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

Abstract

Background CLCN2-related leukoencephalopathy (CC2L) is a rare autosomal recessive disorder caused by biallelic variants of CLCN2 encoding chloride channel 2 (ClC-2) which is one of the nine chloride-transporting proteins in the ClC family. Although CC2L is associated with distinct radiological features, it presents a wide range of clinical features. Case presentation A 34-year-old woman presented to our hospital with a sudden onset of vertigo with headache. The patient reported noticing intermittent headaches and tingling in both arms since the age of 31. On the first visit, the patient was alert and neurologically intact, except for slight hyperflexion of the limbs without laterality. Head MRI showed high-intensity signals on axial T2-weighted fluid-attenuated inversion recovery and diffusion-weighted images bilaterally in the posterior limbs of the internal capsules, cerebral peduncles, superior and middle cerebellar peduncles, decussation of superior cerebellar peduncles, and central tegmental tract. All of the patient’s symptoms were resolved or eased following supportive care. The patient stopped attending our hospital at the age of 46 because her symptoms had ameliorated. At 51 years of age, the patient revisited our hospital because of the recurrence of vertigo, headache, and nausea. She did not present with any abnormalities, including ataxia, on neurological examination. Head MRI showed widespread high-intensity signals similar to those exhibited 17 years ago. Genetic testing revealed compound heterozygous variants in CLCN2 (NM_004366.6): a novel variant c.1828C > T, p.(Arg 610*) from her father and c.61dup, p.(Leu21Profs*27) from her mother. The patient was finally diagnosed with CC2L. She received supportive treatment, which made her symptoms manageable. Conclusions This is a detailed report of a patient with adult-onset CC2L who was successfully diagnosed and followed with head MRI. This report provides new insight into CC2L, highlighting longstanding and distinct characteristics of head MRI and the difficulty performing diagnosis without it when patients have minimal and common symptoms, such as the present case.