Charcot-Marie-Tooth 4B3 Phenotype Expansion and Confounding Factors

Abstract Purpose of Review >Charcot-Marie-Tooth neuropathy type 4B3 (CMT4B3) is a rare inherited neuropathy caused by SBF1 gene defects, presenting with progressive sensory-motor polyneuropathy, cerebellar ataxia, and cranial nerve involvement. Sjögren syndrome may also cause cranial and peripheral neuropathies. Recent Findings We report a woman with mild cerebellar ataxia, progressive sensory-motor polyneuropathy worsened after pregnancy, scoliosis, pes cavus , and oculomotor abnormalities. Elevated anti-SSA/Ro and ANA suggested neuro-Sjögren after excluding other causes. Atypical progression and unclear diagnosis prompted whole-exome sequencing-based testing, revealing two novel heterozygous variants in SBF1 gene. A literature review was performed to describe similar cases. Summary This case highlights the challenge in distinguishing hereditary from acquired neuropathies and emphasizes genetic testing’s role in complex cases, expanding CMT4B3’s clinical spectrum.