The histopathological spectrum of malignant hyperthermia and rhabdomyolysis due to RYR1 mutations

• DOI: 10.1007/s00415-019-09209-z
• Publication Date: 2019-02-20T21:23:48Z
• Authors: G. J. Knuiman; B. Küsters; L. Eshuis; M. Snoeck; M. Lammens; L. Heytens; W. De Ridder; J. Baets; R. S. Scalco; R. Quinlivan; J. Holton; I. Bodi; E. Wraige; A. Radunovic; C. von Landenberg; J. Reimann; E.-J. Kamsteeg; C. Sewry; H. Jungbluth; N. C. Voermans
• Keywords: Malignant hyperthermia; Central core disease; Congenital myopathy

The histopathological features of malignant hyperthermia (MH) and non-anaesthetic (mostly exertional) rhabdomyolysis (RM) due to RYR1 mutations have only been reported in a few cases. We performed retrospective multi-centre cohort study focussing on the patients with MH or RM (1987–2017). All muscle biopsies were reviewed by neuromuscular pathologist. Additional morphometric electron microscopic analysis where possible. Through six participating centres we identified 50 from 46 families, including (n = 31) 19). Overall, biopsy 90% showed one more myopathic including: increased fibre size variability 44), increase number fibres internal nuclei 30), type I predominance 13). Abnormalities oxidative staining, generally considered be specifically associated RYR1-related congenital myopathies, observed 52%, included unevenness 24), central cores 7) multi-minicores 3). Apart staining abnormalities frequently patients, spectrum was similar between two groups. There no correlation presence occurrence clinically detectable weakness (likely) pathogenic variants. Patients exhibit spectrum, ranging mild changes other typical myopathies. Suggestive may support involvement, also cases vitro contracture test is not informative.