|Facioscapulohumeral muscular dystrophy.
|Maarel, S.M. van der; Frants, R.R.; Padberg, G.W.A.M.
|Facioscapulohumeral muscular dystrophy (FSHD) is caused by a cascade of epigenetic events following contraction of the polymorphic macrosatellite repeat D4Z4 in the subtelomere of chromosome 4q. Currently, the central issue is whether immediate downstream effects are local (i.e., at chromosome 4q) or global (genome-wide) and there is evidence for both scenarios. Currently, there is no therapy for FSHD, mostly because of our lack of understanding of the primary pathogenic process in FSHD muscle. Clinical trials based on suppression of inflammatory reactions or increasing muscle mass by drugs or training have been disappointing. A recent, probably the first evidence-based pilot trial to revert epigenetic changes did also not provide grounds for a larger clinical study. Clearly, better disease models need to be developed to identify and test novel intervention strategies to eventually improve the quality of life for patients with FSHD.
|Radboud University Nijmegen
|Biochimica et biophysica acta. Molecular basis of disease, Vol. vol. 1772, p.p. 186-p. 194.
Tuesday, January 26, 2010
Wednesday, January 20, 2010
Received 20 March 2009; received in revised form 5 May 2009; accepted 13 May 2009. published online 08 June 2009.
AbstractFacioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent forms of muscular dystrophy. The aims of this study were: 1) to evaluate the prevalence of sleep disordered breathing (SDB) in patients with FSHD; 2) to define the sleep-related respiratory patterns in FSHD patients with SDB; and 3) to find the clinical predictors of SDB. Fifty-one consecutive FSHD patients were enrolled, 23 women, mean age 45.7±12.3 years (range: 26–72). The diagnosis of FSHD was confirmed by genetic tests. All patients underwent medical and neurological evaluations, subjective evaluation of sleep and full-night laboratory-based polysomnography. Twenty patients presented SDB: 13 presented obstructive apneas, four presented REM related oxygen desaturations and three showed a mixed pattern. Three patients needed positive airways pressure. SDB was not related to the severity of the disease. Body mass index, neck circumference and daytime sleepiness did not allow prediction of SDB. In conclusion, the results suggest a high prevalence of SDB in patients with FSHD. The presence of SDB does not depend on the clinical severity of the disease. SDB is often asymptomatic, and no clinical or physical measure can reliably predict its occurrence. A screening of SDB should be included in the clinical assessment of FSHD.
Tuesday, January 19, 2010
Project Leader: Dr Peter Zammit
Location: King's College London
Duration: 4 Years
Total Project Cost: £60,000 - Jointly funded with King's College London
Official Title: Does perturbed satellite cell function contribute to facioscapulohumeral muscular dystrophy?
Dr Zammit aims to use this 4 year PhD studentship to explore the role that muscle stem cells - also known as satellite cells - have in the progression of facioscapulohumeral muscular dystrophy (FSH). Dr Zammit will deliver two of the genes thought to be involved in FSH into muscle stem cells. This will allow him to find out what effect, if any, these genes have on how well the muscle stem cells are able to repair muscle.
Saturday, January 16, 2010
Journal of neurology, neurosurgery and psychiatry
Résumé / AbstractBackground and aim: Muscle weakness is a potentially important, yet poorly studied, risk factor for falls. Detailed studies of patients with specific myopathies may shed new light on the relation between muscle weakness and falls. Here falls in patients with facioscapulohumeral disease (FSHD) who suffered from lower limb muscle weakness were examined. This study provides insights into the prevalence, relevance and pathophysiology of falls in FSHD. Methods: A validated questionnaire was used as well as a prospective 3 month follow-up to examine the prevalence, circumstances and consequences of falls in 73 patients with FSHD and 49 matched healthy controls. In a subgroup of 28 subjects, muscle strength was also examined and balance was assessed electrophysiologically using body worn gyroscopes. Results: In the questionnaire, 30% of the patients reported falling at least once a month whereas none of the controls did. Injuries occurred in almost 70% of the patients. The prospective study showed that patients fell mostly at home, mainly due to intrinsic (patient related) causes, and usually in a forward direction. Fallers were unstable while climbing stairs, rising from a chair and standing with eyes closed whereas non-fallers had normal balance control. Frequent fallers had greater muscle weakness than infrequent fallers. Conclusion: These findings demonstrate the high prevalence and clinical relevance of falls in FSHD. The relation between muscle weakness and instability among fallers is also highlighted. Because patients fell mainly at home, fall prevention strategies should focus on home adaptations. As mainly intrinsic causes underlie falls, the impact of adopting balance strategies or balance training should be explored in this patient group.
