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Inherited Myopathic Diseases
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
The cores seen in CCD express desmin aggregation, devoid of oxidative enzymes, and are best visualized ultrastructurally (Figure 17.1a–c). The distinction of structured cores from unstructured cores has no diagnostic significance. In unstructured cores, ATPase activity is lost and there is severe myofibrillar disruption with Z-line streaming (Figure 17.1c). Some cases may show multiple centrally positioned nuclei that mimic the diagnosis of centronuclear myopathy. Genetic analysis can confirm the RYR-1 mutation. Mutations in the C-terminal exons often show the classical central core pathology and account for 66% of cases.
Environmental and Exposure-Related Deaths
Published in John M. Wayne, Cynthia A. Schandl, S. Erin Presnell, Forensic Pathology Review, 2017
John M. Wayne, Cynthia A. Schandl, S. Erin Presnell
Answer C is incorrect. RYR1 is a receptor that regulates calcium release in skeletal muscle. Mutations in this receptor are associated with malignant hyperthermia where muscle contractions and markedly elevated core body temperatures follow exposure to common anesthetics. There is some evidence that those with mutations of RYR1 may be predisposed to the development of exertional heat stroke.
The Porcine Hyperthermia and Stress Syndromes
Published in S. Tsuyoshi Ohnishi, Tomoko Ohnishi, Malignant Hyperthermia, 1994
The recent localization of the functional defect responsible for the MH reaction to the ryanodine receptor calcium release channel of the sarcoplasmic reticulum (see Section VI.B.) has afforded us a rational and more accurate insight into the transmission of the PMH/SS trait. In the human, the gene for the ryanodine receptor (ryr 1) has been localized to chromosome 19q 13.1 and susceptibility to MH has been linked to mutations of this gene.4a In the pig, the ryr 1 gene and the PMH (hal) locus have been localized to chromosome 6p11-q21. Fujii et al4 have demonstrated a single point mutation in this gene to be correlated with the PMH/SS phenotype in the five major breeds which manifest the condition - knowledge which has allowed the development of a simple, accurate, and noninvasive diagnostic test that can provide the basis for elimination of this mutation if desired or, in view of its association with leanness and muscularity, its controlled retention as the N/n genotype.
Ophthalmological Manifestations of Hereditary Myopathies
Published in Journal of Binocular Vision and Ocular Motility, 2022
Marta Saint-Gerons, Miguel Angel Rubio, Gemma Aznar, Ana Matheu
Core myopathies (CM) are characterized by reduced oxidative enzyme activity in the central area of myofibers during muscle biopsy.17 Minicores and multi-minicores are variants of the same pathology. Autosomal dominant or recessive mutations in the RyR1 gene are related to them. Some variants of CM with multi-minicores are caused by mutations in the SEPN1 gene (selenoprotein N1). Most patients follow a static or slowly progressive course,18 but severe forms of myopathy can be life-threatening in childhood. Some RYR1 gene mutations have been implicated in malignant hyperthermia susceptibility, a disorder of calcium regulation in the skeletal muscle.10 Congenital ophthalmoplegia is associated with RYR1 mutations and, in particular by multi-minicore myopathy type.19,20
Improving genetic diagnostics of skeletal muscle channelopathies
Published in Expert Review of Molecular Diagnostics, 2020
Vinojini Vivekanandam, Roope Männikkö, Emma Matthews, Michael G. Hanna
Mutations in RYR1, ATP1A2, MT-ATP6, and MT-ATP8 have been recently identified in cases of periodic paralysis. Skeletal muscle ryanodine receptor (RYR1) codes for the main sarcoplasmic reticulum-located calcium release channel in muscle and is critical for excitation contraction coupling. RYR1 mutations are known to cause several muscle phenotypes including congenital myopathies, rhabdomyolysis, myalgia, and malignant hyperthermia [77]. A periodic paralysis phenotype caused by RYR1 mutations has been reported in four cases to date [44,78]. Two patients had childhood onset with congenital myopathy and later episodes of periodic paralysis. The other two did not have myopathy but demonstrated later-onset periodic paralysis. Cramps and myalgia were experienced by all patients and typical periodic paralysis triggers such as cold and exercise were described in some.
Exertional rhabdomyolysis and causes of elevation of creatine kinase
Published in The Physician and Sportsmedicine, 2020
Henrik Constantin Bäcker, Morgan Busko, Fabian Götz Krause, Aristomenis Konstantinos Exadaktylos, Jolanta Klukowska-Roetzler, Moritz Caspar Deml
In analyzing rates of serious medical complications associated with exertional rhabdomyolysis, one patient had to be resuscitated who was otherwise healthy during a long-distance run. No comorbidities were found in the further examination. It remains unclear if the rhabdomyolysis was the cause or consequence of resuscitation as mentioned earlier as this patient likely suffered from an exertional heat stroke. In addition, the mechanic resuscitation and especially fluid resuscitation are known to develop edema of the limb and muscles, which can cause even compartment syndrome and therefore rhabdomyolysis [32]. Otherwise, the patients were relatively healthy without serious complications. However, only in the patient who had to be resuscitated, further examinations for metabolic myopathies or genetic mutations like ryanodine receptor 1 (RYR1) were performed which revealed negative. This mutation causes neuromuscular diseases ranging from congenital myopathies to malignant hyperthermia. The prevalence between genetic mutation (RYR1 and 2 CACNAIS) and malignant hyperthermia is estimated at 1 in 3000 cases; however, the true incidence remains unknown. Hereby, malignant hyperthermia causes hyperthermia, hypermetabolism and muscle breakdown which share triggers such as in exercises [33]. Especially heat and exercises trigger rhabdomyolysis without exertional myalgia and in rare occasion isolated exertional myalgia [34].