J Clin Neurol.  2012 Sep;8(3):212-217. 10.3988/jcn.2012.8.3.212.

Clinical Characteristics and Analysis of CLCN1 in Patients with "EMG Disease"

• Nam TS
• Jung HJ
• Choi SY
• Kim YO
• Kim MK
• Cho KH

• KMID: 2287593
• DOI: http://doi.org/10.3988/jcn.2012.8.3.212

Abstract

BACKGROUND AND PURPOSE
While the etiology and clinical features of "EMG disease" - which is characterized by diffusely increased insertional activity on needle electromyography (EMG) in the absence of neuromuscular disease - are not well known, some authorities believe it may be a form of myotonia congenita (MC). The aims of this study were to determine the clinical features of EMG disease and its relationship with CLCN1 mutations in patients.
METHODS
The detailed clinical and electrophysiological features of EMG disease were evaluated in six patients. All 23 coding exons and exon-intron boundaries in CLCN1 gene were analyzed by direct sequencing to detect nucleotide changes.
RESULTS
The common clinical symptoms of EMG disease were chronic muscle stiffness or generalized myalgia, which were aggravated in a cold environment. Four patients complained of action myotonia several times a year. Short trains of provoked positive sharp waves were documented on needle EMG, but myotonic discharges, fibrillation potentials, and fasciculations were not. Increased insertional activity was identified at the asymptomatic muscles studied. One novel heterozygous mutation was identified in one patient following genetic testing for CLCN1 mutations (c.1679T>C, p.Met560Thr).
CONCLUSIONS
The clinical features of EMG disease might be quite similar to those of MC, but CLCN1 mutation was found in only one subject. It is thus difficult to accept that EMG disease lies within the phenotypic spectrum of MC. Additional testing is needed to verify the pathogenetic cause of the diffusely increased insertional activity associated with this condition.

Keyword

chloride channels; electromyography; myotonia congenita

MeSH Terms

Chloride Channels
Clinical Coding
Cold Temperature
Electromyography
Exons
Fasciculation
Genetic Testing
Humans
Muscles
Myotonia
Myotonia Congenita
Needles
Neuromuscular Diseases
Chloride Channels

Figure

• 

  Fig. 1 DNA sequence analysis of the CLCN1 gene and conservation across species of a novel CLCN1 mutation. A: Electropherogram of SN-V reveals a previously-unreported heterozygous T-to-C substitution at position 1679 of CLCN1 (c.1679T>C, p.Met560Thr). B: Representative electropherogram of 200 normal controls. C: Met560 residue (red) is highly conserved and found in evolutionary distant orthologs down to the zebrafish. The sequences were derived from GenBank records with the following accession numbers: Homo sapiens (NM_000083.2), Callithrix jacchus (XM_002751883.1), Bos Taurus (NM_001143871.1), Equus caballus (XM_001915636.2), Gallus gallus (XM_425521.3), Rattus norvegicus (NM_013147.1), Mus musculus (NM_013491.2), Anolis carolinensis (XP_003226608.), Danio rerio (XP_695866.3). DNA: deoxyribonucleic acid, SN: subject number.

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