Electrophysiological evaluation in myotonic dystrophy: correlation with CTG length expansion

Abstract

-In myotonic dystrophy (MD), disease severity has been correlated with expansion of CTG repeats in chromosome 19. The aims of this study were to evaluate efficacy of electromyography in the diagnosis of MD, access the frequency and the characteristics of peripheral involvement in the disease and to verify whether the CTG repeats correlated with the electrophysiological abnormalities. Twenty-five patients and six relatives at risk of carrying the MD gene were examined. Electrical myotonia (EM) was scored. Sensory and motor conduction velocity (CV) were studied in five nerves. Leukocyte DNA analysis was done in 26 subjects. Myopathy and myotonia were found in 27 cases. EM was most frequent in muscles of hand and in tibialis anterior. No significant correlation was found between EM scores and length of CTG expansions. EM scores correlated significantly with the degree of clinical myopathy, expressed by a muscular disability scale. Peripheral neuropathy was found in eight subjects and was not restricted to those who were diabetics.KEY WORDS: myotonic dystrophy, electromyography, myotonia, myopathy, peripheral neuropathy, CTG repeat. Avaliação eletrofisiológica na distrofia miotônica: correlação com a expansão de tripletos CTG.RESUMO -Na distrofia miotônica (DM) a severidade da doença tem sido correlacionada com a expansão de tripletos CTG, no cromossomo 19. Foram objetivos do estudo avaliar a eficácia da eletromiografia no diagnóstico, verificar a freqüência e tipos de neuropatias periféricas e determinar se a expansão CTG correlacionava-se com as anormalidades eletrofisiológicas nesta doença. Examinamos 25 pacientes e seis familiares sob risco de herdar a doença. A miotonia elétrica (ME) foi graduada, cinco velocidades de condução sensitivas e cinco motoras estudadas. O DNA leucocitário foi analisado em 26 indivíduos. Encontrou-se miopatia miotônica em 27 pacientes, sendo a ME mais freqüente nos músculos da mão e no tibial anterior. Não houve correlação significativa entre os graus de ME e o número de repetições CTG. Os graus de ME correlacionaram-se significantemente com a severidade da miopatia clínica, expressa por escala de disfunção muscular. Neuropatia periférica foi encontrada em oito indivíduos, não exclusivamente em diabéticos. PALAVRAS-CHAVE: distrofia miotônica, eletromiografia, miotonia, miopatia, neuropatia periférica, repetição de tripletos.

Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy

“…Our hypothesis was that the distribution of EM would conform to the distribution of muscle weakness in the two disorders: more distal in DM1 and more proximal in DM2. In DM1, we confirmed that myotonia is far more evocable distally in the arm and leg, as noted by others, 14,21 and all our DM1 patients had distally predominant limb weakness on neurologic examination. Contrary to what we expected, myotonia was also worse distally in DM2, at least in the arm, in which the steepness of the drop-off in myotonia from distal to proximal muscles was not significantly different than in DM1.…”

“…21 A more recent study of 27 patients confirmed these findings using similar methodology to estimate the severity of myotonia. 14 In 1992, it was reported that the genetic defect underlying classic myotonic dystrophy is an unstable expanded CTG triplet repeat in the untranslated region of the DMPK protein kinase gene on chromosome 19. 3 In the middle to late 1990s, a number of investigators 6,17,18,23,25 reported an autosomaldominant systemic disease very similar to classic myotonic dystrophy, except that the distribution of limbmuscle weakness was often more proximal than distal, muscle atrophy was less, and there was no expansion of the CTG triplet repeat sequence.…”

Abnormalities of nerve conduction studies in myotonic dystrophy type 1: Primary involvement of nerves or incidental coexistence?

“…3,4,12 Some authors have insisted that PN is not uncommon and exists in 20%-30% of patients with DM1. [18][19][20][21] This thesis is supported by electrophysiological, 18,21,22 pathological, 20 and clinical findings. The common feature in these reports is that, in DM1 patients, PN is an axonal neuropathy that tends to progress in a stepwise fashion irrespective of the clinical severity of myopathy.…”

Combination of myotonic dystrophy and hereditary motor and sensory neuropathy

“…A linkage to the HMSN genes could not be shown. An association with diabetes mellitus was also largely excluded [4,[6][7][8]. In contrast, in the Index case described in this paper, the reason for polyneuropathy was firmly established by the presence of a CMT1 mutation, in addition to her DM1 mutation.…”

“…In the literature there are controversial results for the involvement of the peripheral nervous system in DM. Axonopathy was reported, involving both the motor and the sensory nerves, rather than demyelination in electrophysiological investigation of DM patients [4][5][6][7][8][9]. However, morphological and morphometric analyses of DM1 transgenic mice, carrying 300 CTG repeats, did not reveal axonal degeneration, sensory and motor neuropathy and a significant demyelination [10].…”