Vocal cord paralysis in Charcot–Marie–Tooth type 4b1 disease associated with a novel mutation in the myotubularin-related protein 2 gene: A case report and review of the literature

Abstract

HighlightsVocal cord paralysis is a relevant symptom of Charcot–Marie–Tooth type 4B1.Patients harboring MTMR2 mutations should be investigated for laryngeal function.A new mutation in the MTMR2 gene is described.The frequency of vocal cord paralysis in early-onset CMT subtypes is explored.

A multicenter retrospective study of charcot‐marie‐tooth disease type 4B (CMT4B) associated with mutations in myotubularin‐related proteins (MTMRs)

“…11 It may range in degree from a hoarse voice to life-threatening stridor leading to respiratory difficulties, requiring ventilatory support and even tracheostomy; laser treatment proved effective in more than one case. 11 It may range in degree from a hoarse voice to life-threatening stridor leading to respiratory difficulties, requiring ventilatory support and even tracheostomy; laser treatment proved effective in more than one case.…”

“…Nerve biopsy was performed in 12 CMT4B1 and 8 CMT4B2 patients and showed the typical myelin outfoldings in all cases. 11,15,19,24,[46][47][48]…”

“…All the variants identified in CMT4B1 and CMT4B2 patients are shown in Figure 1. Overall, we identified 17 mutations in MTMR2 in CMT4B1 patients, located in different domains of the protein, of which nine have been reported, whereas five are novel and three are novel disease associations of known rare variants 7,11,15,16,[19][20][21]24 ( Fig 1A; Table 3). Of note, 15 mutations represent loss-offunction alleles, such as nonsense mutations or frameshifts leading to premature truncated proteins, whereas two are missense mutations.…”

“…[7][8][9][10] Both CMT4B1 and CMT4B2 are characterized by early onset, demyelinating neuropathy, and disabling progression and may be complicated by vocal cord palsy and respiratory involvement. 6,11 CMT4B2 patients may have congenital or juvenile glaucoma. 12 CMT4B3 has been more recently associated with mutations in the MTMR5/SBF1 gene, but is characterized by different phenotypes with either a pure demyelinating neuropathy with myelin outfoldings or an axonal polyneuropathy complicated by multiple cranial involvement, intellectual disability, microcephaly, and dysmorphic features.…”

“…CMT4B1 and CMT4B2 are associated with mutations in the MTMR2 and MTMR13 (myotubularin‐related protein 2 and 13, which is also named SET binding factor 2 [ SBF2 ]) genes, respectively . Both CMT4B1 and CMT4B2 are characterized by early onset, demyelinating neuropathy, and disabling progression and may be complicated by vocal cord palsy and respiratory involvement . CMT4B2 patients may have congenital or juvenile glaucoma .…”