Oculopharyngodistal myopathy: The recent discovery of an old disease

Abstract

Oculopharyngodistal myopathy: The recent discovery of an old diseaseOculopharyngodistal myopathy (OPDM) is a group of genetically heterogenous muscle diseases, characterized clinically by onset in adulthood and slowly progressive weakness affecting ocular, bulbar, and distal limb muscles, and pathologically by the presence of rimmed vacuoles and intranuclear inclusions . [1][2][3] The disease was first described in four Japanese families more than 4 decades ago, and subsequently was also reported from other countries. 2,4,5 It was not until recently that the underlying genetic defects of OPDM were unraveled. To date, the expansion of CGG repeats in the 5 0 untranslated region (5 0 UTR) of LRP12 (OPDM1), GIPC1 (OPDM2), NOTCH2NLC (OPDM3), and RILPL1 (OPDM4) have been reported to cause OPDM in Japan and China. [6][7][8][9][10][11][12][13] Among these 4 OPDM subtypes, OPDM1 is the most common OPDM subtype in Japan, accounting for 31.25% of Japanese OPDM patients, while OPDM2 is the most common OPDM subtype in China, accounting for 37.3% of Chinese OPDM

What Is in the Myopathy Literature?

“…27 OPMD2 is due to pathogenic variants in GAIP/RGS19-interacting protein GIPC1, and OPDM3 is due to variants in notch 2 N-terminal-like C (NOTCH2NLC). 25 So far, the phenotypes are similar except OPDM3 may include CNS features of neuronal intranuclear inclusion disease. 26 Expansions of CGG repeats in the untranslated region of the associated genes are seen in all types of OPDM.…”

“…Most cases are from Japan and China. 25 Manifestations of the OPDM phenotype are ocular (ptosis often with ophthalmoplegia), pharyngeal, facial, and distal weakness with an AD mode of inheritance. Proximal weakness is rare, and central nervous system involvement occurs only in OPDM3.…”