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Oculopharyngeal Muscular Dystrophy

OPMD

Oculopharyngeal muscular dystrophy is a genetic disease distinguished by the onset of ptosis, dysphagia, and weakness of voluntary skeletal muscles in elderly individuals. Choking, food regurgitation, and possibly life-threatening aspiration pneumonia are rare but important complications. Due to a lack of clinical suspicion and the rarity of the disease, the diagnosis is often missed. Demographic and clinical findings, as well as genetic studies, are vital in order to make the diagnosis.


Presentation

With an incidence rate of 0.5-1 per 100,000 individuals in Europe, oculopharyngeal muscular dystrophy (OPMD) is a rare genetic disease in which mutations in genes responsible for the production of polyadenylate binding protein nuclear 1 (PABPN1), an essential molecule for messenger RNA (mRNA) function, leads to a specific type of muscular dystrophy [1] [2] [3] [4]. However, three specific populations have shown a markedly higher prevalence rate - French Canadians (1 in 1,000 individuals), Israel’s Bukharan Jews that emigrated from Uzbekistan (1 in 600 individuals) and Hispanic Mexicans [1] [4] [5] [6]. OPMD is transferred through an autosomal dominant pattern of inheritance in the vast majority of cases, although several reports have confirmed autosomal recessive forms as well [2] [4]. The clinical presentation is distinguished by the appearance of ptosis and dysphagia (as a result of weakness in the levator palpebrae and pharyngeal muscles, respectively) in the fourth to sixth and seventh decades of life, and virtually all individuals who harbor OPMD mutations develop symptoms by the age of 70 [1] [2] [5] [7]. Ptosis is usually bilateral, asymmetric and progressive, as is dysphagia, which may initially be present only with solid foods, but difficulty swallowing liquids, regurgitation and even choking might be seen [1] [2]. Atrophy of the tongue muscles is also a frequent finding in OPMD, while ophthalmoplegia, dysarthria, and weakness of the pelvic and shoulder girdle muscles are less common findings [1] [5] [7]. Complications are rare, but aspiration pneumonia, particularly if recurring episodes are seen, can be life-threatening in the absence of an early diagnosis, and the majority of OPMD-related deaths are attributed to aspiration pneumonia [1]. Malnutrition and starvation, due to profound dysphagia, are other documented complications [1].

