Phenotypic variability in Kennedy’s disease: implication of the early diagnostic features Kennedy’s disease (KD, spinal and bulbar muscu- lar atrophy, bulbospinal neuronopathy) is an X-linked neurodegenerative disease of motor and sensory neuron caused by an expansion of CAG repeat sequence within the first exon of the androgen receptor (AR) gene (1–5). The clinical hallmarks of KD include onset in the third or fourth decade of life, weakness and wasting predominantly of proximal extremity mus- cles, variable weakness of bulbar muscles, abun- dant muscle fasciculations, sensory nerve action potential (SNAP) abnormalities, and signs of androgen insensitivity such as gynecomastia, impo- tence, and testicular atrophy (1–3, 5–7). When a patient has all these classic signs and symptoms of the disease, it is easily distinguished from the diseases which share similar clinical or electro- physiological findings such as spinal muscular atrophy, hereditary sensory and motor neuropa- thy, and amyotrophic lateral sclerosis (ALS) (6, 8), and the diagnosis is straightforward. However, in clinical practice, the patients with KD often present prior to the development of all the typical manifestations of the disease. The onset of KD could be earlier than commonly reported. And the limb weakness, which gives us the first impression of neuromuscular disorder, is not ranked as an initial symptom. Rather, symptoms other than muscle weakness, like gynecomastia, premature exhaustion, muscle cramps and pain, and postural tremor prevail early in the course, leading to the misdiagnoses (8). In order to help to identify KD in early stages and avoid misdiagnosis, we characterized genetic- ally proven 18 Korean patients with KD. We also tried to determine the typical clinical courses of KD, and analyzed the causes of misdiagnosis. Materials and methods All patients were recruited from our neuromuscu- lar clinics. The age at onset of each symptom was Acta Neurol Scand 2005: 112: 57–63 DOI: 10.1111/j.1600-0404.2005.00428.x Copyright Ó Blackwell Munksgaard 2005 ACTA NEUROLOGICA SCANDINAVICA Lee J-H, Shin J-H, Park K-P, Kim I-J, Kim C-M, Lim J-G, Choi Y-C, Kim D-S. Phenotypic variability in Kennedy’s disease: implication of the early diagnostic features. Acta Neurol Scand 2005: 112: 57–63. Ó Blackwell Munksgaard 2005. Objectives – The clinical diagnosis of Kennedy’s disease (KD) is not easy when the typical manifestations are lacking, especially in early stage of the disease. In our study, we tried to identify the relative frequency of common clinical features and early symptoms in KD. Method – Eighteen Korean patients with KD were included. Clinical findings were subdivided into two parts: the age at onset of each clinical symptoms and characteristic signs on investigations. With detailed clinical examinations, the serum creatine kinase (CK) level, electrophysiologic study and DNA analysis were performed and analyzed in detail. Results – In KD, the most consistent clinical findings at evaluations included perioral fasciculation with variable bulbar paresis, limb weakness with wasting, hyporeflexia, hand tremor, and elevated CK level. Some distinguishing features, such as X-linked family history, gynecomastia, and sensory abnormalities were absent in a half of cases. Frequent initial clinical findings include tremor (50%) and symptoms other than weakness, such as cramps and fatigability (33.3%). Conclusion – We conclude that KD shows variable clinical and electrophysiological features. Our description on the onset and subsequent progression of each clinical finding might help to identify KD in early stage and avoid misdiagnosis. Jae-Hyeok Lee 1 , Jin-Hong Shin 1 , Kyung-Pil Park 1 , In-Joo Kim 2 , Cheol-Min Kim 2,3 , Jeong-Geun Lim 4 , Young-Chul Choi 5 , Dae-Seong Kim 1,3 1 Department of Neurology, College of Medicine, Pusan National University, Pusan, Korea; 2 Department of Biochemistry, College of Medicine, Pusan National University, Pusan, Korea; 3 Medical Research Institute, Pusan National University Hospital, Pusan, Korea; 4 Department of Neurology, Keimyung University School of Medicine, Daegu, Korea; 5 Department of Neurology, Yonsei University College of Medicine, Youngdong Severance Hospital, Seoul, Korea Key words: Kennedy's disease; phenotypic variability; tremor; early features Dae-Seong Kim, Department of Neurology, Medical Research Institute, Pusan National University Hospital, 1-Ga-10, Ami-Dong, Seo-Ku, Pusan 602-739, Korea Tel.: +82-51-240-7672 Fax: +82-51-245-2783 e-mail: dskim@pusan.ac.kr Accepted for publication September 22, 2004 57