Megalencephalic Leukoencephalopathy with Subcortical Cysts: A Case Report

Background and Aim : Megalencephalic leukoencephalopathy with subcortical cysts (MLC), which is known as Van Der Knaap s disease is a rare autosomal recessive neurodegenerative disorder. Macrocephaly is one of the most common and earliest clinical characteristics of the MLC during infancy that is often coexisted with seizure, slowly progressive clinical course marked by the motor developmental delay with gradual onset of ataxia and spasticity, and usually the late onset of mental deterioration. Brain magnetic resonance imaging (MRI) shows predominant white matter involvement with the subcortical cyst. MLC is caused by a mutation in the gene MLC1. The age of presentation varied from birth to 27 years. So far, all attempts to treat Van der Knaap syndrome have been failed. The mainstay of treatment is supportive in the form of acetazolamide, anticonvulsants, and rehabilitation. We report a 5-years-old boy megalencephalic leukoencephalopathy with subcortical cysts.Methods : Case presentation: A 5-years-old boy presented with macrocephaly and progressive weakness from the birth in the whole body with spasticity and ataxia. He also had poor mental status and cognitive impairment. On genetic assessments, we found a homozygous pathogenic variant in intron 5 of the MLC1 gene. Brain MRI showed bilateral symmetrical white matter hyper intention on T2/FLAIR and hypointensity on T1 with cystic changes as well as CSF intensity in subcortical of the frontal and occipital lobe. Due to the patient s progressive motor decline, we measured gross and oral motor functions. Gross and oral motor functions were assessed using Gross Motor Function Measurement (GMFM) and Oral Motor Assessment Scale (OMAS), respectively. The result of GMFM and OMAS tests were level 5 and grade 7 for him. The patient was treated by a supportive approach including occupational therapy (cognitive and physical) and speech therapy.Results : Conclusion : MLC1 should be considered in children with macrocephaly and slowly progressive motor decline. This disease can be prenatally diagnosed by parental testing for detected variant and genetic counselling offered for future pregnancies. Early rehabilitation interventions have been necessary to improve the patient s symptoms. Future studies are needed to determine the pathophysiologic mechanisms affected during disease, and strategies and approaches for treating MLC1 patients.

Keywords:

Megalencephalic leukoencephalopathy , neurorehabilitation , subcortical cyst , Van Der Knaap syndrome