P.3.9 Unusual pathologic features in a patient with clinical features of Laing early onset distal myopathy

Abstract

Laing early onset distal myopathy (MPD1) is a rare form of distal myopathy caused by mutations in myosin heavy gene MHY7. While clinical presentation of MPD1 patients is fairly stereotypical (development of complete bilateral foot drop in the early childhood, followed by a very slow or no clinical progression in subsequent years), the biopsy findings are relatively nonspecific except for the lack of rimmed vacuoles (which are a common feature of distal myopathies). Here, we present a patient with clinical features of MPD1 but distinctive light microscopic and ultrastructural findings on muscle biopsy. The patient, a 39 year old male, developed bilateral foot drop at age 5, but is otherwise asymptomatic and physically active. Physical exam showed bilateral weakness of ankle dorsiflexors (1/5), toe extensors (1/5), and finger extensors (4+/5); creatine kinase level was within the normal limits. The disease first developed in the patient’s paternal grandmother and is transmitted in autosomal dominant fashion, with all affected family members showing the same clinical phenotype. The vastus lateralis biopsy showed mild-moderate variation in fiber diameters, mild fibrosis, scattered nuclear clumps, and type 1 fiber predominance (85%), but no rimmed vacuoles; rare fibers contained cytoplasmic or subsarcolemmal desmin-positive inclusions. In addition, scattered type 1 (but no type 2) fibers had unusual, partially septated/lobulated appearance. On ultrastructural analysis, these septations corresponded to complex invaginations of the plasma membrane that were somewhat reminiscent of myotendinous junctions but randomly distributed throughout the biopsy. Genetic analysis, currently in progress, will show whether these unusual histologic and ultrastructural features widen the pathologic spectrum of MPD1 or define a genetically distinct type of MPD1-like distal myopathy.