Abstract
Objective
X-linked Charcot Marie Tooth disease (CMT1X) is a hereditary demyelinating neuropathy
caused by mutations in the GJB1 gene encoding the gap junction protein connexin 32 (Cx32). Some GJB1 mutations have been reported to cause transient clinical CNS dysfunction. We report
a boy with persistent CNS abnormalities possibly caused by CMT1X.
Methods
A five year old boy was evaluated by clinical, electrophysiological, MRI and genetic
testing.
Results
The patient's early motor milestones were normal to age 5 months. His subsequent course
was one of slow improvement punctuated by brief periods of loss of ability to sit
between age 5 and 10 months, loss of language between 12 months and 2 years and 1
episode of non-clinically observed resolved left-sided facial weakness. At age 5,
he had truncal instability, appendicular ataxia, and dysarthric speech. Cognition
was normal. He had mild toe weakness and intrinsic muscle atrophy. MRI evaluation
was abnormal. Electrophysiologic testing revealed slowed motor conduction velocities
and sensory responses of low amplitude. Genetic workup was normal excepting a novel
missense mutation in GJB1, causing a p.54N>H substitution.
Conclusion
The patient has persistent CNS abnormalities characterized by dysarthria and ataxia.
These are similar to transient CNS abnormalities reported in patients with CMT1X.
These CNS findings may be the direct result of his novel Cx32 mutation.
Keywords
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References
- Genetic and clinical aspects of Charcot-Marie-Tooth's disease.Clin Genet. 1974; 6: 98-118
- Charcot-Marie-Tooth disease and related hereditary polyneuropathies: Molecular diagnostics determine aspects of medical management.Genet Med. 2006; 8: 86-92
- Estimation of the mutation frequencies in Charcot-Marie-Tooth disease type 1 and hereditary neuropathy with liability to pressure palsies: a European collaborative study.Eur J Hum Genet. 1996; 4: 25-33
- Connexin mutations in X-linked Charcot-Marie-Tooth disease.Science. 1993; 262: 2039-2042
- Functional gap junctions in the Schwann cell myelin sheath.J Cell Biol. 1998; 142: 1095-104
- Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons.J Neurosci. 2001; 21: 1983-2000
- CMT1X phenotypes represent loss of GJB1 gene function.Neurology. 2007; 68: 849-855
- Slowing of central conduction in X-linked Charcot-Marie-Tooth neuropathy shown by brain auditory evoked responses.J Neurol Neurosurg Psychiatry. 1996; 61: 43-46
- A novel Cx32 mutation causes X-linked Charcot-Marie-Tooth disease with brainstem involvement and brain magnetic resonance spectroscopy abnormalities.Neurol Sci. 2006; 27: 18-23
- Central nervous system involvement in four patients with Charcot-Marie-Tooth disease with connexin 32 extracellular mutations.J Neurol Neurosurg Psychiatry. 1998; 65: 947-948
- Episodes of generalized weakness in two sibs with the C164T mutation of the connexin 32 gene.Neurology. 2001; 57: 1906-1908
- Six novel connexin32 (GJB1) mutations in X-linked Charcot-Marie-Tooth disease.J Neurol Neurosurg Psychiatry. 2002; 73: 304-306
- Transient, Recurrent, White Matter Lesions in X-linked Charcot-Marie-Tooth Disease With Novel Connexin 32 Mutation.Arch Neurol. 2003; 60: 605-609
- Transient cerebral white matter lesions in a patient with connexin 32 missense mutation.Neurology. 2002; 59: 2007-2008
- Transient Central Nervous System White Matter Abnormality in X-Linked Charcot-Marie-Tooth disease.Ann Neurol. 2002; 52: 429-434
- The CNS phenotype of X-linked Charcot-Marie-Tooth disease.Neurology. 2003; 61: 1475-1478
- Electrodiagnostic findings in CMTX: a disorder of the Schwann cell and peripheral nerve myelin.Ann NY Acad Sci. 1999; 883: 504-507
- Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder.Proc Natl Acad Sci USA. 1989; 86: 8128-8131
- Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus-Merzbacher-like disease.Am J Hum Genet. 2004; 75: 251-260
- Phenotypic and cellular expression of two novel connexin32 mutations causing CMT1X.Neurology. 2006; 66: 396-402
- Postlicensure Safety Surveillance for Varicella Vaccine.JAMA. 2000; 284: 1271-1279
- Normal myelination of anatomic nerve fiber bundles: MR analysis.Am J Neuroradiol. 1998; 19: 1129-1136
- Normal maturation of the neonatal and infant brain: MR imaging at 1.5 T.Radiology. 1988; 166: 173-180
- Novel mutation in X-linked Charcot-Marie-Tooth disease associated with CNS impairment.Neurology. 2002; 59: 923-926
Article info
Publication history
Published online: February 04, 2009
Accepted:
December 22,
2008
Received in revised form:
December 15,
2008
Received:
August 6,
2008
Footnotes
☆All authors concur with the manuscript as written. All work included in the manuscript has been approved by the Human Investigations Committee at Wayne State University, Detroit, MI, USA.
Identification
Copyright
© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
