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.
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    . 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    . 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  . 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    . 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  . 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   . 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 . Malnutrition and starvation, due to profound dysphagia, are other documented complications .
Entire Body System
- 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]
Death is usually due to aspiration pneumonia or malnutrition (with severe weight loss) in elderly patients. The documents contained in this web site are presented for information purposes only. [orpha.net]
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. [saintlukeskc.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]
Keywords Percutaneous Endoscopic Gastrostomy Progressive Dysphagia Nicotine Abuse Girdle Muscle Cricopharyngeal Myotomy Case presentation A 57-year old Caucasian male patient with acute pneumonia and a progressive dysphagia was referred to our department [casesjournal.biomedcentral.com]
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]
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]
Symptoms may include: difficulty swallowing (dysphagia) tongue weakness and atrophy weakness in the proximal muscles drooping eyelids (ptosis) difficulty gazing upwards and double vision (diplopia) Treatment may include: surgery speech and occupational [muscle.ca]
[…] and hereditary inclusion body myopathy. [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
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]
- 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]
- 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]
The diagnosis of OPMD is often missed, the principal reason being a lack of clinical suspicion, especially in countries with very low prevalence rates  . 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 , 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  . 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   . 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 .
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]
BB-301 (Benitec Biopharma) is a ddRNAi or “expressed RNAi” treatment derived from the developing company’s gene-silencing technology, which is being investigated for the treatment of ocularpharyngeal muscular dystrophy (OPMD). [healio.com]
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]
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]
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]
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]
Etiology OPMD is caused by an expansion in the polyalanine tract in the poly (A)-binding protein, nuclear 1 ( PABPN1 ) gene (14q11.2), which leads to overexpression of a mutant protein and consequently to the accumulation of nuclear aggregates in the [orpha.net]
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]
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]
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]
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]
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]
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]
Treatments can help with the symptoms and prevent complications. They include physical and speech therapy, orthopedic devices, surgery, and medications. Some people with MD have mild cases that worsen slowly. Others cases are disabling and severe. [medlineplus.gov]
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