Expanded clinical spectrum of oculopharyngodistal myopathy type 1

Introduction/Aims Heterozygous CGG repeat expansions in low-density lipoprotein receptor-related protein 12 (LRP12) have recently been identified as a cause of oculopharyngodistal myopathy (OPDM), and the disease is designated as OPDM type 1 (OPDM1). In contrast to broadening of our knowledge on the genetic background of OPDM, what we know of the clinical phenotype of genetically confirmed OPDM1 remains limited. Methods This investigation was a single-center case series study of OPDM consisting of ten patients from seven families. Repeat-primed polymerase chain reaction and Southern blot analyses were performed to confirm the CGG repeat expansions in LRP12. Clinical findings were retrospectively reviewed. Results Seven patients from five families were identified as having CGG repeat expansions in LRP12. We found a high prevalence of axial muscle involvement, such as neck muscle weakness (6/7) and fatty infiltration in the rectus abdominis muscle, as revealed by computed tomography (5/5). We identified patients with very subtle oculopharyngeal symptoms, mimicking isolated distal myopathy. Muscle specimens were collected from the biceps brachii and tibialis anterior muscles of three patients. Myopathic changes were more severe with more atrophic fibers forming clusters in the tibialis anterior than the biceps brachii muscles of these three patients. No rimmed vacuoles were observed in the biceps brachii muscles in two of the three patients. Discussion This study shows the expanded clinical spectrum of OPDM1, highlighting the importance of axial muscle evaluation in OPDM1. Considering patients with very subtle oculopharyngeal symptoms, genetic analysis of LRP12 should be considered in patients with isolated distal myopathy.