Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied prospectively 105 unselected patients complaining of ptosis and/or diplopia due to extrinsic ophthalmic muscle palsies without other neurological signs. All patients underwent the same diagnostic protocol. The presenting symptoms were: ptosis, 35 patients (33%); diplopia, 27 patients (26%); ptosis and diplopia, 43 patients (41%). The oculomotor nerve was most frequently involved, followed by the abducens nerve. The final diagnoses were: ocular myasthenia, intracranial and/or orbital pathology, thyroid ophthalmopathy, diabetic ophthalmoplegia, mitochondrial myopathy, oculopharyngeal muscular dystrophy. In 26 patients (25%) the cause remained undetermined. Our study confirms the difficulty of establishing an aetiological diagnosis in patients with isolated ocular palsies.
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PMID:Ocular palsies in the absence of other neurological or ocular symptoms: analysis of 105 cases. 940 41

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease with a world-wide distribution. It usually presents in the sixth decade with progressive swallowing difficulties (dysphagia), eyelid drooping (ptosis) and proximal limb weakness. Unique nuclear filament inclusions in skeletal muscle fibres are its pathological hallmark. We isolated the poly(A) binding protein 2 gene (PABP2) from a 217-kb candidate interval on chromosome 14q11 (B.B. et al., manuscript submitted). A (GCG)6 repeat encoding a polyalanine tract located at the N terminus of the protein was expanded to (GCG)8-13 in the 144 OPMD families screened. More severe phenotypes were observed in compound heterozygotes for the (GCG)9 mutation and a (GCG)7 allele that is found in 2% of the population, whereas homozygosity for the (GCG)7 allele leads to autosomal recessive OPMD. Thus the (GCG)7 allele is an example of a polymorphism which can act either as a modifier of a dominant phenotype or as a recessive mutation. Pathological expansions of the polyalanine tract may cause mutated PABP2 oligomers to accumulate as filament inclusions in nuclei.
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PMID:Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. 946 47

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) usually begins with ptosis or dysphagia during the fifth or sixth decade of life. We studied 7 patients with OPMD symptoms starting before the age of 36 years. All were found to be homozygotes for the dominant (GCG)9 OPMD mutation. On average, disease onset was 18 years earlier than in heterozygotes, and patients had a significantly larger number of muscle nuclei containing intranuclear inclusions (INIs) (9.4 vs 4.9%).
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PMID:Homozygotes for oculopharyngeal muscular dystrophy have a severe form of the disease. 1040 88

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease with worldwide distribution. It usually presents in the fifth or sixth decades with progressive dysphagia, eyelid ptosis, and proximal limb weakness. Unique intranuclear filament inclusions in skeletal muscle fibers are its morphological hallmark. Surgical correction of the ptosis and cricopharyngeal myotomy are the only therapies available. Autosomal dominant OPMD is caused by short (GCG)8-13 riplet-repeat expansions in the polyadenylation binding protein 2 (PABP2) gene, which is localized in chromosome 14q11. Autosomal recessive OPMD is caused by a double dose of a (GCG)7 PABP2 allele. The GCG expansions cause lengthening of a predicted polyalanine tract in the protein. The expanded polyalanine domains may cause polyalanine nuclear toxicity by accumulating as nondegradable nuclear filaments.
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PMID:Oculopharyngeal muscular dystrophy. 1071 89

Clinicopathological and molecular genetic findings on a new Japanese family with oculopharyngeal muscular dystrophy are reported. The family has 54 members, ten of whom are affected (seven male and three female), in 3 generations. Three affected males, one affected female and one unaffected female of seven living siblings in the third generation were examined. Bilateral ptosis developed in the 4th and 5th decades in the three male cases, and in the 7th decade in the female, and this was followed by diplopia, nasal voice, dysphagia and muscle weakness. In addition, severe external ophthalmoplegia, dysphonia, and proximal amyotrophy were prominent in this family. Electromyographs revealed myogenic/neurogenic changes, and computed tomography disclosed selective muscle wasting with fatty replacement, predominantly in the lower extremities. Muscle biopsy in the four affected patients showed variation in fiber size, and the presence of small angulated fibers and occasional rimmed vacuoles. Electron microscopic examination revealed an accumulation of filamentous inclusions in muscle fiber nuclei. DNA analysis identified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11) in the four affected cases examined. All studies were negative in the one unaffected. These results confirm that OPMD is caused by GCG short expansion and provides insights into the genetic mechanisms which may contribute to adult onset myopathy, confined to oculopharyngeal muscles.
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PMID:Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene. 1073 63

