsequent study attempted to document the mother-child correlation with regard to the occurrence of fibromyalgia, and also compared sleep disorder patterns between a group of childhood fibromyalgia patients and their mothers [11]. A significant concordance was observed between children and mothers regarding both occurrence of FMS and the sleep disorder. Buskila and colleagues [12] analyzed the occurrence of FMS among 58 offspring of 20 affected mothers with FMS; 16 offspring (28%) were found to have FMS. The male/female ratio among those affected was 0.8 compared with 1.5 in the whole group. Offspring with and without FMS did not differ in anxiety, depression, global well being, quality of life and physical functioning. Because psychological and familial factors were Review Biology and therapy of fibromyalgia Genetic aspects of fibromyalgia syndrome Dan Buskila1 and Piercarlo Sarzi-Puttini2 1Department of Medicine H, Soroka Medical Center and Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel 2Department of Rheumatology, University Hospital L. Sacco, Milan, Italy Corresponding author: Dan Buskila, [email protected] Published: 28 July 2006 Arthritis Research & Therapy 2006, 8:218 (doi:10.1186/ar2005) This article is online at http://arthritis-research.com/content/8/5/218 © 2006 BioMed Central Ltd ASD = affective spectrum disorder; CFS = chronic fatigue syndrome; COMT = catechol-O-methyltransferase; FMS = fibromyalgia syndrome.