Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Mary N. Sheppard in Practical Cardiovascular Pathology, 2022
DCM may also occur in mitochondrial cytopathies and inherited metabolic disorders (e.g. haemochromatosis). Neuromuscular disease may accompany DCM, and in some forms of neuromuscular disease, the presenting feature may be cardiac. LMNA mutations can present with or without muscle disease, and the muscle disease ranges from limb-girdle muscular dystrophy to Emery-Dreifuss muscular dystrophy. In LMNA- and SCN5A-mediated cardiomyopathies, arrhythmias including atrial fibrillation or ventricular arrhythmias may be the presenting finding. Both X-linked and autosomal neuromuscular diseases can present with cardiomyopathy, and this includes Duchenne muscular dystrophy, as well as the autosomal recessive forms of sarcoglycanopathies. In these disorders, skeletal muscle disease usually appears in childhood with a typical DCM arising in the teenage years or early twenties. Both forms of myotonic muscular dystrophy, type 1 and type 2, can be associated with DCM. Atrial and ventricular arrhythmias are common in these tri- and tetra-nucleotide repeat expansion disorders. For several subtypes of genetic cardiomyopathy, arrhythmias may be the earliest manifestation. Myotonic dystrophy type 2 usually presents in older individuals, and the diagnosis can be easily missed especially if neuromuscular symptoms are not so pronounced.22
Neuromuscular disorders
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
The protein product of the DMD locus, dystrophin, was entirely unknown before isolation of the gene. It is largely muscle-specific, but with smaller alternative forms present in the cerebellum and elsewhere in the brain. It is usually absent in typical cases of DMD, in contrast to the allelic disorder Becker muscular dystrophy (BMD, see later in this chapter), where it is present but altered in structure and/or reduced in quantity, and other dystrophies where it is generally normal. If a young boy presents with typical features of DMD and has a grossly raised serum creatine kinase (CK), molecular testing of leucocyte DNA will often be sufficient to establish the diagnosis, thereby completely avoiding the need for a muscle biopsy. However, immunocytochemical assays on muscle biopsy sections can contribute to the investigation of a limb girdle muscular dystrophy if DMD or BMD cannot be confirmed rapidly by molecular genetic testing. This requires properly stored frozen muscle.
Genetic Counseling
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Disease, whether genetic or nongenetic, may be due to a variety of factors. Genetic disease is particularly likely to be heterogeneous in this respect. For example, a muscular dystrophy may result from a number of mutant genes. Among the common types of muscular dystrophy, we have the facioscapulohumeral form, which is characteristically auto-somal dominant, and myotonic dystrophy, also autosomal dominant. “Limb-girdle” muscular dystrophy, a diagnosis that probably comprises a number of disorders, is autosomal recessive. Duchenne, Becker, and Emery–Dreifuss muscular dystrophies are all X-linked recessive, with fairly distinct, but overlapping, phenotypes; under some conditions, they can manifest, usually in mild degree, in females also (e.g., symptomatic carriers). Sometimes investigation of a family with “muscular dystrophy” reveals that the primary disease was not in the muscles at all but, for example, a spinal muscular atrophy, originating in the anterior horn cells, or a more generalized disorder, for example, a glycogenosis (42).
Structural and ultrastructural changes in the skeletal muscles of dysferlin-deficient mice during postnatal ontogenesis
Published in Ultrastructural Pathology, 2022
O. N. Chernova, I. A. Chekmareva, M. O. Mavlikeev, I. A. Yakovlev, A. P. Kiyasov, R.V. Deev
Dysferlin is a protein located in sarcolemma and a t-tubule system encoded by the DYSF gene. Dysferlin is responsible for many functions in muscle fibers, such as the repair of damaged sarcolemma, vesicle fusion, cell adhesion, intercellular signaling,1–5 myoblast fusion6 and t-tubule reorganization during myogenesis.3,7,8 Normally, in sarcolemmal rupture, calcium ions trigger synaptic vesicle fusion with membrane “patch” formation. Without dysferlin, vesicular trafficking to the site of rupture is impaired. Progressive sarcolemma disruption results in necrosis of skeletal muscles with fibrosis and lipoidosis.9 Moreover, the lack of dysferlin expression decreases lysosomal exocytosis.10 Mutations in the DYSF gene cause inherited autosomal-recessive muscle dystrophies called dysferlinopathies. This group of disorders includes three clinical phenotypes: limb-girdle muscular dystrophy (LGMD) R2 (OMIM 254130), Myoshi muscular dystrophy (OMIM 253601) and distal myopathy with anterior tibial onset (OMIM 606678). These patients usually manifest limb-girdle muscle weakness in the second decade of life.11 Approximately 5% of previously described patients develop asymptomatic hyperCPKemia.12,13 This finding indicates a probable prolonged subclinical course of dysferlinopathies. As dysferlinopathy is an orphan disease (prevalence of 7.4:1000000),14 the absence of clinical manifestations prevents patients from being within the health care system. Moreover, studying dysferlinopathy pathogenesis at early stages is almost impossible due to the traumatic nature of muscle biopsy in asymptomatic pediatric patients.
An update on diagnostic options and considerations in limb-girdle dystrophies
Published in Expert Review of Neurotherapeutics, 2018
Corrado Angelini, Laura Giaretta, Roberta Marozzo
Sanger sequencing of genomic DNA of individual genes is largely used in mutation detection, however, should be used especially when clinical features or protein testing suggest which gene should be screened: in this way a large number of LGMD cases can be molecularly diagnosed. Sanger sequencing of cDNA may also be required for identifying deep intronic or elusive exonic variants disrupting the correct splicing, which are over 10% of total pathogenetic mutations. However, this analysis requires a muscle biopsy, even if mRNA may also be successfully extracted from blood in dysferlinopathy.
Limb girdle muscle dystrophy and caesarian delivery: Anesthetic management and brief review of literature
Published in Egyptian Journal of Anaesthesia, 2018
Sumit Soni, Amarjyoti Hazarika, Balbir Kumar
LGMD is a rare genetically inherited disorder. It involves the pelvic or shoulder girdle musculature [3]. Muscle fibers are disintegrated and are replaced with the connective and fiber-fatty tissues which cause myasthenia and atrophy [4].The various forms of limb-girdle muscular dystrophy are caused by mutations in many different genes involved in muscle functioning and maintenance.
Related Knowledge Centers
- Facial Muscles
- Heredity
- Muscle Atrophy
- Muscular Dystrophy
- Shoulder Girdle
- Statin
- Torso
- Skeletal Muscle
- Dominance
- Hmg-Coa Reductase