A phenotypic‐genetic study of a group of Polish patients with spinal and bulbar muscular atrophy

Abstract

We studied phenotype-genotype correlation in a group of Polish males with spinal and bulbar muscular atrophy (SBMA) and in female carriers. Eleven males with suspected SBMA phenotype and three suspected female carriers were examined. Male patients presented with the predominant signs of progressive, symmetrical distal limb weakness with amyotrophy, facial muscular weakness with orofacial fasciculations, nasal voice and slight dysphagia, gynaecomastia, decreased potency, as well as hand tremor and distal peripheral sensory disturbances in a few cases. One of the carriers presented with a 30-year history of fasciculations and minimal distal weakness and cramps in the legs, while the other two were asymptomatic. DNA analysis revealed expanded size of CAG repeats in Xq11-12 in the AR gene in 10 out of 11 men (range 45-52 CAG repeats) and in the women (range 46-48 CAG repeats). There was no correlation between CAG repeat size and the age of disease onset and duration of the disease. A rare, predominantly distal distribution of weakness and amyotrophy was found in our group of the SBMA patients (8 out of 11 cases) from three unrelated kindreds and also in the remaining two sporadic cases. The extended CAG repeats within families were stable.

Bulbar and spinal muscular atrophy (Kennedy’s disease): a review

“…Female carriers show no abnormalities on electromyography in most studies [35] but exhibit skewed methylation of the wild‐type allele [35]. Clinical manifestations in female carriers include hyper‐CK‐emia, fasciculations, minimal distal weakness, or muscle cramps [31]. Muscle biopsy in these female carriers may show mild myopathic or neurogenic alterations [36].…”

Perspectives of Kennedy's disease

“…Frequently, patients present with perioral tremor [23][24][25] or with postural tremor [20]. Further presenting symptoms may be proximal or distal flaccid weakness, although weakness is not a typical initial manifestation, dysarthria, dysphagia, hanging jaw (jaw drop), contraction fasciculations, or flexor muscle cramps [2,20,21,[25][26][27][28].…”

“…The other half may present with fasciculations, minimal distal weakness, muscle cramps, or hyper-CK-emia later in life [19,24,45]. Two sisters, homozygous for the CAG-expansion, manifested with occasional muscle cramps, mild hand tremor, and occasional perioral fasciculations or twitches [48].…”

Spontaneous activity in electromyography may differentiate certain benign lower motor neuron disease forms from amyotrophic lateral sclerosis

“…This may be surprising, because fasciculations have been considered a major feature in both SMAJ and SBMA diseases. Two factors may explain this apparent discrepancy: first, we did not evaluate the presence of EMG fasciculations in general, as in many other studies [8,25], but only unilaterally in these five muscles chosen for statistical analyses. Furthermore, the firing frequency of fasciculation potentials in ALS has been reported to be 8 times higher than in SBMA (24/min vs 3/min) [12].…”