Genetic derminants factors of musculoskeletal health and diseases
PD Dr. Jules Desmeules, Division of Clinical Pharmacology and Toxicology, Multidisciplinary Pain Center, Geneva University Hospitals|
Genomics, neurophysiology and psychological aspects of fibromyalgia
|Fibromyalgia (FM) is a chronic musculoskeletal condition, characterized by generalized pain, a predictable pattern of "tender points", stiffness, fatigue and disturbed sleep. FM patients often experience functional impairments, emotional distress and a resulting negative quality of life. Despite extensive research, the etiology and pathogenesis of FM remain unclear. This syndrome is not associated with any physical, radiologic, or biologic findings that are directly related to dysfunction, and patients generally appear to be well.
This study aims at expand knowledge on FM mechanisms. Data from the physiology of nerve functioning show that the increased sensitivity to pain in FM individuals may be related to a dysfunction of transmission in the central nervous system. This is indeed the case in more than 50% of FM patients.
There are endogenous substances in the brain that act against pain. Theses mechanisms may be dysfunctional in certain individiuals for innate or acquired reasons. This may be related to an enzymatic deficiency which may lead to an increased pain sensitivity.
Various psychosocial factors have been associated with FM. This is in particular the case of psychological co-morbidities and behavioural aspects, such as emotional distress and depression and their contribution to the health-care seeking behaviour in these patients. Psychological factors have been shown to influence pain severity in FM and they may modulate the severity of perceived distress.|
Peter Jüni, MD, Institute of Social and Preventive Medicine (ISPM), University of Bern; Michael Leunig, MD, Orthopedic Surgery, Schulthess Klinik Zürich|
Familial aggregation of femoro-acetabular impingement of the 'cam' type: a pilot study
|Osteoarthritis is one of the leading musculoskeletal causes of pain and disability. A decreased anterior offset i.e. a decreased difference between the anterior contour of the head and the femoral neck may result in repetitive damage of the peripheral articular cartilage of the hip joint during flexion and internal rotation, a phenomenon referred to as femoro-acetabular impingement. Cam type impingement, which is usually seen in men, is caused by the presence of a femoral neck protuberance with a non-spherical femoral head. Impingement can subsequently lead to osteoarthritis. Although several risk factors for femoro-acetabular impingement have been identified (e.g. fractures, surgery) most of the patients with femoro-acetabular impingement seen in orthopedic surgery lack a history of known predisposing factors. Previous studies suggest that femoral head and neck abnormalities develop during organogenesis. |
Dr. Olivier Bonny, Departement of Département de Pharmacologie et de Toxicologie et Service de Néphrologie, Lausanne|
Osteoporosis and genetics of chronic high urinary calcium excretion
|Osteoporosis is a debilitating disease leading to increased risk of fracture and subsequent complications, including chronic pain and increased morbidity. Environmental and genetic factors are relevant for this complex disease. Chronic high urinary calcium excretion, called hypercalciuria, is found in up to 38% of osteoporotic patients, is related to renal stone formation and has a strong genetic background. In addition, more than 50% of patients with recurrent renal calcium stone exhibit hypercalciuria and a reduced bone mass. Hypercalciuria results from several entities, further defined as
• absorptive hypercalciuria, resulting from hyper-absorption of calcium from the small intestine
• resorptive hypercalciuria, resulting from bone resorption and
• renal leak, resulting from renal defects causing calcium leak.
We hypothesise now that a substantial number of patients with recurrent calcium renal stone have a genetic defect accounting for a renal leak of calcium which in turn conduct to chronic negative bone balance and osteoporosis.|
Prof. Dr. Albert Urwyler, Departement Anästhesie und Forschung, Universitätsspital Basel|
Molecular genetic investigations in patients with muscle disorders associated with the ryanodine receptor
|Some defects (mutations) on the ryanodine receptor gene (RYR1) have been shown to be associated with muscle disorders such as malignant hyperthemia (MH) and central core disease (CCD). MH is a pharmacogenetic disease triggered in susceptible individuals by commonly used anesthetics. MH is dominantly inherited and therefore each child of a MH patient has a 50 % chance of inheriting the gene defect and also being MH susceptible. The anesthetized patient rapidly manifests an increase of CO2 production and develops a high fever and muscle rigidity. During this time, muscle tissue is destroyed and the urine may turn dark (myoglobinuria). Death can occur if specific and symptomatic treatment is not initiated immediately. Because MH susceptible (MHS) subjects may be safely anaesthetized using alternative anaesthetic techniques presymptomatic diagnosis is important.
The gold standard in MH diagnosis is the in vitro muscle contracture test (IVCT), which involves an open muscle biopsy. Muscle strips are exposed in vitro to either halothane or caffeine and the contracture response is measured. On the basis of contractile muscle contracture thresholds patients are diagnosed MHS or MH negative (MHN). However, this test is invasive, expensive and time-consuming and cannot be used for young children, handicapped subjects and elderly persons.
CCD is an inherited neuromuscular disorder characterized by muscle weakness and closely associated with MH. It has been found that the majority of CCD patients are susceptible to MH.
We have identified causative RYR1 mutations in 40% of Swiss MH families. Although this allows for molecular genetic testing for MH susceptibility in 40% of the families, the genetic cause of MH is unknown in the remaining 60%.|