This study aimed to describe the clinical, genetic, and epidemiological features of Charcot-Marie-Tooth disease (CMT) in Brazilian patients from a tertiary center, and to compare our data with previously published findings. This retrospective observational study conducted between February 2015 and July 2020 evaluated 503 patients (94 families and 192 unrelated individuals), diagnosed with CMT. Clinical and neurophysiological data were obtained from electronic medical records and blood samples were used for genetic analyses. Multiplex ligation-dependent probe amplification was used to assess duplications/deletions in PMP22. Sanger sequencing of GJB1 was performed in cases of suspected demyelinating CMT. Targeted gene panel sequencing was used for the remaining negative demyelinating cases and all axonal CMT cases. The first decade of life was the most common period of disease onset. In all, 353 patients had demyelinating CMT, 39 had intermediate CMT, and 111 had axonal CMT. Pathogenic or likely pathogenic variants were identified in 197 index cases.The most common causative genes among probands were PMP22 (duplication) (n = 116, 58.88%), GJB1 (n = 23, 11.67%), MFN2 (n = 12, 6.09%), GDAP1 (n = 7, 3.55%), MPZ (n = 6, 3.05%), PMP22 (point mutation) (n = 6, 3.05%), NEFL (n = 3, 1.52%), SBF2 (n = 3, 1.52%), and SH3TC2 (n = 3, 1.52%). Other identified variants were ≤1% of index cases. This study provides further data on the frequency of CMT subtypes in a Brazilian clinical-based population and highlights the importance of rarer and previously undiagnosed variants in clinical practice.

Macrophagic myofasciitis (MMF) is an inflammatory myopathy related to aluminum-containing vaccines. Described in 1998, most cases were reported in adults, with only 22 cases being reported in children. Three children aged between 13 months and 3(1/2) years were investigated in our institution for neuromuscular symptoms. They underwent thorough clinical, familial, and laboratory investigations, electroneuromyography, muscle biopsy with transmission electron microscopy, scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS), and, in one case, brain magnetic resonance imaging. They had received regular immunizations. Two patients were hypotonic and one presented with myotonia. Muscle biopsy of all patients presented macrophagic infiltrates with intracytoplasmic aluminum content as revealed by SEM/EDS analysis. Their diverse clinical picture does not support a direct relationship between local morphologic findings and systemic symptoms. The atypical clinical presentation of these children may not result from the superposition of MMF upon a background systemic neuromyopathy, suggesting instead that they are two coincident and independent conditions. Although the finding of macrophage infiltrates in muscle tissue is not new, the identification of aluminum content is recent. The use of tissue sections for aluminum detection and mapping by SEM/EDS is conclusive for, diagnosis; it has not been reported previously in a pathology journal, to the authors' knowledge.

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