Review Article Congenital myopathies – a comprehensive update of recent advancements Introduction The term Ôcongenital myopathyÕ (CM) was intro- duced in the scientific literature in 1956 (1) when Shy and Magee described a new congenital non- progressive myopathy, which was later termed Ôcentral core diseaseÕ (2, 3). Within a few years after the first description of central core disease (CCD) numerous new myopathies like centronuclear myopathy (CNM), which was initially termed as Ômyotubular myopathy (MM)Õ (4) but later as Ôfamilial CNMÕ (5), nemaline myopathy (NM) (6), myopathy with myogranules (7), multicore (8), minicore (9), CCD and focal loss of cross striations (10) were described. Dubowitz (11) coined the term Ônew myopathiesÕ which was soon replaced by CMs. Epidemiological data are only available for the CMs as a group but not for individual conditions. The incidence of all CMs is estimated at around 0.06 ⁄ 1000 live births, or one tenth of all cases of neuromuscular disorders (12). Regional studies in Northern Ireland and Western Sweden suggest prevalence between 3.5–5.0 ⁄ 100,000 in a pediatric population (13). The CMs are a group of neuromuscular disorders with age of onset mostly in childhood and occa- sionally in adults (14). They are usually familial in nature with occasional sporadic occurrences. They are slowly progressive, but exceptionally may have a more rapid course and most of the patients die from respiratory and cardiac failure (15). The disease specific structural changes seen in the muscle are detected by enzyme histochemistry, immunohistochemistry and electron microscopy. Clinically, muscle weakness, hypotonia, atrophy, and proximal muscle involvement are frequent manifestations. Infants may be floppy. Although no pathognomonic clinical symptoms are associ- ated with any individual CM, some specific clinical findings are more frequent in certain CMs, such as ptosis or extra ocular muscle weakness in multicore disease, NM, CNM, congenital fiber type dispro- portion (CFTD) and congenital myasthenic syn- dromes; respiratory insufficiency in central and multicore diseases, cytoplasmic body myopathy, and desmin related myopathies (DRM); myalgia in spheroid body myopathy, tubular aggregate myop- athy, and cylindrical spirals myopathy; dysphagia Sharma MC, Jain D, Sarkar C, Goebel HH. Congenital myopathies – a comprehensive update of recent advancements. Acta Neurol Scand 2009: 119: 281–292. Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard. The congenital myopathies are relatively newly discovered compared with other categories of muscle diseases. Current research continues to clarify and classify the congenital myopathies. These pose a diagnostic problem and cannot be diagnosed by routine hematoxylin and eosin stain. A lot of special techniques are required to diagnose them correctly and itÕs various subtypes. The disease specific structural changes seen in the muscle are detected by enzyme histochemistry, immunohistochemistry and electron microscopy. Through this review we provide an up-to-date analysis of congenital myopathies including clinical and pathologic aspects. M. C. Sharma 1 , D. Jain 2 , C. Sarkar 1 , H. H. Goebel 3 1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India; 2 Department of Pathology, Maulana Azad Medical College, New Delhi, India; 3 Department of Neuropathology, Johannes Gutenberg University Medical Center, Mainz, Germany Key words: congenital myopathy; clinicopathological; enzyme histochemistry; muscle biopsy; ultra structure Dr M C Sharma, Department of Pathology, All India Institute of Medical Sciences, New Delhi-110029, India Tel.: 91 11 26593371 Fax: 91 11 26588663 e-mail: sharmamehar@yahoo.co.in Accepted for publication September 9, 2008 Acta Neurol Scand 2009: 119: 281–292 DOI: 10.1111/j.1600-0404.2008.01126.x Copyright Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard ACTA NEUROLOGICA SCANDINAVICA 281