Oculopharyngodistal myopathy caused by CGG repeat expansion in 5'untranslated region of LRP12 gene: four cases report

Abstract

Objective To report the clinical and pathological features of 4 patients with oculopharyngodistal myopathy type 1 (OPDM1) caused by CGG repeat expansion in the 5'untranslated region (5'UTR) of LRP12 gene. Methods and Results This study included 4 patients with OPDM1 who were admitted to Peking University First Hospital from January 2008 to August 2023. All 4 patients presented with weakness of eyes closed, dysarthria, dysphagia, facial muscle weakness and muscle weakness mainly involving distal muscles. None of 4 patients had restricted eye movements. Two of the patients had ptosis (Case 1 and Case 2). Serum creatine kinase (CK) levels were mildly to moderately elevated (190- 1211 U/L) in 4 patients. Three patients (Case 1, Case 2 and Case 3) underwent lower extremity muscle MRI which showed varying degrees of fatty infiltration, with the soleus and tibialis anterior muscles being worst affected. Skeletal muscle biopsies in all 4 patients showed rimmed vacuoles with muscular dystrophy‑like pathological changes. Immunofluorescence staining revealed p62 ‑ positive and ubiquitin ‑ positive intranuclear inclusions in all 4 patients. Genetic testing revealed that all 4 patients carried CGG repeat expansion in the 5'UTR of the LRP12 gene. Conclusions Most OPDM1 patients start with weakness in the distal extremities of both limbs and dysarthria. The involvement of muscles in the lower extremities is asymmetrical, and the involvement of tissues and organs other than muscles is not obvious. The remaining clinical phenotype and pathological features are consistent with other subtypes of OPDM.

Keywords

• neuromuscular diseases
• trinucleotide repeat expansion
• pathology