Abstract Body

Congenital muscular dystrophies (CMD) is a heterogenous group of autosomal recessive condititons with or without brain involvement. They are mainly classified as 1. deficiency of proteins at the extracellular matrix (laminin a2, collagen VI), nuclear envelope (lamin A/C), nesprin), endoplasmic reticulum (selenon); 2. Abnormal glycosylation of proteins (alpha-dystroglycan, Dol-P-Man); 3. Others such as mitochondrial CMD. There has been increasing efforts to treat laminin a-2 deficiency with mini agrin gene delivery or upregulating laminin 111.

Congenital myopathies are can be inherited autosomal recessive, autosomal dominant, and X-linked. They are simply classifed as 1. Nemaline myopathies; 2. Core diseases; 3. centronuclear myopathies; 4. Surplus protein myopathies; 5. Congenital fiber type disproportion (which may be a lumper). Nemaline myopathies constitute a distinct phenotypic group along with peculiar genes. Extraocular muscle involvement should remind centronuclear myopathies. High-arched palate is a cardinal sign in myopatihes. Once excluded, the following gene mutations have recently received recognition: RYR1, TTN, Selenon, and as an overlap Lamin A/C. In a clinical setting more than half of the cases may have a mutation in one of the above genes. Multidisciplinary approach and ambulatory measures are essential in management of CMD and congenital myopathies. A gene therapy program for X-linked myotubular myopathy is on the way.

Abstract Body

The limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of rare, genetic and progressive muscle disorders, with predominant involvement of the pelvic and shoulder girdle muscles. The heart and respiratory muscles can sometimes also be involved. The estimated prevalence for all forms of LGMDs ranges from 1/44000 to 1/123000. Muscle biopsy in LGMDs shows dystrophic changes consisting of necrotic and regenerating muscle fibers, that result in an increased creatine kinase (CK) level in serum. Muscle MRI shows fibro-fatty muscle infiltration, consistent with degenerative changes, often revealing a (recognizable) selective pattern of muscle involvement. The inheritance pattern in LGMDs is mostly autosomal recessive (LGMDR; previous nomenclature: LGMD2), and less frequently autosomal dominant (LGMDD; previous nomenclature: LGMD1). To date, 26 subforms of LGMDR (LGMDR1-R26) and five subtypes of LGMDD (LGMDD1-D5) are known, each caused by two pathogenic variants (LGMDR) or one heterozygous mutation (LGMDD) in distinct genes. These genes encode different components of the myofiber, contractile apparatus, sarcolemma or the cytoplasm. The differential diagnosis of LGMDs includes other muscle disorders, such as facioscapulohumeral muscular dystrophy (FSHD), Emery-Dreifuss muscular dystrophy (EDMD), congenital muscular dystrophies (CMD), inflammatory and metabolic myopathies, as well as neurogenic disorders, such as spinal muscular atrophy (SMA). To date, no curative treatments for LGMDs exist, but novel therapeutic compounds and genetic therapies are currently being developed for several LGMDs.

Abstract Body

The major types of idiopathic inflammatory myopathy include dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (AS), and inclusion body myositis (IBM). I will discuss the clinical, laboratory, and histopathological features of these inflammatory myopathies and update the believed pathogenic basis for these disorders.