title: Basal lamina abnormality in the skeletal muscle of Walker-Warburg syndrome.
abstract: The basal lamina of skeletal muscle fibers has been reported to be thinned and disrupted in patients with Fukuyama and laminin-alpha-2-deficient congenital muscular dystrophies. The basal lamina is normal in other, later-onset, muscular dystrophies, but the plasma membrane is disrupted. It is unknown whether the dystrophic process in Walker-Warburg syndrome (WWS) is characterized by a basal laminal abnormality, a sarcolemmal abnormality, or both. The present study examined the skeletal muscle of a 3-month-old patient with WWS by immunohistochemistry and electron microscopy and compared the findings with control muscle samples. In control samples the basal lamina of skeletal muscle fibers was a continuous, uniformly dense structure associated with sarcolemma. In WWS the basal lamina appeared deranged, with disruptions in nonnecrotic muscle fibers. Furthermore, in some fibers the basal lamina was thinner, and in others, it was duplicated. Dystrophin, laminin-alpha-2, and adhalin stains revealed normal immunoreactivity. The disruptions in the basal lamina may play a primary role in the degeneration of muscle fibers in WWS. When compared with the dystrophies with a primary sarcolemmal defect, it appears that those with primary basal lamina abnormalities (WWS, laminin-alpha-2-deficient, and Fukuyama congenital muscular dystrophies) present early in life, and the phenotype is more severe.
authors.affiliation: Division of Neurology, Hospital for Sick Children and University of Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Vajsar
authors.forename: C
authors.initials: C
authors.lastname: Ackerley
authors.forename: D
authors.initials: D
authors.lastname: Chitayat
authors.forename: L E
authors.initials: LE
authors.lastname: Becker
mesh_terms: D001485:Basement Membrane / Q000002:abnormalities; D001921:Brain / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis; D016189:Dystrophin / Q000032:analysis; D005124:Eye Abnormalities / Q000473:pathology*; D017809:Fatal Outcome; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007797:Laminin / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000002:abnormalities* / Q000737:chemistry / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000151:congenital* / Q000473:pathology*; D010641:Phenotype; D049031:Sarcoglycans; D013577:Syndrome
chemical_list: D003598:Cytoskeletal Proteins; D016189:Dystrophin; D007797:Laminin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans