Case report Early onset distal muscular dystrophy with normal dysferlin expression Nobuyuki Murakami a,b, * , Ryoichi Sakuta a,b , Etsuro Takahashi a , Yasuki Katada a , Toshiro Nagai a , Misao Owada c , Ichizo Nishino b , Ikuya Nonaka b a Department of Pediatrics, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan b Department of Neuromuscular disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan c Department of Pediatrics, Nihon University School of Medicine, Chiyoda-ku, Tokyo, Japan Received 26 November 2004; accepted 3 February 2005 Abstract A 7-year-old boy, who was noted to be a slow runner at the age of 2 years, had progressive muscle weakness and atrophy, preferentially affecting distal muscles. At 3 years of age, he had scoliosis and difficulty in standing on tip-toe. Serum creatine kinase was 1074 IU/l. Muscle CT scan showed low-density areas in the lower legs and upper arms, but predominantly in the gastrocnemius and soleus muscles. Biopsy of the biceps brachii muscle showed moderate dystrophic changes with normal dysferlin expression on immunohistochemical and western blot analyses. Although muscle involvement mimicked that seen in Miyoshi myopathy (MM), the very early onset of the disease and scoliosis were quite unusual for MM. We, therefore, made the diagnosis of early onset dysferlin-positive distal muscular dystrophy, probably a new type of distal muscular dystrophy. q 2005 Elsevier B.V. All rights reserved. Keywords: Distal muscular dystrophy; Miyoshi myopathy; Scoliosis; Dysferlin 1. Introduction Although proximal muscles are affected in most myopathies, distal muscles are exceptionally involved in some disorders named distal myopathy. In distal myopathy with rimmed vacuoles (DMRV) and tibial muscular dystrophy, the anterior compartment of the legs, such as anterior tibial muscle, is preferentially affected. On the other hand, in Miyoshi myopathy (MM) posterior compartment of the legs is predominantly involved from the early stage of the disease. MM is a distal muscular dystrophy inherited through an autosomal recessive trait with preferential gastrocnemius and soleus muscle involvement [1]. The responsible gene for MM was cloned and the gene product was named dysferlin [2]. Interestingly limb-girdle muscular dystrophy type 2B (LGMD2B), one of the proximal dominant muscular dystrophies, is also caused by dysferlin deficiency [3]. In some patients with LGMD2B, gastrocnemius and soleus muscles are also involved from an early stage of the disease [4]. In addition, there are patients with MM and LGMD2B in the same family [2,5,6]. Therefore, MM and LGMD2B are thought to be allelic disorders and sometimes called dysferlinopathy. However, 25% of the patients who had the clinical diagnosis of MM were reported to have normal dysferlin expression [7]. MM is therefore thought to be a group of heterogeneous disorders. 2. Clinical observation A 7-year-old Japanese boy, who was born by normal delivery at 39 weeks gestation, was referred to our hospital at the age of 3 years because of muscle weakness and elevated serum creatine kinase (CK) level. His parents were not consanguineous. There was no family history of neuromuscular disorders. He spoke meaningful words at 12 months of age and walked at 13 months. He could not run as fast as other children. At the age of 3 years he was referred to our Brain & Development 27 (2005) 589–591 www.elsevier.com/locate/braindev 0387-7604/$ - see front matter q 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2005.02.002 * Corresponding author. Address: Department of Pediatrics, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minami- Koshigaya, Koshigaya, Saitama 343-8555, Japan. Tel.: C81 48 965 1111; fax: C81 48 965 9367. E-mail address: nobuyuki@dokkyomed.ac.jp (N. Murakami).