Weight Loss
  • The importance of OPMD is emphasized, not only in its differential of ptosis, but also because of the possible sequella from the dysphagia of weight loss, pulmonary infection, choking and tracheal aspiration.[ncbi.nlm.nih.gov]
  • The dysphagia is usually progressive and leads to repetitive regurgitation, increased alimentation time, and weight loss. Immunologic studies generally reveal elevated levels of IgA and IgG, while manometry demonstrates poor pharyngeal contraction.[ncbi.nlm.nih.gov]
  • Over the next 4 years, the patient developed dysphagia, palatal paralysis, weight loss, decreased ocular motility, scoliosis, shortness of breath, and obstructive apnea. Tracheostomy and gastrostomy were required.[ncbi.nlm.nih.gov]
  • With disease progression, dysphagia becomes more severe leading to a significant weight loss, dehydration, malnutrition and repeated events of aspiration pneumonia.[musculardystrophynews.com]
Persistent Cough
  • A patient had chronic, persistent cough as the presenting symptom of the neuromuscular disorder oculopharyngeal dystrophy (OPD). The presence of a significant smoking history initially resulted in the cough incorrectly being attributed to COPD.[ncbi.nlm.nih.gov]
Choking
  • Underdiagnosis and a lack of awareness of OPMD may lead to choking, aspiration pneumonia, and death in multiple members of affected families.[ncbi.nlm.nih.gov]
  • The importance of OPMD is emphasized, not only in its differential of ptosis, but also because of the possible sequella from the dysphagia of weight loss, pulmonary infection, choking and tracheal aspiration.[ncbi.nlm.nih.gov]
  • Choking, food regurgitation, and possibly life-threatening aspiration pneumonia are rare but important complications. Due to a lack of clinical suspicion and the rarity of the disease, the diagnosis is often missed.[symptoma.com]
  • The following complications were collected: death, pneumonia, aspiration pneumonitis, airway obstruction, reintubation, and severe coughing and choking caused by profuse secretions.[ncbi.nlm.nih.gov]
  • Alternatively, some people might first notice that they tend to choke frequently and may have other problems related to difficulty swallowing (called dysphagia ). Most people with OPMD eventually develop some degree of both ptosis and dysphagia .[mda.org]
Progressive Dysphagia
  • We report a 64 year old Chinese-Malaysian woman who presented with progressive dysphagia and bilateral ptosis for about 6 years. Her mother and elder brother (both deceased) were believed to be affected.[ncbi.nlm.nih.gov]
  • Complications of OPMD include ptosis and progressive dysphagia leading to eventual malnutrition and aspiration. We report a rare case of OPMD complicating mechanical ventilator management following emergent surgery.[ncbi.nlm.nih.gov]
  • Most muscular dystrophies manifest as peripheral muscular weakness commencing at various age, however, oculopharyngeal muscular dystrophy (OPMD) is a rare hereditary disorder presenting in middle age with progressive dysphagia and bilateral blepharoptosis[ncbi.nlm.nih.gov]
  • Oculopharyngeal muscular dystrophy is an autosomal dominant myopathy that exhibits the symptoms of progressive dysphagia, with ptosis usually occurring after the age of 40.[ncbi.nlm.nih.gov]
  • Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disorder characterized by progressive dysphagia and bilateral ptosis. Mutations in the polyadenylate binding protein nuclear 1 (PABPN1) gene have been found to cause OPMD.[ncbi.nlm.nih.gov]
Deglutition Disorder
  • Key words: Oculopharyngeal muscular dystrophy — Dysphagia — Deglutition — Deglutition disorders — Progressive disorders. This is a preview of subscription content, log in to check access. Preview Unable to display preview. Download preview PDF.[link.springer.com]
  • Keywords : Deglutition Disorders; Muscular Dystrophy, Oculopharyngeal; Nervous System Diseases; Voice; Speech; Language.[scielo.br]
Drooling
  • The muscle weakness slowly gets worse and symptoms can include: Delayed development of muscle motor skills Difficulty using one or more muscle groups Drooling Eyelid drooping ( ptosis ) Frequent falls Loss of strength in a muscle or group of muscles as[mountsinai.org]
Blepharoptosis
  • PURPOSE: To clinically characterize blepharoptosis in Hispanic New Mexicans with oculopharyngeal muscular dystrophy and examine eyelid surgery outcomes.[ncbi.nlm.nih.gov]
  • Most muscular dystrophies manifest as peripheral muscular weakness commencing at various age, however, oculopharyngeal muscular dystrophy (OPMD) is a rare hereditary disorder presenting in middle age with progressive dysphagia and bilateral blepharoptosis[ncbi.nlm.nih.gov]
  • The recommended treatment for blepharoptosis and the cricopharyngeus muscle pathosis is discussed.[ncbi.nlm.nih.gov]
