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].

• Malnutrition

  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]

  Malnutrition and starvation, due to profound dysphagia, are other documented complications. The diagnosis of OPMD is often missed, the principal reason being a lack of clinical suspicion, especially in countries with very low prevalence rates. [symptoma.com]

  With disease progression, dysphagia becomes more severe leading to a significant weight loss, dehydration, malnutrition and repeated events of aspiration pneumonia. [musculardystrophynews.com]

• 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]

  This progressive loss of contractility will eventually result in aspiration and severe difficulty in swallowing, increasing risk of aspiration pneumonia and severe weight loss which are the most common causes of mortality in OPMD patients. [clinicaltrials.gov]

  Since the onset of symptoms, the patient reported a weight loss of around 13 kg and two episodes of pneumonia. [scielo.br]

• Falling

  At that time, the patient said that his lips began to "fall" ( sic ), along with possible episodes of urinary incontinence. Since the onset of symptoms, the patient reported a weight loss of around 13 kg and two episodes of pneumonia. [scielo.br]

  When to see a doctor Seek medical advice if you notice signs of muscle weakness — such as increased clumsiness and falling — in yourself or your child. Causes Certain genes are involved in making proteins that protect muscle fibers from damage. [mayoclinic.org]

  You may also stumble and fall more easily. Limb-girdle muscular dystrophy affects both males and females. Most people with this form of muscular dystrophy are disabled by age 20. However, many have a normal life expectancy. [healthline.com]

  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]

• Dysphagia

  The patient was assessed regarding his dysphagia complaints. [scielo.br]

  A consistent diet planned with the help of a dietitian along with exercises taught by a speech therapist can assist with mild symptoms of dysphagia. Surgical intervention can also help temporarily manage symptoms related to the ptosis and dysphagia. [en.wikipedia.org]

  Cricopharyngeal myotomy relieves the patient of dysphagia in the majority of cases. [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]

  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]

  Choking or swallowing problems (dysphagia). Dry foods may be the first to cause trouble, but swallowing liquids can later be a challenge. [genpharmservices.com]

• 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]

  OPMD progresses with a clinical picture of progressive ptosis, dysphagia, and weakness of the proximal muscles of the limbs. 1 The disease usually begins in the fifth or sixth decade of life. [scielo.br]

• Blepharoptosis

  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]

• Diplopia

  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]

  Oculopharyngeal myopathy is genetically heterogeneous and most cases are distinct from oculopharyngeal muscular dystrophy. [scielo.br]

  […] with disruption of myofilaments Return to Myopathy & NMJ Index References 1. [neuromuscular.wustl.edu]

• Proximal Muscle Weakness

  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]

• 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]

  Proximal limb muscle weakness and gait abnormalities were common and occurred later than ocular or pharyngeal weakness. [jamanetwork.com]

• Neck Muscle Weakness

  Abnormal walk Impaired gait [ more ] 0001288 Limb muscle weakness Limb weakness 0003690 Neck muscle weakness Floppy neck 0000467 Progressive Worsens with time 0003676 Progressive ptosis Progressive drooping of upper eyelid 0007838 Proximal muscle weakness [rarediseases.info.nih.gov]

• 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]

• Withdrawn

  In addition, alendronate was withdrawn to reduce the risk of erosive lesions on the mucosa of the oesophagus because of its corrosiveness. [elsevier.es]

  Nevertheless, we are encouraged by the fact that the improvement found first in the HOPEMD study is sustainable over an extended period of time and that the difference between patients who continued on treatment and those who were randomized to be withdrawn [globenewswire.com]

• Limb Weakness

  There is currently no treatment available to address the proximal limb weakness. Many of those affected with the proximal limb weakness will eventually require assistive devices such as canes, braces or a wheelchair. [en.wikipedia.org]

  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]

  Ptosis was the first symptom in 8/13 patients followed by limb weakness in the remaining 5 patients Dysphagia was never the presenting symptom. [ncbi.nlm.nih.gov]

• 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]

  OPMD falls within the category of non-congenital, myogenic ptosis, which also includes chronic progressive external ophthalmoplegia and myotonic dystrophy ( Wong et al., 2002 ). [eyerounds.org]

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].

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]

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]

However, medical or surgical treatments can be carried out in order to improve the patient's quality of life. [scielo.br]

Duchenne muscular dystrophy prognosis indicates death at around the age of 20 to 25. Fatal complications Duchenne muscular dystrophy prognosis indicates several fatal complications. [muscleatrophy.net]

Swallowing disorders are determinant in the prognosis of the disease, and potentially life-threatening deglutition, due to aspiration and denutrition. [clinicaltrials.gov]

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]

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]

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]

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]

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]

CONGENITAL & HEREDITARY OPHTHALMOPLEGIAS Oculopharyngeal Muscular Dystrophy 5 ● Polyadenylate-binding protein, Nuclear, 1 (PABPN1; PABN1; PABP2) ; Chromosome 14q11.2; Dominant or Recessive ● Second locus in non-French-Canadian (Italian & Norman) families Epidemiology [neuromuscular.wustl.edu]

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]

The role of the typical intranuclear inclusion in the pathophysiology is unresolved. Objective: The aim of this study was to desc ribe the clinical and histopathological features of oculopharyngeal muscular dystrophy (OPMD). [content.iospress.com]

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]

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]

[…] their clearance from cells through autophagy, thus preventing muscle cell death. [bioblastpharma.com]

However, although this will relax the constriction of the upper esophageal sphincter muscles and improve transitory the swallowing, it will not prevent the progressive degradation of the pharyngeal muscles. [clinicaltrials.gov]

Cabaletta is a chemical chaperone that prevents the pathological aggregation of proteins within cells and acts as an autophagy enhancer. 1 It features a unique intravenous (IV) formulation of the disaccharide trehalose, which prevents the trehalose from [raredr.com]

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.