Abstract
Oculopharyngodistal myopathy (OPDM) is an extremely rare, adult-onset hereditary muscular disease characterized by progressive external ocular, pharyngeal, and distal muscle weakness and myopathological rimmed vacuole changes. The causative gene is currently unknown; therefore, diagnosis of OPDM is based on clinical and histopathological features and genetic exclusion of similar conditions. Moreover, variable manifestations of this disorder are reported in terms of muscle involvement and severity. We present the clinical profile and magnetic resonance imaging (MRI) changes of lower limb muscles in 14 mainland Chinese patients with OPDM, emphasizing the role of muscle MRI in disease identification and differential diagnosis. The patients came from 10 unrelated families and presented with progressive external ocular, laryngopharyngeal, facial, distal limb muscle weakness that had been present since early adulthood. Serum creatine kinase was mildly to moderately elevated. Electromyography revealed myogenic changes with inconsistent myotonic discharge. The respiratory function test revealed subclinical respiratory muscle involvement. Myopathological findings showed rimmed vacuoles with varying degrees of muscular dystrophic changes. All known genes responsible for distal and myofibrillar myopathies, vacuolar myopathies, and muscular dystrophies were excluded by PCR or targeted next-generation sequencing. Muscle MRI revealed that the distal lower legs had more severe fatty replacement than the thigh muscles. Serious involvement of the soleus and long head of the biceps femoris was observed in all patients, whereas the popliteus, gracilis and short head of biceps femoris were almost completely spared, even in advanced stages. Not only does our study widen the spectrum of OPDM in China, but it also demonstrates that OPDM has a specific pattern of muscle involvement that may provide valuable information for its differential diagnosis and show further evidence supporting the conclusion that OPDM is a unique disease phenotype.
Highlights
Oculopharyngodistal myopathy (OPDM; MIM 164310) is a very rare adult-onset neuromuscular disease characterized by slowly progressive blepharoptosis, ophthalmoparesis, facial and bulbar muscle weakness, and distal muscle weakness [1,2]
The genetic basis of oculopharyngeal muscular dystrophy (OPMD) has been identified as an abnormal trinucleotide (GCN) repeat expansion encoding the polyalanine tract in exon 1 of the polyadenylate-binding protein nuclear 1 gene (PABPN1) [11]
Many other distal myopathies share the clinical features of preferentially distal muscle weakness and myopathological changes of rimmed vacuoles with OPDM
Summary
Oculopharyngodistal myopathy (OPDM; MIM 164310) is a very rare adult-onset neuromuscular disease characterized by slowly progressive blepharoptosis, ophthalmoparesis, facial and bulbar muscle weakness, and distal muscle weakness [1,2]. There is considerable clinical and myopathological overlap between OPDM and a wide spectrum of other muscular disorders, such as oculopharyngeal muscular dystrophy (OPMD), myotonic dystrophy 1 (DM1), distal myopathy with rimmed vacuoles, and myofibrillar myopathy [5,6,10]. OPMD is an autosomal dominant late-onset disorder characterized by progressive ptosis, dysphagia, and proximal muscle weakness. DM1 is an adult-onset autosomal dominant disorder caused by a heterozygous trinucleotide repeat expansion (CTG)n in the 3-prime untranslated region of the dystrophia myotonica protein kinase gene (DMPK), which is characterized mainly by myotonia, distal muscle weakness and multiple extramuscular system involvement, including cataracts, hypogonadism, frontal balding, and electrocardiogram (ECG) changes [12]. Many other distal myopathies share the clinical features of preferentially distal muscle weakness and myopathological changes of rimmed vacuoles with OPDM. Advanced molecular genetic techniques have clarified the gene defect in approximately 20 distinct entities in the group of distal myopathies [10]
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