  • Case 1, the father, showed blepharoptosis, but no limitation of ocular movements. Case 2, the son, showed early onset of weakness and more rapid progression of muscle involvement than the father.[ncbi.nlm.nih.gov]
  • Progressive, usually symmetrical blepharoptosis, with or without dysphagia, appears during middle age. Muscular weakness in the limbs can be noted in some patients.[ncbi.nlm.nih.gov]
Diplopia
  • 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.[ncbi.nlm.nih.gov]
  • In 4 patients weakness of extraocular muscle was found and two of them experienced transient diplopia. Mild limb-girdle weakness was observed in 6 patients. Muscle biopsy performed in all cases showed myopathic changes with rare rimmed vacuoles.[ncbi.nlm.nih.gov]
  • Double vision (diplopia) is uncommon. Eventually, additional muscles may become involved including those of the upper legs and arms (proximal limb weakness). In some cases, muscle weakness of the legs may eventually cause difficulty walking.[slodrinks.com]
  • Patients may also develop difficulty with eye movements, though often without diplopia, nasal dysarthria, and mild neck weakness. For more information, see OMIM .[visualdx.com]
Myopathy
  • […] and hereditary inclusion body myopathy.[ncbi.nlm.nih.gov]
  • The question whether oculopharyngodistal myopathy (MIM 164310) is a distinct disease entity or a variant of oculopharyngeal muscular dystrophy (MIM 164300) persists.[ncbi.nlm.nih.gov]
  • We show that oculopharyngeal muscular dystrophy is a systemic myopathy with a marked predeliction for extraocular and non-somatically derived muscles.[ncbi.nlm.nih.gov]
  • The findings indicate that oculopharyngeal muscular dystrophy and distal myopathy are related in their etiology and distal myopathy and inclusion body myositis are regarded as variant forms of the same disease.[ncbi.nlm.nih.gov]
  • From Wikidata Jump to navigation Jump to search Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset progressive myopathy characterized by progressive eyelid ptosis, dysphagia, dysarthria and proximal limb weakness Muscular dystrophy, oculopharyngeal[wikidata.org]
Proximal Muscle Weakness
  • Oculopharyngeal muscular dystrophy (OPMD) is typically inherited in an autosomal dominant fashion and is characterized by late onset proximal muscle weakness, ptosis and difficulty swallowing.[ncbi.nlm.nih.gov]
  • Oculopharyngeal muscular dystrophy (OPMD) is a late onset myopathy usually presenting in the 5th or 6th decade of life with progressive ptosis, dysphagia and proximal muscle weakness.[ncbi.nlm.nih.gov]
  • In the presence of a positive family history and late-onset ptosis, dysphagia, and proximal muscle weakness (its cardinal features), we suggest that PABPN1 gene analysis should be the first-line investigation to rule out this condition.[ncbi.nlm.nih.gov]
  • We describe a 70-year-old Italian woman with an adult-onset ptosis, mild dysphagia and proximal muscle weakness belonging to a family segregating OPMD according to an autosomal dominant mode of inheritance.[ncbi.nlm.nih.gov]
  • Ptosis and mild facial and proximal muscle weakness were present by 9 years of age.[ncbi.nlm.nih.gov]
Pharyngeal Muscle Weakness
  • Evidence of pharyngeal muscle weakness often occurs concomitantly with the ocular signs (43%). Ptosis occurs first in 43% and dysphagia first in 14%. Dysarthria and dysphagia are often associated with facial muscle weakness.[disorders.eyes.arizona.edu]
  • In patients who had both ocular and pharyngeal muscle weakness, ptosis was just as likely to occur before or concurrent with dysphagia.[jamanetwork.com]
Neck Weakness
  • Patients may also develop difficulty with eye movements, though often without diplopia, nasal dysarthria, and mild neck weakness. For more information, see OMIM .[visualdx.com]
Chronic Progressive External Ophthalmoplegia
  • Keywords Muscular Dystrophy Myotonic Dystrophy Inclusion Body Myositis Chronic Progressive External Ophthalmoplegia Levator Palpebrae These keywords were added by machine and not by the authors.[link.springer.com]
  • Codes ICD10CM: G71.0 – Muscular dystrophy SNOMEDCT: 77097004 – Oculopharyngeal muscular dystrophy Differential Diagnosis & Pitfalls Myasthenia gravis Myotonic dystrophy Mitochondrial disorders (eg, chronic progressive external ophthalmoplegia) Fascioscapulohumeral[visualdx.com]
Confusion
  • Abnormal mitochondria are non-specific epiphenomena in OPMD but a potential source of confusion with a late-onset mitochondrial cytopathy.[ncbi.nlm.nih.gov]
  • Non-specific mitochondrial changes in the muscle specimens of these patients should be appreciated, so as to avoid diagnostic confusion.[ncbi.nlm.nih.gov]
Nasal Speech
  • A 13-year-old female of French-Canadian descent developed nasal speech and strabismus at 5 years of age; there was no family history of neuromuscular disease. Ptosis and mild facial and proximal muscle weakness were present by 9 years of age.[ncbi.nlm.nih.gov]

