2023 American Academy of Neurology Abstract Website

Objective:

Background:

CMTX1 is an X-linked dominant form of hereditary sensorimotor polyneuropathy. It is caused by mutations in the gap junction protein beta 1(GJB1) gene on chromosome Xq13.1, which encodes connexin 32 protein. CNS can be affected and lead to transient or persistent CNS symptoms including dysarthria, dysphagia, hemiparesis or quadriparesis, ataxia, aphasia, and encephalopathy.

Design/Methods:

Case Report:

A 22-year-old man presented with acute onset left facial droop, dysarthria and left upper extremity weakness. Two weeks prior he experienced a one-day episode of gastroenteritis.

Neurological examination showed weakness in the left lower face, distal muscle weakness in toe extension, ankle dorsiflexion and hand intrinsic muscles, absent lower extremity reflexes, diminished vibration and temperature senses in length-dependent pattern, high-arched feet and hammertoes.

Family history of early onset polyneuropathy, never genetically tested.

Brain MRI showed marked and symmetric restricted diffusion lesions involving bilateral fronto-parietal white matter, corpus callosum and posterior limb of internal capsule without contrast enhancement.

CSF analysis was unremarkable.

The patient was given pulse steroid therapy for possible demyelinating disease, his symptoms completely resolved within 48 hours.

Two prior similar symptoms, one was diagnosed as acute disseminated encephalomyelitis (ADEM) and treated with steroids. Brain MRI of these two episodes showed similar restricted diffusion abnormalities. Repeat brain MRI seven months after the second episode showed complete resolution of restricted diffusion lesions.

Leukodystrophy genetic panel was negative. Genetic testing showed hemizygous pathogenic mutation c.491G>A in GJB1 gene, associated with X-linked Charcot-Marie-Tooth disease - CMTX1.

Results:

Conclusions:

Young patients with history of polyneuropathy presenting with acute CNS symptoms with bilateral white matter and corpus callosum lesions, CMTX1 should be included in the differential diagnosis. Upon confirmation of CMTX1 diagnosis, patient reassurance is important as well as education regarding potential provoking factors that lead to CNS involvement.