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A boy was diagnosed at age 10 months with megalencephalic leukoencephalopathy with subcortical cysts (MLC) based on progressive macrocephaly and characteristic MRI findings (figure, A–C).1 Over subsequent years, initial motor delays resolved and neurobehavioral difficulties were mild. On repeat MRI at 6 years (figure, D–F), only small areas of frontal and temporal white matter signal alteration remained, consistent with remitting MLC (MLC2b). MLC2b is associated with heterozygous mutations in HEPACAM with autosomal dominant inheritance. Often, one parent has macrocephaly.1 Unlike the more common phenotype seen with MLC1 mutations, MLC2b patients demonstrate remarkable MRI improvement and have a better clinical prognosis.2

Teaching Neuro Images : Resolution of MRI abnormalities in megalencephalic leukoencephalopathy with subcortical cysts