Late-Onset Friedreich's Ataxia (LOFA) Mimicking Charcot-Marie-Tooth Disease Type 2: What Is Similar and What Is Different?

Herein, we report a patient that presented with late-onset progressive steppage gait, neuropathy and pes cavus, suggesting Charcot-Marie-Tooth (CMT) disease. Subsequent genetic investigation confirmed Friedreich's ataxia (FRDA). We demonstrate that late-onset Friedreich's ataxia (LOFA) may be a CMT mimicker. This case reinforces that other genetic conditions may clinically resemble CMT. The clinical similarities between CMT and FRDA include a symmetrical neuropathy (axonal in FRDA), steppage gait, and eventually scoliosis. We suggest that late-onset forms of hereditary neuropathies should be carefully evaluated, since LOFA may be a CMT mimicker.

Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia.

Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay.