Recurrent Stroke-like Events Preceding the X-linked Charcot-Marie-Tooth Disease Diagnosis (P6.011)

OBJECTIVE: To discuss diagnostic difficulties in children presenting with acute encephalopathy syndrome and to emphasize the need for awareness of early presentation of X-linked Charcot-Marie-Tooth disease (CMT1X) BACKGROUND: Mutations of gap junction beta-1 protein Connexin 32 (Cx32) are responsible for CMT1X, a common cause of hereditary peripheral neuropathy presenting in childhood. In addition to the manifestations of peripheral nerve dysfunction, patients occasionally have recurrent stroke-like events - focal weakness, sensory loss, aphasia, and dysarthria. Also, transient diffusion abnormalities are often symmetric and not restricted to vascular territories on imaging. Thus, diagnostic difficulties occur in children with recurrent encephalopathy, especially when CMT diagnosis has not already been established. The stroke-like phenomena often precipitated by acute infections and metabolic stressors. DESIGN/METHODS: A previously healthy boy was evaluated by clinical, laboratory testing, and repeated imaging studies. He initially presented at 11 years of age with acute hemiparesis, ataxia, and dysarthria. Maternal family history is significant for peripheral neuropathy. The CSF and metabolic tests were normal and brain MRI showed symmetrical diffusion abnormalities in the white matter. This pattern resolved but recurred at ages 14 and 17. He later developed peripheral neuropathy - weakness of distal muscles, decreased sensations, areflexia, and foot drop. RESULTS: The brain MRIs performed at the time of recurrences revealed symmetric signal alterations with restricted diffusion involving bilateral centrum semiovale, splenium of the corpus callosum, and cerebellar peduncles. Diffusion abnormalities normalized after 6 months. Genetic testing for hereditary neuropathy revealed mutation in Cx32, suggesting a diagnosis of CMT1X. CONCLUSIONS: The transient encephalopathic syndrome with focal paresis, dysarthria, and ataxia is an under recognized early presentation of CMT1X and it continues to be clinically challenging due to its rarity. Thus, this case emphasizes the need for awareness among practitioners to consider CMT1X in the differential diagnosis of acute encephalopathy with symmetric cerebral white matter signal alterations with restricted diffusion to avoid unnecessary work-up and the associated costs. Study Supported by: none Disclosure: Dr. Kimbason has nothing to disclose. Dr. Anilkumar has nothing to disclose. Dr. Bronov has nothing to disclose.