Blepharoptosis is one of the troublesome ocular complications of myotonic dystrophy. To correct drooping eyelids for two men with myotonic dystrophy, we used Eye Putti, a cosmetic made of natural rubber latex, which induces a new fold in the upper eyelid. The cosmetic rubber latex dramatically improved the sight of a 59-year-old patient who previously had a great difficulty in looking forward and had to bend his head backward to see an object because of severe blepharoptosis. The other patient aged 54 with moderate ptosis also had satisfactory improvement. Appropriate use did not prevent eye blinking and induce corneal erosion or skin rash. The cosmetic rubber latex was effective to patients who had no residual function of the levator palpebrae and frontal muscles. This daily treatment is simple and safe, therefore may have an advantage over surgical correction of blepharoptosis for patients not only with myotonic dystrophy, but with other neuromuscular disorders including oculopharyngeal muscular dystrophy.
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PMID:[Beneficial effect of eyelid make-up (natural rubber latex) to induce a new fold in the treatment of blepharoptosis in myotonic dystrophy]. 1100 33

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder of late onset that commonly presents with ptosis and dysphagia. The genetic basis of the condition has been identified recently as a stable trinucleotide repeat expansion in exon 1 of the poly(A) binding protein 2 gene (PABP2), in which (GCG)(6) is the normal repeat length. The prevalence of OPMD is greatest in patients of French-Canadian origin. It is not clear if expansion repeat length is a reliable test in other populations. In this study, we analysed the phenotypic and genotypic characteristics of 31 patients with OPMD in the UK. Ptosis was the first reported symptom in two-thirds of the patients, and half of the subjects studied had evidence of ophthalmoplegia. All but one family had a pathological expansion in the PABP2 gene, ranging from (GCG)(8) to (GCG)(13). In contrast to the French-Canadian population, (GCG)(10) was almost as common as (GCG)(9), evidence against a strong founder effect in the UK population. There was a weak association between repeat length and age of disease onset. Patients with longer repeat lengths, such as (GCG)(13), developed severe limb weakness early in the disease. We were unable to detect the (GCG)(7) polymorphism in over 200 normal controls, suggesting that the frequency of this expansion is lower than that found in the French-Canadian population. One family was negative for the expansion. Affected members presented with the classical features of OPMD, namely ptosis, dysphagia and cytoplasmic inclusions on muscle biopsy, although with some atypical features, such as early age of onset, high serum levels of creatine kinase and a profound ophthalmoplegia. This family is an example of a GCG expansion-negative oculopharyngeal syndrome requiring further genetic investigation. We conclude that PABP2 analysis is a reliable non-invasive diagnostic test for OPMD in the UK population.
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PMID:Oculopharyngeal muscular dystrophy: phenotypic and genotypic studies in a UK population. 1122 52

A 54-year-old female patient presented with exercise-induced proximal muscle pain and weakness of the lower limbs. One year after the onset of these symptoms she developed bilateral ptosis and dysphagia. Molecular genetic analysis of the poly(A) binding protein 2 gene (PABP2) confirmed the presumptive diagnosis of oculopharyngeal muscular dystrophy (OPMD). Exercise-induced proximal muscle pain and weakness are rarely initial symptoms of OPMD. We discuss therapeutic options and present an overview of the relevant literature.
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PMID:[Proximal weakness and exercise-induced pain as initial symptom of oculopharyngeal muscular dystrophy]. 1151 9

The authors place autosomal dominant oculopharyngeal muscular dystrophy in a historical perspective, look at the genealogy involved, and review the genetic studies. In addition to summarizing what happens at the histopathological level, they examine the clinical characteristics of this late-onset dystrophy. Based on this knowledge, they try to present their rationale for the surgical treatment of the eyelid ptosis, taking into account that this disease is progressive and that treatment should be planned for the lifetime of the patient. Three representative cases are illustrated.
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PMID:Oculopharyngeal muscular dystrophy: What's new? 1204 2

Nine patients over 5 generations developed progressive bilateral blepharoptosis from 40 to 50 years of age, suggesting that they had an autosomal dominantly inherited blepharoptosis. Except for the ptosis, they had no apparent neurological symptoms: normal ocular movement, no bulbar sign and no muscle weakness in the extremities. On laboratory examination, serum creatine kinase and blood lactate levels were within normal limits, and acetylcholine receptor antibody was not elevated. Electrophysiological studies including EMG and nerve conduction velocities were normal. Muscle biopsies from gastrocnemius and palpebral muscles were nondiagnostic with no ragged-red fibers nor rimmed vacuoles. Nuclear inclusions were not recognized by electron microscopy. Since none of patients examined had mitochondrial DNA deletions and GCG repeat expansion in the poly A binding protein P2 (PABP2) gene, this familial disorder is a unique blepharoptosis with no relationship to progressive external ophthalmoplegia or oculopharyngeal muscular dystrophy with PABP2 mutation.
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PMID:[Familial chronic progressive blepharoptosis without other neurological symptoms: a new clinical entity?]. 1235 44


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