Cortically evoked motor responses in patients with Xp22.3-linked Kallmann's syndrome and in female gene carriers

Patients with Kallmann's syndrome show hypothalamic hypogonadism,
hyposmia, and congenital mirror movements. As a correlate, a defect
of gonadotropic neuron migration into the brain was recently
detected. Considering abnormal outgrowth of neurons also as a
possible substrate underlying mirror movements, we studied 3
patients and 2 asymptomatic female gene carriers from a kindred
with proven linkage to Xp22.3, using focal transcranial magnetic
stimulation of motor cortex hand areas with a figure-eight coil. In
all 3 affected brothers, bilateral responses could be evoked almost
simultaneously in their thenar muscles (slight latency differences
were statistically insignificant). In contrast, the mother and the
maternal aunt showed only unilateral, normal thenar responses, even
with maximum tolerable stimulator output and high signal
amplification. Correspondingly, mirror movements were present in
the patients, but not in the gene carriers. Bilaterality of
cortically evoked hand muscle responses and mirror movements,
therefore, behaved as X-chromosomal recessive traits. A likely
cause might be a disorder of neuronal outgrowth in the motor
system, particularly of inhibitory callosal fibers. For normal
anatomical development of the motor system, one intact Xp22.3 gene
seems necessary.