Leukoencephalopathy with bilateral anterior temporal lobe cysts

Leukoencephalopathy with bilateral anterior temporal lobe cysts (also known as van der Knaap disease or megalencephalic leukoencephalopathy with subcortical cysts, MLC) is a rare inherited neurological disorder characterized by progressive white matter deterioration in the brain. The condition is classified among the sphingolipidoses and related disorders (ICD-10: E75.2). It primarily affects the central nervous system, with hallmark features on brain MRI including diffuse swelling and signal abnormality of the cerebral white matter (leukoencephalopathy) along with characteristic cysts in the anterior temporal regions and often the frontoparietal regions. Patients typically present in the first year of life with macrocephaly (abnormally large head), which is often the earliest sign. Over time, affected individuals develop progressive motor deterioration, spasticity, cerebellar ataxia, and seizures. Cognitive decline occurs but is generally slower than motor deterioration, and many patients retain some cognitive abilities for years. The disease is caused by mutations in the MLC1 gene (most commonly) or the GLIALCAM (HEPACAM) gene. MLC1 mutations cause the classic autosomal recessive form (MLC1), while GLIALCAM mutations can cause either an autosomal recessive form (MLC2A, with a progressive course similar to MLC1) or an autosomal dominant form (MLC2B, which may show clinical improvement over time). The MLC1 and GLIALCAM proteins are involved in brain ion and water homeostasis, and their dysfunction leads to vacuolization of myelin and astrocyte swelling. There is currently no cure or disease-specific treatment for this condition. Management is supportive and symptomatic, including antiepileptic medications for seizure control, physical therapy to manage spasticity and motor difficulties, and occupational and speech therapy. The disease follows a slowly progressive course in most cases, with many patients eventually becoming wheelchair-dependent, though life expectancy can extend into adulthood.

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