Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children

Abstract

An identical syndrome of cerebral leukoencephalopathy and megalencephaly with infantile onset was discovered in 8 children, including 2 siblings. Neurological findings were initially normal or near normal, despite megalencephaly and magnetic resonance imaging (MRI) evidence of severe white matter affection. Slowly progressive ataxia and spasticity developed, while intellectual functioning was preserved for years after onset of the disorder. MRI characteristics included diffuse abnormality in signal intensity and swelling of the cerebral hemispheral white matter with cyst-like spaces in the frontoparietal and anterior-temporal subcortical areas. MR spectra were relatively mildly abnormal. Screening for inborn errors, especially those that cause either megalencephaly or white matter disease or both was negative. A distinguishing feature of the present disorder is the apparently severe abnormality of the cerebral white matter as demonstrated by MRI, which contrasts with the remarkably slow course of functional deterioration.

Hypomyelination and Congenital Cataract: Neuroimaging Features of a Novel Inherited White Matter Disorder

“…The significance of this MR imaging finding remains unclear in the absence of direct histologic verification. Increased white matter water content occurs in several metabolic diseases, most notably Alexander disease, Canavan disease, megaloencephalic leukoencephalopathy with subcortical cysts, and vanishing white matter disease, [7][8][9][10] though the white matter is typically more extensively swollen in these disorders than in HCC, often resulting in global enlargement of the affected hemispheres. In these diseases, white matter edema basically results from a variable combination of abnormal myelin formation and vacuolization.…”

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

“…This discrepancy between MLC mice and patients has been discussed before10 and might be related to different compensation by mice to loss of MLC1 function compared to humans. Another likely contributing factor is the much shorter life‐span of mice than that of humans, given that MLC patients develop major neurological dysfunction only after a delay of several years to decades 1, 8…”

“…“Megalencephalic leukoencephalopathy with subcortical cysts” (MLC; MIM 604004) is a rare childhood‐onset leukodystrophy,1, 2 caused by homozygous recessive mutations in MLC1 3 or GLIALCAM 4. MLC1 is a membrane protein almost exclusively expressed in brain astrocytes 5.…”

Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study

“…A known human disorder characterised by intramyelinic oedema is megalencephalic leukoencephalopathy with subcortical cysts. [20][21][22] Mutations in MLC1 have been identifi ed in 75% of patients with this disorder. 23,24 No mutations in CLCN2 were reported in the patients without MLC1 mutations.…”