Oculopharyngeal Muscular Dystrophy
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Oculopharyngeal muscular dystrophy
Pharyngeal muscles
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy caused by a polyalanine expansion mutation in the coding region of the poly-(A) binding protein nuclear 1 (PABPN1) gene. In unaffected individuals, (GCG)(6) encodes the first 6 alanines in a homopolymeric stretch of 10 alanines. In most patients, this (GCG)(6) repeat is expanded to (GCG)(8-13), leading to a stretch of 12-17 alanines in mutant PABPN1, which is thought to confer a toxic gain of function. Thus, OPMD has been modelled by expressing mutant PABPN1 transgenes in the presence of endogenous copies of the gene in cells and mice. In these models, increased apoptosis is seen, but it is unclear whether this process mediates OPMD. The role of apoptosis in the pathogenesis of different muscular dystrophies is unclear. Blocking apoptosis ameliorates muscle disease in some mouse models of muscular dystrophy such as laminin α-2-deficient mice, but not in others such as dystrophin-deficient (mdx) mice. Here we demonstrate that apoptosis is not only involved in the pathology of OPMD but also is a major contributor to the muscle weakness and dysfunction in this disease. Genetically blocking apoptosis by over-expressing BCL2 ameliorates muscle weakness in our mouse model of OPMD (A17 mice). The effect of BCL2 co-expression on muscle weakness is transient, since muscle weakness is apparent in mice expressing both A17 and BCL2 transgenes at late time points. Thus, while apoptosis is a major pathway that causes muscle weakness in OPMD, other cell death pathways may also contribute to the disease when apoptosis is inhibited.
Oculopharyngeal muscular dystrophy
Muscle weakness
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Oculopharyngeal muscular dystrophy
Pharyngeal muscles
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Surgical treatment of oculopharyngeal muscular dystrophy. Report of two casesOculopharyngeal muscular dystrophy (OPMD) is a rare myopathy that is characterized by ocular and pharyngeal muscle involvement.OPMD typically presents with ptosis, dysarthria, and dysphagia.It can also be associated with proximal and distal extremity weakness.We report two patients with the disease.A 79 years old female presenting with ptosis, dysphagia and a history of three aspiration pneumonias.The patient was subjected to a myotomy of the cricopharyngeal muscle of 4.5 cm of length.The patient had a symptomatic improvement and is in good conditions five months after the operation.A 75 years old male presenting with dysphagia and ptosis.He was operated, performing a myotomy of the cricopharyngeal muscle of 3.5 cm of length.Two and a half months after operation the patient is devoid of dysphagia.
Oculopharyngeal muscular dystrophy
Pharyngeal muscles
Cricopharyngeal myotomy
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Oculopharyngeal muscular dystrophy
Pharyngeal muscles
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Key points Millions of elderly individuals have dysphagia, a debilitating and life‐threatening condition in which the ability to swallow is impaired. Several muscles surround the three regions of the pharynx, which are essential for proper swallowing, yet the effects of ageing and disease on these muscles are not well understood. We demonstrate that the fibre size of murine pharyngeal muscles is differentially affected by ageing and muscular dystrophy depending on their location within the pharynx. Using a mouse model of an age‐associated dysphagic disease (oculopharyngeal muscular dystrophy), we show that overexpression of wild‐type polyadenylate binding nuclear protein 1 in muscle tissue prevents age‐related dysphagia and age‐related muscle atrophy of laryngopharyngeal muscles. These results demonstrate that mice are an excellent model for studying mechanisms of ageing and disease on pharyngeal muscle physiology, and such studies could lead to new therapies for individuals with dysphagia. Abstract The inability to swallow, or dysphagia, is a debilitating and life‐threatening condition that arises with ageing or disease. Dysphagia results from neurological or muscular impairment of one or more pharyngeal muscles, which function together to ensure proper swallowing and prevent the aspiration of food or liquid into the lungs. Little is known about the effects of age or disease on pharyngeal muscles as a group. Here we show ageing affected pharyngeal muscle growth and atrophy in wild‐type mice depending on the particular muscle analysed. Furthermore, wild‐type mice also developed dysphagia with ageing. Additionally, we studied pharyngeal muscles in a mouse model for oculopharyngeal muscular dystrophy, a dysphagic disease caused by a polyalanine expansion in the RNA binding protein, PABPN1. We examined pharyngeal muscles of mice overexpressing either wild‐type A10 or mutant A17 PABPN1. Overexpression of mutant A17 PABPN1 differentially affected growth of the palatopharyngeus muscle dependent on its location within the pharynx. Interestingly, overexpression of wild‐type A10 PABPN1 was protective against age‐related muscle atrophy in the laryngopharynx and prevented the development of age‐related dysphagia. These results demonstrate that pharyngeal muscles are differentially affected by both ageing and muscular dystrophy in a region‐dependent manner. These studies lay important groundwork for understanding the molecular and cellular mechanisms that regulate pharyngeal muscle growth and atrophy, which may lead to novel therapies for individuals with dysphagia.
Oculopharyngeal muscular dystrophy
Pharyngeal muscles
Muscle Atrophy
Neuromuscular disease
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The authors report a case of oculopharyngeal muscular dystrophy, an autosomal dominant genetic disease, which leads to miogenic ptosis. This patient presented bilateral palpebral ptosis and dysphagia and underwent ptosis surgical treatment, with a good functional and aesthetic result. Miogenic ptosis in oculopharyngeal muscular dystrophy
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In December, 1962, Victor, Hayes, and Adams9called attention to several patients with a unique combination of progressive dysphagia and ptosis which they appropriately named oculopharyngeal muscular dystrophy. As noted by these authors, Taylor,8in 1915, published a study of a French-Canadian family in which a number of members, all over 50 years of age, became affected with progressive ptosis and dysphagia, which he erroneously ascribed to "degeneration" of cranial nerve nuclei. In 1948 Amyot1described a similar condition in a number of patients, also of French-Canadian descent, in whom there was a familial incidence of ptosis and dysphagia of late onset and progressive severity. He suggested that the ptosis was due to myopathy of the levator muscles. Whereas a number of previous authors had considered progressive ptosis and extraocular muscle paresis to be due to degeneration of cranial nerve nuclei, Kiloh and Nevin,5in 1951
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Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic disorder with late-onset progressive myopathy affecting mainly head and neck striated muscles. It is more common in certain ethnic communities. Dysphagia was usually attributed to the malfunction of striated pharyngeal muscles. We studied a group of Bukharan immigrants affected by this disorder (N = 13). Esophageal studies, including endoscopy, manometry, and scintigraphic emptying were performed. Very low pharyngeal pressures were measured. Upper esophageal pressures (UEP) were in the normal range in eight patients, and above normal in three patients. Four also had low lower esophageal sphincter pressure. Esophageal body peristaltic activity was grossly impaired in all patients: mainly nonpropulsive, simultaneous, retrograde, and failed activity was recorded. Marked retention of isotopic material was demonstrated in all patients studied, usually in the middle and lower parts of the body, ranging from 17 to 100% retention. The dysphagia in OPMD is due not only to dysfunction of pharyngeal and upper esophageal striated muscle, but also has a significant smooth muscle component.
Oculopharyngeal muscular dystrophy
Pharyngeal muscles
Peristalsis
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Oculopharyngeal muscular dystrophy
Pharyngeal muscles
Epiglottis
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Oculopharyngeal muscular dystrophy
Pharyngeal muscles
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