Sequential development of parkinsonism in two patients with oculopharyngodistal type myopathy in GIPC1-related repeat expansion disorder

Abstract

A heterozygous CGG repeat expansion in 5' untranslated region (5' UTR) of GIPC1 is one of the causative factors of oculopharyngodistal myopathy (OPDM), an adult-onset hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, and facial, bulbar, and distal limb muscle weakness. CGG repeat expansion in GIPC1 has also been reported to be associated with Parkinson's disease, but these patients did not exhibit myopathic symptoms. We experienced two unrelated cases of oculopharyngeal type myopathy with CGG repeat expansion in GIPC1 presenting parkinsonism after exhibiting myopathic symptoms. Both cases showed p62-positive intranuclear inclusions in the skin, similar to those in NOTCH2NLC-related disorders. Our cases suggest that GIPC1-related repeat expansions may be associated with a broad spectrum and tissue-differential neuromuscular manifestations, indicating a common mechanism between OPDM2 and other CGG-repeat expansion diseases. It is important to note OPDM2 patients' central neurological symptoms, as myopathic symptoms may obscure central nervous system manifestations.

Keywords: CGG repeat expansion; GIPC1; Intranuclear inclusions; Oculopharyngodistal myopathy; Parkinsonism.