X-linked Bulbospinal Neuronopathy

Objective: To characterize the earliest symptoms of Xlinked bulbospinal neuronopathy (Kennedy disease [KD]) during the course of the disease, including a definition of the age of onset. Methods: We describe the earliest symptoms, signs on clinical investigation, electrophysiological and muscle biopsy specimen findings, and creatine kinase levels in 34 patients with KD. Correlations were made among the CAGrepeat length and clinical symptoms, age at onset, and the presence of electrophysiological and laboratory findings. Results: Our findings indicate that the age at onset of KD is in adolescence which is earlier than previously thought. Most frequently early symptoms are gynecomastia, muscle pain, and premature muscular exhaustion. Weakness is not a typical initial symptom and is frequently found in distal limbs if present early. We found a correlation between the of number of CAG repeats and the age at onset of weakness but not to the age at onset of KD. Furthermore, no correlations were found between the occurrence of gynecomastia, tremor, increased creatine kinase levels, and additional myopathic changes in muscle biopsy specimens. Conclusions: Our data show that KD is a multisystem disorder with onset in adolescence. Because of the heterogeneity of clinical presentation and no correlation between the number of CAG repeats and most of the clinical hallmarks of KD, we suggest that other environmental or genetic factors contribute to the manifestation of specific organ systems in KD. Arch Neurol. 2002;59:1921-1926