Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early-onset distal myopathy.
Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early-onset distal myopathy (MPD1) is a form of distal myopathy caused by mutations in the MYH7 gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy. A 39-year-old professional male cellist presented with a bilateral foot drop that developed by age 8; analysis of the family pedigree showed an autosomal dominant pattern of inheritance. The physical exam demonstrated bilateral weakness of ankle dorsiflexors, toe extensors and finger extensors; creatine kinase level was normal. Biopsy of the quadriceps femoris muscle showed predominance and hypotrophy of type 1 fibers, hybrid fibers with co-expression of slow and fast myosin proteins (both in highly atrophic and normal size range), moth-eaten fibers and mini-cores, lack of rimmed vacuoles and rare desmin-positive eosinophilic sarcoplasmic inclusions. In addition to these abnormalities often observed in MPD1, the biopsy demonstrated frequent clefted fibers with complex sarcolemmal invaginations; on ultrastructural examination, these structures closely mimicked myotendinous junctions but were present away from the tendon and were almost exclusively found in type 1 fibers. Sequencing analysis of the MYH7 gene in the index patient and other affected family members demonstrated a previously described heterozygous c.4522_4524delGAG (p.Glu1508del) mutation. This case widens the pathologic spectrum of MPD1 and highlights the pathologic and clinical variability that can accompany the same genetic mutation, suggesting a significant role for modifier genes in MPD1 pathogenesis.
['Reis|Gerald F|GF|', 'de la Motte|Grant|G|', 'Gooding|Rebecca|R|', 'Laing|Nigel G|NG|', 'Margeta|Marta|M|http://orcid.org/0000-0001-6889-2488']
D000328:Adult D049310:Distal Myopathies D006801:Humans D008297:Male D046529:Microscopy, Electron, Transmission D018482:Muscle, Skeletal D010375:Pedigree D012508:Sarcolemma
distal myopathy type 1 fibers clefted fibers myotendinous junction-like structures slow myosin