Electrical myotonia in heterozygous carriers of recessive myotonia congenita

Abstract

We investigated electrophysiologically the unaffected parents of patients with recessive myotonia congenita. We studied 18 families, in nine of which the diagnosis was confirmed by molecular genetics. Brief myotonic discharges were present in at least one parent in 67% of the families. Fathers were more likely than mothers to show these discharges. The difficulty in distinguishing very mildly affected parents with dominant myotonia congenita from the heterozygous carriers of recessive myotonia congenita is stressed. The recessive type of myotonia congenita (RMC), described by Becker, 2 is more common than the dominant type (Thomsen's disease).2 In RMC, myotonia has a later onset (4-12 years) and usually commences in the legs, spreading after a variable interval (sometimes of years) to the arms and then to the face: it is more severe and is usually associated with transient weakness.2 Not every RMC patient conforms to this pattern and it is sometimes difficult to decide clinically whether a patient has the recessive or the dominant form. The single factor by which RMC can be clinically differentiated with relative certainty from dominant myotonia congenita is the absence of clinical myotonia in the parents. The presence of myotonic discharges on needle electromyography (electrical myotonia) of the parents, however, is compatible with the diagnosis of RMC. Although such an electromyographic finding in the parents is generally considered to be a manifestation of heterozygosity, 3 the possibility of its pointing to the presence of dominant type of inheritance has not been completely excluded. 9The aim of this study was to search for electrical myotonia in the parents of patients with RMC. In nine families, the diagnosis was confirmed by determination of mutations in one or two alleles of the muscle chloride channel gene in the patient. MATERIAL AND METHODSThe electrophysiological work was done at the Department of Neurology, University of Istanbul and the molecular biology at the Department of Physiology, University of Ulm. Consent was obtained from the Review Committees of both institutions. Eighteen families of 21 patients were studied; sibling pairs were present in three families. Seventeen patients (81%) were male. Consanquinity was present in 11 families (61%). None of the parents had myotonia by history or clinical examination.Three muscles, abductor pollicis brevis, flexor pollicis longus, and tibialis anterior, were tested in each of the parents. In each muscle, a minimum of eight sectors were examined at different depths by needle electromyography. RESULTS Myotonic Discharges.Myotonic discharges were present in at least one parent in 12 of the 18 families Abbreviations: EMG, electromyography; RMC, recessive myotonia congenita

Thomsen or Becker myotonia? A novel autosomal recessive nonsense mutation in the CLCN1 gene associated with a mild phenotype

“…Signs of latent myotonia, that is, electrophysiological myotonia, without clinical manifestations, have been described in heterozygous carriers of congenital recessive myotonia. There is no consensus regarding the diagnostic value of this test,3, 5 but in this family even careful electrophysiological study did not identify any myotonic discharges in the tested heterozygotes.…”

Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene

“…Carriers of recessive CLCN1 mutations are usually asymptomatic but subclinical EMG myotonia has been reported (20). Family member IV:3, who is heterozygous for p.Phe413Cys but harboring normal CNPB alleles, experienced muscle stiffness, cold‐induced muscle weakness, and myalgia.…”

Electrodiagnostic studies in the management and prognosis of neuromuscular disorders

“…EMG can be useful in the search for heterozygous carriers of recessive traits causing myotonia. Several reports have detailed the successful diagnosis of heterozygosity for autosomal recessive myotonia congenita 14, 70, 289, 332. Not all parents of affected subjects have electrical myotonia, and fathers are more likely to have myotonia than mothers 70.…”

“…Several reports have detailed the successful diagnosis of heterozygosity for autosomal recessive myotonia congenita 14, 70, 289, 332. Not all parents of affected subjects have electrical myotonia, and fathers are more likely to have myotonia than mothers 70. Electrical myotonia has also been found in asymptomatic family members of patients with autosomal dominant hyperkalemic periodic paralysis167, 170 and myotonia fluctuans 240…”