Episodes of generalized weakness in two sibs with the C164T mutation of the connexin 32 gene

Abstract

Two sibs with Charcot-Marie-Tooth disease had repeated episodes of generalized weakness. The patients had distal weakness and atrophy as well as findings of CNS involvement on brain MRI. Both patients bear the C164T mutation of the connexin 32 gene but no mutations of the genes responsible for hyper- or hypokalemic periodic paralysis. It is possible that both patients have one disease with complex phenotype due to abnormal expression of the connexin 32 gene.

X-linked Charcot-Marie-Tooth Disease (CMTX) in a Severely Affected Female Patient with Scattered Lesions in Cerebral White Matter

“…Here, we reported for the first time a female patient with atypical scattered lesions in cerebral white matter who exhibited all the clinical criteria of CMTX and had a mutation in the GJB1 gene. Previously, CMTX patients were reported with white matter lesions in the periventricular area, the parietal white matter, and in the splenium of corpus callosum (6)(7)(8). Among them, only one male case showed scattered white matter lesions that were similar to those in our case (6) (12).…”

“…Previously, CMTX patients were reported with white matter lesions in the periventricular area, the parietal white matter, and in the splenium of corpus callosum (6)(7)(8). Among them, only one male case showed scattered white matter lesions that were similar to those in our case (6) (12). Although sequence variants in the GJB1 promoter region were detected in this case, direct DNA sequencing of the GJB1 coding region was normal (12).…”

“…Overall 7.1% of CMTX patients show CNS involvement (6)(7)(8)(9). Six male patients with CMTX have been described with transient CNS symptoms and symmetrical white matter lesions that later resolved (6)(7)(8).…”

Transient central nervous system white matter abnormality in X‐linked Charcot‐Marie‐Tooth disease

“…Recently, two Greek brothers have been reported with a Thr55Ile mutation in Cx32 who have had several episodes similar to those described in our patients 25 but without an obvious predisposing cause. Transfection studies in mammalian cells show that this mutant Cx32 cannot be transported to the cell surface 22 and, similar to the mutations in our patients, cannot form functional gap junctions.…”

The Role of Gap Junctions in Charcot-Marie-Tooth Disease

“…Acute transient encephalopathy syndromes associated with brain MRI changes have been described in CMT1X patients with the T55I, R75W, E102del, R142W, R164W and C168Y mutations (Panas et al, 2001;Paulson et al, 2002;Schelhaas et al, 2002;Hanemann et al, 2003;Taylor et al, 2003). In most patients encephalopathy developed under conditions of metabolic stress caused by travel to high altitudes (Paulson et al, 2002), febrile illness (Schelhaas et al, 2002;Hanemann et al, 2003), hyperventilation (Srinivasan et al, 2008), or concussion (Halbrich et al, 2008).…”