Cranial Nerve Involvement With Diplopia as Presenting Feature of CMT1H Caused by Recurring FBLN5 Variant

BACKGROUND AND AIMS: CMT1H is a rare, autosomal dominant, demyelinating subtype of CMT caused by variants in FBLN5. Symptomatic cranial nerve involvement has never been reported in patients with CMT1H. CASE REPORT: We report a 45-year-old woman with a history of long-standing diplopia. On examination, she had bilateral limitation of eye abduction, with double vision in all directions of gaze, particularly horizontally. She was unable to heel-walk, had mild lower limb distal weakness, decreased tendon reflexes with absent Achilles reflexes, reduced distal vibration sense, pes cavus, and hammertoes. A dominant family history was noted. Brain MRI revealed bilateral contrast enhancement and thickening of cranial nerves III through XII. Genetic testing with whole exome sequencing revealed a known, recurring, heterozygous, likely pathogenic missense variant in FBLN5 [c.1117C>T; p. (Arg373Cys)], consistent with a diagnosis of CMT1H. INTERPRETATION: This is the first reported case of FBLN5-related CMT1H with symptomatic cranial nerve involvement, expanding the known phenotypic spectrum of the disease.