Friday, January 15, 2010
Control of the upper body movements during level walking in patients with facioscapulohumeral dystrophy
This study highlighted that the control of upper body oscillations and of head stability is reduced in patients with FSHD, suggesting that the assessment of the upper body movements should be included in the treatment decision process.
Saturday, January 9, 2010
J Korean Neurol Assoc. 2009 Feb;27(1):42-48. Korean.
Clinical Features and Genetic Analysis of Fascioscapulohumeral Muscular Dystrophy.
Hong JM, Kim SM, Sunwoo IN, Seo KD, Shim DS, Suh BC, Kim DS, Cho JH, Choi YC.
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea. firstname.lastname@example.org
Department of Neurology, Kangbuk Samsung Hospital, Seoul, Korea.
Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Korea.
Department of Neurology, KoreaNational Health Insurance Corporation Ilsan Hospital, Goyang, Korea.
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of the polymorphic D4Z4-repeat array in 4q35 and has the distinctive clinical presentation of an initial involvement of the facial, shoulder-girdle, and upper-arm muscles. The aim of the present study was to determine clinical characteristics in Korean patients with FSHD and potential relationships between contracted D4Z4-repeat size and the FSHD phenotype. METHODS: We studied 34 genetically confirmed patients who had repeat sizes less than 38 kb, and analyzed their clinical manifestations with a structured protocol. The expressed phenotypes were scored according to the Clinical Severity Score formulated by Ricci and van Overveld. RESULTS: The clinical spectrum ranged widely, from asymptomatic individuals with minimal signs to wheelchair- bound patients. The initial affects were mainly in the facial muscles (68.8%), followed by the shoulder-girdle muscle (28.1%). Asymmetric features of the face and shoulder girdle were also important findings (71.9% and 90.0%, respectively). Winging scapular (87.5%), transverse smile (84.4%), Beevor's sign (68.8%), and sleeping with eyes opened (59.4%) were clinically important signs. There was a significant negative correlation between repeat size and clinical severity (r=-0.38, p=0.03). CONCLUSIONS: Distinctive clinical characteristics of FSHD are descending progression and asymmetric distribution of the muscle weakness. Our results also confirmed that the severity of FSHD increases with decreasing D4Z4-repeat size.
Thursday, January 7, 2010
Grant helps UI research on infantile form of FSH muscular dystrophy
University of Iowa researchers will study the most prevalent type of muscular dystrophy, thanks to a one-year, $39,998 grant from the FSH Society, Inc. The organization focuses on raising awareness and advancing research on facioscapulohumeral muscular dystrophy (FSHD), which affects about one in 14,286 individuals worldwide and currently has no treatment or cure.
A team led by Yi Xing, Ph.D., UI assistant professor of internal medicine, biomedical engineering and biostatistics, will use advanced technologies to identify RNA splicing differences among healthy people and people with FSHD or its infantile form. RNA splicing differences affect how genetic code is assembled and translated, and can result in defective messenger RNAs or proteins.
Collaborators are Katherine Mathews, M.D., UI professor of pediatrics and neurology, and investigators at the NIH-Funded Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center cell core led by Steven Moore, M.D., Ph.D., professor of pathology.
Learn more at http://www.int-med.uiowa.edu/News/Stories.asp?displayID=248.