Inherited myopathies presenting with rimmed vacuoles, tubulofilamentous inclusions, and no inflammation, known as familial and hereditary inclusion body myopathy (f-IBM), have remained a subject of limited understanding regarding their frequency, inheritance patterns, and clinical manifestations. A distinctive feature, quadriceps sparing, has been observed in f-IBM patients within the Iranian Jewish population. In a comprehensive study spanning four years, researchers investigated 101 patients exhibiting red-rimmed vacuolar myopathy, characteristic of inclusion body myopathy. Among this cohort, 13 Families were identified with f-IBM, representing a 12.8% frequency when considering one member per family.
The study revealed diverse inheritance patterns within these 13 families. Five families displayed an autosomal dominant inheritance, while eight families exhibited an autosomal recessive form. Notably, within the autosomal recessive group, five patients presenting with early-onset disease (comprising two Caucasian Americans, one Asian Indian, and two unrelated Iranian Jews) shared a unique characteristic: quadriceps sparing. This was confirmed through MRI of the thighs, highlighting a specific pattern of muscle involvement.
The disease progression in these patients with quadriceps sparing myopathy commenced with weakness and atrophy affecting the foot extensors, forearm flexors, and first dorsal interossei muscles. Subsequently, the weakness extended to the forearm flexors, girdle, and axial muscles, remarkably sparing the quadriceps muscles. Serum creatine kinase (CK) levels were found to be normal in these individuals. Muscle biopsies provided further insights, revealing rimmed vacuoles, small fibers in groups, amyloid deposition in one patient, tubulofilaments, and notably, the absence of inflammation. Immunocytochemical analysis did not detect abnormalities in various membrane or cytoskeletal proteins. Major histocompatibility complex (MHC) class I antigen expression was limited to a few degenerating fibers invaded by macrophages, and T-cell infiltrates were not observed.
The findings of this study, focusing on 13 families, lead to the conclusion that hereditary and familial forms of IBM with both dominant and recessive inheritance patterns are not uncommon within a large referral population. Furthermore, quadriceps-sparing myopathy emerges as a clinically distinct, autosomal recessive, nonimmune, distal vacuolar myopathy. Importantly, this condition is not exclusive to Iranian-Jewish ethnic groups, suggesting a broader global prevalence.