Workup

The diagnosis of OPMD is often missed, the principal reason being a lack of clinical suspicion, especially in countries with very low prevalence rates [3] [4]. For this reason, physicians must conduct a comprehensive and detailed clinical workup comprised of a complete patient history and a thorough physical examination in order to identify the underlying cause. Assessing family history is perhaps of vital importance in raising clinical suspicion toward OPMD [5], particularly if patients are of French Canadian or Bukharan Jewish ancestry. Furthermore, a complete motor evaluation can identify which muscle groups are affected, and if sufficient evidence exists to suspect a myopathy, appropriate laboratory procedures should be implemented. Electromyography (EMG) is useful in excluding other more common conditions responsible for muscle weakness, whereas muscle biopsy is one of the tools to make the diagnosis, although it is not frequently performed [1] [4]. The presence of filamentous intranuclear inclusions (INIs) on electron microscopy is practically pathognomonic for OPMD and mandates genetic testing for PABPN1 mutations, and is regarded as the definite method [1] [4] [7]. Because genetic testing is expensive and scarcely available, however, the diagnosis often rests on clinical criteria and the ability of the physician to recognize progressive ptosis and dysphagia in the elderly population, implying that clinical suspicion and awareness of OPMD as a possible diagnosis is the crucial step [4].

Treatment

  • The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment.[ncbi.nlm.nih.gov]
  • We conclude that the development of treatment-resistant weakness in myasthenia gravis should spur further work up for other neuromuscular disorders including oculopharyngeal muscular dystrophy.[ncbi.nlm.nih.gov]
  • INTRODUCTION: Despite multiple studies reporting marked benefit of botulinum toxin (BTX) for treatment of cricopharyngeal dysphagia, little is known about its safety for this indication.[ncbi.nlm.nih.gov]
  • However, for a majority of people, the benefits from such treatments are only temporary. There is currently no treatment available to address the proximal limb weakness.[en.wikipedia.org]
  • Median total treatment period was 13 years (range 3-15), median number of dilatations per patient was 7.2 (range 1-16), and median interval between treatments was 15 months (range 4.5-45). All patients recorded sustained symptom improvement.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis Ptosis and dysphagia typically recur within five to fifteen years after surgery. There is usually no decrease in life expectancy, but quality of life can be reduced in those where the disease is debilitating.[orpha.net]
  • Outlook (Prognosis) The severity of disability depends on the type of muscular dystrophy. All types of muscular dystrophy slowly get worse, but how fast this happens varies widely.[mountsinai.org]
  • Hoarse & Nasal voice Tongue weakness Limbs Legs Arms Distal: Anterior tibial; Finger extensors Onset: 5 years after disease onset Limb strength normal (20%) Progression: To proximal muscles Respiratory Common May develop while ambulant Postural drop Prognosis[neuromuscular.wustl.edu]

Etiology

  • By using a systematic diagnostic approach, the correct etiology was determined.[ncbi.nlm.nih.gov]
  • Oculopharyngeal muscular dystrophy must be considered as a distinct, well-defined, autosomal dominant systemic myopathy of later life whose etiology remains obscure.[ncbi.nlm.nih.gov]
  • The findings indicate that oculopharyngeal muscular dystrophy and distal myopathy are related in their etiology and distal myopathy and inclusion body myositis are regarded as variant forms of the same disease.[ncbi.nlm.nih.gov]
  • Given the domain specificity of VHH-mediated aggregation interference, this approach at least allows the definition of the nucleation kernel in aggregation-prone proteins, thus facilitating etiological insight into this and other protein aggregation disorders[ncbi.nlm.nih.gov]
  • To date OPMD is considered as a primary myopathic disorder and there is little morphologic evidence for neurogenic etiology, though the peripheral nervous system (PNS) seems to be affected in some rare cases.[genome.jp]

Epidemiology

  • We suggest that genetic intervention should be undertaken to understand the genetic epidemiology and provide counseling for carriers of OPMD in Taiwan.[ncbi.nlm.nih.gov]
  • On the basis of a patient with "classical" OPMD, this review summarises the clinical, therapeutic, epidemiological, pathomechanistic and genetic aspects of OPMD, provides practical information about the differential diagnosis of OPMD, and presents a survey[ncbi.nlm.nih.gov]
  • An epidemiologic review of the literature is presented and the prevalence of OPMD is discussed. This is a China-born Chinese patient with both morphologically and genetically proven of OPMD.[ncbi.nlm.nih.gov]
  • Epidemiology and inheritance of oculophyaryngeal muscular dystrophy in Israel. Neuromuscul Disord 6:S38-40. Brais et al. (1998) Short GCG expansion in the PABP3 gene cause oculopharyngeal muscular dystrophy. Nat Genet 18:164-7.[genedx.com]
  • Summary Epidemiology OPMD is seen worldwide with varying prevalence rates. The estimated prevalence rate in Europe is 1/200,000-1/100,000.[orpha.net]
Sex distribution
Age distribution

