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.
Danek
A
A
Neurologische Klinik, Ludwig-Maximilians-Universität, München, Germany.
Heye
B
B
Schroedter
R
R
D061085:Agenesis of Corpus Callosum; D002465:Cell Movement; D004292:Dominance, Cerebral; D004558:Electric Stimulation; D004576:Electromyography; D005071:Evoked Potentials; D005260:Female; D005808:Genes, Recessive; D007987:Gonadotropin-Releasing Hormone / Q000172:deficiency; D006579:Heterozygote; D006801:Humans; D007006:Hypogonadism / Q000196:embryology / Q000235:genetics* / Q000503:physiopathology; D007031:Hypothalamus / Q000196:embryology; D008297:Male; D009044:Motor Cortex / Q000196:embryology / Q000503:physiopathology*; D009069:Movement Disorders / Q000196:embryology / Q000235:genetics* / Q000503:physiopathology; D000857:Olfaction Disorders / Q000235:genetics; D009833:Olfactory Pathways / Q000196:embryology; D010375:Pedigree; D011930:Reaction Time; D013577:Syndrome; D014960:X Chromosome
D007987:Gonadotropin-Releasing Hormone