Discerning inherited neuropathies from CIDP, particularly in instances with a subacute onset, poses a diagnostic challenge. Crucial indicators such as disease progression, familial history, and an insufficient response to Intravenous Immunoglobulin (IVIG) therapy serve as red flags for an inherited neuropathy, particularly Charcot-Marie-Tooth (CMT), with the PMP22 gene mutation emerging as the most prevalent.

We describe three siblings exhibiting the CMT phenotype. The eldest, a 51-year-old female, experienced a subacute onset of proximal weakness at 40 years old, a nerve conduction study demonstrated conduction block, alongside a cerebrospinal fluid analysis indicating albumino-cytological dissociation. These findings led to the diagnosis of CIDP, for which she received IVIG treatment resulting in partial symptom improvement. The second sibling, a 48-year-old female, received a CIDP diagnosis at 30 years old, confirmed by CSF analysis and nerve conduction study, also experiencing improvement after IVIG treatment. The youngest brother presented inflammatory CSF and proximal weakness at 39 years old, with improvement observed following glucocorticosteroid therapy. All three patients underwent genetic testing for hereditary neuropathies. On physical examination, all three exhibited bilateral pes cavus, legs with an inverted champagne bottle appearance, balance issues, and distal atrophy. All tests confirmed CMT 1A with pathogenic mutation in PMP22. The eldest sister demonstrated significant balance impairment and carried a heterozygous PMP22 mutation at chr17:14.236.572 - 15.574.201, while the other sister primarily struggled with neuropathic pain and possessed a PMP22 gain copy number of 3. The youngest brother faced progressive balance difficulties and weakening over subsequent years, with a PMP22 mutation at chr17: 14.095.305 - 15.492.541.

This scenario unveils a rare overlap of CMT and CIDP within a Brazilian family, underscored by PMP22 mutations. Despite distinct clinical diagnoses and treatment responses, genetic testing provided unequivocal confirmation of this intriguing overlap, shedding light on the complex interplay between genetic neuropathies and CIDP.