Oculopharyngodistal Myopathy

Abstract

Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease, clinically characterized by progressive ptosis and weakness affecting extraocular, bulbar and distal limb musculature. It is characterized myopathologically by rimmed vacuoles and intra-myonuclear inclusions. Recently, four genes (LRP12, GIPC1, NOTCH2NLC, and RILPL1) have been reported to cause OPDM. OPDM is caused by CGG repeat expansions in the 5′UTR of one of these genes. These four genetically distinct OPDM subtypes are pathologically and radiologically indistinguishable. Clinically, NOTCH2NLC-OPDM patients may have peripheral neuropathy or central nervous system manifestations, which distinguish them from other OPDM subtypes. OPDM patients generally have both cranial and distal limb weakness at presentation, but RILPL1-OPDM patients may not develop distal weakness up to 10 to 20 years after the onset of oculobulbar symptoms. OPDM with CGG expansions in NOTCH2NLC and RILPL1 may be attributed to both RNA toxicity and polyglycine accumulation.