Limb Girdle Muscular Dystrophies

Abstract

Autosomal dominant and recessive limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetic diseases with a wide spectrum of clinical involvement and severity. In contrast to the more common X-linked dystrophinopathies, onset is often later during late childhood or at adult age. LGMD patients usually show progressive weakness predominantly at the limb musculature, proximal greater than distal. Onset, progression, and distribution of the weakness and wasting can greatly vary between individual patients and genetic subtypes. Most LGMD patients have typical histopathological dystrophic changes consisting of degeneration and regeneration of muscle fibers which usually leads to elevated serum creatine kinase levels. Diagnosis often can be achieved when performing protein immunostaining—or blotting. In addition, a specific pattern of muscular involvement on muscle magnetic resonance imaging (MRI) can be observed in many LGMD subtypes. There is considerable clinical and or pathological overlap with other early onset congenital myopathies, distal myopathies, and myofibrillar myopathies. Not all of these entities are described in the chapter as some of these LGMD causing genes may also manifest with a different clinical (e.g., distal) or histopathological phenotype. Autosomal recessive forms are much more common and have been referred to as LGMD2, whereas autosomal dominant forms are referred to as LGMD1. For myotilinopathy (LGMD1A) see Sect. 20.4; for Laminopathies (LGMD1B), see Chap. 18; for dystroglycan-related myopathies (LGMD2I, LGMD2K, LGMD2M, LGMD2N) see Sect. 16.5; for titin-related limb-girdle myopathy (LGMD2J) see Sect. 21.2.1; and for Anoctamin (ANO5)-related myopathy (LGMD2L) see Sect. 21.3.2.