X-linked Charcot–Marie–Tooth Disease Presenting with Stuttering Stroke-like Symptoms

Abstract

X-linked Charcot–Marie–Tooth disease (CMTX1) is the second most common form of Charcot–Marie–Tooth disease (CMT). It is caused by a mutation in the gap junction β 1 (GJB1) gene, which encodes for connexin-32. In addition to the peripheral neuropathy and foot deformities observed in classic CMT, central nervous system symptoms and magnetic resonance imaging (MRI) signal abnormalities in the brain have been reported in patients with CMTX1. Here we describe two cases of adolescent males who presented with stuttering neurologic deficits that were initially suggestive of acute ischemic stroke and were ultimately diagnosed with genetically confirmed CMTX1. Both patients had evidence of T2 hyperintensity and decreased diffusion on MRI in the centrum semiovale, posterior corona radiata, posterior periventricular white matter, and corpus callosum. Though rare, these cases illustrate the importance of comprehensive neurologic history, physical examination, and appropriate diagnostic evaluation.

Keywords

X-linked Charcot–Marie–Tooth disease - gap junction β 1 gene - neuropathy - stroke-like symptoms

• References

• 1 Wang Y, Yin F. A review of X-linked Charcot-Marie-Tooth disease. J Child Neurol 2016; 31 (06) 761-772
• 2 Scherer SS, Kleopa KA. X-linked Charcot-Marie-Tooth disease. J Peripher Nerv Syst 2012; 17 (Suppl. 03) 9-13
• 3 Bird TD. Charcot-Marie-Tooth Neuropathy X Type 1. In: GeneReviews [online]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1374 . Accessed October 24, 2018
• 4 Al-Mateen M, Craig AK, Chance PF. The central nervous system phenotype of X-linked Charcot-Marie-Tooth disease: a transient disorder of children and young adults. J Child Neurol 2014; 29 (03) 342-348
• 5 Taylor RA, Simon EM, Marks HG, Scherer SS. The CNS phenotype of X-linked Charcot-Marie-Tooth disease: more than a peripheral problem. Neurology 2003; 61 (11) 1475-1478
• 6 Sagnelli A, Piscosquito G, Chiapparini L. , et al. X-linked Charcot-Marie-Tooth type 1: stroke-like presentation of a novel GJB1 mutation. J Peripher Nerv Syst 2014; 19 (02) 183-186
• 7 Hanemann CO, Bergmann C, Senderek J, Zerres K, Sperfeld AD. Transient, recurrent, white matter lesions in X-linked Charcot-Marie-Tooth disease with novel connexin 32 mutation. Arch Neurol 2003; 60 (04) 605-609
• 8 Paulson HL, Garbern JY, Hoban TF. , et al. Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease. Ann Neurol 2002; 52 (04) 429-434
• 9 Abrams CK, Scherer SS. Gap junctions in inherited human disorders of the central nervous system. Biochim Biophys Acta 2012; 1818 (08) 2030-2047