Muscular Dystrophies Monisha Mukherjee and Balraj Mittal Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, India. Abstract. Muscular dystrophies are a heterogeneous group of inherited disorders characterized by progressive muscle wasting and weakness. Majority of genes and their protein products responsible for the dystrophies have been identified in recent years. Using molecular studies, now it is possible to establish a precise diagnosis, provide prognosis, detect preclinical cases, identify carriers, and offer prenatal diagnostic testing. Molecular genetic approaches also seem to offer the best prospect for developing effective treatments in the future. [Indian J Pf~liatr 2004; 71 (2) : 161-168] E-mail : balraj @ sgpgi.ac.in; bml_pgi @ yahoo.com Key words : Inherited disorders; Molecular testing; Prenatal diagnosis; Genetic counseling DEFINITION OF MUSCULAR DYSTROPHY The muscular dystrophies are a group of inherited disorders characterized by progressive muscle wasting and weakness. 1 Muscular dystrophy includes many genetically distinct disorders. The list of causative genes for muscular dystrophies has been expanding rapidly, including those for congenital muscular dystrophies. Although clinical signs and symptoms are important but immunohistochemical and DNA based mutation analysis have made it possible to establish precise diagnosis of the dystrophies. Most of the dystrophies unfortunately have a very poor prognosis; therefore genetic counseling based on reliable prenatal diagnosis, and carrier detection can be useful in providing help to the affected families. Duchenne/Becker dystrophy (D/BMD) is the commonest form of hereditary muscular dystrophy. Using positional cloning approaches, search for the gene responsible for the disease resulted in the discovery of the protein 'dystrophin'. The protein was found to be deficient or absent in D/BMD patients. Further studies showed that dystrophin and its associated proteins form a multimeric complex which plays crucial role in stabilization of sarcolemmal membrane 2 (Fig. 1). The importance of the complex can be gauged from the fact that as many as eight hereditary muscular dystrophies result due to mutations in the dystrophin complex. In addition, several other genes have been identified which are defective in other muscular dystrophies. CLASSIFICATION OF MUSCULAR DYSTROPHIES 3 General classification is still based on clinical signs and symptoms while immunohistochemistryand gene studies Reprint requests : Dr. B. Mittal,Professor,Departmentof Medical Genetics,Sanjay GandhiPostgraduateInstituteof Medical Sciences, RaebareliRoad,Lucknow-226014. Fax:91-522-2668017/2668078 Fig. 1. SchematicDiagramof the DystrophinComplex are useful for subtyping. 1. Duchenne and Becker Muscular Dystrophy 2. Emery-Dreifuss Muscular Dystrophy 3. Limb-Girdle Muscular Dystrophy 4. Congenital Muscular Dystrophies 5. Distal Myopathies 6. Facioscapulohumeral Dystrophy 7. Oculopharyngeal Dystrophy 8. Myotonic Dystrophy 9. Hereditary Inclusion Body Myopathies 1. Duchenne and Becker Muscular Dystrophies (Dystrophinopathies) Duchenne and Becker are allelic disorders. DMD is a disease of muscle that becomes evident in early childhood but BMD is milder with late onset. 4 The disease is inherited as an X-linked recessive trait and predominantly Indian Journal of Pediatrics, Volume 71--February, 2004 161