Megalencephalic leukoencephalopathy with subcortical cysts

TY - JOUR

T1 - Megalencephalic leukoencephalopathy with subcortical cysts

T2 - Characterization of disease variants

AU - Hamilton, Eline M C

AU - Tekturk, Pinar

AU - Cialdella, Fia

AU - van Rappard, Diane F

AU - Wolf, Nicole I

AU - Yalcinkaya, Cengiz

AU - Çetinçelik, Ümran

AU - Rajaee, Ahmad

AU - Kariminejad, Ariana

AU - Paprocka, Justyna

AU - Yapici, Zuhal

AU - Bošnjak, Vlatka Mejaški

AU - van der Knaap, Marjo S

AU - MLC Research Group

N1 - Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2018/4/17

Y1 - 2018/4/17

N2 - OBJECTIVE: To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features.METHODS: We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review.RESULTS: We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B.CONCLUSION: Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype.

AB - OBJECTIVE: To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features.METHODS: We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review.RESULTS: We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B.CONCLUSION: Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype.

KW - Adolescent

KW - Cell Cycle Proteins

KW - Cerebral Cortex/diagnostic imaging

KW - Child

KW - Child, Preschool

KW - Cross-Sectional Studies

KW - Cysts/diagnostic imaging

KW - Female

KW - Hereditary Central Nervous System Demyelinating Diseases/diagnostic imaging

KW - Humans

KW - International Cooperation

KW - Magnetic Resonance Imaging

KW - Male

KW - Membrane Proteins/genetics

KW - Mutation/genetics

KW - Proteins/genetics

KW - Retrospective Studies

KW - Severity of Illness Index

KW - Young Adult

U2 - 10.1212/WNL.0000000000005334

DO - 10.1212/WNL.0000000000005334

M3 - SCORING: Journal article

C2 - 29661901

VL - 90

SP - e1395-e1403

JO - NEUROLOGY

JF - NEUROLOGY

SN - 0028-3878

IS - 16

ER -