Pain, Physical and Social Functioning, and Quality of Life in Individuals with Multiple Hereditary Exostoses in the Netherlands
ABSTRACT This study aimed to assess pain and quality of life in a large cohort of patients with multiple hereditary exostoses.
All 322 known patients with multiple hereditary exostoses in The Netherlands were asked to participate. An age-specific questionnaire was sent to children (less than eighteen years old) and adults. The questionnaire focused on pain, daily activities, and school and/or professional situation. Adults also filled out the RAND-36 questionnaire. Results were statistically analyzed with use of the SPSS 15.0 software and with the chi-square test and multiple logistic regression. A p value of <0.05 was regarded as significant.
Two hundred and eighty-three patients (88%), including 184 adults (65%) and ninety-nine children (35%), completed the questionnaire. Multiple hereditary exostoses resulted in various physical and social consequences. The majority of adults (119) were employed; however, thirty-three (28%) had changed jobs because of the symptoms of multiple hereditary exostoses and twenty-five (21%) required adjustments in their working environment. Of the sixty-five adults who were not employed, thirteen were medically unfit to work. Of eighty-five children attending school, forty-five (53%) experienced problems at school. The symptoms of multiple hereditary exostoses caused twenty-seven children (27%) and eighty-five adults (46%) to stop participating in sporting activities. Pain was the greatest problem, with sixty-two children (63%) and 152 adults (83%) who reported recent pain. On multivariate analysis, pain in adults was correlated most significantly with age and problems at work, and pain in children was correlated with the perception of the disease and problems at school. Adult patients with multiple hereditary exostoses had a lower quality of life than the Dutch reference groups, with lower scores on six of eight RAND-36 subscales.
Our study confirms that multiple hereditary exostoses is a chronic disease causing a profound impact on quality of life. The results suggest that pain is not the only problem associated with multiple hereditary exostoses, as it has an extensive influence on daily activities, as well as on social and psychological well-being, causing significant disability.
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ABSTRACT: Nerve growth factor (NGF) is the founding member of the neurotrophins family of proteins. It was discovered more than half a century ago through its ability to promote sensory and sympathetic neuronal survival and axonal growth during the development of the peripheral nervous system, and is the paradigmatic target-derived neurotrophic factor on which the neurotrophic hypothesis is based. Since that time, NGF has also been shown to play a key role in the generation of acute and chronic pain and in hyperalgesia in diverse pain states. NGF is expressed at high levels in damaged or inflamed tissues and facilitates pain transmission by nociceptive neurons through a variety of mechanisms. Genetic mutations in NGF or its tyrosine kinase receptor TrkA, leads to a congenital insensitivity or a decreased ability of humans to perceive pain. The hereditary sensory autonomic neuropathies (HSANs) encompass a spectrum of neuropathies that affect one's ability to perceive sensation. HSAN type IV and HSAN type V are caused by mutations in TrkA and NGF respectively. This review will focus firstly on the biology of NGF and its role in pain modulation. We will review neuropathies and clinical presentations that result from the disruption of NGF signalling in HSAN type IV and HSAN type V and review current advances in developing anti-NGF therapy for the clinical management of pain. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12093.Journal of Neurochemistry 11/2012; 124(3). DOI:10.1111/jnc.12093 · 4.24 Impact Factor
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ABSTRACT: Purpose Children with multiple hereditary exostoses (MHE) have numerous osteochondromas, with the most prominent lesions typically over the appendicular skeleton. A recent report noted a high rate of intracanal lesions in this patient population and recommended preventative spinal screening with magnetic resonance imaging (MRI) or computed tomography (CT). We sought to evaluate the prevalence of spinal stenosis from intracanal osteochondromas at our pediatric orthopedic center in order to evaluate if routine screening is warranted. Methods All pediatric patients treated for MHE were retrospectively identified. Records were reviewed to determine demographics, previous orthopedic surgery, and indication and results of axial spine imaging (CT or MRI). Imaging studies were reviewed to evaluate the presence of intracanal and compressive spinal lesions. Results Between 1990 and 2011, axial imaging was performed in nine patients with MHE due to concerns of pain, weakness, and/or dizziness. These patients had moderate disease involvement, with a mean of 4.9 previous orthopedic surgeries to address skeletal osteochondromas. Two patients with MHE had cervical spinal stenosis secondary to intracanal osteochondromas. Both children successfully underwent spinal decompression. Thus, of our MHE population undergoing axial imaging, 22 % were noted to have intracanal lesions. Conclusions Our experience reveals a >20 % rate of compressive intracanal osteochondromas in MHE patients undergoing spinal imaging. These two patients represent 5 % of the MHE patients treated at our center. These lesions may be slow growing, and significant consequences can occur if not identified promptly. Thus, we confer that routine axial screening of the spinal canal may be warranted in these children.Journal of Children s Orthopaedics 06/2013; 7(3). DOI:10.1007/s11832-013-0484-9
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ABSTRACT: Heparan sulfate (HS) is an essential component of cell surface and matrix-associated proteoglycans (HSPGs). Due to their sulfation patterns, the HS chains interact with numerous signaling proteins and regulate their distribution and activity on target cells. Many of these proteins, including bone morphogenetic protein family members, are expressed in the growth plate of developing skeletal elements, and several skeletal phenotypes are caused by mutations in HS-synthesizing and modifying enzymes. The disease we discuss here is Hereditary Multiple Exostoses (HME), a disorder caused by mutations in HS synthesizing enzymes EXT1 and EXT2, leading to HS deficiency. The exostoses are benign cartilaginous-bony outgrowths, form next to growth plates, can cause growth retardation and deformities, chronic pain and impaired motion, and progress to malignancy in 2-5% of patients. We describe recent advancements on HME pathogenesis and exostosis formation deriving from studies that have determined distribution, activities and roles of signaling proteins in wild type and HS-deficient cells and tissues. Aberrant distribution of signaling factors combined with aberrant responsiveness of target cells to those same factors appear to be a major culprit in exostosis formation. Insights from these studies suggest plausible and cogent ideas about how HME could be treated in the future. Developmental Dynamics, 2013. © 2013 Wiley Periodicals, Inc.Developmental Dynamics 09/2013; 242(9). DOI:10.1002/dvdy.24010 · 2.67 Impact Factor