The following is a summary of “Expanding the Clinical Spectrum of DRP2-Associated Charcot-Marie-Tooth Disease,” published in the March 2024 issue of Neurology by Sivera et al.
Researchers conducted a retrospective study investigating the causality and phenotypic impact of germline truncating variants in DRP2 causing Charcot-Marie-Tooth (CMT) disease.
In an observational study, they examined 9 patients diagnosed with CMT with DRP2 gene mutations at 6 medical centers across Spain.
The results showed 7 Spanish families exhibiting 4 distinct likely pathogenic germline variants of DRP2. According to X-linked inheritance patterns, males with hemizygous DRP2 variants displayed an intermediate form of CMT, while heterozygous females remained asymptomatic. Symptom onset varied (36.6 ± 16 years), featuring mild-to-moderate functional impairment due to lower limb weakness and multimodal sensory loss. Nerve echography demonstrated increased cross-sectional area in nerve roots and proximal nerves. Muscle magnetic resonance imaging of lower limbs confirmed length-dependent fatty infiltration. Immunostaining of intradermal nerve fibers indicated the absence of DRP2, while electron microscopy revealed abnormal myelin thickness, detectable in sural nerve sections.
Investigators concluded that DRP2 variants were linked to late-onset CMT with leg weakness, slow nerve signals, and thickened upper nerves.