J Korean Med Sci 2007; 22: 1098-1101 ISSN 1011-8934 DOI: 10.3346/jkms.2007.22.6.1098 Copyright The Korean Academy of Medical Sciences Autosomal Dominant Centronuclear Myopathy with Unique Clinical Presentations Centronuclear myopathies are clinically and genetically heterogenous diseases with common histological findings, namely, centrally located nuclei in muscle fibers with a predominance and hypotrophy of type 1 fibers. We describe two cases from one family with autosomal dominant centronuclear myopathy with unusual clinical features that had initially suggested distal myopathy. Clinically, the patients pre- sented with muscle weakness and atrophy localized mainly to the posterior com- partment of the distal lower extremities. Magnetic resonance imaging revealed pre- dominant atrophy and fatty changes of bilateral gastrocnemius and soleus mus- cles. This report demonstrates the expanding clinical heterogeneity of autosomal dominant centronuclear myopathy. Key Words : Myopathies, Structural, Congenital; Autosomal Dominant Inheritance; Distal Myopathies Jee-Young Lee, Ju-Hong Min, Yoon-Ho Hong, Jung-Joon Sung, Sung-Hye Park*, Seong-Ho Park, Kwang-Woo Lee, Kyung Seok Park Departments of Neurology and Pathology*, Seoul National University College of Medicine, Seoul, Korea Received : 14 September 2006 Accepted : 6 February 2007 Address for correspondence Kyung Seok Park, M.D. Department of Neurology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, Korea Tel : +82.31-787-7469, Fax : +82.31-718-9327 E-mail : pks1126@chol.com *This study was supported by grant No. (02-2006-025) from the Seoul National University Bundang Hospital Research Fund. INTRODUCTION Centronuclear myopathy (CNM) is a congenital myopathy with the characteristic morphology of centrally located nuclei in the vast majority of muscle fibers. After the disease was first reported in 1966 by Spiro et al. as myotubular myopathy (1), three distinctive inheritance patterns in CNM have been dis- covered, i.e., a severe neonatal onset with X-linked recessive type (XRCNM), a less severe infantile or childhood onset with autosomal recessive type (ARCNM), and a milder late child- hood or adult onset with autosomal dominant type (ADCNM) (2). To date, six cases have been reported in Korea (3-7). XR- CNM is a relatively uniform disorder clinically characterized by severe hypotonia, rapidly progressive muscle weakness, and respiratory failure at birth often leading to early mortality. This form is also called as X-linked myotubular myopathy. How- ever, unlike XRCNM, the clinical features of autosomal dom- inant CNM (ADCNM) are quite variable among reported fam- ilies. We describe unusual manifestations of ADCNM with preferential involvement of the distal lower extremities, espe- cially in the gastrocnemius and soleus muscles, with a brief review of clinical features of previously reported ADCNM. 1098 CASE REPORTS Case 1 A 49-yr-old woman presented with slowly progressive we- akness of both legs, which had developed at the age of forty. Initially, she felt her gait waddling slightly, and she had dif- ficulty in climbing stairs and standing on her toes. Weakness was dominant in the distal part of both lower extremities, which did not affect daily activities. She was a product of a full-term spontaneous vaginal delivery, without perinatal or develop- mental problems. She had no history of medical illness or drug use, including steroids and herb medicines. She had two dughters. One was an 18-yr-old girl, who developed similar symptoms at the age of fifteen (see case 2), and the other, a 15-yr-old girl, was not affected. Her 70-yr-old mother had the same gait abnormality and progressive weakness and wast- ing of both calf muscles, which occurred in late-fifties with- out impairment of daily activities. Other family members did not have a history of neuromuscular diseases. Neurological examinations revealed a mild symmetrical weakness of the dis- tal lower extremities. Muscle powers of the ankle dorsiflexors and plantar flexors were Medical Research Council (MRC) grade 5- and 4, respectively. Muscle-strength testing was