Clinical and Muscle Imaging Findings in 14 Mainland Chinese Patients with Oculopharyngodistal Myopathy

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.

CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations

“…Another study reported markedly involved soleus in patients with OPDM_GIPC1 [ 2 ]. The results of muscle CT in the present three patients with OPDM_NOTCH2NLC are similar to previous reports [ 2 , 22 ], suggesting that the myodegeneration mechanism for those three OPDM types may be similar.…”

“…In terms of the pattern of muscle involvement on muscle imaging, one study described predominantly involved soleus and long head of the biceps femoris, relatively preserved rectus femoris, and asymmetric involvement pattern in OPDM (without genetic diagnosis) [ 22 ]. Another study reported markedly involved soleus in patients with OPDM_GIPC1 [ 2 ].…”

Respiratory management of patients with neuromuscular disease: current perspectives

“…Recently, muscle magnetic resonance imaging (MRI) abnormalities were described in this condition, showing fatty infiltration of primarily distal leg muscles. 13 …”

CGG expansion inNOTCH2NLCis associated with oculopharyngodistal myopathy with neurological manifestations

“…In terms of the pattern of muscle involvement on muscle imaging, one study described predominantly involved soleus and long head of the biceps femoris, relatively preserved rectus femoris, and asymmetric involvement pattern in OPDM (without genetic diagnosis), 22 and another reported markedly involved soleus in patients with OPDM_GIPC1. 4 The findings of muscle CT in the present three patients with OPDM_NOTCH2NLC are similar to the previous reports, 4 22 suggesting that the myodegeneration mechanism might be similar between those three OPDM types.…”