Background: X-linked Charcot-Marie-Tooth type 1 (CMTX1) is the second most frequent form of CMT, which is caused by mutations in the gap junction beta 1 gene (GJB1) coding for connexin 32 protein. In addition to typical peripheral neuropathy, central nervous system (CNS) involvement in patients with CMTX1 has been reported as a special feature, but female patients are rarely affected. Case presentation: We describe a 29-year-old female who had a history of two cesarean deliveries. After each delivery, she presented transient and recurrent slurred speech and limb weakness. Magnetic resonance imaging (MRI) showed diffuse abnormal signals in the corpus callosum, posterior limbs of bilateral internal capsule, and centrum semiovale. Electromyogram showed sensorimotor peripheral neuropathy with the characteristics of intermediate CMT. The C.622G>A mutation (p.Glu208Lys) in the GJB1 gene was detected by PCR-sequencing. Conclusion: The diagnosis of CMTX1 should be considered, even in female patients, when the disease presents with recurrent stroke-like symptoms and abnormal white matter signals on MRI. The puerperium after delivery may be one of the precipitating factors.

A 32-year-old woman showed transient central type facial nerve palsy and bulbar symptoms. Brain MRI revealed high intensity signals in the cerebral white matter, splenium of corpus callosum, and posterior limb of internal capsule. Two elder brothers of the patient had distal dominant peripheral neuropathies in four limbs. In this family, the point mutation of GJB1 gene, encoding connexin 32, was revealed and X-linked Charcot-Marie-Tooth disease (CMTX1) was diagnosed. The presented case was a heterozygote of this mutation. She showed severe transient central nervous system (CNS) symptoms and subclinical demyelinating peripheral neuropathy. The CNS symptoms and alterations of brain images were very similar among three siblings. There are many reports on male patients with CMTX1 who show associated CN symptoms, but female patients are very rare. There has been no previous report of a CMTX1 patient similar to the patient presented here. The trigger factors have been recognized at the onset of transient CN symptoms in these cases. The prevention of these factors is important for the management of such patients.

X-linked Charcot-Marie-Tooth type 1 (CMTX1) is the second most common type of CMT and is caused by mutations in the Gap-Junction Beta-1 gene (GJB1), encoding connexin 32 which is expressed in Schwann cells as well as in oligodendrocytes. More than 400 GJB1 mutations have been described to date. Many mutation-carrier males have subclinical central nervous system (CNS) involvement, a few show mild CNS clinical signs, whereas only rarely overt though transient CNS dysfunction occurs. We report a 29-year-old man with CMTX1 who, at 16 years, showed short-lived CNS symptoms with transitory white matter abnormalities on cerebral magnetic resonance imaging (MRI) as first clinical presentation of a novel GJB1 mutation (p.Gln99_His100insGln). He had three consecutive episodes of right hemiparesis, together with sensory loss in the paretic limbs and expressive aphasia, all lasting a few hours, over a 2-day period, with concurrent white matter hyperintensity on MRI. These \"stroke-like\" episodes occurred just after arriving at sea level, after travelling from home at 700 m of altitude. Only a few years later did symptoms of peripheral neuropathy appear. In conclusion, CMTX1 should be included in the differential diagnosis of diseases characterized by transient CNS symptoms and white matter abnormalities on MRI.

BACKGROUND: X-linked Charcot-Marie-Tooth (CMT1X) disease is caused by mutations in the GJB1 gene. We describe a young man who presented with recurrent central nervous symptoms and transient white matter changes in the setting of a novel mutation in the GJB1 gene.
METHODS: Evaluation included clinical examination, neuroimaging, electrophysiological, and molecular genetic studies.
RESULTS: Clinical examination on 2 admissions 5 years apart demonstrated hemiparesis with findings of underlying peripheral neuropathy. Electrophysiologic studies revealed a sensorimotor polyneuropathy. MRI studies from both admissions revealed white matter changes, with improvement on an intervening study. Mutation analysis showed a novel mutation (c.98T>A; p.Ile33Asn) in the GJB1 gene.
CONCLUSIONS: Mutations in GJB1 can result in recurrent central nervous system symptoms with transient white matter signal changes on MRI. In patients presenting with hemiparesis, the presence of signs of a peripheral neuropathy may facilitate identification of CMT1X, and is likely to affect clinical management.