title: Megalencephalic leukoencephalopathy with subcortical cysts: a third confirmed case with literature review.
abstract: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) causes early-onset, slowly progressive central nervous system white matter disease, macrocephaly, and later cognitive and motor decline. We describe brain structure in a patient with MLC and proven MLC1 mutations. A male, normal at birth, had macrocephaly at 6 months followed by developmental delay. Magnetic resonance imaging showed extensive signal abnormality in cerebral white matter and subcortical progressive cystic changes in the bilateral temporal and right frontal areas. Biopsy of frontal gyrus at age 15 months showed normal gray matter. The subcortical white matter was pale due to prominent fine uniform 2- to 4-mu-thick vacuoles with a few interspersed myelinated axons and rare microglia. The vacuoles had a single-, double-, or, rarely, triple-unit membrane (resembling myelin) and contained occasional organelles but no intermediate filaments. Both normal myelinated and thinly myelinated axons were observed. The outer and occasionally the inner layers of myelin surrounding intact axons formed blebs that may represent a source for vacuoles. Genetic analysis identified 2 heterozygous mutations of intron 3 (c.322-1 G>A) and intron 7 (c.597+1G>A), the 1st leading to deletion of amino acids 60 to 89 and the 2nd to deletion of amino acids 194 to 199. Fine uniform vacuolation of white matter with wide separation of myelinated axons is the hallmark of MLC in early childhood.
authors.affiliation: Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Miles
authors.forename: Ton J
authors.initials: TJ
authors.lastname: DeGrauw
authors.forename: Argirios
authors.initials: A
authors.lastname: Dinopoulos
authors.forename: Kim M
authors.initials: KM
authors.lastname: Cecil
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bove
mesh_terms: D001369:Axons / Q000648:ultrastructure; D020863:Central Nervous System Cysts / Q000235:genetics / Q000473:pathology*; D015140:Dementia, Vascular / Q000235:genetics / Q000473:pathology*; D005865:Gestational Age; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure; D017354:Point Mutation
chemical_list: C425069:MLC1 protein, human; D008565:Membrane Proteins