Diversity in MRI findings in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL)

CLCN2-related leukoencephalopathy with novel compound heterozygous variants followed with magnetic resonance imaging (MRI) over 17 years: a case report

“…These features are compatible with the head MRI ndings in the current case. In addition, the central tegmental tracts in the medulla, the middle cerebellar peduncles, and the decussation of the superior cerebellar peduncles in the midbrain showed similar intensity abnormalities, which are considered to be supportive criteria for CC2L (2). Restricted diffusion in some affected structures in patients with CC2L has been reported previously, and was attributed to intramyelinic edema caused by small vacuoles and extracellular spaces (3).…”

“…The American College of Medical Genetics and Genomics has recommended that these two variants be classi ed as likely pathogenic (PVS1, PM2_supporting, PM3) (9). Patients with CC2L have been reported to have various variants (2,4,10,11). To the best of our knowledge, among previous studies published in English, only two Japanese cases of patients with CC2L have been reported, and both of them had the homozygous c.61dup variant: a 22-month-old female with generalized tonic-clonic seizures during infancy and a 6-year-old male with aseptic meningitis (1,12).…”

“…The clinical features of CC2L include a variable combination of neurological symptoms, such as ataxia, headache, spasticity, seizures, and other symptoms, with a broad range of age of onset(3). The most common neurological ndings are mild cerebellar ataxia, which could include action tremor and gait instability following initially normal motor function (2,4). Most CC2L patients demonstrate mild clinical phenotypes with prolonged survival.…”

“…CLCN2-related leukoencephalopathy (CC2L) is a rare disorder known to be associated with biallelic mutations of CLCN2 (1). Ataxia, learning disabilities, headaches, mild visual impairment, and male infertility have been reported as symptoms of CC2L (2). CLCN2 encodes chloride channel 2 (ClC-2), and various mutations of CLCN2 have been reported (3).…”

“…CC2L is not associated with any speci c neurological ndings, and its diagnosis is often made through characteristic ndings on brain magnetic resonance imaging (MRI) scans and the establishment of a proband via identi cation of biallelic pathogenic variants in CLCN2 using genetic testing (2). In a previous study, MRI in CC2L demonstrated restricted diffusion suggesting myelin vacuolation con ned to the speci ed white matter structures in adult patients (4).…”