Pathophysiology

  • This paper reviews basic and clinical research on OPMD, with special emphasis on recent developments in the understanding of its pathophysiology.[ncbi.nlm.nih.gov]
  • These familial cases are important because they imply a genetic component in the pathophysiology of these arachnoid cysts.[ncbi.nlm.nih.gov]
  • Research on oculopharyngeal muscular dystrophy focuses mainly on genetic and pathophysiological aspects.[ncbi.nlm.nih.gov]
  • The role of the typical intranuclear inclusion in the pathophysiology is unresolved. OBJECTIVE: The aim of this study was to describe the clinical and histopathological features of oculopharyngeal muscular dystrophy (OPMD).[ncbi.nlm.nih.gov]
  • […] post-transcriptional processing of pre-mRNAs, the INI-dependent molecular reorganization of these nuclear compartments in muscle fibers may cause a severe dysfunction in nuclear trafficking and processing of polyadenylated mRNAs, thereby contributing to the molecular pathophysiology[ncbi.nlm.nih.gov]

Prevention

  • When expressed intracellularly as intrabodies in a cellular model for OPMD, aggregation of PABPN1 was prevented in a dose-dependent manner. More importantly yet, these intrabodies could also reduce the presence of already existing aggregates.[ncbi.nlm.nih.gov]
  • […] their clearance from cells through autophagy, thus preventing muscle cell death.[bioblastpharma.com]
  • However, co-transduction with shRNA-HBVpol-optPABPN1 prevented cell death. Bar, 100 μm.[doi.org]
  • Aspiration pneumonia and its complications can be prevented with careful monitoring. Surgery may also help relieve problems due to dysphagia and should be considered if there is marked weight loss, near-fatal choking, or recurrent pneumonia.[genpharmservices.com]
  • It is expected to work by preventing the clumping together of a protein known as PABPN1, which occurs in muscles of patients with oculopharyngeal muscular dystrophy and is linked to the muscle weakness.[ema.europa.eu]

References

Article

  1. Abu-Baker A, Rouleau GA. Oculopharyngeal muscular dystrophy: recent advances in the understanding of the molecular pathogenic mechanisms and treatment strategies. Biochim Biophys Acta. 2007;1772(2):173-185.
  2. Werling S, Schrank B, Eckardt AJ, Hauburger A, Deschauer M, Müller M. Oculopharyngeal muscular dystrophy as a rare cause of dysphagia. Ann Gastroenterol. 2015;28(2):291-293.
  3. Chien YY. Oculopharyngeal muscular dystrophy --an under-diagnosed disease in China? Report a China-born Chinese with PABPN1 mutation and epidemiology review of the literature. J Formos Med Assoc. 2012;111(7):397-402.
  4. Luk HM, Lo IF, Fu KH, et al. Oculopharyngeal muscular dystrophy: underdiagnosed disease in Hong Kong. Hong Kong Med J. 2013;19(6):556-559.
  5. Mensah A, Witting N, Duno M, Milea D, Vissing J. Delayed diagnosis of oculopharyngeal muscular dystrophy in Denmark: from initial ptosis to genetic testing. Acta Ophthalmol. 2014;92(3):e247-e249.
  6. Blumen SC, Kesler A, Dabby R, et al. Oculopharyngeal muscular dystrophy among Bulgarian Jews: a new cluster? Isr Med Assoc J. 2013;15(12):748-752.
  7. Bumm K, Zenker M, Bozzato A. Oculopharyngeal muscular dystrophy as a rare differential diagnosis for unexplained dysphagia: a case report. Cases J. 2009;2:94.

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Last updated: 2019-07-11 20:02